{"text_format":"1","workbook":"xlsx","n_sheets":17,"sheets":["Instructions","LookUp","LinkAB","LinkYZMammals","LinkYZFish","LinkYZAmphibian","LinkYZAvian","LinkInVitro","Interpretation","Data","Data summary_APPL","LoE T","LoE EAS","LoE sensitive to EATS","LoE TOT","LoE sys tox","Study overview"],"not_rendered":{"charts":0,"images":0,"macros":1,"external_links":4,"defined_names":85,"comments":2,"pivot_tables":0},"unopened":[],"bounds":{"document_bytes":16777216,"sheet_cells":100000,"rows_first":2000,"rows_last":500,"rows_between":2000,"halvings":0,"cell_chars":16384,"cell_head_chars":4096},"cells_cut":0,"cells_raw":0,"read":"whole","date_system":"1900"}

{"sheet":"Instructions","index":0,"n_rows":4,"n_cols":14,"rows_kept":4,"cut":false,"hidden":true,"merged":[]}
["Instructions of use",null,null,null,null,null,null,null,null,null,null,null,"OLD","NEW"]
[null,null,null,null,null,null,null,null,null,null,null,"names management rules",70,27]
[null,"New occurrences on Y column"]
[null,"Add a sheet and name it as \"LinkYZnew"]

{"sheet":"LookUp","index":1,"n_rows":19,"n_cols":9,"rows_kept":19,"cut":false,"hidden":true,"merged":[]}
["LookUp Column","L","N","O","S","U","V","AD"]
["Header","Sex (administration)","Route of administration","Method of administration","Dose unit","Duration unit","Generation/Life stage","Effect direction","Relevance"]
[null,"M","Oral","Feed","mg/kg bw/day","Minutes","Adult","Increase","Yes"]
[null,"F","Inhalation","Gavage/Intubation","mg/L water","Hours","Adult (P1)","Decrease","No"]
[null,"M + F","Dermal","Whole-Body","mg/L","Days","Adult (F0)","Change","N/A"]
[null,null,"Direct","Capsule","µg ai/L","Weeks","Adult (F1)","Induction"]
[null,null,"Uptake from water","Water","Molar","Months","Adult (F2)","No effect"]
[null,null,"Uptake from the medium (in vitro)","Topical","ppm","Years","Adult (F0+F1)"]
[null,null,"[Not in list]","Not specified","µM",null,"Offspring (F1)"]
[null,null,null,"Subcutaneous","other",null,"Offspring (F2)"]
[null,null,null,"Intravenous",null,null,"Offspring (F3)"]
[null,null,null,"Nose only",null,null,"Offspring (F1+F2)"]
[null,null,null,"[Not in list]",null,null,"Fetus"]
[null,null,null,null,null,null,"Embryo"]
[null,null,null,null,null,null,"Larval"]
[null,null,null,null,null,null,"Juvenile"]
[null,null,null,null,null,null,"Tadpole"]
[null,null,null,null,null,null,"Eggs"]
[null,null,null,null,null,null,"[Not in list]"]

{"sheet":"LinkAB","index":2,"n_rows":32,"n_cols":15,"rows_kept":32,"cut":false,"hidden":true,"merged":[]}
["Column A","Column B Study principle","Column B Study principle","Column B Study principle","Column B Study principle","Column B Study principle","Column B Study principle","Column B Study principle","Column B Study principle","Column B Study principle","Column B Study principle","Column B Study principle","Column B Study principle","Column B Study principle","Column B Study principle"]
["TypeOfToxicity","Mammals","Fish","Amphibian","Avian","InVitroEstrogen","InVitroAndrogen","InVitroThyroid","InVitroSteroidogenesis","InVitroToxCast Estrogen","InVitroToxCast Androgen","InVitroToxCast Thyroid","InVitroToxCast Steroidogenesis","InVitroHepatocytes","InVitroGeneral"]
[null,"Adult male assay","Fish short-term reproduction assay","Amphibian metamorphosis assay","Avian reproduction test","ER Binding Assay","AR Binding Assay","TR binding assay","H295R steroidogenesis assay","ToxCast ER prediction model","ToxCast AR prediction model","ATG_THRa1_TRANS_up","NVS_ADME_hCYP19A1","In vitro hepatocytes","In vitro method (general)"]
[null,"Carcinogenicity","21-day fish assay","Xenopus embryonic thyroid signalling assay XETA","US EPA avian two-generation study","Stably Transfected Human ERα Transcriptional Activation Assay (ER STTA)","Stably Transfected Human AR Transactivation Assay (AR STTA)","Other TR in vitro assay","Aromatase Assay","NVS_NR_bER","ATG_AR_TRANS_up","NVS_NR_hTRa","TOX21_Aromatase_Inhibition"]
[null,"Chronic toxicity","Androgenised female stickleback screen","Larval amphibian growth and development assay","Avian Not il list","BG1Luc Estrogen Receptor Transactivation Assay","Other AR in vitro assay",null,"Other Steroidogenesis in vitro assay","NVS_NR_hER","NVS_NR_cAR","Tox21_TR_LUC_GH3_Agonist","CEETOX_H295R_11DCORT_dn"]
[null,"Combined chronic toxicity/carcinogenicity studies","EASZY assay","Amphibian Not il list",null,"Other ER in vitro assay",null,null,null,"NVS_NR_mERa","NVS_NR_hAR","Tox21_TR_LUC_GH3_Antagonist","CEETOX_H295R_OHPREG_dn"]
[null,"Combined\nrepeated dose toxicity study with the reproduction/developmental toxicity screening test","Juvenile medaka anti-androgen screening assay",null,null,null,null,null,null,"OT_ER_ERaERa_0480","NVS_NR_rAR",null,"CEETOX_H295R_OHPREG_up"]
[null,"Developmental neurotoxicity study","Rapid androgen disruption adverse outcome reporter assay",null,null,null,null,null,null,"OT_ER_ERaERa_1440","OT_AR_ARELUC_AG_1440",null,"CEETOX_H295R_OHPROG_dn"]
[null,"Extended one-generation reproductive toxicity study","Fish sexual development test",null,null,null,null,null,null,"OT_ER_ERaERb_048","OT_AR_ARSRC1_0480",null,"CEETOX_H295R_ANDR_dn"]
[null,"Female pubertal assay (PP Female Assay)","Medaka extended one-generation reproduction test",null,null,null,null,null,null,"OT_ER_ERaERb_1440","OT_AR_ARSRC1_0960",null,"CEETOX_H295R_CORTISOL_dn"]
[null,"Fertility (Segment I)","Fish life cycle toxicity test",null,null,null,null,null,null,"OT_ER_ERbERb_0480","Tox21_AR_BLA_Agonist_ratio",null,"CEETOX_H295R_DOC_dn"]
[null,"Hershberger assay","Fish reproduction partial lifecycle test",null,null,null,null,null,null,"OT_ER_ERbERb_1440","Tox21_AR_BLA_Antagonist_ratio",null,"CEETOX_H295R_ESTRADIOL_dn"]
[null,"Male pubertal assay (PP Male Assay)","Fish early life stage toxicity test",null,null,null,null,null,null,"OT_ERa_EREGFP_0120","Tox21_AR_LUC_MDAKB2_Agonist",null,"CEETOX_H295R_ESTRONE_dn"]
[null,"Multigenerational reproductive toxicity","Fish Not il list",null,null,null,null,null,null,"OT_ERa_EREGFP_0480","Tox21_AR_LUC_MDAKB2_Antagonist",null,"CEETOX_H295R_PROG_dn"]
[null,"One-generation reproduction toxicity study",null,null,null,null,null,null,null,"ATG_ERa_TRANS_up",null,null,"CEETOX_H295R_PROG_up"]
[null,"Peripubertal male and female assays",null,null,null,null,null,null,null,"ATG_ERE_CIS_up",null,null,"CEETOX_H295R_TESTO_dn"]
[null,"Prenatal developmental toxicity study",null,null,null,null,null,null,null,"Tox21_ERa_BLA_Agonist_ratio"]
[null,"Repeated dose 28-day oral toxicity study in non-rodents",null,null,null,null,null,null,null,"Tox21_ERa_LUC_BG1_Agonist"]
[null,"Repeated dose 28-day oral toxicity study in rodents",null,null,null,null,null,null,null,"ACEA_T47D_80 h"]
[null,"Repeated dose 90-day oral toxicity study in non-rodents",null,null,null,null,null,null,null,"Tox21_ERa_BLA_Antagonist_ratio"]
[null,"Repeated dose 90-day oral toxicity study in rodents",null,null,null,null,null,null,null,"Tox21_ERa_LUC_BG1_Antagonist"]
[null,"Repeated dose dermal toxicity"]
[null,"Reproduction/developmental toxicity screening test"]
[null,"Subacute inhalation toxicity"]
[null,"Subacute oral in non-rodent "]
[null,"Subacute oral in rodent "]
[null,"Subchronic oral toxicity in rodents"]
[null,"Subchronic \ninhalation toxicity: 90-day study"]
[null,"Subchronic dermal toxicity: 90-day study"]
[null,"Two-generation reproduction toxicity test"]
[null,"Uterotrophic assay"]
[null,"Mammals Not il list"]

{"sheet":"LinkYZMammals","index":3,"n_rows":51,"n_cols":9,"rows_kept":51,"cut":false,"hidden":true,"merged":[]}
["Column Y","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target"]
["Effect type","In life observation","Organ Weight","Organ histopathology","Reproductive","Developmental","Abnormalities","Clinical chemistry/hormones","No relevant effect observed"]
[null,"Body weight","Adrenals weight","Accessory sex organs histopathology","Age at balanopreputial separation","Auditory startle","Ano-Genital distance","Estradiol level","No relevant effect observed"]
[null,"Clinical chemistry and haematology","Adrenals weight (Hershberger)","Adrenals histopathology","Age at first estrus","Brain morphometric (quantitative) evaluation","Genital abnormalities","Follicle Stimulating Hormone (FSH) level"]
[null,"Clinical signs","Brain weight","Aorta histopathology","Age at Vaginal opening","Fetal development","Nipple Development","HDL/LDL ratio (considered T-mediated only in combination with other thyroid endpoints)"]
[null,"Food consumption","Coagulating gland weight","Bone histopathology","Dystocia","Functional observation battery","Presence of anomalies (external, visceral, skeletal","Luteinizing Hormone (LH) level"]
[null,"Mortality","Cowper's gland weight","Bone marrow histopathology","Estrus cyclicity","Learning and memory in offspring","[Not in list]","Steroidogenesis (genes/enzyme changes)"]
[null,"[Not in list]","Cowpers glands weight (Hershberger)","Brain histopathology examination","Fertility (mammals)","Litter/pup weight",null,"T3 and T4 level"]
[null,null,"Epididymis weight","Cervix histopathology","Gestation length","Motor activity",null,"Testosterone level"]
[null,null,"Epididymis weight (Hershberger)","Coagulating gland histopathology","Litter size","Motor and sensory function",null,"Thyroid-stimulating hormone level (TSH)"]
[null,null,"Glans penis weight","Colloid area (thyroid histopathology)","Litter viability","Pup development",null,"Thyroid-releasing hormone level (TRH)"]
[null,null,"Glans penis weight  (Hershberger)","Epididymis histopathology","Number of implantations, corpora lutea","[Not in list]",null,"Prolactin"]
[null,null,"Heart weight","Eyes histopathology","Number of live births",null,null,"Progesterone"]
[null,null,"Kidney weight","Follicular cell height (thyroid histopathology)","Number of ovarian follicles",null,null,"Cortisol"]
[null,null,"LABC weight","Gall bladder histopathology","Numbers of embryonic or foetal deaths and viable foetuses",null,null,"Androstenedione"]
[null,null,"LABC weight (Hershberger)","Heart histopathology","Post implantation loss",null,null,"Other hormones"]
[null,null,"Liver weight","Keratinisation and cornification of vagina","Pre implantation loss",null,null,"Nuclear receptor (in vivo)"]
[null,null,"Liver weight (Hershberger, considered T-mediated only in combination with other thyroid endpoints)","Keratinisation and cornification of vagina (UT assay)","Pup survival index",null,null,"CAR nuclear receptor (in vivo)"]
[null,null,"Liver weight (considered T-mediated only in combination with other thyroid endpoints)","Kidney histopathology","Reproduction",null,null,"PXR nuclear receptor (in vivo)"]
[null,null,"Ovary weight","Liver histopathology","Sex ratio",null,null,"PPAR nuclear receptor (in vivo)"]
[null,null,"Pituitary weight","Lung histopathology","Sperm morphology",null,null,"TSH receptor"]
[null,null,"Prostate weight","Lymph nodes histopathology","Sperm motility",null,null,"Phase I enzyme induction (in vivo)"]
[null,null,"Prostate weight (Hershberger)","Mammary gland histopathology (female)","Sperm numbers",null,null,"Phase II enzyme induction (in vivo)"]
[null,null,"Seminal vesicles weight","Mammary gland histopathology (male)","Time to mating",null,null,"Thyroid hormone clearance"]
[null,null,"Seminal vesicles weight (Hershberger)","Oesophagus histopathology","Vaginal opening (UT assay)",null,null,"Iodine uptake"]
[null,null,"Spleen weight","Ovary histopathology","[Not in list]",null,null,"Thyroperoxidase activity (TPO)"]
[null,null,"Testis weight","Oviduct histopathology",null,null,null,"Sodium-iodide symporter (NIS)"]
[null,null,"Testis weight (Hershberger)","Pancreas histopathology",null,null,null,"Thyroxin-binding protein (TBG)"]
[null,null,"Thymus weight","Peripheral nerve histopathology",null,null,null,"Transthyretin (TTR)"]
[null,null,"Thyroid weight","Pituitary histopathology",null,null,null,"Deiodination enzyme activity"]
[null,null,"Uterus weight (UT assay)","Proliferation of endometrial epithelium",null,null,null,"[Not in list]"]
[null,null,"Uterus weight (with cervix)","Proliferation of endometrial epithelium (UT assay)"]
[null,null,"[Not in list]","Prostate histopathology (with seminal vesicles and coagulating glands)"]
[null,null,null,"Salivary glands histopathology"]
[null,null,null,"Seminal vesicles histopathology"]
[null,null,null,"Skeletal muscle histopathology"]
[null,null,null,"Skin histopathology"]
[null,null,null,"Small and large intestines histopathology"]
[null,null,null,"Spinal cord histopathology"]
[null,null,null,"Spleen histopathology"]
[null,null,null,"Stomach histopathology"]
[null,null,null,"Testis histopathology"]
[null,null,null,"Thymus histopathology"]
[null,null,null,"Thyroid histopathology"]
[null,null,null,"Trachea histopathology"]
[null,null,null,"Urinary bladder histopathology"]
[null,null,null,"Uterus histopathology (UT assay)"]
[null,null,null,"Uterus histopathology (with cervix)"]
[null,null,null,"Vagina histopathology"]
[null,null,null,"Vaginal smears"]
[null,null,null,"[Not in list]"]

{"sheet":"LinkYZFish","index":4,"n_rows":13,"n_cols":7,"rows_kept":13,"cut":false,"hidden":true,"merged":[]}
["Column Y","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target"]
["Effect type","In life observation","Organ histopathology","Reproductive","Abnormalities","Clinical chemistry/hormones","No relevant effect observed"]
[null,"Behaviour (fish)","Kidney histopathology (fish)","Embryo time-to-hatch","Morphological abnormalities","Estradiol level","No relevant effect observed"]
[null,"Body weight (fish)","Liver histopathology (fish)","Gonado-somatic index",null,"Levels of thyroid hormones"]
[null,"Hepatosomatic index","Specific gonad histopathology","Hatching success",null,"Spiggin"]
[null,"Larval survival and length","[Not in list]","Male 2nd sex characteristics in females",null,"T3 and T4 level"]
[null,"Length (fish)",null,"Male 2nd sex characteristics in males",null,"Testosterone level"]
[null,"Mortality",null,"Reproduction (fecundity, fertility)",null,"Vitellogenin (VTG) in females"]
[null,"Survival (fish)",null,"Sex ratio (Female biased) ",null,"Vitellogenin (VTG) in males"]
[null,"Survival of embryos",null,"Sex ratio (Male biased) ",null,"[Not in list]"]
[null,"[Not in list]",null,"Time to maturity (time to first spawn)"]
[null,null,null,"Transcriptional activity of cyp19a1b"]
[null,null,null,"[Not in list]"]

{"sheet":"LinkYZAmphibian","index":5,"n_rows":7,"n_cols":9,"rows_kept":7,"cut":false,"hidden":true,"merged":[]}
["Column Y","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target"]
["Effect type","In life observation","Organ Weight","Organ histopathology","Reproductive","Developmental","Abnormalities","Clinical chemistry/hormones","No relevant effect observed"]
[null,"Behaviour (amphibian)","Liver weight (liver-somatic index;) (amphibian)","Histopathology (gonad, reproductive ducts)","Sex ratio (phenotypic [gonad histology], genetic)","Developmental stage","Malformations","Plasma level of vitellogenin","No relevant effect observed"]
[null,"Body weight (amphibian)","[Not in list]","Kidney histopathology (amphibian)",null,"Hind limb length","[Not in list]","Transcriptional activity of THbZIP"]
[null,"Mortality (amphibian)",null,"Liver histopathology (amphibian)",null,"Time to metamorphosis (NF stage 62)",null,"[Not in list]"]
[null,"Snout-vent length/growth",null,"Thyroid histopathology (amphibian)",null,"[Not in list]"]
[null,"[Not in list]",null,"[Not in list]"]

{"sheet":"LinkYZAvian","index":6,"n_rows":17,"n_cols":6,"rows_kept":17,"cut":false,"hidden":true,"merged":[]}
["Column Y","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target"]
["Effect type","In life observation","Organ histopathology","Reproductive","Clinical chemistry/hormones","No relevant effect observed"]
[null,"Body weight (bird)","Gonad histopathology (bird)","Cracked eggs","Estradiol, testosterone and thyroid hormone measurements (egg yolk, adult, thyroid hormone from thyroid gland)","No relevant effect observed"]
[null,"Mortality","Gross pathology (bird)","Egg fertility (embryonic day 8)","[Not in list]"]
[null,"[Not in list]","Kidney histopathology (bird)","Egg production"]
[null,null,"Liver histopathology (bird)","Egg viability (% viable embryo of egg set)"]
[null,null,"Thyroid gland histopathology (bird)","Eggshell strength (newton)"]
[null,null,"[Not in list]","Eggshell thickness"]
[null,null,null,"Embryo viability (embryonic day 15)"]
[null,null,null,"Hatchability"]
[null,null,null,"No of 14 day-old survivors"]
[null,null,null,"Phenotypic and genotypic sex ratio"]
[null,null,null,"Survival (bird)"]
[null,null,null,"Time to female reproductive maturation (first egg production)"]
[null,null,null,"Time to male reproductive maturation (first foam production)"]
[null,null,null,"Viable embryos"]
[null,null,null,"[Not in list]"]

{"sheet":"LinkInVitro","index":7,"n_rows":38,"n_cols":13,"rows_kept":38,"cut":false,"hidden":true,"merged":[]}
["Column Y","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target","Column Z Effect target"]
["Effect type","Receptor binding","Receptor (trans)activation","Receptor dimerization","Cofactor Recruitment","DNA Binding","Enzyme inhibition","Proliferation","Steroidogenesis","Transport protein binding","Enzyme inhibition/induction","Hormones measurments","[Not in list]"]
[null,"Estrogen receptor","Estrogen receptor","Estrogen receptor","Estrogen receptor","Estrogen receptor","Estrogen receptor","Estrogen receptor","Estrogen receptor","Estrogen receptor","Estrogen receptor","Estrogen receptor","No relevant effect observed"]
[null,"Estrogen related receptor","Estrogen related receptor","Estrogen related receptor","Estrogen related receptor","Estrogen related receptor","Estrogen related receptor","Estrogen related receptor","Estrogen related receptor","Estrogen related receptor","Estrogen related receptor","Estrogen related receptor"]
[null,"Androgen receptor","Androgen receptor","Androgen receptor","Androgen receptor","Androgen receptor","Androgen receptor","Androgen receptor","Androgen receptor","Androgen receptor","Androgen receptor","Androgen receptor"]
[null,"Thyroid receptor","Thyroid receptor","Thyroid receptor","Thyroid receptor","Thyroid receptor","Thyroid receptor","Thyroid receptor","Thyroid receptor","Thyroid receptor","Thyroid receptor","Thyroid receptor"]
[null,"Nuclear receptor (in vitro)","Nuclear receptor (in vitro)","Nuclear receptor (in vitro)","Nuclear receptor (in vitro)","Nuclear receptor (in vitro)","Nuclear receptor (in vitro)","Nuclear receptor (in vitro)","Nuclear receptor (in vitro)","Nuclear receptor (in vitro)","Nuclear receptor (in vitro)","Nuclear receptor (in vitro)"]
[null,"CAR nuclear receptor (in vitro)","CAR nuclear receptor (in vitro)","CAR nuclear receptor (in vitro)","CAR nuclear receptor (in vitro)","CAR nuclear receptor (in vitro)","CAR nuclear receptor (in vitro)","CAR nuclear receptor (in vitro)","CAR nuclear receptor (in vitro)","CAR nuclear receptor (in vitro)","CAR nuclear receptor (in vitro)","CAR nuclear receptor (in vitro)"]
[null,"PXR nuclear receptor (in vitro)","PXR nuclear receptor (in vitro)","PXR nuclear receptor (in vitro)","PXR nuclear receptor (in vitro)","PXR nuclear receptor (in vitro)","PXR nuclear receptor (in vitro)","PXR nuclear receptor (in vitro)","PXR nuclear receptor (in vitro)","PXR nuclear receptor (in vitro)","PXR nuclear receptor (in vitro)","PXR nuclear receptor (in vitro)"]
[null,"PPAR nuclear receptor (in vitro)","PPAR nuclear receptor (in vitro)","PPAR nuclear receptor (in vitro)","PPAR nuclear receptor (in vitro)","PPAR nuclear receptor (in vitro)","PPAR nuclear receptor (in vitro)","PPAR nuclear receptor (in vitro)","PPAR nuclear receptor (in vitro)","PPAR nuclear receptor (in vitro)","PPAR nuclear receptor (in vitro)","PPAR nuclear receptor (in vitro)"]
[null,"TSH receptor (in vitro)","TSH receptor (in vitro)","TSH receptor (in vitro)","TSH receptor (in vitro)","TSH receptor (in vitro)","TSH receptor (in vitro)","TSH receptor (in vitro)","TSH receptor (in vitro)","TSH receptor (in vitro)","TSH receptor (in vitro)","TSH receptor (in vitro)"]
[null,"Estradiol synthesis","Estradiol synthesis","Estradiol synthesis","Estradiol synthesis","Estradiol synthesis","Estradiol synthesis","Estradiol synthesis","Estradiol synthesis","Estradiol synthesis","Estradiol synthesis","Estradiol synthesis"]
[null,"Testosterone synthesis","Testosterone synthesis","Testosterone synthesis","Testosterone synthesis","Testosterone synthesis","Testosterone synthesis","Testosterone synthesis","Testosterone synthesis","Testosterone synthesis","Testosterone synthesis","Testosterone synthesis"]
[null,"CYP19","CYP19","CYP19","CYP19","CYP19","CYP19","CYP19","CYP19","CYP19","CYP19","CYP19"]
[null,"Steroidogenesis (genes/enzyme changes) (in vitro)","Steroidogenesis (genes/enzyme changes) (in vitro)","Steroidogenesis (genes/enzyme changes) (in vitro)","Steroidogenesis (genes/enzyme changes) (in vitro)","Steroidogenesis (genes/enzyme changes) (in vitro)","Steroidogenesis (genes/enzyme changes) (in vitro)","Steroidogenesis (genes/enzyme changes) (in vitro)","Steroidogenesis (genes/enzyme changes) (in vitro)","Steroidogenesis (genes/enzyme changes) (in vitro)","Steroidogenesis (genes/enzyme changes) (in vitro)","Steroidogenesis (genes/enzyme changes) (in vitro)"]
[null,"Estradiol level (in vitro)","Estradiol level (in vitro)","Estradiol level (in vitro)","Estradiol level (in vitro)","Estradiol level (in vitro)","Estradiol level (in vitro)","Estradiol level (in vitro)","Estradiol level (in vitro)","Estradiol level (in vitro)","Estradiol level (in vitro)","Estradiol level (in vitro)"]
[null,"Testosterone level (in vitro)","Testosterone level (in vitro)","Testosterone level (in vitro)","Testosterone level (in vitro)","Testosterone level (in vitro)","Testosterone level (in vitro)","Testosterone level (in vitro)","Testosterone level (in vitro)","Testosterone level (in vitro)","Testosterone level (in vitro)","Testosterone level (in vitro)"]
[null,"11-Deoxycortisol (in vitro)","11-Deoxycortisol (in vitro)","11-Deoxycortisol (in vitro)","11-Deoxycortisol (in vitro)","11-Deoxycortisol (in vitro)","11-Deoxycortisol (in vitro)","11-Deoxycortisol (in vitro)","11-Deoxycortisol (in vitro)","11-Deoxycortisol (in vitro)","11-Deoxycortisol (in vitro)","11-Deoxycortisol (in vitro)"]
[null,"17-alpha-hydroxypregnelone (in vitro)","17-alpha-hydroxypregnelone (in vitro)","17-alpha-hydroxypregnelone (in vitro)","17-alpha-hydroxypregnelone (in vitro)","17-alpha-hydroxypregnelone (in vitro)","17-alpha-hydroxypregnelone (in vitro)","17-alpha-hydroxypregnelone (in vitro)","17-alpha-hydroxypregnelone (in vitro)","17-alpha-hydroxypregnelone (in vitro)","17-alpha-hydroxypregnelone (in vitro)","17-alpha-hydroxypregnelone (in vitro)"]
[null,"17-alpha-hydroxyprogesterone (in vitro)","17-alpha-hydroxyprogesterone (in vitro)","17-alpha-hydroxyprogesterone (in vitro)","17-alpha-hydroxyprogesterone (in vitro)","17-alpha-hydroxyprogesterone (in vitro)","17-alpha-hydroxyprogesterone (in vitro)","17-alpha-hydroxyprogesterone (in vitro)","17-alpha-hydroxyprogesterone (in vitro)","17-alpha-hydroxyprogesterone (in vitro)","17-alpha-hydroxyprogesterone (in vitro)","17-alpha-hydroxyprogesterone (in vitro)"]
[null,"Androstenedione (in vitro)","Androstenedione (in vitro)","Androstenedione (in vitro)","Androstenedione (in vitro)","Androstenedione (in vitro)","Androstenedione (in vitro)","Androstenedione (in vitro)","Androstenedione (in vitro)","Androstenedione (in vitro)","Androstenedione (in vitro)","Androstenedione (in vitro)"]
[null,"Cortisol (in vitro)","Cortisol (in vitro)","Cortisol (in vitro)","Cortisol (in vitro)","Cortisol (in vitro)","Cortisol (in vitro)","Cortisol (in vitro)","Cortisol (in vitro)","Cortisol (in vitro)","Cortisol (in vitro)","Cortisol (in vitro)"]
[null,"11-Deoxycorticosterone (in vitro)","11-Deoxycorticosterone (in vitro)","11-Deoxycorticosterone (in vitro)","11-Deoxycorticosterone (in vitro)","11-Deoxycorticosterone (in vitro)","11-Deoxycorticosterone (in vitro)","11-Deoxycorticosterone (in vitro)","11-Deoxycorticosterone (in vitro)","11-Deoxycorticosterone (in vitro)","11-Deoxycorticosterone (in vitro)","11-Deoxycorticosterone (in vitro)"]
[null,"Estrone (in vitro)","Estrone (in vitro)","Estrone (in vitro)","Estrone (in vitro)","Estrone (in vitro)","Estrone (in vitro)","Estrone (in vitro)","Estrone (in vitro)","Estrone (in vitro)","Estrone (in vitro)","Estrone (in vitro)"]
[null,"Progesterone (in vitro)","Progesterone (in vitro)","Progesterone (in vitro)","Progesterone (in vitro)","Progesterone (in vitro)","Progesterone (in vitro)","Progesterone (in vitro)","Progesterone (in vitro)","Progesterone (in vitro)","Progesterone (in vitro)","Progesterone (in vitro)"]
[null,"T3 and T4 level (in vitro)","T3 and T4 level (in vitro)","T3 and T4 level (in vitro)","T3 and T4 level (in vitro)","T3 and T4 level (in vitro)","T3 and T4 level (in vitro)","T3 and T4 level (in vitro)","T3 and T4 level (in vitro)","T3 and T4 level (in vitro)","T3 and T4 level (in vitro)","T3 and T4 level (in vitro)"]
[null,"Thyroid-stimulating hormone level (TSH) (in vitro)","Thyroid-stimulating hormone level (TSH) (in vitro)","Thyroid-stimulating hormone level (TSH) (in vitro)","Thyroid-stimulating hormone level (TSH) (in vitro)","Thyroid-stimulating hormone level (TSH) (in vitro)","Thyroid-stimulating hormone level (TSH) (in vitro)","Thyroid-stimulating hormone level (TSH) (in vitro)","Thyroid-stimulating hormone level (TSH) (in vitro)","Thyroid-stimulating hormone level (TSH) (in vitro)","Thyroid-stimulating hormone level (TSH) (in vitro)","Thyroid-stimulating hormone level (TSH) (in vitro)"]
[null,"Other hormones (in vitro)","Other hormones (in vitro)","Other hormones (in vitro)","Other hormones (in vitro)","Other hormones (in vitro)","Other hormones (in vitro)","Other hormones (in vitro)","Other hormones (in vitro)","Other hormones (in vitro)","Other hormones (in vitro)","Other hormones (in vitro)"]
[null,"Phase I enzyme induction (in vitro)","Phase I enzyme induction (in vitro)","Phase I enzyme induction (in vitro)","Phase I enzyme induction (in vitro)","Phase I enzyme induction (in vitro)","Phase I enzyme induction (in vitro)","Phase I enzyme induction (in vitro)","Phase I enzyme induction (in vitro)","Phase I enzyme induction (in vitro)","Phase I enzyme induction (in vitro)","Phase I enzyme induction (in vitro)"]
[null,"Phase II enzyme induction (in vitro)","Phase II enzyme induction (in vitro)","Phase II enzyme induction (in vitro)","Phase II enzyme induction (in vitro)","Phase II enzyme induction (in vitro)","Phase II enzyme induction (in vitro)","Phase II enzyme induction (in vitro)","Phase II enzyme induction (in vitro)","Phase II enzyme induction (in vitro)","Phase II enzyme induction (in vitro)","Phase II enzyme induction (in vitro)"]
[null,"Thyroid hormone clearance (in vitro)","Thyroid hormone clearance (in vitro)","Thyroid hormone clearance (in vitro)","Thyroid hormone clearance (in vitro)","Thyroid hormone clearance (in vitro)","Thyroid hormone clearance (in vitro)","Thyroid hormone clearance (in vitro)","Thyroid hormone clearance (in vitro)","Thyroid hormone clearance (in vitro)","Thyroid hormone clearance (in vitro)","Thyroid hormone clearance (in vitro)"]
[null,"Thyroperoxidase activity (TPO) (in vitro)","Thyroperoxidase activity (TPO) (in vitro)","Thyroperoxidase activity (TPO) (in vitro)","Thyroperoxidase activity (TPO) (in vitro)","Thyroperoxidase activity (TPO) (in vitro)","Thyroperoxidase activity (TPO) (in vitro)","Thyroperoxidase activity (TPO) (in vitro)","Thyroperoxidase activity (TPO) (in vitro)","Thyroperoxidase activity (TPO) (in vitro)","Thyroperoxidase activity (TPO) (in vitro)","Thyroperoxidase activity (TPO) (in vitro)"]
[null,"Sodium-iodide symporter (NIS) (in vitro)","Sodium-iodide symporter (NIS) (in vitro)","Sodium-iodide symporter (NIS) (in vitro)","Sodium-iodide symporter (NIS) (in vitro)","Sodium-iodide symporter (NIS) (in vitro)","Sodium-iodide symporter (NIS) (in vitro)","Sodium-iodide symporter (NIS) (in vitro)","Sodium-iodide symporter (NIS) (in vitro)","Sodium-iodide symporter (NIS) (in vitro)","Sodium-iodide symporter (NIS) (in vitro)","Sodium-iodide symporter (NIS) (in vitro)"]
[null,"Thyroxin-binding protein (TBG) (in vitro)","Thyroxin-binding protein (TBG) (in vitro)","Thyroxin-binding protein (TBG) (in vitro)","Thyroxin-binding protein (TBG) (in vitro)","Thyroxin-binding protein (TBG) (in vitro)","Thyroxin-binding protein (TBG) (in vitro)","Thyroxin-binding protein (TBG) (in vitro)","Thyroxin-binding protein (TBG) (in vitro)","Thyroxin-binding protein (TBG) (in vitro)","Thyroxin-binding protein (TBG) (in vitro)","Thyroxin-binding protein (TBG) (in vitro)"]
[null,"Transthyretin (TTR) (in vitro)","Transthyretin (TTR) (in vitro)","Transthyretin (TTR) (in vitro)","Transthyretin (TTR) (in vitro)","Transthyretin (TTR) (in vitro)","Transthyretin (TTR) (in vitro)","Transthyretin (TTR) (in vitro)","Transthyretin (TTR) (in vitro)","Transthyretin (TTR) (in vitro)","Transthyretin (TTR) (in vitro)","Transthyretin (TTR) (in vitro)"]
[null,"Deiodination enzyme activity (in vitro)","Deiodination enzyme activity (in vitro)","Deiodination enzyme activity (in vitro)","Deiodination enzyme activity (in vitro)","Deiodination enzyme activity (in vitro)","Deiodination enzyme activity (in vitro)","Deiodination enzyme activity (in vitro)","Deiodination enzyme activity (in vitro)","Deiodination enzyme activity (in vitro)","Deiodination enzyme activity (in vitro)","Deiodination enzyme activity (in vitro)"]
[null,"Cellular proliferation","Cellular proliferation","Cellular proliferation","Cellular proliferation","Cellular proliferation","Cellular proliferation","Cellular proliferation","Cellular proliferation","Cellular proliferation","Cellular proliferation","Cellular proliferation"]
[null,"[Not in list]","[Not in list]","[Not in list]","[Not in list]","[Not in list]","[Not in list]","[Not in list]","[Not in list]","[Not in list]","[Not in list]","[Not in list]"]

{"sheet":"Interpretation","index":8,"n_rows":251,"n_cols":5,"rows_kept":251,"cut":false,"hidden":true,"merged":[]}
["Column A","Column Y","Column Z","Column AA","Indicative of"]
["Mammals","Abnormalities","Ano-Genital distance","EATS-mediated","E, A, S"]
["Mammals","Abnormalities","Genital abnormalities","EATS-mediated","E, A, S"]
["Mammals","Abnormalities","Nipple Development","EATS-mediated","A"]
["Mammals","Abnormalities","Presence of anomalies (external, visceral, skeletal","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Clinical chemistry","Estradiol level","In vivo mechanistic","E, A, S"]
["Mammals","Clinical chemistry","Follicle Stimulating Hormone (FSH) level","In vivo mechanistic","E, A, S"]
["Mammals","Clinical chemistry","Luteinizing Hormone (LH) level","In vivo mechanistic","E, A, S"]
["Mammals","Clinical chemistry","Steroidogenesis (genes/enzyme changes)","In vivo mechanistic","E, A, S"]
["Mammals","Clinical chemistry","T3 and T4 level","In vivo mechanistic","T"]
["Mammals","Clinical chemistry","Testosterone level","In vivo mechanistic","E, A, S"]
["Mammals","Clinical chemistry","Thyroid-stimulating hormone level (TSH)","In vivo mechanistic","T"]
["Mammals","Clinical chemistry","Thyroid-releasing hormone level (TRH)","In vivo mechanistic","T"]
["Mammals","Clinical chemistry","Prolactin","In vivo mechanistic","E, A, T, S"]
["Mammals","Clinical chemistry","Progesterone","In vivo mechanistic","E, A, S"]
["Mammals","Clinical chemistry","Cortisol","In vivo mechanistic","E, A, S"]
["Mammals","Clinical chemistry","Androstenedione","In vivo mechanistic","E, A, S"]
["Mammals","Clinical chemistry","Other hormones","In vivo mechanistic","_"]
["Mammals","Clinical chemistry","Nuclear receptor (in vivo)","In vivo mechanistic","E, A, T, S"]
["Mammals","Clinical chemistry","CAR nuclear receptor (in vivo)","In vivo mechanistic","E, A, T, S"]
["Mammals","Clinical chemistry","PXR nuclear receptor (in vivo)","In vivo mechanistic","E, A, T, S"]
["Mammals","Clinical chemistry","PPAR nuclear receptor (in vivo)","In vivo mechanistic","E, A, T, S"]
["Mammals","Clinical chemistry","TSH receptor","In vivo mechanistic","T"]
["Mammals","Clinical chemistry","Phase I enzyme induction (in vivo)","In vivo mechanistic","E, A, T, S"]
["Mammals","Clinical chemistry","Phase II enzyme induction (in vivo)","In vivo mechanistic","E, A, T, S"]
["Mammals","Clinical chemistry","Thyroid hormone clearance","In vivo mechanistic","T"]
["Mammals","Clinical chemistry","Iodine uptake","In vivo mechanistic","T"]
["Mammals","Clinical chemistry","Thyroperoxidase activity (TPO)","In vivo mechanistic","T"]
["Mammals","Clinical chemistry","Sodium-iodide symporter (NIS)","In vivo mechanistic","T"]
["Mammals","Clinical chemistry","Thyroxin-binding protein (TBG)","In vivo mechanistic","T"]
["Mammals","Clinical chemistry","Transthyretin (TTR)","In vivo mechanistic","T"]
["Mammals","Clinical chemistry","Deiodination enzyme activity","In vivo mechanistic","T"]
["Mammals","Clinical chemistry","HDL/LDL ratio (considered T-mediated only in combination with other thyroid endpoints)","EATS-mediated","T"]
["Mammals","Developmental","Auditory startle","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Developmental","Brain morphometric (quantitative) evaluation","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Developmental","Fetal development","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Developmental","Functional observation battery","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Developmental","Learning and memory in offspring","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Developmental","Litter/pup weight","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Developmental","Motor activity","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Developmental","Motor and sensory function","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Developmental","Pup development","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Organ histopathology","Keratinisation and cornification of vagina (UT assay)","In vivo mechanistic","E"]
["Mammals","Organ histopathology","Proliferation of endometrial epithelium (UT assay)","In vivo mechanistic","E"]
["Mammals","Organ histopathology","Uterus histopathology (UT assay)","In vivo mechanistic","E"]
["Mammals","Organ histopathology","Accessory sex organs histopathology","EATS-mediated","E, A, S"]
["Mammals","Organ histopathology","Cervix histopathology","EATS-mediated","E, A, S"]
["Mammals","Organ histopathology","Coagulating gland histopathology","EATS-mediated","E, A, S"]
["Mammals","Organ histopathology","Colloid area (thyroid histopathology)","EATS-mediated","T"]
["Mammals","Organ histopathology","Epididymis histopathology","EATS-mediated","E, A, S"]
["Mammals","Organ histopathology","Follicular cell height (thyroid histopathology)","EATS-mediated","T"]
["Mammals","Organ histopathology","Mammary gland histopathology (male)","EATS-mediated","E, A, S"]
["Mammals","Organ histopathology","Mammary gland histopathology (female)","EATS-mediated","E, A, S"]
["Mammals","Organ histopathology","Ovary histopathology","EATS-mediated","E, A, S"]
["Mammals","Organ histopathology","Oviduct histopathology","EATS-mediated","E, A, S"]
["Mammals","Organ histopathology","Keratinisation and cornification of vagina","EATS-mediated","E"]
["Mammals","Organ histopathology","Proliferation of endometrial epithelium","EATS-mediated","E"]
["Mammals","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)","EATS-mediated","E, A, S"]
["Mammals","Organ histopathology","Seminal vesicles histopathology","EATS-mediated","E, A, S"]
["Mammals","Organ histopathology","Testis histopathology","EATS-mediated","E, A, S"]
["Mammals","Organ histopathology","Thyroid histopathology","EATS-mediated","T"]
["Mammals","Organ histopathology","Uterus histopathology (with cervix)","EATS-mediated","E, A, S"]
["Mammals","Organ histopathology","Vagina histopathology","EATS-mediated","E, A, S"]
["Mammals","Organ histopathology","Vaginal smears","EATS-mediated","E, A, S"]
["Mammals","Organ histopathology","Adrenals histopathology","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Organ histopathology","Brain histopathology examination","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Organ histopathology","Pituitary histopathology","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Organ histopathology","Aorta histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Bone histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Bone marrow histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Eyes histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Gall bladder histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Heart histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Kidney histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Liver histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Lung histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Lymph nodes histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Oesophagus histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Pancreas histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Peripheral nerve histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Salivary glands histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Skeletal muscle histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Skin histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Small and large intestines histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Spinal cord histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Spleen histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Stomach histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Thymus histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Trachea histopathology","Target organ toxicity","_"]
["Mammals","Organ histopathology","Urinary bladder histopathology","Target organ toxicity","_"]
["Mammals","Organ Weight","Adrenals weight (Hershberger)","In vivo mechanistic","N"]
["Mammals","Organ Weight","Cowpers glands weight (Hershberger)","In vivo mechanistic","A"]
["Mammals","Organ Weight","Epididymis weight (Hershberger)","In vivo mechanistic","E, A, S"]
["Mammals","Organ Weight","Glans penis weight  (Hershberger)","In vivo mechanistic","A"]
["Mammals","Organ Weight","LABC weight (Hershberger)","In vivo mechanistic","A"]
["Mammals","Organ Weight","Liver weight (Hershberger, considered T-mediated only in combination with other thyroid endpoints)","In vivo mechanistic","T"]
["Mammals","Organ Weight","Prostate weight (Hershberger)","In vivo mechanistic","A"]
["Mammals","Organ Weight","Seminal vesicles weight (Hershberger)","In vivo mechanistic","A"]
["Mammals","Organ Weight","Testis weight (Hershberger)","In vivo mechanistic","E, A, S"]
["Mammals","Organ Weight","Uterus weight (UT assay)","In vivo mechanistic","E, A"]
["Mammals","Organ Weight","Coagulating gland weight","EATS-mediated","E, A, S"]
["Mammals","Organ Weight","Cowper's gland weight","EATS-mediated","E, A, S"]
["Mammals","Organ Weight","Epididymis weight","EATS-mediated","E, A, S"]
["Mammals","Organ Weight","Glans penis weight","EATS-mediated","E, A, S"]
["Mammals","Organ Weight","LABC weight","EATS-mediated","E, A, S"]
["Mammals","Organ Weight","Liver weight (considered T-mediated only in combination with other thyroid endpoints)","EATS-mediated","T"]
["Mammals","Organ Weight","Ovary weight","EATS-mediated","E, A, S"]
["Mammals","Organ Weight","Prostate weight","EATS-mediated","E, A, S"]
["Mammals","Organ Weight","Seminal vesicles weight","EATS-mediated","E, A, S"]
["Mammals","Organ Weight","Testis weight","EATS-mediated","E, A, S"]
["Mammals","Organ Weight","Thyroid weight","EATS-mediated","T"]
["Mammals","Organ Weight","Uterus weight (with cervix)","EATS-mediated","E, A, S"]
["Mammals","Organ Weight","Adrenals weight","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Organ Weight","Brain weight","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Organ Weight","Pituitary weight","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Organ Weight","Heart weight","Target organ toxicity","_"]
["Mammals","Organ Weight","Kidney weight","Target organ toxicity","_"]
["Mammals","Organ Weight","Liver weight","Target organ toxicity","_"]
["Mammals","Organ Weight","Spleen weight","Target organ toxicity","_"]
["Mammals","Organ Weight","Thymus weight","Target organ toxicity","_"]
["Mammals","Reproductive","Vaginal opening (UT assay)","In vivo mechanistic","E, A"]
["Mammals","Reproductive","Age at first estrus","EATS-mediated","E, A"]
["Mammals","Reproductive","Age at balanopreputial separation","EATS-mediated","E, A, S"]
["Mammals","Reproductive","Age at vaginal opening","EATS-mediated","E, A, S"]
["Mammals","Reproductive","Estrus cyclicity","EATS-mediated","E, A, S"]
["Mammals","Reproductive","Sperm morphology","EATS-mediated","E, A, S"]
["Mammals","Reproductive","Sperm motility","EATS-mediated","E, A, S"]
["Mammals","Reproductive","Sperm numbers","EATS-mediated","E, A, S"]
["Mammals","Reproductive","Dystocia","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Reproductive","Fertility (mammals)","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Reproductive","Gestation length","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Reproductive","Litter size","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Reproductive","Litter viability","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Reproductive","Number of implantations, corpora lutea","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Reproductive","Number of live births","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Reproductive","Numbers of embryonic or foetal deaths and viable foetuses","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Reproductive","Number of ovarian follicles","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Reproductive","Post implantation loss","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Reproductive","Pre implantation loss","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Reproductive","Pup survival index","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Reproductive","Reproduction","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Reproductive","Sex ratio","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","Reproductive","Time to mating","Sensitive to, but not diagnostic of, EATS","N"]
["Mammals","In life observation","Body weight","Systemic toxicity","_"]
["Mammals","In life observation","Clinical chemistry and haematology","Systemic toxicity","_"]
["Mammals","In life observation","Clinical signs","Systemic toxicity","_"]
["Mammals","In life observation","Food consumption","Systemic toxicity","_"]
["Mammals","In life observation","Mortality","Systemic toxicity","_"]
["Fish","Abnormalities","Morphological abnormalities","Sensitive to, but not diagnostic of, EATS","N"]
["Fish","Clinical chemistry","Vitellogenin (VTG) in females","In vivo mechanistic","E, A, S"]
["Fish","Clinical chemistry","Vitellogenin (VTG) in males","In vivo mechanistic","E, A, S"]
["Fish","Clinical chemistry","Spiggin","In vivo mechanistic","A"]
["Fish","Clinical chemistry","Estradiol level","In vivo mechanistic"]
["Fish","Clinical chemistry","Levels of thyroid hormones","In vivo mechanistic"]
["Fish","Clinical chemistry","T3 and T4 level","In vivo mechanistic"]
["Fish","Clinical chemistry","Testosterone level","In vivo mechanistic"]
["Fish","Clinical chemistry","Transcriptional activity of cyp19a1b","In vivo mechanistic","E"]
["Fish","Developmental","Behaviour (fish)","Sensitive to, but not diagnostic of, EATS","N"]
["Fish","Developmental","Length (fish)","Sensitive to, but not diagnostic of, EATS","N"]
["Fish","Organ histopathology","Specific gonad histopathology","EATS-mediated","E, A, S"]
["Fish","In life observation","Liver histopathology (fish)","Systemic toxicity","_"]
["Fish","In life observation","Kidney histopathology (fish)","Systemic toxicity","_"]
["Fish","In life observation","Body weight (fish)","Sensitive to, but not diagnostic of, EATS","N"]
["Fish","Reproductive","Male 2nd sex characteristics in females","EATS-mediated","A"]
["Fish","Reproductive","Male 2nd sex characteristics in males","EATS-mediated","E, A, S"]
["Fish","Reproductive","Sex ratio (Female biased) ","EATS-mediated","E, A"]
["Fish","Reproductive","Sex ratio (Male biased) ","EATS-mediated","E, A, S"]
["Fish","Reproductive","Gonado-somatic index","Sensitive to, but not diagnostic of, EATS","N"]
["Fish","Reproductive","Embryo time-to-hatch","Sensitive to, but not diagnostic of, EATS","N"]
["Fish","Reproductive","Reproduction (fecundity, fertility)","Sensitive to, but not diagnostic of, EATS","N"]
["Fish","In life observation","Survival (fish)","Systemic toxicity","_"]
["Fish","Reproductive","Larval survival and length","Sensitive to, but not diagnostic of, EATS","N"]
["Fish","Reproductive","Survival of embryos","Sensitive to, but not diagnostic of, EATS","N"]
["Fish","Reproductive","Time to maturity (time to first spawn)","Sensitive to, but not diagnostic of, EATS","N"]
["Fish","Reproductive","Hatching success","Sensitive to, but not diagnostic of, EATS","N"]
["Fish","In life observation","Hepatosomatic index","Systemic toxicity","_"]
["Fish","In life observation","Mortality","Systemic toxicity","_"]
["Amphibians","Abnormalities","Malformations","Sensitive to, but not diagnostic of, EATS","N"]
["Amphibians","Clinical chemistry","Plasma level of vitellogenin","In vivo mechanistic","E, A, S"]
["Amphibians","Clinical chemistry","Transcriptional activity of THbZIP","In vivo mechanistic","T"]
["Amphibians","Developmental","Hind limb length","EATS-mediated","T"]
["Amphibians","Developmental","Developmental stage","EATS-mediated","T"]
["Amphibians","Developmental","Time to metamorphosis (NF stage 62)","EATS-mediated","T"]
["Amphibians","Developmental","Snout-vent length/growth","Sensitive to, but not diagnostic of, EATS","N"]
["Amphibians","Developmental","Behaviour (amphibian)","Sensitive to, but not diagnostic of, EATS","N"]
["Amphibians","In life observation","Mortality (amphibian)","Systemic toxicity","_"]
["Amphibians","Organ histopathology","Thyroid histopathology (amphibian)","EATS-mediated","T"]
["Amphibians","Organ histopathology","Histopathology (gonad, reproductive ducts)","EATS-mediated","E, A"]
["Amphibians","In life observation","Liver histopathology (amphibian)","Systemic toxicity","_"]
["Amphibians","In life observation","Kidney histopathology (amphibian)","Systemic toxicity","_"]
["Amphibians","In life observation","Body weight (amphibian)","Sensitive to, but not diagnostic of, EATS","N"]
["Amphibians","Organ Weight","Liver weight (liver-somatic index;) (amphibian)","Sensitive to, but not diagnostic of, EATS","N"]
["Birds","Clinical chemistry","Estradiol, testosterone and thyroid hormone measurements (egg yolk, adult, thyroid hormone from thyroid gland)","In vivo mechanistic","E, A, T, S"]
["Birds","Organ histopathology","Thyroid gland histopathology (bird)","EATS-mediated","T"]
["Birds","Organ histopathology","Gonad histopathology (bird)","EATS-mediated","E, A"]
["Birds","Organ histopathology","Gross pathology (bird)","Sensitive to, but not diagnostic of, EATS","N"]
["Birds","In life observation","Liver histopathology (bird)","Systemic toxicity","_"]
["Birds","In life observation","Kidney histopathology (bird)","Systemic toxicity","_"]
["Birds","In life observation","Body weight (bird)","Sensitive to, but not diagnostic of, EATS","N"]
["Birds","Reproductive","Phenotypic and genotypic sex ratio","EATS-mediated","E, A"]
["Birds","Reproductive","Hatchability","Sensitive to, but not diagnostic of, EATS","N"]
["Birds","Reproductive","Egg fertility (embryonic day 8)","Sensitive to, but not diagnostic of, EATS","N"]
["Birds","Reproductive","Eggshell thickness","Sensitive to, but not diagnostic of, EATS","N"]
["Birds","Reproductive","Eggshell strength (newton)","Sensitive to, but not diagnostic of, EATS","N"]
["Birds","Reproductive","Egg viability (% viable embryo of egg set)","Sensitive to, but not diagnostic of, EATS","N"]
["Birds","Reproductive","Embryo viability (embryonic day 15)","Sensitive to, but not diagnostic of, EATS","N"]
["Birds","Reproductive","Egg production","Sensitive to, but not diagnostic of, EATS","N"]
["Birds","Reproductive","Cracked eggs","Sensitive to, but not diagnostic of, EATS","N"]
["Birds","In life observation","Survival (bird)","Systemic toxicity","_"]
["Birds","Reproductive","Viable embryos","Sensitive to, but not diagnostic of, EATS","N"]
["Birds","Reproductive","No of 14 day-old survivors","Sensitive to, but not diagnostic of, EATS","N"]
["Birds","Reproductive","Time to female reproductive maturation (first egg production)","Sensitive to, but not diagnostic of, EATS","N"]
["Birds","Reproductive","Time to male reproductive maturation (first foam production)","Sensitive to, but not diagnostic of, EATS","N"]
["Birds","In life observation","Mortality","Systemic toxicity","_"]
["In vitro",null,"Estrogen receptor","In vitro mechanistic","E"]
["In vitro",null,"Estrogen related receptor","In vitro mechanistic","E"]
["In vitro",null,"Androgen receptor","In vitro mechanistic","A"]
["In vitro",null,"Thyroid receptor","In vitro mechanistic","T"]
["In vitro",null,"Nuclear receptor (in vitro)","In vitro mechanistic","E, A, T, S"]
["In vitro",null,"CAR nuclear receptor (in vitro)","In vitro mechanistic","E, A, T, S"]
["In vitro",null,"PXR nuclear receptor (in vitro)","In vitro mechanistic","E, A, T, S"]
["In vitro",null,"PPAR nuclear receptor (in vitro)","In vitro mechanistic","E, A, T, S"]
["In vitro",null,"TSH receptor (in vitro)","In vitro mechanistic","T"]
["In vitro",null,"Estradiol synthesis","In vitro mechanistic","E, A, S"]
["In vitro",null,"Testosterone synthesis","In vitro mechanistic","E, A, S"]
["In vitro",null,"CYP19","In vitro mechanistic","S"]
["In vitro",null,"Steroidogenesis (genes/enzyme changes) (in vitro)","In vitro mechanistic","S"]
["In vitro",null,"Estradiol level (in vitro)","In vitro mechanistic","E"]
["In vitro",null,"Testosterone level (in vitro)","In vitro mechanistic","A"]
["In vitro",null,"T3 and T4 level (in vitro)","In vitro mechanistic","T"]
["In vitro",null,"Thyroid-stimulating hormone level (TSH) (in vitro)","In vitro mechanistic","T"]
["In vitro",null,"Other hormones (in vitro)","In vitro mechanistic","_"]
["In vitro",null,"Phase I enzyme induction (in vitro)","In vitro mechanistic","E, A, T, S"]
["In vitro",null,"Phase II enzyme induction (in vitro)","In vitro mechanistic","E, A, T, S"]
["In vitro",null,"Thyroid hormone clearance (in vitro)","In vitro mechanistic","T"]
["In vitro",null,"Thyroperoxidase activity (TPO) (in vitro)","In vitro mechanistic","T"]
["In vitro",null,"Sodium-iodide symporter (NIS) (in vitro)","In vitro mechanistic","T"]
["In vitro",null,"Thyroxin-binding protein (TBG) (in vitro)","In vitro mechanistic","T"]
["In vitro",null,"Transthyretin (TTR) (in vitro)","In vitro mechanistic","T"]
["In vitro",null,"Deiodination enzyme activity (in vitro)","In vitro mechanistic","T"]
["In vitro",null,"Cellular proliferation","In vitro mechanistic","E, A, T, S"]
["In vitro",null,"11-Deoxycortisol (in vitro)","In vitro mechanistic","E, A, S"]
["In vitro",null,"17-alpha-hydroxypregnelone (in vitro)","In vitro mechanistic","E, A, S"]
["In vitro",null,"17-alpha-hydroxyprogesterone (in vitro)","In vitro mechanistic","E, A, S"]
["In vitro",null,"Androstenedione (in vitro)","In vitro mechanistic","E, A, S"]
["In vitro",null,"Cortisol (in vitro)","In vitro mechanistic","E, A, S"]
["In vitro",null,"11-Deoxycorticosterone (in vitro)","In vitro mechanistic","E, A, S"]
["In vitro",null,"Estrone (in vitro)","In vitro mechanistic","E, A, S"]
["In vitro",null,"Progesterone (in vitro)","In vitro mechanistic","E, A, S"]
[null,null,"[Not in list]","[Not in list]"]
[null,null,"No relevant effect observed","No relevant effect observed"]

{"sheet":"Data","index":9,"n_rows":2102,"n_cols":37,"rows_kept":2102,"cut":false,"hidden":false,"merged":[]}
["Compound:","Glyphosate"]
["CAS:","1071-83-6 "]
["Comments:",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"E = Endpoints for estrogen-mediated activity"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"A = Endpoints for androgen-mediated activity"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"T = Endpoints for thyroid-related activity"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"S = Endpoints for steroidogenesisrelated activity"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"N = Endpoints potentially sensitive to, but not diagnostic of, EATS modalities"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"_ = Endpoints related to target organ toxicity and systemic toxicity"]
[]
[]
["Type of toxicity","Study principle","Study ID Matrix","Study reference ID"," Study guideline (OECD/US EPA) or remarks","Source","Reference (citation)","Reporting date","Species","Strain or in vitro model","Animals/sex/group","Sex (administration)","Purity (%)","Route of administration","Method of administration","Doses tested","Lowest dose tested","Highest dose tested","Dose unit","Duration of exposure","Duration unit","Generation/Life stage","Sex (effect dose)","Lowest Effect dose","Effect type","Effect target","Effect classification","Effect description","Effect determination","Effect direction","NOAEL/NOEL/NOEC","LOAEL/LOEL/LOEC","Unit","Effect indicative of","Additional remarks","Relevance","Reliability"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","In life observation","Mortality",{"$f":"IF(Z12<>0,VLOOKUP(Z12,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z12<>0,VLOOKUP(Z12,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","In life observation","Clinical signs",{"$f":"IF(Z13<>0,VLOOKUP(Z13,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Low incidence of diarrhoea and pale faeces in both sexes at 20000 ppm in week 2, reversible, not unequivocally related to treatment\nophthalmoscopy: incidences of abnormal findings occasionally observed in control and 20000 ppm rats, not treatment-related",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z13<>0,VLOOKUP(Z13,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",20000,"In life observation","Body weight",{"$f":"IF(Z14<>0,VLOOKUP(Z14,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased in males at 20000 ppm over the whole study period, -8% in final bw (no effect in females), treatment-related",null,"Decrease",5000,20000,"ppm",{"$f":"IF(Z14<>0,VLOOKUP(Z14,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",20000,"In life observation","Food consumption",{"$f":"IF(Z15<>0,VLOOKUP(Z15,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: reduced in males at 20000 ppm from week 5, not significant, treatment-related\nfood efficiency: reduced in males at 20000 ppm throughout the study, treatment-related",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z15<>0,VLOOKUP(Z15,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",20000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z16<>0,VLOOKUP(Z16,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: reduced platelet count in both sexes at ≥ 5000 ppm, marginal increase in prothrombin time in males at all doses, both considered to be not tox. relevant\nClinical chemistry: ALT↑ and ALP ↑in both sexes at 20000 ppm throughout the study, treatment-related (non-treatment related findings: AST ↑ in females at 20000 ppm at week 4, ALT in males+females ocassionally increased at 5000 ppm, ALP in males at 1000 and 5000 ppm marginally increased, ALP↑ in each one females at control group and 1000 ppm in week 13, no dose-response relationship; ↓plasma urea (both sexes), plasma glucose (males) and triglyceride levels (males) at 20000 ppm)\nUrinalysis: lower pH in both sexes at 20000 ppm and higher values at 1000 and 5000 ppm for females, marginal changes within historical control data",null,"Change",5000,20000,"ppm",{"$f":"IF(Z16<>0,VLOOKUP(Z16,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ Weight","Adrenals weight",{"$f":"IF(Z17<>0,VLOOKUP(Z17,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z17<>0,VLOOKUP(Z17,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ Weight","Brain weight",{"$f":"IF(Z18<>0,VLOOKUP(Z18,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z18<>0,VLOOKUP(Z18,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",10000,"Organ Weight","Liver weight",{"$f":"IF(Z19<>0,VLOOKUP(Z19,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Abs. weight in males reduced at 1000 and 20000 ppm, no consistent trend, changes at 20000 ppm attributed to reduced body weight",null,"Decrease",5000,20000,"ppm",{"$f":"IF(Z19<>0,VLOOKUP(Z19,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",">20000","Organ Weight","Testis weight",{"$f":"IF(Z20<>0,VLOOKUP(Z20,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Reduced weight in all treatment groups (high value of single male in control group), not statistically significant, not treatment-related",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z20<>0,VLOOKUP(Z20,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",20000,"Organ Weight","Heart weight",{"$f":"IF(Z21<>0,VLOOKUP(Z21,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Abs. weight in males reduced at 20000 ppm, attributed to reduced body weight",null,"Decrease",20000,">20000","ppm",{"$f":"IF(Z21<>0,VLOOKUP(Z21,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",20000,"Organ Weight","Kidney weight",{"$f":"IF(Z22<>0,VLOOKUP(Z22,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Rel. weight increased in males at 20000 ppm, not considered treatment related (no histopathological findings)",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z22<>0,VLOOKUP(Z22,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","F",">20000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z23<>0,VLOOKUP(Z23,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z23<>0,VLOOKUP(Z23,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females); histopathology performed for control and high dose group.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z24<>0,VLOOKUP(Z24,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z24<>0,VLOOKUP(Z24,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females); histopathology performed for control and high dose group.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","F",">20000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z25<>0,VLOOKUP(Z25,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z25<>0,VLOOKUP(Z25,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females); histopathology performed for control and high dose group.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Testis histopathology",{"$f":"IF(Z26<>0,VLOOKUP(Z26,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z26<>0,VLOOKUP(Z26,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females); histopathology performed for control and high dose group.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z27<>0,VLOOKUP(Z27,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z27<>0,VLOOKUP(Z27,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females); histopathology performed for control and high dose group.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","F",">20000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z28<>0,VLOOKUP(Z28,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z28<>0,VLOOKUP(Z28,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females); histopathology performed for control and high dose group.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z29<>0,VLOOKUP(Z29,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z29<>0,VLOOKUP(Z29,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Liver histopathology",{"$f":"IF(Z30<>0,VLOOKUP(Z30,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z30<>0,VLOOKUP(Z30,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z31<>0,VLOOKUP(Z31,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z31<>0,VLOOKUP(Z31,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",12,"M + F",97.4,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z32<>0,VLOOKUP(Z32,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z32<>0,VLOOKUP(Z32,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females); histopathology performed for control and high dose group.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M + F",">50000","In life observation","Mortality",{"$f":"IF(Z33<>0,VLOOKUP(Z33,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",50000,">20000","ppm",{"$f":"IF(Z33<>0,VLOOKUP(Z33,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M + F",50000,"In life observation","Clinical signs",{"$f":"IF(Z34<>0,VLOOKUP(Z34,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Soft faeces and diarrhoea in 10/10 males and 10/10 females at 50000 ppm from Day 4 until termination, treatment-related ",null,"Increase",10000,50000,"ppm",{"$f":"IF(Z34<>0,VLOOKUP(Z34,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M + F",50000,"In life observation","Body weight",{"$f":"IF(Z35<>0,VLOOKUP(Z35,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Reduced body weight gain in males and females at 50000 ppm during the fist 4 weeks, effects partially reversible in males and fully reversible in females, treatment-related",null,"Decrease",10000,50000,"ppm",{"$f":"IF(Z35<>0,VLOOKUP(Z35,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M + F",50000,"In life observation","Food consumption",{"$f":"IF(Z36<>0,VLOOKUP(Z36,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption/efficiency: reduced in males and females at 50000 ppm during the first 4 weeks, effects partially reversible in males and fully reversible in females, effects in line with reduced bw development, treatment-related",null,"Decrease",10000,50000,"ppm",{"$f":"IF(Z36<>0,VLOOKUP(Z36,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M + F",10000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z37<>0,VLOOKUP(Z37,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: MCHC ↑ in females at 50000 ppm within historical control data, Neutrophils ↑ in males at 1000 and 50000 ppm, no dose-relation, findings incidental\nClinical chemistry: Ca ↓ and ALP ↑ in both sexes at ≥ 10000 ppm, P↑ and Creat↓ in both sexes at 50000 ppm, total plama protein and albumin ↓ in females at 50000 ppm, treatment-related (non-treatment-related findings: plasma urea↓ and Na ↓ in both sexes at 50000, within historical control data) \nUrinalysis: haemoglobin in urine ↑ in both sexes at 50000 ppm, particulate matter in sediment in males at 50000 ppm, findings may be attributed to faecal contamination",null,"Change",10000,50000,"ppm",{"$f":"IF(Z37<>0,VLOOKUP(Z37,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M + F",50000,"Organ Weight","Liver weight",{"$f":"IF(Z38<>0,VLOOKUP(Z38,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Rel. weight increased in both sexes at 50000 ppm, treatment-related",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z38<>0,VLOOKUP(Z38,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","F",">50000","Organ Weight","Ovary weight",{"$f":"IF(Z39<>0,VLOOKUP(Z39,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z39<>0,VLOOKUP(Z39,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M",">50000","Organ Weight","Seminal vesicles weight",{"$f":"IF(Z40<>0,VLOOKUP(Z40,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z40<>0,VLOOKUP(Z40,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M",50000,"Organ Weight","Testis weight",{"$f":"IF(Z41<>0,VLOOKUP(Z41,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Relative weight increased in all treatment groups, no histopathological correlate, effect at 50000 ppm attributed to reduced body weight and considered to be without toxicological relevance, in other dose groups attributable to slighly lower control group means",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z41<>0,VLOOKUP(Z41,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M",50000,"Organ Weight","Adrenals weight",{"$f":"IF(Z42<>0,VLOOKUP(Z42,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Relative weight increased in males at 50000 ppm, minimal effect, considered incidental in the absence of histopathological findings",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z42<>0,VLOOKUP(Z42,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M",10000,"Organ Weight","Brain weight",{"$f":"IF(Z43<>0,VLOOKUP(Z43,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Relative weight increased in males at ≥ 10000 ppm, effect at 10000 ppm considered incidental, effect at 50000 ppm attributed to reduced body weight and considered to be without toxicological relevance",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z43<>0,VLOOKUP(Z43,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M",50000,"Organ Weight","Pituitary weight",{"$f":"IF(Z44<>0,VLOOKUP(Z44,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Absolute weight decreased in males at 50000 ppm, attributed to the reduced bw, toxicologically not significant; abs. weight decreased in females at ≥ 10000 ppm, not treatment-related, effect attributed to one control  group female with abnormally high value",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z44<>0,VLOOKUP(Z44,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M + F",50000,"Organ Weight","Kidney weight",{"$f":"IF(Z45<>0,VLOOKUP(Z45,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Relative weight increased in both sexes at 50000 ppm. However, no relevant treatment-related histopathological changes were observed.",null,"Increase",10000,50000,"ppm",{"$f":"IF(Z45<>0,VLOOKUP(Z45,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M + F",50000,"Organ Weight","Heart weight",{"$f":"IF(Z46<>0,VLOOKUP(Z46,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute weight reduced in both sexes and rel. weight increased in males at 50000 ppm, attributed to reduced body weight, considered to be without toxicological significance",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z46<>0,VLOOKUP(Z46,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M",50000,"Organ Weight","Spleen weight",{"$f":"IF(Z47<>0,VLOOKUP(Z47,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute weight reduced in both sexes at 50000 ppm, attributed to reduced body weight, without toxicological significance",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z47<>0,VLOOKUP(Z47,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z48<>0,VLOOKUP(Z48,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Hydronephrosis in one or both kidneys in 2/10, 1/10 and 1/10 males at 1000, 10000 and 50000 ppm and in 3/10 females at 1000 ppm, not treatment-related ",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z48<>0,VLOOKUP(Z48,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z49<>0,VLOOKUP(Z49,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z49<>0,VLOOKUP(Z49,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M + F",1000,"Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z50<>0,VLOOKUP(Z50,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Caecum: macroscopical findings: enlarged and fluid-filled in 10/10 males and 10/10 females at 50000 ppm; microscopical findings: atrophy in 5/10 males and 5/10 females at 50000 ppm and for 1/10 males and 2/10 females at 10000 ppm, probably attributed to caecal distention ",null,"Change",1000,10000,"ppm",{"$f":"IF(Z50<>0,VLOOKUP(Z50,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z51<>0,VLOOKUP(Z51,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z51<>0,VLOOKUP(Z51,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Testis histopathology",{"$f":"IF(Z52<>0,VLOOKUP(Z52,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z52<>0,VLOOKUP(Z52,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z53<>0,VLOOKUP(Z53,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z53<>0,VLOOKUP(Z53,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Liver histopathology",{"$f":"IF(Z54<>0,VLOOKUP(Z54,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z54<>0,VLOOKUP(Z54,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only (exception: liver)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z55<>0,VLOOKUP(Z55,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z55<>0,VLOOKUP(Z55,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z56<>0,VLOOKUP(Z56,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z56<>0,VLOOKUP(Z56,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z57<>0,VLOOKUP(Z57,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z57<>0,VLOOKUP(Z57,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z58<>0,VLOOKUP(Z58,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z58<>0,VLOOKUP(Z58,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z59<>0,VLOOKUP(Z59,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z59<>0,VLOOKUP(Z59,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z60<>0,VLOOKUP(Z60,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z60<>0,VLOOKUP(Z60,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Vagina histopathology",{"$f":"IF(Z61<>0,VLOOKUP(Z61,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z61<>0,VLOOKUP(Z61,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z62<>0,VLOOKUP(Z62,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z62<>0,VLOOKUP(Z62,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",2,"434/016","JMAFF (1985), equivalent to OECD 408 (2018)","DAR",null,1996,"Rat","Sprague-Dawley",10,"M + F",95.3,"Oral","Feed","1000; 10000; 50000",1000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z63<>0,VLOOKUP(Z63,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z63<>0,VLOOKUP(Z63,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M + F",">30000","In life observation","Mortality",{"$f":"IF(Z64<>0,VLOOKUP(Z64,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z64<>0,VLOOKUP(Z64,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M + F",">30000","In life observation","Clinical signs",{"$f":"IF(Z65<>0,VLOOKUP(Z65,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Poor general condition in 1/12 females (emaciation, decreased spontaneous motor activity), not treatment-related",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z65<>0,VLOOKUP(Z65,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M + F",30000,"In life observation","Body weight",{"$f":"IF(Z66<>0,VLOOKUP(Z66,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased bw (5--10% ) in both sexes at 30000 ppm, treatment-related",null,"Decrease",10000,30000,"ppm",{"$f":"IF(Z66<>0,VLOOKUP(Z66,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M + F",30000,"In life observation","Food consumption",{"$f":"IF(Z67<>0,VLOOKUP(Z67,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: statistically significantly decreased in both sexes at 30000 ppm during the first week, in line with reduced body weight, treatment-related (not treatment-related findings: decreased  food consumption in both sexes at 3000 ppm)\nfood efficiency: statistically significantly decreased (-5-6 %) in both sexes at 30000 ppm during the first week, in line with reduced body weight, treatment-related ",null,"Decrease",10000,30000,"ppm",{"$f":"IF(Z67<>0,VLOOKUP(Z67,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M + F",30000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z68<>0,VLOOKUP(Z68,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: no abnormalities observed\nClinical chemistry:  ALP ↑ in females at 30000 ppm, treatment-related (findings without toxicological relevance: Alb ↓ in females at 30000 ppm)\nUrinalysis: lower pH in males at ≥ 10000 ppm and in females at 30000 ppm, attributed to the acidic nature of the test substance (findings without toxicological significante: decreased urine protein in males at ≥ 10000 ppm and in females at 30000 ppm, not treatment-related findings: increased urine volume in females at 30000 ppm)",null,"Change",10000,30000,"ppm",{"$f":"IF(Z68<>0,VLOOKUP(Z68,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M + F",">30000","Organ Weight","Adrenals weight",{"$f":"IF(Z69<>0,VLOOKUP(Z69,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z69<>0,VLOOKUP(Z69,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","F",30000,"Organ Weight","Brain weight",{"$f":"IF(Z70<>0,VLOOKUP(Z70,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Rel. weight increased in females at 30000 ppm, considered to be the secondary change attributed to decreased body weight (no change in males)",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z70<>0,VLOOKUP(Z70,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","F",">30000","Organ Weight","Liver weight",{"$f":"IF(Z71<>0,VLOOKUP(Z71,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Rel. weight increased in females at 30000 ppm, not treatment-related, effect attributable to the genetic disorder of one animal",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z71<>0,VLOOKUP(Z71,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M + F",30000,"Organ Weight","[Not in list]",{"$f":"IF(Z72<>0,VLOOKUP(Z72,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Caecum: abs. + rel. weight statistically significantly increased in both sexes,  in line with pathological findings, treatment related",null,"Increase",10000,30000,"ppm",{"$f":"IF(Z72<>0,VLOOKUP(Z72,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M + F",30000,"Organ Weight","Kidney weight",{"$f":"IF(Z73<>0,VLOOKUP(Z73,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z73<>0,VLOOKUP(Z73,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M",">30000","Organ Weight","Testis weight",{"$f":"IF(Z74<>0,VLOOKUP(Z74,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z74<>0,VLOOKUP(Z74,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M + F",10000,"Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z75<>0,VLOOKUP(Z75,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Caecum: distention in 9/12 males and 7/12 females at 30000 ppm and in 3/12 males and 0/12 females at 10000 ppm, macroscopical finding, treatment-related",null,"Change",3000,10000,"ppm",{"$f":"IF(Z75<>0,VLOOKUP(Z75,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M + F",">30000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z76<>0,VLOOKUP(Z76,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Polycystic kidney in 1/12 males at 10000 ppm and in 1/12 females at 30000 ppm, not treatment-related",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z76<>0,VLOOKUP(Z76,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M + F",">30000","Organ histopathology","Liver histopathology",{"$f":"IF(Z77<>0,VLOOKUP(Z77,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Bile duct proliferation and cholangiectatis in 1/12 males at 10000 ppm and in 1/12 females at 30000 ppm, not treatment-related",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z77<>0,VLOOKUP(Z77,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M",">30000","Organ histopathology","Coagulating gland histopathology",{"$f":"IF(Z78<>0,VLOOKUP(Z78,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z78<>0,VLOOKUP(Z78,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","F",">30000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z79<>0,VLOOKUP(Z79,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z79<>0,VLOOKUP(Z79,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M",">30000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z80<>0,VLOOKUP(Z80,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z80<>0,VLOOKUP(Z80,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","F",">30000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z81<>0,VLOOKUP(Z81,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z81<>0,VLOOKUP(Z81,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M",">30000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z82<>0,VLOOKUP(Z82,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z82<>0,VLOOKUP(Z82,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","F",">30000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z83<>0,VLOOKUP(Z83,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z83<>0,VLOOKUP(Z83,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M",">30000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z84<>0,VLOOKUP(Z84,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z84<>0,VLOOKUP(Z84,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M",">30000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z85<>0,VLOOKUP(Z85,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z85<>0,VLOOKUP(Z85,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M",">30000","Organ histopathology","Testis histopathology",{"$f":"IF(Z86<>0,VLOOKUP(Z86,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z86<>0,VLOOKUP(Z86,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M + F",">30000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z87<>0,VLOOKUP(Z87,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z87<>0,VLOOKUP(Z87,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","F",">30000","Organ histopathology","Vagina histopathology",{"$f":"IF(Z88<>0,VLOOKUP(Z88,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z88<>0,VLOOKUP(Z88,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","F",">30000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z89<>0,VLOOKUP(Z89,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z89<>0,VLOOKUP(Z89,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M + F",">30000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z90<>0,VLOOKUP(Z90,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z90<>0,VLOOKUP(Z90,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",3,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Rat","Sprague-Dawley",12,"M + F","95.68, 95.0 and 97.56%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",90,"Days","Adult","M + F",">30000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z91<>0,VLOOKUP(Z91,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z91<>0,VLOOKUP(Z91,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","In life observation","Mortality",{"$f":"IF(Z92<>0,VLOOKUP(Z92,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z92<>0,VLOOKUP(Z92,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","In life observation","Clinical signs",{"$f":"IF(Z93<>0,VLOOKUP(Z93,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z93<>0,VLOOKUP(Z93,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M",50000,"In life observation","Body weight",{"$f":"IF(Z94<>0,VLOOKUP(Z94,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased body weight (-9% at week 13) in males at 50000 ppm, occasionally statistically significant, treatment-related",null,"Decrease",10000,50000,"ppm",{"$f":"IF(Z94<>0,VLOOKUP(Z94,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",50000,"In life observation","Food consumption",{"$f":"IF(Z95<>0,VLOOKUP(Z95,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: decreased (-6%) in males at 50000 ppm during the treatment period, treatment-related \nfood efficiency: decreased (m:-21%; f: -12%  ) in both sexes at 50000 ppm during the treatment period, treatment-related ",null,"Decrease",10000,50000,"ppm",{"$f":"IF(Z95<>0,VLOOKUP(Z95,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",50000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z96<>0,VLOOKUP(Z96,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: ↓ Ht, ↓ Hb and ↓ RBC and anemia in females at 50000 ppm, treatment-related; no changes in males\nClinical chemistry:  ↑ALP in both sexes at 50000 ppm, ↑ P in females at 50000 ppm, treatment-related (not treatment-related findings: ↓GPT in females at 50000 ppm, ↑ Creat.phosphokinase in females at 5000 and 50000 ppm, ↑BUN in females at 10000 ppm)\nUrinalysis: reduced pH in males of all treatment-groups, attributed to the acidic nature of the test substance",null,"Change",10000,50000,"ppm",{"$f":"IF(Z96<>0,VLOOKUP(Z96,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",10000,"Organ Weight","[Not in list]",{"$f":"IF(Z97<>0,VLOOKUP(Z97,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Caecum: abs+rel weight increased (m: +15%/+11%; f: +22%/+17%) in both sexes at ≥ 10000 ppm (stat.significant at 50000 ppm), treatment-related",null,"Increase",5000,10000,"ppm",{"$f":"IF(Z97<>0,VLOOKUP(Z97,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ Weight","Liver weight",{"$f":"IF(Z98<>0,VLOOKUP(Z98,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z98<>0,VLOOKUP(Z98,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ Weight","Kidney weight",{"$f":"IF(Z99<>0,VLOOKUP(Z99,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z99<>0,VLOOKUP(Z99,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M",">50000","Organ Weight","Testis weight",{"$f":"IF(Z100<>0,VLOOKUP(Z100,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z100<>0,VLOOKUP(Z100,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ Weight","Adrenals weight",{"$f":"IF(Z101<>0,VLOOKUP(Z101,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z101<>0,VLOOKUP(Z101,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ Weight","Brain weight",{"$f":"IF(Z102<>0,VLOOKUP(Z102,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z102<>0,VLOOKUP(Z102,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",50000,"Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z103<>0,VLOOKUP(Z103,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Macroscopic finding: caecum distention in 12/12 males and 10/12 females at 50000 ppm and in 1/12 females at 10000 ppm at necropsy, no histopathological findings",null,"Change",10000,50000,"ppm",{"$f":"IF(Z103<>0,VLOOKUP(Z103,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M",50000,"Organ histopathology","Urinary bladder histopathology",{"$f":"IF(Z104<>0,VLOOKUP(Z104,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Cystitis of the urinary bladder in 4/12 males at 50000 ppm (0/12 in the control group), treatment-related; no effects in females",null,"Change",10000,50000,"ppm",{"$f":"IF(Z104<>0,VLOOKUP(Z104,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z105<>0,VLOOKUP(Z105,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z105<>0,VLOOKUP(Z105,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Coagulating gland histopathology",{"$f":"IF(Z106<>0,VLOOKUP(Z106,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z106<>0,VLOOKUP(Z106,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z107<>0,VLOOKUP(Z107,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z107<>0,VLOOKUP(Z107,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z108<>0,VLOOKUP(Z108,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z108<>0,VLOOKUP(Z108,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Liver histopathology",{"$f":"IF(Z109<>0,VLOOKUP(Z109,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z109<>0,VLOOKUP(Z109,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z110<>0,VLOOKUP(Z110,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z110<>0,VLOOKUP(Z110,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z111<>0,VLOOKUP(Z111,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z111<>0,VLOOKUP(Z111,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z112<>0,VLOOKUP(Z112,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z112<>0,VLOOKUP(Z112,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z113<>0,VLOOKUP(Z113,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z113<>0,VLOOKUP(Z113,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Testis histopathology",{"$f":"IF(Z114<>0,VLOOKUP(Z114,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z114<>0,VLOOKUP(Z114,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z115<>0,VLOOKUP(Z115,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z115<>0,VLOOKUP(Z115,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z116<>0,VLOOKUP(Z116,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z116<>0,VLOOKUP(Z116,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Vagina histopathology",{"$f":"IF(Z117<>0,VLOOKUP(Z117,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z117<>0,VLOOKUP(Z117,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z118<>0,VLOOKUP(Z118,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z118<>0,VLOOKUP(Z118,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",4,null,"OECD 408 (1981), JMAFF (1985) ","DAR",null,1995,"Mouse","ICR (Crj:CD-1)",12,"M + F",97.56,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z119<>0,VLOOKUP(Z119,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z119<>0,VLOOKUP(Z119,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M + F",1000,"In life observation","Mortality",{"$f":"IF(Z120<>0,VLOOKUP(Z120,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Each 1/4 males and 1/4 females were sacrificed for human reasons on Days 61 and 72, associated with clinical signs and histopathological findings, treatment-related",null,"Change",300,1000,"mg/kg bw/day",{"$f":"IF(Z120<>0,VLOOKUP(Z120,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M + F",1000,"In life observation","Clinical signs",{"$f":"IF(Z121<>0,VLOOKUP(Z121,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"At 1000 mg/kg bw/day: liquid/soft feces in 3/3 males and 3/3 females, vomiting in 2/3 females, thin appearance in 1/3 males and 3/3 females, dehydration in 1/3 males and 2/3 females, pallor of ears and mouth in 1/3 females, treatment-related",null,"Increase",300,1000,"mg/kg bw/day",{"$f":"IF(Z121<>0,VLOOKUP(Z121,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M + F",1000,"In life observation","Body weight",{"$f":"IF(Z122<>0,VLOOKUP(Z122,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Reduced mean body weight (-28%) and lower weight gain in males (+4% vs +31% in controls) and body weight loss in females (-7% vs. +14% in controls) at 1000 mg/kg bw/day (males: study week 4-11, females: study week 1-11), treatment-related",null,"Decrease",300,1000,"mg/kg bw/day",{"$f":"IF(Z122<>0,VLOOKUP(Z122,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M + F",1000,"In life observation","Food consumption",{"$f":"IF(Z123<>0,VLOOKUP(Z123,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: reduced food consumption, varying from 25-75% of the amount given, was observed on many occasions in both sexes at 1000 mg/kg bw (males: study week 4-11, females: study week 1-11), treatment-related",null,"Decrease",300,1000,"mg/kg bw/day",{"$f":"IF(Z123<>0,VLOOKUP(Z123,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M + F",1000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z124<>0,VLOOKUP(Z124,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: no treatment-related findings (ocassional changes in Hb, Ht in females at 1000 mg/kg bw/day, reduced RBC in males at 30 and 300 mg/kg bw/day and reduced leucocytes in females at 30 mg/kg bw/day were without dose relation)\nClinical chemistry: ALT ↑ in 2/3 males and 1/3 females at 1000 mg/kg bw, ALP↓ in 3/3 females at 1000 mg/kg bw/day, T.Prot and Alb ↓ in 3/3 females at 1000 mg/kg bw/day, treatment-related (not treatment-related findings: ocassionally Na↓, Creat↓ and urea ↓ in males at 1000 mg/kg bw, P↑ in females at 30 mg/kg bw/day, Gluc↓ in both sexes at 1000 mg/kg bw/day, findings not consistent throughout the study or not dose-related)\nUrinalysis: ↓ mean specific gravity in 1/3 males and 3/3 females at 1000 mg/kg bw/day, ↑ mean urinary volume and less marked colour in 3/3 females at 1000 mg/kg bw/day, treatment-related",null,"Change",300,1000,"mg/kg bw/day",{"$f":"IF(Z124<>0,VLOOKUP(Z124,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M",300,"Organ Weight","Adrenals weight",{"$f":"IF(Z125<>0,VLOOKUP(Z125,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Absolute and relative organ weights were increased in males at  300 mg/kg bw/day (+18 and +25%) and 1000 mg/kg bw/day (+21 and +70%), statistical significance only for rel. weight at 1000 mg/kg bw, no histopathological findings, toxicological significance doubtful",null,"Increase",30,300,"mg/kg bw/day",{"$f":"IF(Z125<>0,VLOOKUP(Z125,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M",1000,"Organ Weight","Prostate weight",{"$f":"IF(Z126<>0,VLOOKUP(Z126,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute and relative organ weights were decreased at 1000 mg/kg bw/day (-68 and -56%; statistical significance only for absolute weight).",null,"Decrease",300,1000,"mg/kg bw/day",{"$f":"IF(Z126<>0,VLOOKUP(Z126,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M",30,"Organ Weight","Spleen weight",{"$f":"IF(Z127<>0,VLOOKUP(Z127,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute and relative organ weights were decreased in males at 30 mg/kg bw/day (-16 and -7%), at 300 mg/kg bw/day (-25 and -19%) and at 1000 mg/kg bw/day (-35 and -10%), findings not statistically significant, no histopathological findings and no effects in females, thus toxicological significance doubtful",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z127<>0,VLOOKUP(Z127,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M",">1000","Organ Weight","Epididymis weight",{"$f":"IF(Z128<>0,VLOOKUP(Z128,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z128<>0,VLOOKUP(Z128,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ Weight","Liver weight",{"$f":"IF(Z129<>0,VLOOKUP(Z129,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z129<>0,VLOOKUP(Z129,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ Weight","Kidney weight",{"$f":"IF(Z130<>0,VLOOKUP(Z130,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z130<>0,VLOOKUP(Z130,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","F",">1000","Organ Weight","Ovary weight",{"$f":"IF(Z131<>0,VLOOKUP(Z131,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z131<>0,VLOOKUP(Z131,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M",">1000","Organ Weight","Testis weight",{"$f":"IF(Z132<>0,VLOOKUP(Z132,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z132<>0,VLOOKUP(Z132,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ Weight","Thyroid weight",{"$f":"IF(Z133<>0,VLOOKUP(Z133,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z133<>0,VLOOKUP(Z133,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","F",">1000","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z134<>0,VLOOKUP(Z134,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z134<>0,VLOOKUP(Z134,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ Weight","Brain weight",{"$f":"IF(Z135<>0,VLOOKUP(Z135,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z135<>0,VLOOKUP(Z135,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ Weight","Pituitary weight",{"$f":"IF(Z136<>0,VLOOKUP(Z136,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z136<>0,VLOOKUP(Z136,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","F",1000,"Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z137<>0,VLOOKUP(Z137,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Decreased uterus size at macroscopical examination at 1000 mg/kg bw/day, uterine atrophy in 2/3 females at 1000 mg/kg bw/day, treatment-related",null,"Change",300,1000,"mg/kg bw/day",{"$f":"IF(Z137<>0,VLOOKUP(Z137,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M",">1000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z138<>0,VLOOKUP(Z138,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z138<>0,VLOOKUP(Z138,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M",1000,"Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z139<>0,VLOOKUP(Z139,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Prostate atrophy was observed in 2/3 animals at 1000 mg/kg bw/day. ",null,"Change",300,1000,"mg/kg bw/day",{"$f":"IF(Z139<>0,VLOOKUP(Z139,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M + F",1000,"Organ histopathology","Bone histopathology",{"$f":"IF(Z140<>0,VLOOKUP(Z140,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Sternum: increased number of adipocytes in 2/3 males and 3/3 females at 1000 mg/kg bw/day, treatment-related",null,"Change",300,1000,"mg/kg bw/day",{"$f":"IF(Z140<>0,VLOOKUP(Z140,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M",">1000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z141<>0,VLOOKUP(Z141,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z141<>0,VLOOKUP(Z141,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M",">1000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z142<>0,VLOOKUP(Z142,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z142<>0,VLOOKUP(Z142,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M",">1000","Organ histopathology","Liver histopathology",{"$f":"IF(Z143<>0,VLOOKUP(Z143,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z143<>0,VLOOKUP(Z143,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M",">1000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z144<>0,VLOOKUP(Z144,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z144<>0,VLOOKUP(Z144,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","F",">1000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z145<>0,VLOOKUP(Z145,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z145<>0,VLOOKUP(Z145,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","F",">1000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z146<>0,VLOOKUP(Z146,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z146<>0,VLOOKUP(Z146,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M",">1000","Organ histopathology","Testis histopathology",{"$f":"IF(Z147<>0,VLOOKUP(Z147,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z147<>0,VLOOKUP(Z147,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z148<>0,VLOOKUP(Z148,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z148<>0,VLOOKUP(Z148,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z149<>0,VLOOKUP(Z149,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z149<>0,VLOOKUP(Z149,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",5,null,"OECD 409 (1998), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 300; 1000",300,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z150<>0,VLOOKUP(Z150,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z150<>0,VLOOKUP(Z150,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M + F",">10000","In life observation","Mortality",{"$f":"IF(Z151<>0,VLOOKUP(Z151,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z151<>0,VLOOKUP(Z151,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M + F",">10000","In life observation","Clinical signs",{"$f":"IF(Z152<>0,VLOOKUP(Z152,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z152<>0,VLOOKUP(Z152,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M + F",">10000","In life observation","Body weight",{"$f":"IF(Z153<>0,VLOOKUP(Z153,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z153<>0,VLOOKUP(Z153,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M + F",10000,"In life observation","Food consumption",{"$f":"IF(Z154<>0,VLOOKUP(Z154,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: decreased in both sexes at 10000 ppm during study week 2, fully reversible\nfood efficiency: no adverse effects observed",null,"Decrease",null,10000,"ppm",{"$f":"IF(Z154<>0,VLOOKUP(Z154,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M + F",">10000","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z155<>0,VLOOKUP(Z155,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: after 45 days of treatment: dose-related increase in clotting time in both sexes at all dose , treatment-related but fully reversible (non-treatment-related findings: MCH  ↑ in females at 10000 ppm, but within normal range); after 90 days of treatment: Neutrophils↓ in males at 2000 ppm, WBC↑ in females at 200 ppm, and Hct, MCV and MCH↑in females at 10000 ppm, within HCD); all effects were considered non-adverse\nClinical chemistry:  after 45 days of treatment: ALP↑ and GGT ↑ in males at 10000 ppm, GGT ↑ in females at 10000 ppm (non-treatment-related findings: T.Bilirubin ↑ in females at ≥ 2000 ppm and Ca ↑ in females at 10000 ppm, but within normal range); after 90 days of treatment: T.Bilirubin ↑ in both sexes at 10000 ppm, treatment- and dose-related; all effects were considered non-adverse\nUrinalysis: no adverse effects observed",null,"Change",10000,">10000","ppm",{"$f":"IF(Z155<>0,VLOOKUP(Z155,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M + F",">10000","Organ Weight","Liver weight",{"$f":"IF(Z156<>0,VLOOKUP(Z156,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z156<>0,VLOOKUP(Z156,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M + F",">10000","Organ Weight","Kidney weight",{"$f":"IF(Z157<>0,VLOOKUP(Z157,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z157<>0,VLOOKUP(Z157,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M",">10000","Organ Weight","Testis weight",{"$f":"IF(Z158<>0,VLOOKUP(Z158,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z158<>0,VLOOKUP(Z158,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M + F",">10000","Organ Weight","Thyroid weight",{"$f":"IF(Z159<>0,VLOOKUP(Z159,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z159<>0,VLOOKUP(Z159,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M + F",">10000","Organ Weight","Adrenals weight",{"$f":"IF(Z160<>0,VLOOKUP(Z160,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z160<>0,VLOOKUP(Z160,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","F",">10000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z161<>0,VLOOKUP(Z161,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z161<>0,VLOOKUP(Z161,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M + F",">10000","Organ histopathology","Liver histopathology",{"$f":"IF(Z162<>0,VLOOKUP(Z162,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Minimal to mild leucocyte infiltration in 3/4 and 3/4 males and in 4/4 and 4/4 females at 0 and 10000 ppm, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z162<>0,VLOOKUP(Z162,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M + F",">10000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z163<>0,VLOOKUP(Z163,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Minimal to mild mineralisation and mild cytoplasmic vacuolisation of the tubular epithelium, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z163<>0,VLOOKUP(Z163,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M + F",">10000","Organ histopathology","Oesophagus histopathology",{"$f":"IF(Z164<>0,VLOOKUP(Z164,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Minimal to mild lymphocytic infiltration, not treatment-related ",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z164<>0,VLOOKUP(Z164,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M + F",">10000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z165<>0,VLOOKUP(Z165,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z165<>0,VLOOKUP(Z165,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M + F",">10000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z166<>0,VLOOKUP(Z166,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z166<>0,VLOOKUP(Z166,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M",">10000","Organ histopathology","Testis histopathology",{"$f":"IF(Z167<>0,VLOOKUP(Z167,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z167<>0,VLOOKUP(Z167,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","F",">10000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z168<>0,VLOOKUP(Z168,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z168<>0,VLOOKUP(Z168,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",6,1816,"OECD 409 (1981)","DAR",null,1999,"Dog","Beagle",4,"M + F","> 95 (2 different batches used)","Oral","Feed","200; 2000; 10000",200,10000,"ppm",90,"Days","Adult","M + F",">10000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z169<>0,VLOOKUP(Z169,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z169<>0,VLOOKUP(Z169,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M + F",">40000","In life observation","Mortality",{"$f":"IF(Z170<>0,VLOOKUP(Z170,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z170<>0,VLOOKUP(Z170,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M + F",">40000","In life observation","Clinical signs",{"$f":"IF(Z171<>0,VLOOKUP(Z171,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z171<>0,VLOOKUP(Z171,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M + F",">40000","In life observation","Body weight",{"$f":"IF(Z172<>0,VLOOKUP(Z172,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z172<>0,VLOOKUP(Z172,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M + F",">40000","In life observation","Food consumption",{"$f":"IF(Z173<>0,VLOOKUP(Z173,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z173<>0,VLOOKUP(Z173,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M + F",">40000","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z174<>0,VLOOKUP(Z174,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: no treatment-related findings (statistically significant changes: RBC ↑ in males at 1600 and 8000 ppm, MCV ↓in males at 1600 ppm, MCHC ↓ in females at 40000 ppm, considered incidental as no other findings were observed)\nClinical chemistry: no treatment-related findings (statistically significant changes: Cl ↑ in males at 2000 and 40000 ppm (minimal magnitude, no dose-relation), Alb ↑ in females at 2000 ppm, no dose relation)\nUrinalysis: decreased pH in 3/4 females at 40000 ppm, statistically not significant, attributed to the acidic nature of the test item",null,"No effect",40000,">40000","ppm",{"$f":"IF(Z174<>0,VLOOKUP(Z174,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M + F",">40000","Organ Weight","Adrenals weight",{"$f":"IF(Z175<>0,VLOOKUP(Z175,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z175<>0,VLOOKUP(Z175,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M + F",">40000","Organ Weight","Liver weight",{"$f":"IF(Z176<>0,VLOOKUP(Z176,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z176<>0,VLOOKUP(Z176,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M + F",">40000","Organ Weight","Kidney weight",{"$f":"IF(Z177<>0,VLOOKUP(Z177,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z177<>0,VLOOKUP(Z177,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","F",">40000","Organ Weight","Ovary weight",{"$f":"IF(Z178<>0,VLOOKUP(Z178,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z178<>0,VLOOKUP(Z178,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M",">40000","Organ Weight","Prostate weight",{"$f":"IF(Z179<>0,VLOOKUP(Z179,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z179<>0,VLOOKUP(Z179,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M",">40000","Organ Weight","Testis weight",{"$f":"IF(Z180<>0,VLOOKUP(Z180,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z180<>0,VLOOKUP(Z180,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M + F",">40000","Organ Weight","Thyroid weight",{"$f":"IF(Z181<>0,VLOOKUP(Z181,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z181<>0,VLOOKUP(Z181,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M + F",">40000","Organ Weight","Brain weight",{"$f":"IF(Z182<>0,VLOOKUP(Z182,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z182<>0,VLOOKUP(Z182,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M + F",">40000","Organ Weight","Pituitary weight",{"$f":"IF(Z183<>0,VLOOKUP(Z183,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z183<>0,VLOOKUP(Z183,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M",">40000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z184<>0,VLOOKUP(Z184,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z184<>0,VLOOKUP(Z184,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","F",">40000","Organ histopathology","Skin histopathology",{"$f":"IF(Z185<>0,VLOOKUP(Z185,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Cutaneous histiocytoma in 1/4 females at 40000, not treatment-related",null,"No effect",40000,">40000","ppm",{"$f":"IF(Z185<>0,VLOOKUP(Z185,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","F",">40000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z186<>0,VLOOKUP(Z186,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z186<>0,VLOOKUP(Z186,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M",">40000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z187<>0,VLOOKUP(Z187,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z187<>0,VLOOKUP(Z187,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M",">40000","Organ histopathology","Liver histopathology",{"$f":"IF(Z188<>0,VLOOKUP(Z188,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z188<>0,VLOOKUP(Z188,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M",">40000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z189<>0,VLOOKUP(Z189,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z189<>0,VLOOKUP(Z189,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","F",">40000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z190<>0,VLOOKUP(Z190,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z190<>0,VLOOKUP(Z190,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M",">40000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z191<>0,VLOOKUP(Z191,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z191<>0,VLOOKUP(Z191,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M + F",">40000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z192<>0,VLOOKUP(Z192,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z192<>0,VLOOKUP(Z192,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M",">40000","Organ histopathology","Testis histopathology",{"$f":"IF(Z193<>0,VLOOKUP(Z193,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z193<>0,VLOOKUP(Z193,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M + F",">40000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z194<>0,VLOOKUP(Z194,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z194<>0,VLOOKUP(Z194,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","F",">40000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z195<>0,VLOOKUP(Z195,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z195<>0,VLOOKUP(Z195,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",7,null,"OECD 409 (1981), JMAFF (1985), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",90,"Days","Adult","M + F",">40000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z196<>0,VLOOKUP(Z196,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z196<>0,VLOOKUP(Z196,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M + F",">50000","In life observation","Mortality",{"$f":"IF(Z197<>0,VLOOKUP(Z197,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z197<>0,VLOOKUP(Z197,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M + F",">50000","In life observation","Clinical signs",{"$f":"IF(Z198<>0,VLOOKUP(Z198,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Findings of minor nature were not related to treatment",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z198<>0,VLOOKUP(Z198,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M + F",50000,"In life observation","Body weight",{"$f":"IF(Z199<>0,VLOOKUP(Z199,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Depressed in males (not statistically significant) and females (occasionally statistically significant) at 50000 ppm, treatment-related",null,"Decrease",10000,50000,"ppm",{"$f":"IF(Z199<>0,VLOOKUP(Z199,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M + F",">50000","In life observation","Food consumption",{"$f":"IF(Z200<>0,VLOOKUP(Z200,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z200<>0,VLOOKUP(Z200,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M + F",50000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z201<>0,VLOOKUP(Z201,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: no treatment-related findings\nClinical chemistry: at 50000 ppm Alb ↓, Ca ↓and T.Protein ↓ in males , treatment-related, and ALP ↑ in females\nUrinalysis: no treatment-related findings",null,"Change",10000,50000,"ppm",{"$f":"IF(Z201<>0,VLOOKUP(Z201,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ Weight","Adrenals weight",{"$f":"IF(Z202<>0,VLOOKUP(Z202,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z202<>0,VLOOKUP(Z202,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ Weight","Brain weight",{"$f":"IF(Z203<>0,VLOOKUP(Z203,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z203<>0,VLOOKUP(Z203,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M",">50000","Organ Weight","Epididymis weight",{"$f":"IF(Z204<>0,VLOOKUP(Z204,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z204<>0,VLOOKUP(Z204,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M",10000,"Organ Weight","Liver weight",{"$f":"IF(Z205<>0,VLOOKUP(Z205,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Abs+rel weight increased in males at ≥ 10000 ppm, treatment-related but considered toxicologically not relevant due to the absence of histopathological findings",null,"Increase",2000,10000,"ppm",{"$f":"IF(Z205<>0,VLOOKUP(Z205,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M",10000,"Organ Weight","Kidney weight",{"$f":"IF(Z206<>0,VLOOKUP(Z206,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Abs+rel weight increased in males at ≥ 10000 ppm, treatment-related but considered toxicologically not relevant due to the absence of histopathological findings",null,"Increase",2000,10000,"ppm",{"$f":"IF(Z206<>0,VLOOKUP(Z206,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","F",">50000","Organ Weight","Ovary weight",{"$f":"IF(Z207<>0,VLOOKUP(Z207,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z207<>0,VLOOKUP(Z207,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M",">50000","Organ Weight","Testis weight",{"$f":"IF(Z208<>0,VLOOKUP(Z208,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z208<>0,VLOOKUP(Z208,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","F",2000,"Organ Weight","Thyroid weight",{"$f":"IF(Z209<>0,VLOOKUP(Z209,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Rel weight reduced in females at 2000 and 10000 ppm, no dose-relation, considered to be without toxicological significance",null,"Decrease",null,2000,"ppm",{"$f":"IF(Z209<>0,VLOOKUP(Z209,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Lung histopathology",{"$f":"IF(Z210<>0,VLOOKUP(Z210,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Minor granulomatous/inflammatory lesions were occasionally observed, no dose-relation, incidental, not treatment-related",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z210<>0,VLOOKUP(Z210,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z211<>0,VLOOKUP(Z211,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Minor granulomatous/inflammatory lesions were occasionally observed, no dose-relation, incidental, not treatment-related",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z211<>0,VLOOKUP(Z211,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z212<>0,VLOOKUP(Z212,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z212<>0,VLOOKUP(Z212,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z213<>0,VLOOKUP(Z213,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z213<>0,VLOOKUP(Z213,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z214<>0,VLOOKUP(Z214,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z214<>0,VLOOKUP(Z214,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z215<>0,VLOOKUP(Z215,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z215<>0,VLOOKUP(Z215,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z216<>0,VLOOKUP(Z216,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z216<>0,VLOOKUP(Z216,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z217<>0,VLOOKUP(Z217,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Imperfect spermatogenesis and minimal secretory activity in 1/4, 1/4, 1/4 and 2/4 males at 0, 2000, 10000 and 50000 ppm, not treatment-related",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z217<>0,VLOOKUP(Z217,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Testis histopathology",{"$f":"IF(Z218<>0,VLOOKUP(Z218,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z218<>0,VLOOKUP(Z218,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z219<>0,VLOOKUP(Z219,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z219<>0,VLOOKUP(Z219,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Liver histopathology",{"$f":"IF(Z220<>0,VLOOKUP(Z220,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z220<>0,VLOOKUP(Z220,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z221<>0,VLOOKUP(Z221,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z221<>0,VLOOKUP(Z221,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z222<>0,VLOOKUP(Z222,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z222<>0,VLOOKUP(Z222,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z223<>0,VLOOKUP(Z223,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z223<>0,VLOOKUP(Z223,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in non-rodents",8,null,"OECD 409 (1981), US EPA 82-1 (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",99.1,"Oral","Feed","2000; 10000; 50000",2000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z224<>0,VLOOKUP(Z224,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z224<>0,VLOOKUP(Z224,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","In life observation","Mortality",{"$f":"IF(Z225<>0,VLOOKUP(Z225,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z225<>0,VLOOKUP(Z225,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","In life observation","Clinical signs",{"$f":"IF(Z226<>0,VLOOKUP(Z226,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Vomiting, soft feces, thin appearance, hyperactivity, ptyalism, cutaneous signs and nodules on the ears were occasionally observed among all dose groups, not treatment-related",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z226<>0,VLOOKUP(Z226,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M",">500","In life observation","Body weight",{"$f":"IF(Z227<>0,VLOOKUP(Z227,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased body weight in males at 500 mg/kg bw/day, within historical control data, >10% decerease compared to control, considered adverse. sporadic body weight changes in single dogs among all dose groups, not treatment-related",null,"Decrease",125,500,"mg/kg bw/day",{"$f":"IF(Z227<>0,VLOOKUP(Z227,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","In life observation","Food consumption",{"$f":"IF(Z228<>0,VLOOKUP(Z228,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Occasional fluctuations (25-75% of amount given) in control and treated animals, not test item-related",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z228<>0,VLOOKUP(Z228,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z229<>0,VLOOKUP(Z229,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: no treatment-related findings (not treatment-related findings: APTT↓, MCHC↓, Eosinophils↓, all slight and/or not dose-related)\nClinical chemistry: no treatment-related findings (not treatment-related findings: Pi↓, Ca↓, T.Protein↓, Gluc↑, A/G ratio↑, ALP↑, all slight and/or not dose-related or within historical controls)\nUrinalysis: no treatment-related findings",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z229<>0,VLOOKUP(Z229,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ Weight","Adrenals weight",{"$f":"IF(Z230<>0,VLOOKUP(Z230,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z230<>0,VLOOKUP(Z230,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ Weight","Brain weight",{"$f":"IF(Z231<>0,VLOOKUP(Z231,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Abs. weight stat. significantly reduced in males at 125 mg/kg bw/day, no dose-relation, no macroscopic/microscopic findings, not toxicologically relevant",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z231<>0,VLOOKUP(Z231,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M",">500","Organ Weight","Epididymis weight",{"$f":"IF(Z232<>0,VLOOKUP(Z232,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z232<>0,VLOOKUP(Z232,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ Weight","Liver weight",{"$f":"IF(Z233<>0,VLOOKUP(Z233,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z233<>0,VLOOKUP(Z233,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ Weight","Kidney weight",{"$f":"IF(Z234<>0,VLOOKUP(Z234,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z234<>0,VLOOKUP(Z234,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","F",">500","Organ Weight","Ovary weight",{"$f":"IF(Z235<>0,VLOOKUP(Z235,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z235<>0,VLOOKUP(Z235,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M",">500","Organ Weight","Prostate weight",{"$f":"IF(Z236<>0,VLOOKUP(Z236,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z236<>0,VLOOKUP(Z236,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M",">500","Organ Weight","Testis weight",{"$f":"IF(Z237<>0,VLOOKUP(Z237,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z237<>0,VLOOKUP(Z237,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ Weight","Thyroid weight",{"$f":"IF(Z238<>0,VLOOKUP(Z238,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z238<>0,VLOOKUP(Z238,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","F",">500","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z239<>0,VLOOKUP(Z239,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z239<>0,VLOOKUP(Z239,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ Weight","Pituitary weight",{"$f":"IF(Z240<>0,VLOOKUP(Z240,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z240<>0,VLOOKUP(Z240,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M",">500","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z241<>0,VLOOKUP(Z241,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z241<>0,VLOOKUP(Z241,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M",">500","Organ histopathology","Liver histopathology",{"$f":"IF(Z242<>0,VLOOKUP(Z242,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z242<>0,VLOOKUP(Z242,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M",">500","Organ histopathology","Kidney histopathology",{"$f":"IF(Z243<>0,VLOOKUP(Z243,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z243<>0,VLOOKUP(Z243,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","F",">500","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z244<>0,VLOOKUP(Z244,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z244<>0,VLOOKUP(Z244,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M",">500","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z245<>0,VLOOKUP(Z245,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z245<>0,VLOOKUP(Z245,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","F",">500","Organ histopathology","Ovary histopathology",{"$f":"IF(Z246<>0,VLOOKUP(Z246,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z246<>0,VLOOKUP(Z246,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M",">500","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z247<>0,VLOOKUP(Z247,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z247<>0,VLOOKUP(Z247,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M",">500","Organ histopathology","Testis histopathology",{"$f":"IF(Z248<>0,VLOOKUP(Z248,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z248<>0,VLOOKUP(Z248,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z249<>0,VLOOKUP(Z249,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z249<>0,VLOOKUP(Z249,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","F",">500","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z250<>0,VLOOKUP(Z250,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z250<>0,VLOOKUP(Z250,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","F",">500","Organ histopathology","Vagina histopathology",{"$f":"IF(Z251<>0,VLOOKUP(Z251,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z251<>0,VLOOKUP(Z251,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z252<>0,VLOOKUP(Z252,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z252<>0,VLOOKUP(Z252,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",9,null,"OECD 452 (1981), JMAFF (2000)","DAR",null,2007,"Dog","Beagle",4,"M + F",95.7,"Oral","Capsule","30; 125; 500",30,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z253<>0,VLOOKUP(Z253,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z253<>0,VLOOKUP(Z253,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M + F",">50000","In life observation","Mortality",{"$f":"IF(Z254<>0,VLOOKUP(Z254,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z254<>0,VLOOKUP(Z254,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M + F",50000,"In life observation","Clinical signs",{"$f":"IF(Z255<>0,VLOOKUP(Z255,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Loose stool in 3/4 males and 4/4 females at 50000 ppm, treatment-related",null,"Increase",8000,50000,"ppm",{"$f":"IF(Z255<>0,VLOOKUP(Z255,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M + F",50000,"In life observation","Body weight",{"$f":"IF(Z256<>0,VLOOKUP(Z256,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Retarded body weight gain in both sexes at 50000 ppm (terminated bw were -6% in males, -11% in females when compared to controls, not statistically significant), treatment-related",null,"Decrease",8000,50000,"ppm",{"$f":"IF(Z256<>0,VLOOKUP(Z256,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M + F",">50000","In life observation","Food consumption",{"$f":"IF(Z257<>0,VLOOKUP(Z257,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z257<>0,VLOOKUP(Z257,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M + F",50000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z258<>0,VLOOKUP(Z258,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: Ht↓, Hb↓and RBC↓ in females at 50000 ppm, anemic condition may be caused by malnutrition, treatment-related (no abnormalities in males)\nClinical chemistry: Cl↑ (week 26), Alb↓ and Pi↓ (both week 52) in females at 50000 ppm, treatment-related (not treatment-related: Ca↓ in females at 1600 and 50000 ppm at week 52, CPK↓ in males at 8000 ppm in week 52, no dose-relation)\nUrinalysis: reduced pH in both sexes at 50000 ppm, attributed to the acidic nature of the test item",null,"Change",8000,50000,"ppm",{"$f":"IF(Z258<>0,VLOOKUP(Z258,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M",">50000","Organ Weight","Pituitary weight",{"$f":"IF(Z259<>0,VLOOKUP(Z259,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Abs+rel weight decreased in males at 1600 ppm, no dose-relation, not treatment-related",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z259<>0,VLOOKUP(Z259,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M + F",">50000","Organ Weight","Liver weight",{"$f":"IF(Z260<>0,VLOOKUP(Z260,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z260<>0,VLOOKUP(Z260,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M + F",">50000","Organ Weight","Kidney weight",{"$f":"IF(Z261<>0,VLOOKUP(Z261,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z261<>0,VLOOKUP(Z261,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","F",">50000","Organ Weight","Ovary weight",{"$f":"IF(Z262<>0,VLOOKUP(Z262,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z262<>0,VLOOKUP(Z262,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M",">50000","Organ Weight","Prostate weight",{"$f":"IF(Z263<>0,VLOOKUP(Z263,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z263<>0,VLOOKUP(Z263,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M",">50000","Organ Weight","Testis weight",{"$f":"IF(Z264<>0,VLOOKUP(Z264,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z264<>0,VLOOKUP(Z264,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M + F",">50000","Organ Weight","Thyroid weight",{"$f":"IF(Z265<>0,VLOOKUP(Z265,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z265<>0,VLOOKUP(Z265,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M + F",">50000","Organ Weight","Adrenals weight",{"$f":"IF(Z266<>0,VLOOKUP(Z266,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z266<>0,VLOOKUP(Z266,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M + F",">50000","Organ Weight","Brain weight",{"$f":"IF(Z267<>0,VLOOKUP(Z267,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z267<>0,VLOOKUP(Z267,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M + F",">50000","Organ histopathology","Lung histopathology",{"$f":"IF(Z268<>0,VLOOKUP(Z268,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Slight focal pneumonia / focal granulumatous pneumonia in1/4, 1/4, 1/4 and 4/4 females at 0, 1600, 8000 and 50000 ppm, common finding in untreated rats, statistically not significant, not related to treatment",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z268<>0,VLOOKUP(Z268,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M + F",">50000","Organ histopathology","Liver histopathology",{"$f":"IF(Z269<>0,VLOOKUP(Z269,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z269<>0,VLOOKUP(Z269,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M + F",">50000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z270<>0,VLOOKUP(Z270,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z270<>0,VLOOKUP(Z270,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","F",">50000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z271<>0,VLOOKUP(Z271,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z271<>0,VLOOKUP(Z271,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M + F",">50000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z272<>0,VLOOKUP(Z272,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z272<>0,VLOOKUP(Z272,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","F",">50000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z273<>0,VLOOKUP(Z273,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z273<>0,VLOOKUP(Z273,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M",">50000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z274<>0,VLOOKUP(Z274,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z274<>0,VLOOKUP(Z274,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","F",">50000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z275<>0,VLOOKUP(Z275,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z275<>0,VLOOKUP(Z275,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M",">50000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z276<>0,VLOOKUP(Z276,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z276<>0,VLOOKUP(Z276,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M",">50000","Organ histopathology","Testis histopathology",{"$f":"IF(Z277<>0,VLOOKUP(Z277,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z277<>0,VLOOKUP(Z277,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M + F",">50000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z278<>0,VLOOKUP(Z278,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z278<>0,VLOOKUP(Z278,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","F",">50000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z279<>0,VLOOKUP(Z279,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z279<>0,VLOOKUP(Z279,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",10,null,"OECD 409 (1981), JMAFF (1985), US EPA 83-1 (1984)","DAR",null,1997,"Dog","Beagle",4,"M + F",94.61,"Oral","Feed","1600; 8000; 50000",1600,50000,"ppm",1,"Year","Adult","M",">50000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z280<>0,VLOOKUP(Z280,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z280<>0,VLOOKUP(Z280,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M + F",">30000","In life observation","Mortality",{"$f":"IF(Z281<>0,VLOOKUP(Z281,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z281<>0,VLOOKUP(Z281,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M + F",">30000","In life observation","Clinical signs",{"$f":"IF(Z282<>0,VLOOKUP(Z282,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Salivation in both sexes among all doses with increased incidences in 2/4 males and 1/4 females the high dose group, attributed to anticipation of feeding, not related to treatment; low incidence of scrotal skin redddening in 2/4 males at 15000 ppm and in 1/4 males at 30000 ppm, not treatment-related; incidences of fluid feces, vomiting, blood or mucus in feces were noted but not related to treatment\nophthalmology: low incidence of corneal or lentiocular opacities among treatment and control animals, not treatment-related",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z282<>0,VLOOKUP(Z282,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","F",30000,"In life observation","Body weight",{"$f":"IF(Z283<>0,VLOOKUP(Z283,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Reduced body weight (-11%) in females at 30000 ppm during the second half of the study, reflects a palatability effect",null,"Decrease",15000,30000,"ppm",{"$f":"IF(Z283<>0,VLOOKUP(Z283,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M + F",">30000","In life observation","Food consumption",{"$f":"IF(Z284<>0,VLOOKUP(Z284,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z284<>0,VLOOKUP(Z284,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M + F",">30000","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z285<>0,VLOOKUP(Z285,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: no treatment-related findings \nClinical chemistry: no toxicologically relevant findings (not treatment-related findings:  T.Chol.↑ was increased in both sexes at 3000 and 30000 ppm in weeks 26+52, no dose-relation; P↓ in males in week 52, due to higher control levels; Na↓, in males at 30000 ppm due to one male of this group; ALT, AST, Creat. kinase occasionally increaased, no dose-relation)\nUrinalysis: no treatment-related findings ",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z285<>0,VLOOKUP(Z285,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M",">30000","Organ Weight","Epididymis weight",{"$f":"IF(Z286<>0,VLOOKUP(Z286,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z286<>0,VLOOKUP(Z286,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M + F",">30000","Organ Weight","Liver weight",{"$f":"IF(Z287<>0,VLOOKUP(Z287,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z287<>0,VLOOKUP(Z287,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M + F",">30000","Organ Weight","Kidney weight",{"$f":"IF(Z288<>0,VLOOKUP(Z288,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z288<>0,VLOOKUP(Z288,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M",">30000","Organ Weight","Testis weight",{"$f":"IF(Z289<>0,VLOOKUP(Z289,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z289<>0,VLOOKUP(Z289,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M + F",">30000","Organ Weight","Thyroid weight",{"$f":"IF(Z290<>0,VLOOKUP(Z290,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z290<>0,VLOOKUP(Z290,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M + F",">30000","Organ Weight","Adrenals weight",{"$f":"IF(Z291<>0,VLOOKUP(Z291,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Abs+rel weight slightly increased in males at 3000 ppm, exaggerated by a low value for one male in the control group, not treatment-related",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z291<>0,VLOOKUP(Z291,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M + F",">30000","Organ Weight","Brain weight",{"$f":"IF(Z292<>0,VLOOKUP(Z292,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z292<>0,VLOOKUP(Z292,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M + F",">30000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z293<>0,VLOOKUP(Z293,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z293<>0,VLOOKUP(Z293,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M + F",">30000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z294<>0,VLOOKUP(Z294,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z294<>0,VLOOKUP(Z294,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","F",">30000","Organ histopathology","Urinary bladder histopathology",{"$f":"IF(Z295<>0,VLOOKUP(Z295,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Red areas or diffuse reddening in 1/4, 2/4 and 2/4 females at 3000, 15000 and 30000 ppm, no dose-relation, in the absence of a similar effect in males the findings were considered not treatment-related",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z295<>0,VLOOKUP(Z295,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","F",">30000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z296<>0,VLOOKUP(Z296,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z296<>0,VLOOKUP(Z296,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M",">30000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z297<>0,VLOOKUP(Z297,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z297<>0,VLOOKUP(Z297,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M",">30000","Organ histopathology","Liver histopathology",{"$f":"IF(Z298<>0,VLOOKUP(Z298,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z298<>0,VLOOKUP(Z298,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M",">30000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z299<>0,VLOOKUP(Z299,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z299<>0,VLOOKUP(Z299,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","F",">30000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z300<>0,VLOOKUP(Z300,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z300<>0,VLOOKUP(Z300,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","F",">30000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z301<>0,VLOOKUP(Z301,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z301<>0,VLOOKUP(Z301,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M",">30000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z302<>0,VLOOKUP(Z302,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z302<>0,VLOOKUP(Z302,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M",">30000","Organ histopathology","Testis histopathology",{"$f":"IF(Z303<>0,VLOOKUP(Z303,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z303<>0,VLOOKUP(Z303,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","M + F",">30000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z304<>0,VLOOKUP(Z304,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z304<>0,VLOOKUP(Z304,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",11,null,"OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b) (1984)","DAR",null,1996,"Dog","Beagle",4,"M + F",95.6,"Oral","Feed","3000; 15000; 30000",3000,30000,"ppm",1,"Year","Adult","F",">30000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z305<>0,VLOOKUP(Z305,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z305<>0,VLOOKUP(Z305,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M + F",">20000","In life observation","Mortality",{"$f":"IF(Z306<>0,VLOOKUP(Z306,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z306<>0,VLOOKUP(Z306,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M + F",20000,"In life observation","Clinical signs",{"$f":"IF(Z307<>0,VLOOKUP(Z307,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Slight increase in urinary staining (wet and dry) at 20000 ppm in both sexes ",null,"Increase",8000,20000,"ppm",{"$f":"IF(Z307<>0,VLOOKUP(Z307,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M + F",8000,"In life observation","Body weight",{"$f":"IF(Z308<>0,VLOOKUP(Z308,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Reduced body weight at ≥ 8000 ppm in both sexes, treatment-related",null,"Decrease",2000,8000,"ppm",{"$f":"IF(Z308<>0,VLOOKUP(Z308,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M + F",8000,"In life observation","Food consumption",{"$f":"IF(Z309<>0,VLOOKUP(Z309,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: reduced in both sexes at ≥ 8000 ppm, treatment-related (20000 ppm: reduced during the first 12 weeks of the study, 8000 ppm: occasionally reduced at the end of the study)\nfood efficiency: reduced in both sexes at 20000 ppm, treatment-related  (reduced during the first 4 weeks of the study)",null,"Decrease",2000,8000,"ppm",{"$f":"IF(Z309<>0,VLOOKUP(Z309,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M + F",2000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z310<>0,VLOOKUP(Z310,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: no treatment-related findings (changes on several parameters were found but there was no dose-relation and differences were small + inconsistent)\nClinical chemistry: ALP↑ in females at ≥ 2000 and in males at ≥ 8000 ppm, treatment-related but toxicologically not significant as no pathological change was found; Creat↓ in males at ≥ 2000 ppm, no dose-relation; T.Chol↓ and TG↓ in males at ≥ 8000 ppm at weeks 14+27; ALT↑ in both sexes at ≥8000 ppm; Creat. Kinase↑ in both sexes at 20000 ppm, treatment-related (further parameters were occasionally changed in both sexes but there was no dose-relation, differences were small and inconsistent)\nUrinalysis: reduced volume in males at ≥ 8000 ppm in week 13+26 and in 2000 ppm at week 26, treatment-related",null,"Change",8000,20000,"ppm",{"$f":"IF(Z310<>0,VLOOKUP(Z310,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M + F",">20000","Organ Weight","Kidney weight",{"$f":"IF(Z311<>0,VLOOKUP(Z311,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Abs. weight reduced in females at 8000 ppm, not dose-related, not treatment-related",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z311<>0,VLOOKUP(Z311,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M + F",">20000","Organ Weight","Liver weight",{"$f":"IF(Z312<>0,VLOOKUP(Z312,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Abs. weight reduced in females at 8000 ppm, not dose-related, not treatment-related",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z312<>0,VLOOKUP(Z312,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M",">20000","Organ Weight","Epididymis weight",{"$f":"IF(Z313<>0,VLOOKUP(Z313,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Abs + rel weights reduced in males at 2000 ppm, not dose-related, not treatment-related",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z313<>0,VLOOKUP(Z313,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M",">20000","Organ Weight","Testis weight",{"$f":"IF(Z314<>0,VLOOKUP(Z314,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z314<>0,VLOOKUP(Z314,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M + F",">20000","Organ Weight","Adrenals weight",{"$f":"IF(Z315<>0,VLOOKUP(Z315,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z315<>0,VLOOKUP(Z315,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M + F",">20000","Organ Weight","Brain weight",{"$f":"IF(Z316<>0,VLOOKUP(Z316,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z316<>0,VLOOKUP(Z316,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M + F",">20000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z317<>0,VLOOKUP(Z317,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Chronic progressive glomerulonenephropathy in 23/24 and 22/24 males at 0 and 20000 ppm, intratubular microlithiasis in 22/24 and 18/24 females at 0 and 20000 ppm, no treatment-related",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z317<>0,VLOOKUP(Z317,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M + F",">20000","Organ histopathology","Liver histopathology",{"$f":"IF(Z318<>0,VLOOKUP(Z318,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Minor degree of proliferative cholangitis in 12/24 and 11/24 males and 10/24 and 19/24 females at 0 and 20000 ppm, in line with historical control data, not treatment-related ",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z318<>0,VLOOKUP(Z318,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M + F",8000,"Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z319<>0,VLOOKUP(Z319,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Mild focal basophilia of the acinar cells of the parotid salivary glands in both sexes at ≥ 8000 ppm, treatment-related but not toxicologically significant (2/24, 0/24, 3/24 and 13/24 males and 2/24, 0/24, 6/24 and 15/24 females at 0, 2000, 8000 and 20000 ppm)",null,"Change",2000,8000,"ppm",{"$f":"IF(Z319<>0,VLOOKUP(Z319,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M + F",">20000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z320<>0,VLOOKUP(Z320,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z320<>0,VLOOKUP(Z320,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M + F",">20000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z321<>0,VLOOKUP(Z321,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z321<>0,VLOOKUP(Z321,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M",">20000","Organ histopathology","Testis histopathology",{"$f":"IF(Z322<>0,VLOOKUP(Z322,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z322<>0,VLOOKUP(Z322,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M + F",">20000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z323<>0,VLOOKUP(Z323,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z323<>0,VLOOKUP(Z323,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","F",">20000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z324<>0,VLOOKUP(Z324,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z324<>0,VLOOKUP(Z324,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","F",">20000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z325<>0,VLOOKUP(Z325,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z325<>0,VLOOKUP(Z325,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M",">20000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z326<>0,VLOOKUP(Z326,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z326<>0,VLOOKUP(Z326,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","F",">20000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z327<>0,VLOOKUP(Z327,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z327<>0,VLOOKUP(Z327,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","F",">20000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z328<>0,VLOOKUP(Z328,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z328<>0,VLOOKUP(Z328,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M",">20000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z329<>0,VLOOKUP(Z329,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z329<>0,VLOOKUP(Z329,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Chronic toxicity",12,null,"OECD 452 (1981), US EPA 83-1 (1984)","DAR",null,1996,"Rat","Alpk:APfSD (Wistar derived)",24,"M + F",95.6,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",1,"Year","Adult","M",">20000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z330<>0,VLOOKUP(Z330,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z330<>0,VLOOKUP(Z330,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","In life observation","Mortality",{"$f":"IF(Z331<>0,VLOOKUP(Z331,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related findings (no mortality before interim kill, after 24 month pre-terminal deaths were 23/50, 21/50, 23/50 and 16/50 in males and 16/50, 11/50, 10/50 and 18/50 in females; higher survival in pre-terminally dead females at 10000 ppm was considered incidental)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z331<>0,VLOOKUP(Z331,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","In life observation","Clinical signs",{"$f":"IF(Z332<>0,VLOOKUP(Z332,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related findings (weakness, loss of body weight, nasal discharge and snuffling were common toxic signs among both sexes of all treatment and control groups, soft stool/diarrhoea and alopecia were found in males of all groups, no dose-relation)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z332<>0,VLOOKUP(Z332,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","In life observation","Body weight",{"$f":"IF(Z333<>0,VLOOKUP(Z333,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related effect (reduced body weight in males during the first 4 weeks in all treatment groups, statistically not significant; significant increase in females at 1000 ppm at 12 month was considered incidental)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z333<>0,VLOOKUP(Z333,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","In life observation","Food consumption",{"$f":"IF(Z334<>0,VLOOKUP(Z334,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: no treatment-related findings (occasional fluctuations in males of all groups; reduced in females in all treatment groups during months 8-13 and 18-22, statistically not significant)\nfood efficiency: no treatment-related findings",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z334<>0,VLOOKUP(Z334,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",10000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z335<>0,VLOOKUP(Z335,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: no treatment-related findings (not treatment-related findings: surviving rats: occasional fluctuations of several parameters were all witihn historical control data, no dose-relation; Ht↑ (after 6 months) and Eosinophils↑ (after 18 months) in females at 10000 ppm were slightly outside historical control data, not consistent/ moribund rats: lymphocyte count↓ and neutrophil count↑ in both sexes among all treatment and control groups)\nClinical chemistry: Alb↓  and ALP↑ in females at 10000 after 6 months, treatment-related, GGT↓ in males at 10000 ppm after 12 months, treatment-related (not treatment-related findings, occasional fluctuations were all within historical control range, not consistent or without dose relation)\nUrinalysis: Protein↑ in females at 10000 ppm, treatment-related (non treatment-related findings: occasional fluctuations  of other parameters were not consistent throughout the study and/or not dose-related)",null,"Change",1000,10000,"ppm",{"$f":"IF(Z335<>0,VLOOKUP(Z335,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ Weight","Liver weight",{"$f":"IF(Z336<>0,VLOOKUP(Z336,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Interim kill: no change\nterminal kill: weighing not performed as too many tumors were present",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z336<>0,VLOOKUP(Z336,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","F",">10000","Organ Weight","Ovary weight",{"$f":"IF(Z337<>0,VLOOKUP(Z337,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z337<>0,VLOOKUP(Z337,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","F",">10000","Organ Weight","Kidney weight",{"$f":"IF(Z338<>0,VLOOKUP(Z338,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z338<>0,VLOOKUP(Z338,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M",">10000","Organ Weight","Testis weight",{"$f":"IF(Z339<>0,VLOOKUP(Z339,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z339<>0,VLOOKUP(Z339,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ Weight","Adrenals weight",{"$f":"IF(Z340<>0,VLOOKUP(Z340,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z340<>0,VLOOKUP(Z340,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ Weight","Brain weight",{"$f":"IF(Z341<>0,VLOOKUP(Z341,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z341<>0,VLOOKUP(Z341,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z342<>0,VLOOKUP(Z342,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Interim kill: no abnormal findings \nterminal kill: vacuolar degeneration in dead/moribund and surviving rats among all treatment and control groups, blood filled cystic spaces in dead/moribund rats and medullary cell hyperplasia in surviving rats at similar incidences, not treatment-related\nNeoplastic findings, dead/moribund animals: no treatment-related findings (cortical cell adenoma in 2/30 males at 0 ppm and in 1/17 females at 1000 ppm; pheochromocytoma in 7/30, 3/30, 4/32 and 4/21 males at 0, 100, 1000 and 10000 ppm and in 2/29 females at 10000 ppm)\nNeoplastic findings, surviving rats: no treatment-related findings (cortical cell adenoma in 1/20 and 1/4 males at 0 and 1000 ppm and in 2/7 and 1/21 females at 1000 and 10000 ppm; pheochromocytoma in 6/20, 2/3, 2/4 and 12/29 males and 1/24, 0/4, 4/7 and 2/21 females at 0, 100, 1000 and 10000 ppm; malignant pheochromocytoma in 1/4 and 1/29 males at 1000 and 10000 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z342<>0,VLOOKUP(Z342,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","F",">10000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z343<>0,VLOOKUP(Z343,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Interim kill: no abnormal findings \nterminal kill: ductectasia and acinectasia in 4/26, 1/24, 4/17 and 6/29 dead and moribund rats and 4/24, 2/26, 10/32 and 1/21 surviving rats of the 0, 100, 1000 and 10000 ppm group, statistically not significant, no dose-relation, age-related (not treatment-related: altered massed (adenoma/adenocarcinoma) at gross necropsy)\nNeoplastic findings, dead/moribund animals: no treatment-related findings (adenoma in 1/23, 1/22, 3/16 and 3/28 females at 0, 100, 1000 and 10000 ppm)\nNeoplastic findings, surviving animals: not treatment-related findings (adenoma in 1/17, 2/8, 5/17 and 2/20 females at 0, 100, 1000 and 10000 ppm; adenocarcinoma in 1/17 females at 0 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z343<>0,VLOOKUP(Z343,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","F",">10000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z344<>0,VLOOKUP(Z344,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Interim kill: cysts in 5/10 and 8/20 females of control and 10000 ppm at gross necropsy, not treatment-related\nterminal kill: cysts in 8/26, 3/24, 0/17 and 3/29 dead and moribund rats and 1/24, 4/26, 5/32 and 1/21 surviving rats of the 0, 100, 1000 and 10000 ppm group, age-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z344<>0,VLOOKUP(Z344,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z345<>0,VLOOKUP(Z345,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Interim kill: no abnormal findings \nterminal kill: incidences of enlargement in 5/44, 12/46, 7/51 and 3/50 rats at gross necropsy, treatment-related but without dose-relation\nNeoplastic findings, dead/moribund animals: no treatment-related findings (adenocarcinoma in 1/27 males at 100 ppm; adenoma in 2/29, 2/27, 3/30 and 1/20 males and in 5/25, 8/22, 3/16 and 5/29 females at 0, 100, 1000 and 10000 ppm)\nNeoplastic findings, surviving rats: no treatment-related findings (adenocarcinoma in 1/24 females at 0 ppm; adenoma in 1/20, 2/3, 0/1 and 4/29 males and 2/24, 5/11, 4/7 and 1/21 females at 0, 100, 1000 and 10000 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z345<>0,VLOOKUP(Z345,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M",">10000","Organ histopathology","Testis histopathology",{"$f":"IF(Z346<>0,VLOOKUP(Z346,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Interim kill: no abnormal findings \nterminal kill: small in size in 6/20, 4/20, 2/18 and 8/29 males and flabby in 6/20, 5/20, 0/18 and 8/29 males at gross necropsy and lower incidences of atrophy in 7/30, 10/30, 6/32 and 4/21 dead or moribund males and 8/20, 7/20, 1/18 and 11/29 surviving males in the 0, 100, 1000 and 10000 ppm group, not dose-related\nNeoplastic findings, dead/moribund animals: no treatment-related findings (Leydig cell tumor in 2/31 males at 1000 ppm; seminoma in 1/31 males at 1000 ppm)\nNeoplastic findings, surviving rats: no treatment-related findings (Leydig cell tumor in 2/20 and 3/29 males at 0 and 10000 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z346<>0,VLOOKUP(Z346,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","F",">10000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z347<>0,VLOOKUP(Z347,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Interim kill: small masses or polyps in 3/10 and 3/20 females at 0 and 10000 ppm at gross necropsy, not treatment-related\nterminal kill: focal irregular thickening in 7/24, 3/26, 12/33 and 6/21 females at gross necropsy, treatment-related but without dose-relation (not treatment-related: inflammatory changes at histopathology in 3/24, 2/26, 9/32 and 4/21 females at 0, 100, 1000 and 10000, not significant, no dose-relation)\nNeoplastic findings, dead/moribund animals: no treatment-related findings (adenocarcinoma in 1/17 females at 1000 ppm; anaplastic carcinoma in 1/24 females at 100 ppm; leiomyosarcoma in 1/29 females at 10000 ppm)\nNeoplastic findings, surviving animals: no treatment-related findings (adenoma in 1/21 females at 10000 ppm; adenocarcinoma in 2/22 females at 1000 ppm; adenomal papillary in 1/10 females at 100 ppm; hemangioma in 1/22 females at 1000 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z347<>0,VLOOKUP(Z347,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Eyes histopathology",{"$f":"IF(Z348<>0,VLOOKUP(Z348,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Interim kill: no abnormal findings \nterminal kill: cateract in 4/44, 4/46, 6/51 and 10/50 and corneal opacity in 4/44, 2/46, 5/51 and 3/50 rats at 0, 100, 1000 and 10000 ppm, not treatment-related",null,"Change",10000,">10000","ppm",{"$f":"IF(Z348<>0,VLOOKUP(Z348,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z349<>0,VLOOKUP(Z349,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Colon: no treatment-related findings (not treatment-related: colon lymphoid hyperplasia at histopathology in 4/56, 3/54, 8/49 and 3/50 dead and moribund rats and 8/44, 0/46, 0/50 and 12/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, considered age-related)\nCaecum: Neoplastic findings, surviving animals: no treatment-related findings (histiocytic sarcoma in 1 of 1/20 examined male tissues at 100 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z349<>0,VLOOKUP(Z349,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Liver histopathology",{"$f":"IF(Z350<>0,VLOOKUP(Z350,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Interim kill: focal discolouration in 0/10 and 13/20 male and 1/10 and 4/20 females, haemorrhages in 0/10 and 3/20 males and 1/10 and 6/20 females, small cysts in 0/10 and 4/20 males and 0/10 and 1/20 females of the 0 and 10000 ppm group at gross necropsy, treatment-related (not treatment-related: clear cell foci and areas at histopathology)\nterminal kill: decrease in masses in 34/44, 36/46, 31/51 and 30/50 rats at gross necropsy in the 0, 100, 1000 and 10000 ppm group, treatment-related, clear cell foci and area in  26/56, 38/54, 38/49 and 27/50 dead and moribund rats and 61, 80, 66 and 70 incidences in 44, 46, 50 and 50 surviving rats of the 0, 100, 1000 and 10000 ppm group, pre-neoplastic changes, no dose-relation (not treatment-related: foci of discoloration and cysts, frequently observed adenoma/carcinoma in all groups)\nNeoplastic findings, dead/moribund rats: no treatment-related findings (cholangiocarcinoma in 0/30, 2/30, 2/32 and 2/21 males at 0, 100, 1000 and 10000 ppm and 1/26 females at 0 ppm; hepatocellular adenoma in 9/30, 9/30, 6/32 and 6/21 males and 2/26, 8/23, 3/17 and 5/29 females at 0, 100, 1000 and 10000 ppm; hepatocellular carcinoma in 12/30, 12/30, 9/32 and 5/21 males and 4/26, 4/23, 2/17 and 5/29 females at 0, 100, 1000 and 10000 ppm; intrahepatic bile duct adenoma in 1/30 and 1/30 males at 0 and 100 ppm; histiocytic sarcoma in 2/30, 2/32 and 1/21 males at 0, 1000 and 10000 ppm and in 1/26 females at 0 ppm; tumour emboli in 1/32 and 1/21 males at 1000 and 10000 ppm; fibrosarcoma in 1/30 males at 100 ppm)\nNeoplastic findings, surviving rats: no treatment-related findings (cholangiocarcinoma in 1/20, 1/20 and 1/29 males at 0, 100 and 10000 ppm; hepatocellular adenoma in 15/20, 13/20, 4/16 and 15/29 males and 16/24, 10/25, 16/32 and 8/21 females at 0, 100, 1000 and 10000 ppm; hepatocellular carcinoma in in 9/20, 16/20, 9/16 and 19/29 males and 6/24, 11/25, 12/32 and 4/21 females at 0, 100, 1000 and 10000 ppm; intrahepatic bile duct adenoma in 1/20 males at 0 ppm and in 1/25 females at 100 ppm; histiocytic sarcoma in 1/20 and 1/16 males at 100 and 1000 ppm and in 3/32 females at 1000 ppm; tumour emboli in 1/20 and 1/16 males at 0 and 1000 ppm; lymphosarcoma in 1/20 males at 0 ppm; benign mixes intrahepatic bile duct adenoma in 1/16 males at 1000 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z350<>0,VLOOKUP(Z350,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Lung histopathology",{"$f":"IF(Z351<>0,VLOOKUP(Z351,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Interim kill: no treatment-related findings (not treatment-related findings: petechiae/ecchymoses, collapse, consolidation, emphysema at gross necropsy, congestion, atelectatis, perivascular lymphocytic aggregations at histopathology, findings were explained by subclinical infections or age-related)\nterminal kill: no treatment related findings (suppurative pneumonia/ bronchopneumonia in 26/56, 21/54, 20/49 and 21/50 dead and moribund rats and chronic inflammation in 7/44, 6/46, 5/50 and 8/50 surviving rats of the 0, 100, 1000 and 10000 ppm group at histopathology; consolidation/ focal consolidation in 19/56, 13/54, 12/49 and 18/50 rats at gross necropsy in the 0, 100, 1000 and 10000 ppm group)\nNeoplastic findings, dead/moribund rats: no treatment-related findings (adenoma in 1/24 females at 100 ppm; metastatic histiocytic sarcoma in 1/30, 1/31 and 1/21 males at 0, 1000 and 10000 ppm and in 1/26 females at 0 ppm; metaastatic cholangiosarcoma in 1/30 males at 100 ppm; metastatic hepatocellular carcinoma in 1/30 and 1/21 males at 100 and 10000 ppm; bronchio alveolar adenoma in 1/17 females at 1000 ppm; metastatic squamous cell carcinoma in 1/30 males at 0 ppm; giant cell tumor in 1/21 males at 10000 ppm; fibroma in 1/24 females at 100 ppm; metastatic round cell sarcoma in 1/17 females at 1000 ppm)\nNeoplastic findings, surviving rats: no treatment-related findings (bronchio-alveolar adenocarcinoma in 1/3 males at 1000 ppm; metastatic hepatocellular carcinoma in 1/3 males at 1000 ppm; bronchio-alveolar adenoma in 1/24 females at 0 ppm; histiocytic sarcoma in 1/5 females at 1000 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z351<>0,VLOOKUP(Z351,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z352<>0,VLOOKUP(Z352,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Interim kill: no abnormal findings \nterminal kill: lymphoid hyperplasia of the mandibular lymph node in 11/56, 30/54, 15/49 and 23/50 dead and moribund rats and 24/44, 14/46, 10/50 and 35/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, no dose-relation (not treatment-related: lymphoid hyperplasia of the mediastinal lymph nodes at 100 ppm in dead/moribund rats)\nNeoplastic findings, dead/moribund rats: no treatment-related findings in mediastinal lymph nodes (metastatic histiocytic sarcoma in 1/28 and 1/30 males at 0 and 1000 ppm and in 1/26 females at 0 ppm; metastatic cholangiocarcinoma in 1/28 males at 100 ppm and in 1/26 females at 0 ppm; metastatic hepatocellular carcinoma in 1/28 males at 100 ppm; giant cell tumor and histiocytic sarcoma in 1/20 males at 10000 ppm)\nNeoplastic findings, surviving rats: no treatment-related findings (histiocytic sarcoma of mesenteric lymph nodes in 1/20 males at 0 ppm; histiocytic sarcoma of mediastinal lymph nodes in 1 of 1/26 examined female tissues at 100 ppm; lymphoma of mandibular lymph nodes in 2/29 males at 10000 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z352<>0,VLOOKUP(Z352,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M",">10000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z353<>0,VLOOKUP(Z353,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Cysts in 16/30, 13/30, 18/32 and 12/21 dead or moribund males and 16/20, 0/20, 0/18 and 22/29 surviving males in the 0, 100, 1000 and 10000 ppm group",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z353<>0,VLOOKUP(Z353,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z354<>0,VLOOKUP(Z354,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Lymphoid hyperplasia in 2/56, 8/54, 2/49 and 4/50 dead and moribund rats and 7/44, 0/46, 3/50 and 2/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, not treatment-related\nNeoplastic findings, dead/moribund animals: no treatment-related findings (metastatic cholangiocarcinoma in 1/30 males at 100 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z354<>0,VLOOKUP(Z354,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Thymus histopathology",{"$f":"IF(Z355<>0,VLOOKUP(Z355,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Involution in 25/56, 35/54, 40/49 and 32/50 dead and moribund rats and 25/44, 0/46, 0/50 and 34/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, age-related\nNeoplastic findings, surviving animals: no treatment-related findings (thyoma in 1/24 females at 0 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z355<>0,VLOOKUP(Z355,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Trachea histopathology",{"$f":"IF(Z356<>0,VLOOKUP(Z356,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Suppurative inflammation in 4/56, 10/54, 1/49 and 6/50 dead and moribund rats and chronic inflammation in 6/44, 0/46, 0/50 and 8/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, not treatment-related\nNeoplastic findings, surviving animals: no treatment-related findings (metastatic histiocytic sarcoma in 1/1 females at 100 ppm)\n",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z356<>0,VLOOKUP(Z356,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z357<>0,VLOOKUP(Z357,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Neoplastic findings, dead/moribund animals: no treatment-related effect (C-cell adenoma in each 1/29 males and 1/17 females at 1000 ppm)\nNeoplastic findings, surviving animals: no treatment-related findings (C-cell adenoma in 2/19 and 1/29 males and 2/24 and 1/20 females at 0 and 10000 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z357<>0,VLOOKUP(Z357,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M",">10000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z358<>0,VLOOKUP(Z358,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z358<>0,VLOOKUP(Z358,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M",">10000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z359<>0,VLOOKUP(Z359,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Neoplastic findings, dead/moribund animals: no treatment-related findings (undifferentiated sarcoma in 1/32 males at 1000 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z359<>0,VLOOKUP(Z359,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M",">10000","Organ histopathology","Coagulating gland histopathology",{"$f":"IF(Z360<>0,VLOOKUP(Z360,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z360<>0,VLOOKUP(Z360,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z361<>0,VLOOKUP(Z361,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Interim kill: lymphocytic infiltration, not treatment-related\nterminal kill: nephritis-tubulo/tubulo-interstitial/interstitial in 18/56, 14/54, 15/49 and 12/50 dead and moribund rats and 20/44, 2/46, 2/50 and 19/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, attributed to subclinical infections and/or age\nNeoplastic findings, dead/moribund animals: no treatment-related findings (metastatic cholangio carcinoma in 1/30 males at 100 ppm; metastatic histiosarcoma in 1/32 males at 1000 ppm)\nNeoplastic findings, surviving animals: no treatment-related findings (lymphosarcoma in 1 of 1/26 examined female tissues at 1000 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z361<>0,VLOOKUP(Z361,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Heart histopathology",{"$f":"IF(Z362<>0,VLOOKUP(Z362,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Neoplastic findings, dead/moribund animals: no treatment-related findings (metastatic histiocytic sarcoma in 1/30, 1/32 and 1/21 males at 0, 1000 and 10000 ppm; round cell sarcoma of pericardium in 1/17 females at 1000 ppm)\nNeoplastic findings, surviving animals: no treatment-related findings (metastatic histiocytic sarcoma in 1 of 1/26 and 1 of 1/26 examined female tissues at 100 and 1000 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z362<>0,VLOOKUP(Z362,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Urinary bladder histopathology",{"$f":"IF(Z363<>0,VLOOKUP(Z363,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Neoplastic findings, dead/moribund animals: no treatment-related findings (transitional cell carcinoma in 1/28 females at 10000 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z363<>0,VLOOKUP(Z363,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z364<>0,VLOOKUP(Z364,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Neoplastic findings, dead/moribund animals: no treatment-related findings (islet adenoma in 1/28 males of the 0 ppm group; metastatic cholangio-carcinoma in 1/30 males at 100 ppm and 1/26 females at 0 ppm; undifferentiated metastatic sarcoma in 1/32 males at 1000 ppm and metastatic histiocytic sarcoma in 1/26 females at 0 ppm, considered to be incidental)\nNeoplastic findings, surviving animals: no treatment-related findings (islet cell adenoma in 1/20 and 1/29 males at 0 and 10000 ppm and in 1/21 females at 10000 ppm; metastatic lymphosarcoma in 1/20 males at 0 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z364<>0,VLOOKUP(Z364,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",13,"886.C.C-R","OECD 453 (1981)","DAR",null,1996,"Rat","Wistar","main: 50\ninterim: 10 control, 20 high dose","M + F","96.8 and 96%","Oral","Feed","100; 1000; 10000",100,10000,"ppm",2,"Years","Adult","M + F",">10000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z365<>0,VLOOKUP(Z365,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Neoplastic findings, dead/moribund animals: not treatment-related findings (metastatic squamous cell carcinoma in 1/21 males at 10000 ppm)\nNeoplastic findings in surviving rats: no treatment-related findings (metastatic pituitary adenocarcinoma in 1/24 females at 0 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z365<>0,VLOOKUP(Z365,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",">30000","In life observation","Mortality",{"$f":"IF(Z366<>0,VLOOKUP(Z366,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased in males at 30000 ppm (42%) when compared to control (64%) during the last study year, not treatment-related (temporal findings: increased in males at 10000 ppm during the first study year, decreased in males at 3000 ppm during the last study year, final mortality rate comparable to those of controls), no effect in females",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z366<>0,VLOOKUP(Z366,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",30000,"In life observation","Clinical signs",{"$f":"IF(Z367<>0,VLOOKUP(Z367,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Loose stool and soiled and/or wetted fur in perianal/genital region in both sexes at 30000 ppm, bradypnea and integument mass (tail) in males at 30000 ppm,  treatment-related (non treatment-related findings: decreased spontaneous motor activity and bradypnea in males at 3000 ppm, ptosis in females at 3000 ppm, reduced tactile hairloss in males at ≥ 3000 ppm and in females at 3000 and 10000 ppm, reduced integument wounds and hairloss in males at 30000 ppm)",null,"Increase",10000,30000,"ppm",{"$f":"IF(Z367<>0,VLOOKUP(Z367,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",10000,"In life observation","Body weight",{"$f":"IF(Z368<>0,VLOOKUP(Z368,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased body weight gain in males at ≥ 10000 ppm and in females at 30000 ppm (terminal bw: 93-95% of control) during the treatment period, treatment-related, in line with reduced food consumption and low food efficiency ",null,"Decrease",3000,10000,"ppm",{"$f":"IF(Z368<>0,VLOOKUP(Z368,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M",30000,"In life observation","Food consumption",{"$f":"IF(Z369<>0,VLOOKUP(Z369,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: decreased in males at 30000 ppm during the first weeks of treatment, treatment-related (not treatment-related findings: increased in females at 3000 ppm during study week 48)\nfood efficiency: decreased in both sexes at 30000 ppm during the first 13 weeks of treatment (not treatment-related findings: reduced in males at 10000 ppm during the first 6 weeks)",null,"Decrease",10000,30000,"ppm",{"$f":"IF(Z369<>0,VLOOKUP(Z369,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",10000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z370<>0,VLOOKUP(Z370,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: Ht↑ and PT↓ in males at 30000 ppm in week 104, attributed to altered values of the control animals which had callosities in the hind paw and anemia due to haemorrhage from the ulcered surfaces of the callosities\nClinical chemistry: Gluc↓ and Glob↓ in females at 30000 ppm, considered secondary to the decreased body weight gain , Creat↓ (week 26) in females at ≥ 10000 ppm, GPT↓ in males (week 52) at 30000 ppm, treatment-related but considered not to be of toxicological significance, ALP↑(week 52) in females at 30000 ppm, treatment-relation unclear  (not treatment-related findings: ALP↑ in males at 3000 ppm in week 78, Alb↓ in females at 3000 ppm in week 26, A/G↓ in females at 3000 ppm in week 26 and in males at 30000 ppm in week 104, attributed to the presence of callosities in control animals, T.Bil↓ in females at 3000 ppm in week 26, Cl↓ in males at 3000 and 10000 ppm in week 104, no dose-relation) \nUrinalysis: low pH in both sexes at ≥ 10000 ppm throughout the treatment period, attributed to the metabolic features of the test item; reduced protein in males at 30000 ppm at study week 26, treatment-related but toxicologically not significant as no blood chemistry or histopathological findings were noted (not treatment-related findings: dark coloured urine in females at ≥ 3000 ppm at study week 104, increased volume in males at 3000 ppm at week 104, no dose-relation)",null,"Change",3000,10000,"ppm",{"$f":"IF(Z370<>0,VLOOKUP(Z370,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",">30000","Organ Weight","Adrenals weight",{"$f":"IF(Z371<>0,VLOOKUP(Z371,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z371<>0,VLOOKUP(Z371,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M",">30000","Organ Weight","Brain weight",{"$f":"IF(Z372<>0,VLOOKUP(Z372,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Increased rel. weight in males at 30000 ppm in week 26, considered secondary to body weight changes or sporadic",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z372<>0,VLOOKUP(Z372,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M",">30000","Organ Weight","Liver weight",{"$f":"IF(Z373<>0,VLOOKUP(Z373,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increased rel. weight in males at 30000 ppm in week 26, considered secondary to body weight changes or sporadic",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z373<>0,VLOOKUP(Z373,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M",30000,"Organ Weight","Testis weight",{"$f":"IF(Z374<>0,VLOOKUP(Z374,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Increased rel. weight in males at 30000 ppm in week 26, considered secondary to body weight changes or sporadic",null,"Increase",10000,30000,"ppm",{"$f":"IF(Z374<>0,VLOOKUP(Z374,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","F",">30000","Organ Weight","Kidney weight",{"$f":"IF(Z375<>0,VLOOKUP(Z375,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increased in females at 30000 ppm in week 26, considered secondary to body weight changes or sporadic",null,"Increase",30000,">30000","ppm",{"$f":"IF(Z375<>0,VLOOKUP(Z375,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",10000,"Organ Weight","[Not in list]",{"$f":"IF(Z376<>0,VLOOKUP(Z376,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Caecum: abs+rel weight increased (>20%) in both sexes at 10000 ppm (occasional stat. significance), at 30000 ppm stat. significant over the entire study period , treatment-related and in line with pathological findings (not treatment-related: increased abs+rel weight in females at 3000 ppm in week 104)\n",null,"Increase",3000,10000,"ppm",{"$f":"IF(Z376<>0,VLOOKUP(Z376,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",">30000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z377<>0,VLOOKUP(Z377,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Gross necropsy: \nall animals: decrease in masses in females at 30000 ppm (5/78, 3/79, 6/78 and 0/78 females at 0, 3000, 10000 and 30000 ppm)\nanimals found dead/killed in extremis: enlarged organ in 8/35, 3/31, 1/34 and 2/36 females at 0, 3000, 10000 and 30000 ppm\nHistopathology, non-neoplastic: \nanimals found dead/killed in extremis: decreased incidence of peliosis adrenalis in females at 3000 ppm: 18/35, 8/31, 13/34 and 10/36 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings (pheochromocytoma in 8/18, 4/20, 3/18 and 4/29 terminally killed males and in 14/76, 9/75, 5/80 and 10/78 in all males at 0, 3000, 10000 and 30000 ppm)\n",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z377<>0,VLOOKUP(Z377,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",">30000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z378<>0,VLOOKUP(Z378,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z378<>0,VLOOKUP(Z378,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M",">30000","Organ histopathology","Coagulating gland histopathology",{"$f":"IF(Z379<>0,VLOOKUP(Z379,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z379<>0,VLOOKUP(Z379,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M",">30000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z380<>0,VLOOKUP(Z380,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z380<>0,VLOOKUP(Z380,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M",">30000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z381<>0,VLOOKUP(Z381,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z381<>0,VLOOKUP(Z381,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","F",">30000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z382<>0,VLOOKUP(Z382,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z382<>0,VLOOKUP(Z382,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","F",">30000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z383<>0,VLOOKUP(Z383,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z383<>0,VLOOKUP(Z383,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M",">30000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z384<>0,VLOOKUP(Z384,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: decreased incidences of inflammation at 30000 ppm: 6/18, 5/20, 2/18 and 2/29 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z384<>0,VLOOKUP(Z384,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M",">30000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z385<>0,VLOOKUP(Z385,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z385<>0,VLOOKUP(Z385,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","F",">30000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z386<>0,VLOOKUP(Z386,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z386<>0,VLOOKUP(Z386,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","F",">30000","Organ histopathology","Vagina histopathology",{"$f":"IF(Z387<>0,VLOOKUP(Z387,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z387<>0,VLOOKUP(Z387,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M",">30000","Organ histopathology","Testis histopathology",{"$f":"IF(Z388<>0,VLOOKUP(Z388,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nanimals at terminal kill: increased incidence of arteritis at 3000 ppm: 1/18, 7/20, 3/18 and 2/29 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z388<>0,VLOOKUP(Z388,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M",">30000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z389<>0,VLOOKUP(Z389,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: coarse surface in males found dead/killed in extremis at 30000 ppm, attributed to chronic nephropathy\nHistopathology, non-neoplastic: \niniterim kill animals week 52: decreased incidendes of chronic nephropathy in males at 10000 ppm: 9/10, 9/10, 4/10 and 9/10 at 0, 3000, 10000 and 30000 ppm\nanimals found dead/killed in extremis: decreased incidence of mineralization in pelvic epithelium in females at 30000 ppm: 6/35, 3/31, 3/34 and 0/36 at 0, 3000, 10000 and 30000 ppm; decreased incidences of pyelitis/pyelonephritis in females at 30000 ppm: 7/35, 3/31, 3/34 and 1/36 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: increased incidence of adenomas in males found dead/killed in extremis at 30000 ppm (3/23 males), not significant\n",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z389<>0,VLOOKUP(Z389,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",">30000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z390<>0,VLOOKUP(Z390,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Gross necropsy: reduced masses in males found dead/killed in extremis at 10000 ppm\nHistopathology, non-neoplastic: no treatment-related findings\nHistopathology, neoplastic: no treatment-related findings (lower incidences of anterior adenoma in males at 10000 ppm (22/32, 21/30, 14/32 and 18/21 decedent males and 34/35, 29/31, 28/33 and 31/36 decedent females at 0, 3000, 10000 and 30000 ppm, no toxicological significance)\n",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z390<>0,VLOOKUP(Z390,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",10000,"Organ histopathology","Skin histopathology",{"$f":"IF(Z391<>0,VLOOKUP(Z391,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: \nall animals: hair loss in females at 30000 ppm (treatment relation unclear), thickened areas in males at 30000 ppm and in females at ≥ 10000 ppm, callosities in paw in females at 10000 ppm\nanimals found dead/killed in extremis: hair loss in females at 30000 ppm, thickened areas in both sexes at 30000 ppm, callosities in paw in females at 30000 ppm\nanimals terminal kill: callosities in paw reduced in males at 30000 ppm, increased in females at 10000 ppm\nHistopathology, non-neoplastic: \nterminal kill animals: decreased incidences of plantar granuloma in males at 30000 ppm (12/18, 11/20, 11/18 and 8/29) and increased incidences in females at 10000 ppm (6/15, 8/19, 13/16 and 7/14) at 0, 3000, 10000 and 30000 ppm\nanimals found dead/killed in extremis: follicular hyperkeratosis in males at 30000 ppm (3/32, 2/30, 1/32 and 10/21) and plantar granuloma in females at 30000 ppm (3/35, 6/31, 7/34 and 10/36) at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings",null,"Change",3000,10000,"ppm",{"$f":"IF(Z391<>0,VLOOKUP(Z391,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M",">30000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z392<>0,VLOOKUP(Z392,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nall animals: increased extramedullary hematopoesis in males at 10000 ppm (11/76, 18/75, 23/80 and 18/78 in males and 22/78, 28/79, 23/78 and 26/78 in females at 0, 3000, 10000 and 30000 ppm)\nterminal kill animals: increased extramedullary hematopoesis in males at 10000 ppm (1/18, 5/20, 8/18 and 6/29 in males and 10/15, 10/19, 11/16 and 9/14 females at 0, 3000, 10000 and 30000 ppm)\nHistopathology, neoplastic: no treatment-related findings\n",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z392<>0,VLOOKUP(Z392,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M",">30000","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z393<>0,VLOOKUP(Z393,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Large intestine: Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nall animals: reduced incidences of granuloma in males at 10000 ppm (5/76, 3/75, 0/80 and 2/78 at 0, 3000, 10000 and 30000 ppm)\nHistopathology, neoplastic: no treatment-related findings\n",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z393<>0,VLOOKUP(Z393,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",">30000","Organ histopathology","Heart histopathology",{"$f":"IF(Z394<>0,VLOOKUP(Z394,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: no abnormal findings observed\nHistopathology, non-neoplastic: \nall animals: decreased incidences of myocardial atrophy/fibrosis in females: 22/78, 19/79, 20/78 and 8/78 females at 0, 3000, 10000 and 30000 ppm\ninterim kill animals week 78: increasede incidences of myocardial atrophy/fibrosis in males: 2/6, 5/5, 5/10 and 1/8 at 0, 3000, 10000 and 30000 ppm\nanimals found dead/killed in extremis: decreased incidences of myocardial atrophy/fibrosis in females: 9/35, 7/31, 6/34 and 3/36 females at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z394<>0,VLOOKUP(Z394,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",">30000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z395<>0,VLOOKUP(Z395,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nanimals found dead/killed in extremis: decreased incidences of C-cell hyperplasia in females at 30000 ppm: 8/35, 6/31, 3/34 and 2/36 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z395<>0,VLOOKUP(Z395,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",">30000","Organ histopathology","Liver histopathology",{"$f":"IF(Z396<>0,VLOOKUP(Z396,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: reduced incidence of focal hepatocellular fatty change in females of the interim kill at week 26: 4/10, 0/10, 2/10 and 0/10 at 0, 3000, 10000 and 30000 ppm, reduced incidence of micro granuloma in females of the interim kill at week 78: 5/8, 0/9, 3/8 and 1/8 at 0, 3000, 10000 and 30000 ppm and in females of the terminal kill: 4/15, 0/19, 3/16 and 0/14 at 0, 3000, 10000 and 30000 ppm, reduced incidences of spongiosis hepatitis in males of the terminal kill: 7/18, 6/20, 2/18 and 3/29 at 0, 3000, 10000 and 30000 ppm, peliosis hepatis in 6/30 males at 3000 ppm found dead/killed in extremis when compared to control (1/32)\nHistopathology, neoplastic: no treatment-related findings\n",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z396<>0,VLOOKUP(Z396,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",">30000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z397<>0,VLOOKUP(Z397,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nanimals found dead/killed in extremis: decreased incidences of plasma cell hyperplasia in females at 30000 ppm: 5/35, 2/31, 2/34 and 0/36 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z397<>0,VLOOKUP(Z397,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",">30000","Organ histopathology","Peripheral nerve histopathology",{"$f":"IF(Z398<>0,VLOOKUP(Z398,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nterminal kill animals: decreased incidences of sciatic nerve fibre degerenation in females at 3000 ppm: 5/15, 1/19, 3/16 and 1/14 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z398<>0,VLOOKUP(Z398,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",">30000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z399<>0,VLOOKUP(Z399,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nanimals at terminal kill: acinar cell atrophy in males at 3000 ppm: 3/18, 10/20, 7/18 and 10/29 and arteritis in males at 3000 ppm: 0/18, 5/20, 1/18, 3/29 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z399<>0,VLOOKUP(Z399,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",">30000","Organ histopathology","Bone histopathology",{"$f":"IF(Z400<>0,VLOOKUP(Z400,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nanimals at terminal kill: bone marrow femur: decreased incidences of hematopoesis in males at 3000 ppm: 9/18, 8/20, 10/18 and 6/29 at 0, 3000, 10000 and 30000 ppm; bone marrow sternum: decreased incidences of hematopoesis in males at 3000 ppm: 10/18, 8/20, 10/18 and 6/29 at 0, 3000, 10000 and 30000 ppm; bone marrow vertebra: decreased incidences of hematopoesis in males at 3000 ppm: 9/18, 8/20, 10/18 and 6/29 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z400<>0,VLOOKUP(Z400,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",">30000","Organ histopathology","Lung histopathology",{"$f":"IF(Z401<>0,VLOOKUP(Z401,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nanimals at terminal kill: decreased incidences of foam cell aggregation in males at 30000 ppm: 6/18, 6/20, 2/18 and 2/29 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z401<>0,VLOOKUP(Z401,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",14,null,"OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","DAR",null,1997,"Rat","Sprague-Dawley","main: 50\nsatellite: 30\ninterim kill week 26, 52 and 78: 10","M + F","97.56 and 94.61%","Oral","Feed","3000; 10000; 30000",3000,30000,"ppm",2,"Years","Adult","M + F",30000,"Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z402<>0,VLOOKUP(Z402,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Caecum: significantly increased incidence of distention  (m: 32/78; f: 18/78)  in both sexes at 30000 ppm (macroscopical finding) , treatment-related but without histopathological abnomalities\n",null,"Change",10000,30000,"ppm",{"$f":"IF(Z402<>0,VLOOKUP(Z402,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M",20000,"In life observation","Mortality",{"$f":"IF(Z403<>0,VLOOKUP(Z403,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Statistically increased in males at 20000 ppm, attributed to the overall decreased severity of glomerula nephropathy occuring as a consequence of lower food consumption and body weight gain in this group; no effect in females",null,"Increase",6000,20000,"ppm",{"$f":"IF(Z403<>0,VLOOKUP(Z403,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",20000,"In life observation","Clinical signs",{"$f":"IF(Z404<>0,VLOOKUP(Z404,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Clinical signs: red-brown staining of tray papers, particularly in males at 20000 ppm, treatment-related (not treatment-related findings: red/brown colored urine in 3/52 males and 1/52 females at 20000 ppm)\nFunctional observational battery: decreased landing foot splay in females at 20000 ppm, not treatment-related",null,"Increase",6000,20000,"ppm",{"$f":"IF(Z404<>0,VLOOKUP(Z404,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",20000,"In life observation","Body weight",{"$f":"IF(Z405<>0,VLOOKUP(Z405,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased in males (-5%) and females (-8%) at 20000 ppm throughout the study, treatment-related",null,"Decrease",6000,20000,"ppm",{"$f":"IF(Z405<>0,VLOOKUP(Z405,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",20000,"In life observation","Food consumption",{"$f":"IF(Z406<>0,VLOOKUP(Z406,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: statistically significantly reduced in males (-6%) and females (-5-6%) at 20000 ppm during the first study year, treatment-related\nfood efficiency: statistically significantly reduced in both sexes at 20000 ppm during study weeks 1-4, reduced in males at 20000 ppm in weeks 1-12, treatment-related (not treatment-related: slightly increased in females at 20000 ppm during weels 9-12)",null,"Decrease",6000,20000,"ppm",{"$f":"IF(Z406<>0,VLOOKUP(Z406,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",20000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z407<>0,VLOOKUP(Z407,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: no treatment-related findings (Hb↑ and PT↓ in all females at the interim kill, no dose-relation)\nClinical chemistry: ALP↑ (weeks 1-79) in both sexes at 20000 ppm, ALT↑ in males (weeks 1-79) and occasionally in females at 20000 ppm, T.Bil↑ (throughout the study) and AST↑ (at interim kill) in males at 20000 ppm, findings in males in line with increased liver weight, hepatitis and proliferative cholangitis, treatment-related (not treatment-related/ no tox. relevance: occasionally reduced TG and Chol. in males at 20000 ppm, ALP↑ during the first study year and variations in ALT at 6000 ppm, considered to be without toxicological significance as no histopathological abnormalities were found, Creat↓ in females at 6000 ppm in week 27 and at 20000 ppm in week 14 )\nUrinalysis: pH↓ in males at 20000 ppm, attributed to the acidic nature of the test material; blood/RBC↑  in both sexes at 20000 ppm, treatment-related",null,"Change",6000,20000,"ppm",{"$f":"IF(Z407<>0,VLOOKUP(Z407,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","F",6000,"Organ Weight","Adrenals weight",{"$f":"IF(Z408<>0,VLOOKUP(Z408,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Abs+rel weight decreased in females at ≥ 6000 ppm, partly significant but mainly within historical control data, not considered toxicologically relevant due to the absence of effects in males and histopathological findings",null,"Decrease",2000,6000,"ppm",{"$f":"IF(Z408<>0,VLOOKUP(Z408,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","Organ Weight","Brain weight",{"$f":"IF(Z409<>0,VLOOKUP(Z409,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z409<>0,VLOOKUP(Z409,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M",">20000","Organ Weight","Epididymis weight",{"$f":"IF(Z410<>0,VLOOKUP(Z410,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z410<>0,VLOOKUP(Z410,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M",20000,"Organ Weight","Liver weight",{"$f":"IF(Z411<>0,VLOOKUP(Z411,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Abs+rel. weight decreased (-7%) in interim killed males at 20000 ppm, in line with histopathological findings, treatment-related",null,"Decrease",6000,20000,"ppm",{"$f":"IF(Z411<>0,VLOOKUP(Z411,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","F",">20000","Organ Weight","Ovary weight",{"$f":"IF(Z412<>0,VLOOKUP(Z412,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z412<>0,VLOOKUP(Z412,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M",">20000","Organ Weight","Testis weight",{"$f":"IF(Z413<>0,VLOOKUP(Z413,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Abs+rel weight reduced in all treated groups at terminal kill, considered as not treatment-related as no effect was seen at the interim kill in week 53 and a dose-response was lacking, however, histopathological changes were evident",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z413<>0,VLOOKUP(Z413,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","F",">20000","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z414<>0,VLOOKUP(Z414,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z414<>0,VLOOKUP(Z414,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M",">20000","Organ Weight","Kidney weight",{"$f":"IF(Z415<>0,VLOOKUP(Z415,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Abs+rel weight increased (+10%) in males at 6000 ppm, not treatment-related since no dose-response",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z415<>0,VLOOKUP(Z415,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","F",">20000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z416<>0,VLOOKUP(Z416,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z416<>0,VLOOKUP(Z416,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M",">20000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z417<>0,VLOOKUP(Z417,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z417<>0,VLOOKUP(Z417,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","F",">20000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z418<>0,VLOOKUP(Z418,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z418<>0,VLOOKUP(Z418,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","F",">20000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z419<>0,VLOOKUP(Z419,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z419<>0,VLOOKUP(Z419,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M",20000,"Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z420<>0,VLOOKUP(Z420,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gross necropsy: increased (3/64) firmness at 20000 ppm, treatment-related\nHistopathology, non-neoplastic findings: prostatitis at 20000 ppm, increased incidences in all treated group within historical control range, but as the control value in this study was low the treatment-relationship cannot be dismissed entirely\nHistopathology, neoplastic findings: no treatment-related findings",null,"Change",2000,20000,"ppm",{"$f":"IF(Z420<>0,VLOOKUP(Z420,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M",">20000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z421<>0,VLOOKUP(Z421,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z421<>0,VLOOKUP(Z421,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M",">20000","Organ histopathology","Testis histopathology",{"$f":"IF(Z422<>0,VLOOKUP(Z422,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings: decreased incidence of tubular degeneration at 20000 ppm, treatment-related, considered to be without adverse consequence\nHistopathology, neoplastic findings: no treatment-related findings",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z422<>0,VLOOKUP(Z422,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z423<>0,VLOOKUP(Z423,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z423<>0,VLOOKUP(Z423,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","F",">20000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z424<>0,VLOOKUP(Z424,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z424<>0,VLOOKUP(Z424,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z425<>0,VLOOKUP(Z425,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z425<>0,VLOOKUP(Z425,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M",6000,"Organ histopathology","Liver histopathology",{"$f":"IF(Z426<>0,VLOOKUP(Z426,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: increased masses in males at 20000 and/or 6000 ppm, treatment-related\nHistopathology, non-neoplastic findings: proliferative cholangitis and hepatitis in males at 20000 ppm at interim and terminal kill, treatment-related (not treatment-related: fatty vacuolisation in males at ≥ 6000 ppm, below historical control levels)\nHistopathology, neoplastic findings: no treatment-related findings (hepatocellular adenoma in males at 20000 ppm, not statistically significant with Fisher'S Exact test but with Peto test, as no preneoplastic foci or adenocarcinomas were found and a dose-response was absent, findings were considered to be unrelated to treatment)",null,"Change",2000,6000,"ppm",{"$f":"IF(Z426<>0,VLOOKUP(Z426,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M",6000,"Organ histopathology","Kidney histopathology",{"$f":"IF(Z427<>0,VLOOKUP(Z427,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: enlarged in males at 6000 ppm and 20000 ppm, treatment-related\nHistopathology, non-neoplastic findings: papillary necrosis with varying degrees of mineralisation of the papilla and/or transitional cell hyperplasia in both sexes but particularly in males at 20000 ppm, papillary haemorrhage in 2 males and 2 females at 20000 ppm, treatment-related (papillary haemorrhage in one male at 2000 ppm considered to be incidental, hydronephrosis in males at ≥ 6000 ppm, within historical control data)\nHistopathology, neoplastic findings: no treatment-related findings",null,"Change",2000,6000,"ppm",{"$f":"IF(Z427<>0,VLOOKUP(Z427,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","Organ histopathology","Lung histopathology",{"$f":"IF(Z428<>0,VLOOKUP(Z428,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: increased incidences of mottled lungs in males at 20000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings\nHistopathology, neoplastic findings: no treatment-related findings",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z428<>0,VLOOKUP(Z428,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z429<>0,VLOOKUP(Z429,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: increased incidences of cystic changes at cervical lymph node in males at 20000 ppm, enlarged redded thymic lymph nodes in females at ≥ 6000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings\nHistopathology, neoplastic findings: no treatment-related findings",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z429<>0,VLOOKUP(Z429,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z430<>0,VLOOKUP(Z430,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Gross necropsy: compression of the base in females at 20000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings\nHistopathology, neoplastic findings: no treatment-related findings",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z430<>0,VLOOKUP(Z430,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",15,null,"OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","DAR",null,2001,"Rat","Alpk:APfSD (Wistar derived)","main: 52\ninterim kill: 12","M + F",97.6,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",2,"Years","Adult","M",">20000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z431<>0,VLOOKUP(Z431,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Slight exocrine hyperplasia in males at 20000 ppm, within historical control data, not treatment-related",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z431<>0,VLOOKUP(Z431,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M + F",">1000","In life observation","Mortality",{"$f":"IF(Z432<>0,VLOOKUP(Z432,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z432<>0,VLOOKUP(Z432,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M + F",300,"In life observation","Clinical signs",{"$f":"IF(Z433<>0,VLOOKUP(Z433,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Pale faeces in males and females at ≥ 300 mg/kg bw/day from weeks 16-104, treatment-related, considered to be not toxicologically significant",null,"Increase",100,300,"mg/kg bw/day",{"$f":"IF(Z433<>0,VLOOKUP(Z433,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M + F",1000,"In life observation","Body weight",{"$f":"IF(Z434<>0,VLOOKUP(Z434,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Reduced body weight gain in both sexes at 1000 mg/kg bw/day in week 52 and 104 (m: -14-32%; f: -11-17%) and, treatment-related (not treatment-related findings: reduced at interim kill at 100 and 300 mg/kg bw/day, not reproduced at terminal kill, occasional fluctuations among all groups, no dose-relation)",null,"Decrease",300,1000,"mg/kg bw/day",{"$f":"IF(Z434<>0,VLOOKUP(Z434,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M + F",">1000","In life observation","Food consumption",{"$f":"IF(Z435<>0,VLOOKUP(Z435,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z435<>0,VLOOKUP(Z435,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M + F",100,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z436<>0,VLOOKUP(Z436,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: Ht and MCH were occasionally increased at 100 and 1000 mg/kg bw/day in males, Hb occasionally increased in males at ≥ 100 mg/kg bw/day and in females at 1000 mg/kg bw/day, MCH occasionally increased in females at 1000 mg/kg bw/day, not treatment-related as changes were of small magnitude and inconsistent during the study, Eosinophils↓, Lymphocytes↓ and WBC↓ in females, effect not dose-related and not consistent throughout the study, high degree of individual variation, not reproducible\nClinical chemistry: ALP↑ in males at 1000 mg/kg bw/day and in females at 100 mg/kg bw/day, treatment-related but without histopathological abnormalities (not treatment-related findings: T.Bil↑ in females, effect not consistent, high degree of individual variation, not reproducible, T.Chol↓ in males at 100 and 1000 mg/kg bw/day, no dose relationship, reproducibility questionable, occasional variations in BUN, Glc and Ca, ALT and AST, Alb, T.Chol in males, no dose-relation, incidental, occasional variations of Creat and P in females, no dose-relation and/or inconsistent effect)\nUrinalysis: pH↓ in males at 1000 mg/kg bw/day, toxicological significance unknown",null,"Change",10,100,"mg/kg bw/day",{"$f":"IF(Z436<>0,VLOOKUP(Z436,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","F",100,"Organ Weight","Liver weight",{"$f":"IF(Z437<>0,VLOOKUP(Z437,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Rel weight reduced in interim kill females at ≥ 100 mg/kg bw/day, treatment-related but without histopathological findings (not treatment-related findings: abs weight decreased in interim kill males at ≥ 300 mg/kg bw/day, not treatment-related as changes were not seen after body weight correction;  abs weight reduced in interim kill females at 100 and 1000 mg/kg bw/day)",null,"Decrease",10,100,"mg/kg bw/day",{"$f":"IF(Z437<>0,VLOOKUP(Z437,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); organ weights examined in 10/70 animals each sex only and all interim killed animals ","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","F",">1000","Organ Weight","Ovary weight",{"$f":"IF(Z438<>0,VLOOKUP(Z438,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z438<>0,VLOOKUP(Z438,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); organ weights examined in 10/70 animals each sex only and all interim killed animals ","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M",">1000","Organ Weight","Prostate weight",{"$f":"IF(Z439<>0,VLOOKUP(Z439,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z439<>0,VLOOKUP(Z439,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); organ weights examined in 10/70 animals each sex only and all interim killed animals ","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M",">1000","Organ Weight","Testis weight",{"$f":"IF(Z440<>0,VLOOKUP(Z440,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z440<>0,VLOOKUP(Z440,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); organ weights examined in 10/70 animals each sex only and all interim killed animals ","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","F",">1000","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z441<>0,VLOOKUP(Z441,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z441<>0,VLOOKUP(Z441,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); organ weights examined in 10/70 animals each sex only and all interim killed animals ","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M",">1000","Organ Weight","Adrenals weight",{"$f":"IF(Z442<>0,VLOOKUP(Z442,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Abs weight decreased in interim kill males at ≥ 300 mg/kg bw/day, not treatment-related as changes were not seen after body weight correction (examined in 10/70 animals each sex and all interim killed animals )",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z442<>0,VLOOKUP(Z442,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); organ weights examined in 10/70 animals each sex only and all interim killed animals ","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","F",">1000","Organ Weight","Brain weight",{"$f":"IF(Z443<>0,VLOOKUP(Z443,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z443<>0,VLOOKUP(Z443,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); organ weights examined in 10/70 animals each sex only and all interim killed animals ","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M + F",">1000","Organ Weight","Pituitary weight",{"$f":"IF(Z444<>0,VLOOKUP(Z444,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z444<>0,VLOOKUP(Z444,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); organ weights examined in 10/70 animals each sex only and all interim killed animals ","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","F",">1000","Organ Weight","Heart weight",{"$f":"IF(Z445<>0,VLOOKUP(Z445,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Abs weight increased in terminal kill females at 300 mg/kg bw/day, no dose-relation",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z445<>0,VLOOKUP(Z445,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); organ weights examined in 10/70 animals each sex only and all interim killed animals ","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M",100,"Organ Weight","Kidney weight",{"$f":"IF(Z446<>0,VLOOKUP(Z446,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute and relative weight decreased in terminal kill males at 100 and 1000 mg/kg bw/day, which was reported as not relevant.",null,"Decrease",10,100,"mg/kg bw/day",{"$f":"IF(Z446<>0,VLOOKUP(Z446,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); organ weights examined in 10/70 animals each sex only and all interim killed animals ","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M + F",100,"Organ Weight","[Not in list]",{"$f":"IF(Z447<>0,VLOOKUP(Z447,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Paratoid salivary glands: abs+rel weight increased in interim kill males at ≥ 100 mg/kg bw/day, treatment-related\nSublingual and submaxillary salivary glands: abs+rel weight increased in interim kill animals of both sexes at 1000 mg/kg bw/day, increased abs+rel weight in terminal kill females at 300 mg/kg bw/day, treatment-related (not treatment-related: rel weight increased in interim kill females at 10 mg/kg bw/day)",null,"Increase",10,100,"mg/kg bw/day",{"$f":"IF(Z447<>0,VLOOKUP(Z447,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); organ weights examined in 10/70 animals each sex only and all interim killed animals ","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M",">1000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z448<>0,VLOOKUP(Z448,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z448<>0,VLOOKUP(Z448,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","F",">1000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z449<>0,VLOOKUP(Z449,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z449<>0,VLOOKUP(Z449,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M",">1000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z450<>0,VLOOKUP(Z450,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z450<>0,VLOOKUP(Z450,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","F",">1000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z451<>0,VLOOKUP(Z451,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z451<>0,VLOOKUP(Z451,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","F",">1000","Organ histopathology","Liver histopathology",{"$f":"IF(Z452<>0,VLOOKUP(Z452,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z452<>0,VLOOKUP(Z452,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M",">1000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z453<>0,VLOOKUP(Z453,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z453<>0,VLOOKUP(Z453,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M",">1000","Organ histopathology","Testis histopathology",{"$f":"IF(Z454<>0,VLOOKUP(Z454,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z454<>0,VLOOKUP(Z454,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M + F",">1000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z455<>0,VLOOKUP(Z455,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z455<>0,VLOOKUP(Z455,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","F",">1000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z456<>0,VLOOKUP(Z456,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z456<>0,VLOOKUP(Z456,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M + F",">1000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z457<>0,VLOOKUP(Z457,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z457<>0,VLOOKUP(Z457,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M + F",">1000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z458<>0,VLOOKUP(Z458,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z458<>0,VLOOKUP(Z458,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females); histopathology: control and high dose examined only","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M",">1000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z459<>0,VLOOKUP(Z459,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Decreased incidence of nephropathy in interim kill males at ≥ 100 mg/kg bw/day and reduced severity of nephropathy in terminal kill males at 1000 mg/kg bw/day, toxicologically not relevant (findings of unknown toxicological significance: decreased incidence of urothelial hyperplasia in terminal kill females at ≥ 300 mg/kg bw/day)",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z459<>0,VLOOKUP(Z459,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",16,7867,"US EPA 83-5 (1984)","DAR",null,1993,"Rat","Sprague-Dawley","main: 70\ninterim kill: 15","M + F","98-9 and 98.7","Oral","Feed","10; 100; 300; 1000",10,1000,"mg/kg bw/day",2,"Years","Adult","M + F",100,"Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z460<>0,VLOOKUP(Z460,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Interim kill: mild cellular alterations of submaxillary salivary glands at ≥ 300 mg/kg bw/day in males and at 1000 mg/kg bw/day in females, treatment-related; mild to severe cellular alterations of the parotid salivary gland in males at ≥ 100 mg/kg bw/day  and in females at ≥ 300 mg/kg bw/day, treatment-related\nterminal kill:  cellular alterations of submaxillary salivary glands at ≥ 100 mg/kg bw/day in males and at 1000 mg/kg bw/day in females, treatment-related; cellular alterations of the parotid salivary gland in both sexes at ≥ 100 mg/kg bw/day, treatment-related",null,"Change",10,100,"mg/kg bw/day",{"$f":"IF(Z460<>0,VLOOKUP(Z460,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","In life observation","Mortality",{"$f":"IF(Z461<>0,VLOOKUP(Z461,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z461<>0,VLOOKUP(Z461,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",20000,"In life observation","Clinical signs",{"$f":"IF(Z462<>0,VLOOKUP(Z462,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No signs of clinical toxicity\nOphthalmology (examined by 3 independent experts): increased incidences of degenerative lens changes in males at 20000 ppm, within historical control range, treatment-related as histopathological abnormalities were exacerbated by treatment",null,"Increase",8000,20000,"ppm",{"$f":"IF(Z462<>0,VLOOKUP(Z462,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","F",20000,"In life observation","Body weight",{"$f":"IF(Z463<>0,VLOOKUP(Z463,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Statistically significantly decreased in females at 20000 ppm from study Day 51 until month 20 (bw 86% of control after 20 month, -23% bw gain after 20 month), treatment-related, no effects in males",null,"Decrease",8000,20000,"ppm",{"$f":"IF(Z463<>0,VLOOKUP(Z463,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","In life observation","Food consumption",{"$f":"IF(Z464<>0,VLOOKUP(Z464,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: occasionally increased in males at 2000 and 20000 ppm, considered toxicologically not significant\nFood efficiency: no abnormalities observed",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z464<>0,VLOOKUP(Z464,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z465<>0,VLOOKUP(Z465,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: occasional fluctuations without toxicological significance (data within historical control range, of small magnitude and/or not dose-related)\nClinical chemistry: occasional fluctuations, ALP↑ in females at 20000 ppm was attributed to a single animal)\nUrinalysis: increased specific gravity (month 6) and decreased pH (months 6, 18 and 24) in males at 20000 ppm, treatment-related, considered toxicologically not significant as histopathological findings were absent",null,"Change",20000,">20000","ppm",{"$f":"IF(Z465<>0,VLOOKUP(Z465,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","Organ Weight","Brain weight",{"$f":"IF(Z466<>0,VLOOKUP(Z466,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z466<>0,VLOOKUP(Z466,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M",20000,"Organ Weight","Liver weight",{"$f":"IF(Z467<>0,VLOOKUP(Z467,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Bw rel weight increased at interim kill and abs+brain rel weight increased at terminal kill in males at 20000 ppm, treatment-related",null,"Increase",8000,20000,"ppm",{"$f":"IF(Z467<>0,VLOOKUP(Z467,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M",20000,"Organ Weight","Kidney weight",{"$f":"IF(Z468<>0,VLOOKUP(Z468,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z468<>0,VLOOKUP(Z468,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M",">20000","Organ Weight","Testis weight",{"$f":"IF(Z469<>0,VLOOKUP(Z469,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z469<>0,VLOOKUP(Z469,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females); testis weight was recorded together with epididymides weight","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","Organ histopathology","Stomach histopathology",{"$f":"IF(Z470<>0,VLOOKUP(Z470,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology: inflammation of gastric squamous mucosa in females at 8000 ppm (0/59, 3/60, 9/60 and 6/59 at 0, 2000, 8000 and 20000 ppm), findings predominantly observed in decedent animals, inflammation in surviving animals restricted to each one surviving male and female at 20000 ppm",null,"Change",20000,">20000","ppm",{"$f":"IF(Z470<>0,VLOOKUP(Z470,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M",">20000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z471<>0,VLOOKUP(Z471,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z471<>0,VLOOKUP(Z471,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","F",">20000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z472<>0,VLOOKUP(Z472,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z472<>0,VLOOKUP(Z472,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M",">20000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z473<>0,VLOOKUP(Z473,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z473<>0,VLOOKUP(Z473,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","F",">20000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z474<>0,VLOOKUP(Z474,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z474<>0,VLOOKUP(Z474,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M",">20000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z475<>0,VLOOKUP(Z475,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z475<>0,VLOOKUP(Z475,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M",">20000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z476<>0,VLOOKUP(Z476,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z476<>0,VLOOKUP(Z476,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M",">20000","Organ histopathology","Testis histopathology",{"$f":"IF(Z477<>0,VLOOKUP(Z477,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z477<>0,VLOOKUP(Z477,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z478<>0,VLOOKUP(Z478,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z478<>0,VLOOKUP(Z478,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","F",">20000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z479<>0,VLOOKUP(Z479,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z479<>0,VLOOKUP(Z479,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","F",">20000","Organ histopathology","Vagina histopathology",{"$f":"IF(Z480<>0,VLOOKUP(Z480,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z480<>0,VLOOKUP(Z480,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z481<>0,VLOOKUP(Z481,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z481<>0,VLOOKUP(Z481,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z482<>0,VLOOKUP(Z482,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z482<>0,VLOOKUP(Z482,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","F",">20000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z483<>0,VLOOKUP(Z483,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z483<>0,VLOOKUP(Z483,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z484<>0,VLOOKUP(Z484,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Pancreas islet cell adenomas in males at 2000 ppm, not dose-related (2/58, 8/57, 5/60 and 7/59 males and 5/60, 1/60, 4/60 and 0/59 females at 0, 2000, 8000 and 20000 ppm), not attributed to treatment (no further corresponding effects of hyperplasia or carcinoma)",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z484<>0,VLOOKUP(Z484,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","Organ histopathology","Liver histopathology",{"$f":"IF(Z485<>0,VLOOKUP(Z485,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increase in liver adenoma in males only (8 at 20000 ppm versus 3 in control)",null,"Change",20000,">20000","ppm",{"$f":"IF(Z485<>0,VLOOKUP(Z485,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",17,null,"US EPA 83-5 (1984)","DAR",null,1990,"Rat","Sprague-Dawley","main: 50\ninterim kill: 10","M + F",96.5,"Oral","Feed","2000; 8000; 20000",2000,20000,"ppm",2,"Years","Adult","M + F",">20000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z486<>0,VLOOKUP(Z486,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z486<>0,VLOOKUP(Z486,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","In life observation","Mortality",{"$f":"IF(Z487<>0,VLOOKUP(Z487,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related mortality. There were no deaths within the satellite/interim kill groups.",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z487<>0,VLOOKUP(Z487,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","In life observation","Clinical signs",{"$f":"IF(Z488<>0,VLOOKUP(Z488,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Clinical signs: No treatment-related findings\nFunctional observation: No treatment-related findings",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z488<>0,VLOOKUP(Z488,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","In life observation","Body weight",{"$f":"IF(Z489<>0,VLOOKUP(Z489,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Overall body weight gain was comparable for all treatment groups (91% for males and 97% for females at 15000 ppm when compared to controls)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z489<>0,VLOOKUP(Z489,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","In life observation","Food consumption",{"$f":"IF(Z490<>0,VLOOKUP(Z490,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: occasional fluctuations, not treatment-related\nFood efficiency: occasional fluctuations, not treatment-related",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z490<>0,VLOOKUP(Z490,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",15000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z491<>0,VLOOKUP(Z491,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: no treatment-related findings (not treatment-related findings: APTT↑ in males at ≥ 1500 ppm at 6 months, APTT↑ and leucocytes↓ in females at ≥ 1500 ppm at 18 months, PT↑ in females at 15000 ppm after 6 months, neutrophils↑ in males at 15000 ppm and in females at 5000 ppm after 18 months, Hb↓ in females at ≥ 5000 ppm after 12 months, Hb↑ and Ht↑ in males at 1500 ppm after 6 months, lymphocytes↓ in females at 15000 ppm after 18 months, monocytes↑ in females at 1500 ppm after 24 months, MCHC↓ in males at ≥ 5000 ppm at 6 months)\nClinical chemistry:  ALP↑ in males at 15000 ppm 6, 12 and 18 months, marginal, considered to be a minor adaptive change to test substance intake; increase in plasma electrolytes in both sexes at 15000 ppm, treatment-related, considered minor and adaptive responses (further findings without toxicological relevance: changes in plasma electrocytes in all groups (Na↑ and Cl↑ in both sexes and K↑ in males at ≥ 1500 ppm and Ca↓ in females at 15000 ppm after 18 months, Na↓ in satellite females at 15000 ppm after 12 months, P↓ in both sexes at 1500 ppm after 18 months and P↑ in males at 15000 ppm after 24 months) no dose relation, toxicological significance unclear; TBil↑ in males at ≥ 1500 ppm after 18 months, A/G ratio↓ in females at ≥ 1500 ppm after 24 months, ALT↑ in satellite males at 150000 ppm after 6 months, in females after 12 months and in males after 18 months, TG↑ in females at 150000 ppm after 12 months, ALP↑ in satellite males at 5000 ppm after 12 months, urea↑ in females at 1500 ppm after 6 months, all findings without dose-relation and/or inconsistency throughout the study)\nUrinalysis: no treatment-related findings",null,"Change",5000,15000,"ppm",{"$f":"IF(Z491<>0,VLOOKUP(Z491,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M",">15000","Organ Weight","Epididymis weight",{"$f":"IF(Z492<>0,VLOOKUP(Z492,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z492<>0,VLOOKUP(Z492,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ Weight","Liver weight",{"$f":"IF(Z493<>0,VLOOKUP(Z493,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z493<>0,VLOOKUP(Z493,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ Weight","Kidney weight",{"$f":"IF(Z494<>0,VLOOKUP(Z494,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z494<>0,VLOOKUP(Z494,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","F",">15000","Organ Weight","Ovary weight",{"$f":"IF(Z495<>0,VLOOKUP(Z495,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z495<>0,VLOOKUP(Z495,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M",">15000","Organ Weight","Testis weight",{"$f":"IF(Z496<>0,VLOOKUP(Z496,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z496<>0,VLOOKUP(Z496,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","F",">15000","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z497<>0,VLOOKUP(Z497,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z497<>0,VLOOKUP(Z497,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ Weight","Adrenals weight",{"$f":"IF(Z498<>0,VLOOKUP(Z498,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z498<>0,VLOOKUP(Z498,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ Weight","Brain weight",{"$f":"IF(Z499<>0,VLOOKUP(Z499,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z499<>0,VLOOKUP(Z499,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","F",">15000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z500<>0,VLOOKUP(Z500,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic: rare instances of keratinisation of the cervix, not treatment-related",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z500<>0,VLOOKUP(Z500,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M",">15000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z501<>0,VLOOKUP(Z501,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic: no treatment-related findings (reduced spermatozoal count, spermatocoel granuloma formation, abscess formation and sclerotic nodule observed with low incidences, considered age-related)\nhistopathology, neoplastic: no treatment-related findings (mesothelioma in 1/51 control and 2/51 males at 1500 ppm)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z501<>0,VLOOKUP(Z501,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","F",">15000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z502<>0,VLOOKUP(Z502,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic: no treatment-related findings (secretory glandular hyperplasia in the majority of females examined with lower incidence in high dose females; secretory distention of ducts and galactocoel formation occasionally seen, common findings in aging rats, isolated findings of keratin cyst formation and acute inflammatory cell infiltrates)\nhistopathology, neoplastic: no treatment-related findings (fibroadenoma, adenoma, adenocarcinoma in 9/51, 12/51, 8/51 and 13/51 females at 0, 1500, 5000 and 15000 ppm, attributed to aging)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z502<>0,VLOOKUP(Z502,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M",">15000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z503<>0,VLOOKUP(Z503,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic: no significant changes\nhistopathology, neoplastic: no significant changes",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z503<>0,VLOOKUP(Z503,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","F",">15000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z504<>0,VLOOKUP(Z504,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic: no treatment-related findings (atrophy and absence of recent corpora lutea, follicular and non-follicular cysts, interstitial cell hyperplasia occasionally observed in all groups, age-related; isolated instances of abscess formation, peripheral inflammatory cells and thrombus formation, considered to be spontaneous)\nhistopathology, neoplastic: no treatment-related findings (granulosa cell tumors, granulosa-theca cell tumors, anaplasstic sacroma in 5/51, 3/51, 1/51 and 0/51 females at 0, 1500, 5000 and 15000 ppm)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z504<>0,VLOOKUP(Z504,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M",">15000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z505<>0,VLOOKUP(Z505,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic: no treatment-related findings (atrophic changes commonly observed in control and treated groups, age-related; focal epithelial hyperplasia, inflammatory cell infiltrates, interstitial fibrosis, interstitial haemorrhage and prostatis occasionally observed, considered as spontaneous changes)\nhistopathology, neoplastic: no neoplastic lesions found",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z505<>0,VLOOKUP(Z505,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M",">15000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z506<>0,VLOOKUP(Z506,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic: no treatment-related findings (reduced secretory content of one or both vesicles occasionally observed among all groups, increased incidences of bilateral secretory reduction in high dose males, not considered treatment-related; isolated instances of secretory distention, generalised atrophy of vesicles and atrophy or degeneration of the secretory content, age-related; peripheral and luminal inflammatory cells and abscess formation rarely observed in all groups)\nhistopathology, neoplastic: no neoplastic lesions observed",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z506<>0,VLOOKUP(Z506,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","F",">15000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z507<>0,VLOOKUP(Z507,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No treatment-related histopathological changes were observed. (Histopathology, non-neoplastic: no treatment-related findings: cystic endometrial hyperplasia in control and treatment-groups, age-related; uterine dilatation statistically significantly increased in high dose females, considered to be without toxicological significance; rare instances of keratinisation of the cervix, haemorrhage, pyometra, keratin cyst formation, abscess formation and squamous cell carcinoma; Neoplastic: no treatment-related findings (52 uterine tumours in 46 rats, 7/46 rats had more than 1 tumour type, 24/52 incidences of endometrial stromal polyps, 21/52 incidences of adenocarcinomas and 7/52 incidences of leiomyoma, stromal sarcoma or angiosarcoma in females over all groups (16/51, 12/51, 9/51 and 15/51 females at 0, 1500, 5000 and 15000 ppm))",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z507<>0,VLOOKUP(Z507,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M",">15000","Organ histopathology","Testis histopathology",{"$f":"IF(Z508<>0,VLOOKUP(Z508,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No treatmen-related effects observed",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z508<>0,VLOOKUP(Z508,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z509<>0,VLOOKUP(Z509,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic: no treatment-related findings (C-cell hyperplasia among all rats of all groups, age-related; focal hyperplasia in the parathoid glands of a few male rats)\nhistopathology, neoplastic: no treatment-related findings (follicular adenoma in 5/51, 1/51, 0/51 and 6/51 males and in 3/51, 0/51, 0/51 and 2/51 females at 0, 1500, 5000 and 15000 ppm; follicular adenocarcinoma in in 1/51 males at 5000 ppm and in 0/51 and 1/51 females at 0and 1500 ppm; parafollicular adenoma in in 9/51, 1/51, 0/51 and 3/51 males and in 6/51, 1/51, 1/51 and 0/51 females at 0, 1500, 5000 and 15000 ppm; parafollicular adenocarcinoma in in 2/51and 1/51 males at 0 and 1500 ppm and in 1/51 female 1500 ppm and hibernoma in 1/51 males at 15000 ppm)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z509<>0,VLOOKUP(Z509,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","F",">15000","Organ histopathology","Vagina histopathology",{"$f":"IF(Z510<>0,VLOOKUP(Z510,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No histopathological abnormalities observed",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z510<>0,VLOOKUP(Z510,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z511<>0,VLOOKUP(Z511,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Histopathology, non-neoplastic: no treatment-related findings, foci of altered cortical cells (hypertrophic or vacuolated) were frequently observed in both sexes among all groups, haemocysts in females of all groups, no dose-relation, attributed to aging; mononuclear cell foci, focal hyperplasia of medullary and cortical cells, focal extramedullary hematopoesis, focal necrosis, complete atrophy and congestion were occasionally observed\nhistopathology, neoplastic: no treatment-related findings (tumors of adrenal gland (cortical tumors, phaeochromocytomas, ganglioneuroma) in 4/51, 1/51, 3/51 and 2/51 males and  1/51, 1/51, 0/51 and 1/51 females at 0, 1500, 5000 and 15000 ppm)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z511<>0,VLOOKUP(Z511,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M",15000,"Organ histopathology","Bone marrow histopathology",{"$f":"IF(Z512<>0,VLOOKUP(Z512,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: increased incidence of severe adipose infiltration in males at 15000 ppm at terminal kill, treatment-related, attributed to myeloid hyperplasia, no abnormalities in high dose females (not treatment-related: increased incidence of severe adipose infiltration in premature dead animals at 1500 and 5000 ppm)\nhistopathology, neoplastic: myeloid hyperplasia was noted in a few rats of either sex, no dose relation, no treatment relation, no primary neoplastic lesions were seen",null,"Change",5000,15000,"ppm",{"$f":"IF(Z512<>0,VLOOKUP(Z512,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",15000,"Organ histopathology","Kidney histopathology",{"$f":"IF(Z513<>0,VLOOKUP(Z513,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: renal mineralisation, reduced pelvic mineralisation and increased corticomedullary mineralisation in premature death and terminal kill females at 15000 ppm, reduced incidences of hyperplasia in the renal pelvic/papillary epithelium in females at 15000 ppm, reduced pelvic mineralisation in males at 15000 ppm, treatment-related (not treatment-related findings: progressive glomerulonephropathy in rats of both sexes with greater prevalence in males, age-related, pyelitis in males at 5000 ppm, tubular necrosis in premature dead control females, renal tubular hyperplasia in 1/51 females at 1500 ppm and in 1/51 males and 1/51 females at 15000 ppm, occasional findings without dose relation included papillary necrosis, pyeliti, hydronephrosis, cortical cyst formation, tubular dilatation, generalised tubular basophilia, tubular mineralisation, cortical scarring, hypertrophy of the collecting duct epithelium, congestion)\nhistopathology, neoplastic findings: no treatment-related findings (renal tumors (lipoma, tubular carcinoma, clear cell carcinoma) in 1/51 and 1/51 males at 0 and 15000 ppm and in 1/51 females at 5000 ppm)",null,"Change",5000,15000,"ppm",{"$f":"IF(Z513<>0,VLOOKUP(Z513,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Bone histopathology",{"$f":"IF(Z514<>0,VLOOKUP(Z514,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: no significant lesions\nhistopathology, neoplastic: benign osteoma of the cranium in 1/51 males at 15000 ppm",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z514<>0,VLOOKUP(Z514,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z515<>0,VLOOKUP(Z515,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Histopathology, non-neoplastic: isolated necrotic, degenerative or inflammatory lesions occasionally observed, no toxicological significance; occasional instances of distortion of the brain and dilatation of the lateral ventricles, consequence of expansive pituitary neoplasia in either sex\nhistopathology, neoplastic: no treatment-related findings (astrocytoma, meningeal granular cell tumor, oligodendroglioma or ependymoma in 1/51, 1/51, 0/51 and 2/51 males and 2/51, 1/51, 0/51 and 0/51 females at 0, 1500, 5000 and 15000 ppm)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z515<>0,VLOOKUP(Z515,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Spinal cord histopathology",{"$f":"IF(Z516<>0,VLOOKUP(Z516,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: isolated necrotic, degenerative or inflammatory lesions occasionally observed, no toxicological significance\nhistopathology, neoplastic: no treatment-related findings (ependymoma in 1/51 females of the control group)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z516<>0,VLOOKUP(Z516,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Eyes histopathology",{"$f":"IF(Z517<>0,VLOOKUP(Z517,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: eyes: no treatment-related effects (retinal atrophy and lenticular degeneration were occasionally observed in rats of either sex, within historical control range; keratitis, corneal vacuolation, focal mineralisation of the cornea, posterior adhesions occasionally observed, spontaneous lesions)/ harderian gland: mononuclear ell foci and/or focal atrophy occasionally observed in both sexes, age-related, glandular epithelial hyperplasia/hypertrophy was frequently observed, spontaneous change, no treatment relation\nhistopathology, neoplastic: no treatment-related findings: no abnormalities observed",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z517<>0,VLOOKUP(Z517,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Heart histopathology",{"$f":"IF(Z518<>0,VLOOKUP(Z518,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: focal myocarditis/fibrosis commonly observed in both sexes bit mainly in males, no dose relation, not treatment-related; focal mineralisation and Schwann cell hyperplasia observed rarely as spontaneous lesion, not treatment-related\nhistopathology, neoplastic: no treatment-related findings (malignant Schwannoma in 1/51 males at 1500 ppm and in 2/51 control females)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z518<>0,VLOOKUP(Z518,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Urinary bladder histopathology",{"$f":"IF(Z519<>0,VLOOKUP(Z519,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Urinary bladder: histopathology, non-neoplastic: no treatment-related findings (epithelial/subepithelial or peripheral inflammatory cell infiltrates, epithelial erosion, subepithelial haemorrhage, epithelial hyperplasia and focal mineralisation were occasionally observed)\nhistopathology, neoplastic: no treatment-related findings (benign transitional cell papilloma in 1/51 males at 1500 ppm)\nUrether: distention in 1/51 females at 5000 ppm, not treatment-related",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z519<>0,VLOOKUP(Z519,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Liver histopathology",{"$f":"IF(Z520<>0,VLOOKUP(Z520,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: no treatment-related findings (mononuclear cell foci frequently observed in both sexes but with a higher incidence in males at 1500 and 5000 ppm, highly variable finding in aging rats; lipid vacuolation, focal, diffuse or zonal distribution was frequently observed in either sex, no treatment relation/dose relation, statistically significant excess pigment in high dose females at terminal kill, considered not treatment-related due to low incidence and secondary nature of the condition; occasionally observed hepatic necrosis, focal/centrilobular distribution, subcaspular congestion/telangiecatsis, focal haemorrhage, cyst formation, congestion, bile duct proliferation, hyperplasia, dilatation or thickening, focal myelopoesis, malformation, thrombus formation, inflammatory cell infiltration, dilatation of sinusoids, basophilia or enlargement, periportal fibrosis, not treatment-related, foci/areas of altered hepatocytes as precursors of hepatic neoplasia in 0/51, 2/51, 6/51 and 2/51 males and in 32/51, 37/51, 33/51 and 36/51 females at 0, 1500, 5000 and 15000 ppm)\nhistopathology, neoplastic: no treatment-related findings (hepatocellular adenoma/carcinoma, cholangiocarcinoma in 1/51, 2/51, 1/51 and 1/51 males and 2/51, 0/51, 2/51 and 1/51 females at 0, 1500, 5000 and 15000 ppm)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z520<>0,VLOOKUP(Z520,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z521<>0,VLOOKUP(Z521,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: no treatment-related findings (cysts, cystic distentiion of sinusoids, lymphoid atrophy, accumulations histiocytes, focal endothelial hyperplasia and haemorrhage were occasionally observed, common findings in aging rats)\nhistopathology, neoplastic: no treatment-related findings (angioma, angiosarcoma in 11/51, 4/51, 3/51 and 6/51 males and in 3/51, 1/51, 0/51 and 1/51 females at 0, 1500, 5000 and 15000 ppm)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z521<>0,VLOOKUP(Z521,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Thymus histopathology",{"$f":"IF(Z522<>0,VLOOKUP(Z522,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: no treatment-related findings (moderate to severe lymphoid atrophy in rats of both sexes among all groups, no effect on thymic atrophy)\nhistopathology, neoplastic: no treatment-related findings (lymphocytic thymoma, carcinoma in 0/51, 1/51, 1/51 and 2/51 males and 7/51, 2/51, 4/51 and 4/51 females at 0, 1500, 5000 and 15000 ppm)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z522<>0,VLOOKUP(Z522,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z523<>0,VLOOKUP(Z523,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: isolated instances of mucosal ulceration and diverticulum formation, not treatment-related\nhistopathology, neoplastic: no treatment-related findings (leiomyoma in the rectum of 1/51 males at 5000 ppm and leiomyosarcoma in 1/51 females at 15000 ppm)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z523<>0,VLOOKUP(Z523,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Lung histopathology",{"$f":"IF(Z524<>0,VLOOKUP(Z524,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: no treatment-related findings (accumulations of perivascular/peribroncheolar lymphocytes among all groups, statistically significantly increased in females at 15000 ppm, considered to be without toxicological significance as the difference was numerically small; lower incidence and severity of accumulations of alveolar macrophages in females at 15000 ppm, non-adverse; focal pneumonitis, cuboidal cell metaplasia, thickening of alveolar walls, thrombus formation, granulomas reaction, diffuse mononuclear cell infiltrates, abscess formation and pleural thickening occasionally observed among all groups, not treatment-related)\nhistopathology, neoplastic: no pulmonary neoplastic findings",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z524<>0,VLOOKUP(Z524,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","[Not in list]",{"$f":"IF(Z525<>0,VLOOKUP(Z525,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Nasal cavities: histopathology, non-neoplastic: no treatment-related findings (dilatation of subepithelial glands in rats of either sex, spontaneous change, statistically significantly decreased in males at 15000 ppm, incidental; chronic inflammatory lesions adjacent to the palate, associated with plant material/ hair fragments, reaction to foreign material impacted ti gland ducts; inflammatory/non-inflammatory exudate overlying the endothelium, focal epithelial ulceration, thrombus formation, fungal growth and dental hyperplasia occasionally observed)\nhistopathology, neoplastic: no treatment-related findings (polypoid adenoma in 2/51, 1/51, 0/51 and 0/51 males at 0, 1500, 5000 and 15000 ppm)\nPharynx: histopathology, non-neoplastic: no treatment-related findings (inflammatory cell lesions, inflammatory exudate and mucous cell hyperplasia/hypertrophy in a few animals)\nhistopathology, neoplastic: squamous cell papilloma in 1/51 females at 15000 ppm\nLarynx: histopathology, non-neoplastic: no treatment-related findings (distention of glands commonly observed among all control and treated rats of either sex; focal ulceration and debris in the ventral pouch, considered incidental)\nhistopathology, neoplastic: no neoplastic findings\nTongue: histopathology, neoplastic: no treatment-related findings (isolated instances of mononuclear cell infiltrates and mucous cysts in the epithelium in males, without toxicological significance)\nhistopathology, neoplastic: no treatment-related findings (benign granular cell tumor in 1/51 females at 15000 ppm)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z525<>0,VLOOKUP(Z525,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z526<>0,VLOOKUP(Z526,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: no treatment-related findings (islet cell hyperplasia frequently noted in males and occasionally in females, no dose relation; lower incidence of exocrine atrophy in males at 15000 ppm; occasional observations of exocrine hypertrophy, inflammatory lesions, cystic distention, dilatation or epithelial hyperplasia of ducts, peripheral abscess formation)\nhistopathology, neoplastic: no treatment-related findings (islet cell adenoma/carcinoma in 4/51, 1/51, 2/51 and 1/51 males and in 0/51, 0/51, 1/51 and 0/51 females at 0, 1500, 5000 and 15000 ppm)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z526<>0,VLOOKUP(Z526,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Peripheral nerve histopathology",{"$f":"IF(Z527<>0,VLOOKUP(Z527,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: no treatment-related findings (fibre degeneration/necrosis in a few treated and control animals, isolated instances of mononuclear cell infiltration and nuclear pyknosis)\nhistopathology, neoplastic: no neoplasms observed",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z527<>0,VLOOKUP(Z527,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z528<>0,VLOOKUP(Z528,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Histopathology, non-neoplastic: focal hyperplasia, focal haemorrhage and cyst formation occasionally observed without toxicological significance\nhistopathology, neoplastic: no treatment-related findings (age related adenoma and adenocarcinoma observed in both sex, not treatment related)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z528<>0,VLOOKUP(Z528,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z529<>0,VLOOKUP(Z529,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: no treatment-related findings (isolated instances of secretory depletion, focal hyperplasia and focal hypertrophy of the mucous acini in the submandibulary gland)\nhistopathology, neoplastic: no treatment-related findings (acinar adenoma in the paratoid gland of 1/51 males at 15000 ppm, considered to be spontaneous)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z529<>0,VLOOKUP(Z529,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Skeletal muscle histopathology",{"$f":"IF(Z530<>0,VLOOKUP(Z530,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: no treatment-related findings (isolated instances of mononuclear cell foci, fibre atrophy and fibre degeneration/necrosis among all groups, age-related)\nhistopathology, neoplastic: no neoplasms observed",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z530<>0,VLOOKUP(Z530,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Skin histopathology",{"$f":"IF(Z531<>0,VLOOKUP(Z531,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: no treatment-related findings but several spontaneous lesions observed (dilatation of hair folicles, subepithelial inflammatory cell infiltrates, abscess formation, epidermal ulceration, cystic cutaneous lymph node, nodule fat necrosis, cystic hair follicles, keratin cyst formation, focal acanthosis, subcutaneous fibrosis and dermal thickening occasionally observed among all groups; areas of necrosis/giant cell reaction to keratin in males with statistically increased significance at 15000 ppm, secondary lesion associated with development of keratoacanthoma)\nhistopathology, neoplastic: no treatment-related findings (8 types of cutaneous tumors with benign keratoacanthoma as most pervalent in male rats of all groups, 6 types of subcutaneous tumors among all groups, none of them with special prevalence; most of the tumor types diagnosed occured in males of all groups, 7 of them were fibrosarcoma)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z531<>0,VLOOKUP(Z531,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z532<>0,VLOOKUP(Z532,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: no treatment-related findings (extramedullary hematopoesis in the majority of rats among both sexes and all groups, within historical control data; atrophy of lymphoid tissue, atrophy of the red pulp, mononuclear cell proliferation, areas of necrosis and hyperaemia were occasionally observed)\nhistopathology, neoplastic: no treatment-related findings (angioma in 1/51 males at 15000 ppm and angiosarcoma in 1/51 control males)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z532<>0,VLOOKUP(Z532,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Stomach histopathology",{"$f":"IF(Z533<>0,VLOOKUP(Z533,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: no treatment-related findings (acanthosis/hyperkeratosis in both sexes among all groups, no treatment relation; occasional observations included dilatation of gastric glands, subepithelial inflammatory cell infiltrates, acanthosis, hyperkeratosis, subepithelial oedema, ulceration of the forestomach or mucosa, mucosal erosion, focal mineralisation and mucosal atropy)\nhistopathology, neoplastic: no treatment-related findings (squamous papilloma in the forestomach of 1/51, 0/51, 2/51 and 1/51 males and 0/51, 1/51, 0/51 and 0/51 females at 0, 1500, 5000 and 15000 ppm)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z533<>0,VLOOKUP(Z533,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",18,null,"OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","DAR",null,2009,"Rat","Wistar","main: 51\ninterim kill: 12 (0, 1500 and 5000 ppm) and 21 (15000 ppm)","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",2,"Years","Adult","M + F",">15000","Organ histopathology","Trachea histopathology",{"$f":"IF(Z534<>0,VLOOKUP(Z534,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic: no treatment-related findings (dilatation of subepithelial glands noted in a few control and treated rats of either sex; isolated instances of inflammation and excess mineralisation of cartilage)\nhistopathology, neoplastic: no neoplasms observed",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z534<>0,VLOOKUP(Z534,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",10000,"In life observation","Mortality",{"$f":"IF(Z535<>0,VLOOKUP(Z535,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Increased mortality at 10000 ppm (survival was 56, 60, 56 and 46% in males and 62, 64, 58 and 53% in females at 0, 100, 1000 and 10000 ppm); mortality rates at study termination were 44, 40, 44 and 54% at 0, 100, 1000 and 10000 ppm, life expectancy was not affected in any treated group",null,"Increase",1000,10000,"ppm",{"$f":"IF(Z535<>0,VLOOKUP(Z535,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","In life observation","Clinical signs",{"$f":"IF(Z536<>0,VLOOKUP(Z536,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Clinical signs: no treatment-related findings (incidences of alopecia and skin injuries among all test groups, common finding in this species)\nOpthalmology: no treatment-related findings (cataract in 1/50 females at 100 ppm, corneal opacity in 1/50, 1/50 and 2/50 at 0, 100 and 1000 ppm. considered incidental)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z536<>0,VLOOKUP(Z536,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","In life observation","Body weight",{"$f":"IF(Z537<>0,VLOOKUP(Z537,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Occasional fluctuations of body weight in males at 100 and 1000 ppm, no dose response, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z537<>0,VLOOKUP(Z537,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","In life observation","Food consumption",{"$f":"IF(Z538<>0,VLOOKUP(Z538,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: occasionally altered in both sexes among all groups throughout the study, no dose relation, of minor degree and/or not consistent, considered to be incidental\nFood efficiency: no treatment-related findings",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z538<>0,VLOOKUP(Z538,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z539<>0,VLOOKUP(Z539,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: only differential leukocyte count was analysed, data appeared to be within the range of biological variation\nClinical chemistry: not performed\nUrinalysis: not performed",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z539<>0,VLOOKUP(Z539,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ Weight","Liver weight",{"$f":"IF(Z540<>0,VLOOKUP(Z540,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z540<>0,VLOOKUP(Z540,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ Weight","Kidney weight",{"$f":"IF(Z541<>0,VLOOKUP(Z541,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z541<>0,VLOOKUP(Z541,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ Weight","Adrenals weight",{"$f":"IF(Z542<>0,VLOOKUP(Z542,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z542<>0,VLOOKUP(Z542,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M",">10000","Organ Weight","Testis weight",{"$f":"IF(Z543<>0,VLOOKUP(Z543,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z543<>0,VLOOKUP(Z543,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","F",">10000","Organ Weight","Ovary weight",{"$f":"IF(Z544<>0,VLOOKUP(Z544,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z544<>0,VLOOKUP(Z544,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M",">10000","Organ histopathology","Coagulating gland histopathology",{"$f":"IF(Z545<>0,VLOOKUP(Z545,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z545<>0,VLOOKUP(Z545,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M",">10000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z546<>0,VLOOKUP(Z546,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings dead/moribund animals: lymphocyte infiltration in 4/22, 1/20, 0/22 and 3/27 males and cell debris in tubules in 0/22, 1/20, 4/22 and 0/27 males at 0, 100, 1000 and 10000 ppm, no dose response, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z546<>0,VLOOKUP(Z546,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","F",">10000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z547<>0,VLOOKUP(Z547,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z547<>0,VLOOKUP(Z547,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","F",">10000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z548<>0,VLOOKUP(Z548,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gross pathology, terminal kill animals: bursal cysts in 13/34, 11/34, 11/30 and 13/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z548<>0,VLOOKUP(Z548,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M",">10000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z549<>0,VLOOKUP(Z549,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z549<>0,VLOOKUP(Z549,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M",">10000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z550<>0,VLOOKUP(Z550,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings dead/moribund animals: atrophy in 3/22, 3/20, 5/22 and 5/27 males at 0, 100, 1000 and 10000 ppm, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z550<>0,VLOOKUP(Z550,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M",">10000","Organ histopathology","Testis histopathology",{"$f":"IF(Z551<>0,VLOOKUP(Z551,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings dead/moribund animals: atrophy/ degenerative changes in 9/22, 4/20, 11/22 and 9/27 males at 0, 100, 1000 and 10000 ppm, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z551<>0,VLOOKUP(Z551,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z552<>0,VLOOKUP(Z552,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings dead/moribund animals: amyloidosis in 4/22, 3/20, 5/22 and 5/27 males and 3/16, 1/16, 1/20 and 2/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z552<>0,VLOOKUP(Z552,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","F",">10000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z553<>0,VLOOKUP(Z553,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings dead/moribund animals: cystic glands in 5/16, 3/16, 2/20 and 7/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nhistopathology, non-neoplastic findings terminal kill animals: cystic endometrial hyperplasia in 17/34, 5/34, 4/30 and 8/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nhistopathology, neoplastic findings: 10 tumours observed, mostly endometrial stromal sarcomas. No dose- or treatment-relation identified.",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z553<>0,VLOOKUP(Z553,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z554<>0,VLOOKUP(Z554,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Histopathology, non-neoplastic findings dead/moribund animals: subcapsular cell hyperplasia in 3/22, 8/20, 7/22 and 10/27 males and 12/16, 11/16, 13/20 and 15/20 females at 0, 100, 1000 and 10000 ppm; amyloidosis in 7/22, 9/20, 10/22 and 11/27 males and 3/16, 0/16, 1/20 and 3/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nhistopathology, non-neoplastic findings terminal kill animals: subcapsular cell hyperplasia in 15/28 and 13/23 males and 27/34 and 22/30 females at 0 and 10000 ppm and amyloidosis in 7/28 and 8/23 males and 1/27 and 3/30 females at 0 and 10000 ppm, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z554<>0,VLOOKUP(Z554,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z555<>0,VLOOKUP(Z555,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z555<>0,VLOOKUP(Z555,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","F",">10000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z556<>0,VLOOKUP(Z556,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z556<>0,VLOOKUP(Z556,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ histopathology","Stomach histopathology",{"$f":"IF(Z557<>0,VLOOKUP(Z557,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings dead/moribund animals: cystic glands in 8/22, 8/20, 9/22 and 16/27 males and 1/16, 4/16, 5/20 and 6/20 females at 0, 100, 1000 and 10000 ppm, within historical control range, considered to be incidental\nhistopathology, non-neoplastic findings terminal kill animals: cystic glands in 9/28, 19/30, 22/28 and 17/23 males and 22/34, -/34, -/30 and 19/30 females at 0, 100, 1000 and 10000 ppm, no dose-dependent increase in severity",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z557<>0,VLOOKUP(Z557,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z558<>0,VLOOKUP(Z558,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings dead/moribund animals: amyloidosis in 1/22, 6/20, 4/22 and 4/27 males at 0, 100, 1000 and 10000 ppm and in 1/16 control females, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z558<>0,VLOOKUP(Z558,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ histopathology","Liver histopathology",{"$f":"IF(Z559<>0,VLOOKUP(Z559,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross pathology, dead/moribund animals: enlarged in 3/22, 1/20, 3/22 and 1/27 males and 3/16, 4/16, 2/20 and 2/20 females at 0, 100, 1000 and 10000 ppm, no dose depedency but associated with histopathological findings\ngross pathology, terminal kill animals: masses in 4/28, 4/30, 2/28 and 2/23 males and 1/34, 1/34, 2/30 and 2/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nHistopathology, non-neoplastic findings dead/moribund animals: amyloidosis in 10/22, 9/20, 10/22 and 11/27 males and 5/16, 1/16, 4/20 and 5/20 females at 0, 100, 1000 and 10000 ppm, no dose dependency, not treatment-related\nhistopathology, non-neoplastic findings terminal kill animals: necrobiotic foci in 2/28, 0/30, 0/28 and 1/23 males and 4/34, 1/34, 0/30 and 7/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related; extramedullary hematopoesis in 5/28, 0/30, 2/28 and 5/23 males and 2/34, 2/34, 0/30 and 6/30 females at 0, 100, 1000 and 10000 ppm; amyloidosis in 9/28, 1/30, 3/28 and 8/23 males and 2/34, 2/34, 0/30 and 5/30 females at 0, 100, 1000 and 10000 ppm\nhistopathology, neoplastic findings: 26 tumors observed, mostly hepatocellular adenomas, no treatment relation",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z559<>0,VLOOKUP(Z559,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ histopathology","Heart histopathology",{"$f":"IF(Z560<>0,VLOOKUP(Z560,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings dead/moribund animals: degenerative changes in 11/22, 14/20, 13/22 and 16/27 males and 4/16, 2/16, 4/20 and 1/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z560<>0,VLOOKUP(Z560,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z561<>0,VLOOKUP(Z561,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross pathology, dead/moribund animals: enlarged in 8/22, 8/20, 11/22 and 13/27 males and 10/16, 11/16, 12/20 and 7/20 females at 0, 100, 1000 and 10000 ppm, no dose depedency but associated with histopathological findings\ngross pathology, terminal kill animals: enlarged in 8/28, 11/30, 11/28 and 10/23 males and 9/34, 15/34, 6/30 and 14/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related, associated with neoplasia of the hemolymphoreticular system, amyloidosis and increased extramedullary hematopoesis\nHistopathology, non-neoplastic findings dead/moribund animals: increased extramedullary hematopoesis in 3/22, 7/20, 1/22 and 3/27 males and 5/16, 5/16, 3/20 and 6/20 females at 0, 100, 1000 and 10000 ppm; amyloidosis in 12/22, 8/20, 10/22 and 12/27 males and 5/16, 1/16, 4/20 and 4/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nhistopathology, non-neoplastic findings terminal kill animals: increased extramedullary hematopoesis in 10/28, 13/30, 11/28 and 5/23 males and 9/34, 18/34, 10/30 and 10/30 females at 0, 100, 1000 and 10000 ppm; amyloidosis in 10/28, 9/30, 9/28 and 8/23 males and 2/34, 5/34, 3/30 and 5/30 females at 0, 100, 1000 and 10000 ppm, no dose relation, considered to be incidental",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z561<>0,VLOOKUP(Z561,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z562<>0,VLOOKUP(Z562,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross pathology, dead/moribund animals: enlarged superficial lymph nodes in 7/22, 5/20, 5/22 and 6/27 males and 2/16, 6/16, 9/20 and 4/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related; enlarged mandibular lymph nodes in 3/22, 6/20, 3/22 and 3/27 males and 1/16, 2/16, 3/20 and 3/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related; enlarged mesenteric lymphnodes in 8/22, 9/20, 8/22 and 11/27 males and 8/16, 9/16, 10/20 and 7/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related\ngross pathology, terminal kill animals: enlarged axillary lymph nodes in 5/28, 3/30, 5/28 and 0/23 males and 3/34, 6/34, 1/30 and 4/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related; enlarged superficial ing. lymph nodes in 3/28, 1/30, 2/28 and 2/23 males and 0/34, 3/34, 1/30 and 2/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related; enlarged mandibular lymph nodes in 12/28, 19/30, 19/28 and 14/23 males and 15/34, 15/34, 12/30 and 13/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related; discolourated mesenteric lymph nodes in 7/28, 9/30, 7/28 and 6/23 males and 2/34, 3/34, 2/30 and 12/30 females at 0, 100, 1000 and 10000 ppm, no dose relation, not treatment-related; enlarged mesenteric lymph nodes in 13/28, 14/30, 15/28 and 10/23 males and 10/34, 12/34, 9/30 and 19/30 females at 0, 100, 1000 and 10000 ppm, no dose relation, not treatment-related, associated with neoplasia of the hemolymphoreticular system and lymphoid hyperplasia\nHistopathology, non-neoplastic findings dead/moribund animals: mandibular lymph node hyperplasia in 6/22, 5/20, 3/22 and 7/27 males and 3/16, 3/16, 2/20 and 6/20 females at 0, 100, 1000 and 10000 ppm; extramedullary hematopoesis in 3/22, 2/20, 5/22 and 3/27 males and 1/16, 1/16, 1/20 and 2/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nhistopathology, non-neoplastic findings terminal kill animals: mesenteric lymph nodes hyperplasia in 12/28, 12/30, 17/28 and 9/23 males and 13/34, 20/34, 16/30 and 11/30 females at 0, 100, 1000 and 10000 ppm; meseneteric extramedullary hematopoesis in 8/28, 10/30, 9/28 and 6/23 males and 6/34, 9/34, 4/30 and 8/30 females at 0, 100, 1000 and 10000 ppm; mandibular lymph node hyperplasia in 13/28, 24/30, 24/28 and 14/23 males and 21/34, 24/34, 23/30 and 11/30 females at 0, 100, 1000 and 10000 ppm; mandibular extramedullary hematopoesis in 5/28, 7/30, 9/28 and 9/23 males and 3/34, 9/34, 7/30 and 4/30 females at 0, 100, 1000 and 10000 ppm, considered to be incidental; hyperplasia in superficial ing lymph nodes in 3/28, 0/30, 0/28 and 6/23 males and 6/34, 2/34, 0/30 and 6/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nhistopathology, neoplastic findings: mesenteric lymph nodes: 9 tumours observed among all groups (1/16 and 2/20 dead/moribund females at 0 and 10000 ppm, 1/16 dead/moribund males at 100 ppm and 1/28, 1/27 and 1/23 terminal kill males at 0, 1000 and 10000 ppm and in 2/30 terminal kill females at 10000 ppm), mostly hemangiomas (7/9), no treatment relation",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z562<>0,VLOOKUP(Z562,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z563<>0,VLOOKUP(Z563,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross pathology, terminal kill animals: rough/ uneven surface in 1/28, 2/30, 2/28 and 5/23 males at 0, 100, 1000 and 10000 ppm, considered incidental as histopathological findings were absent\nHistopathology, non-neoplastic findings dead/moribund animals: nephropathy in 9/22, 7/20, 10/22 and 12/27 males and 5/16, 1/16, 5/20 and 3/20 females at 0, 100, 1000 and 10000 ppm; amyloidosis in 6/22, 4/20, 10/22 and 9/27 males and 3/16, 2/16, 2/20 and 4/20 females at 0, 100, 1000 and 10000 ppm\nhistopathology, non-neoplastic findings terminal kill animals: nephropathy in 7/28, 4/30, 3/28 and 6/23 males and 5/34, 2/34, 0/30 and 2/30 females at 0, 100, 1000 and 10000 ppm and amyloidosis in 7/28, 2/30, 2/28 and 8/23 males and 0/34, 1/34, 0/30 and 3/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z563<>0,VLOOKUP(Z563,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ histopathology","Skin histopathology",{"$f":"IF(Z564<>0,VLOOKUP(Z564,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross pathology, dead/moribund animals: alopecia/patchy alopecia in 2/22, 1/20, 0/22 and 3/27 males and 1/16, 0/16, 2/20 and 0/20 females at 0, 100, 1000 and 10000 ppm, not dose- or treatment-related\nHistopathology, non-neoplastic findings dead/moribund animals: epidermal hyperplasia in 10/22, 13/20, 7/22 and 10/27 males and 6/16, 5/16, 6/20 and 6/20 females at 0, 100, 1000 and 10000 ppm; suppurative necrotising dermatitis/healing in 5/22, 6/20, 2/22 and 5/27 males and 3/16, 1/16, 4/20 and 1/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z564<>0,VLOOKUP(Z564,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ histopathology","Bone histopathology",{"$f":"IF(Z565<>0,VLOOKUP(Z565,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings dead/moribund animals: increased granulopoesis in femur in 5/22, 3/20, 2/22 and 2/27 males and 1/16, 3/16, 0/20 and 4/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related; increased hematopoesis in femur in 1/22, 1/20, 8/22 and 5/27 males and 0/16, 1/16, 2/20 and 3/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related; increased hematopoesis in sternum with marrow in 2/22, 1/20, 5/22 and 6/27 males and 0/16, 1/16, 3/20 and 3/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nhistopathology, non-neoplastic findings terminal kill animals: increased hematopoesis in sternum with marrow in 5/28 and 2/23 males and 6/34 and 8/30 females at 0 and 10000 ppm, not treatment-related\nhistopathology, neoplastic findings: 11 tumors observed, osteomas, no treatment relation",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z565<>0,VLOOKUP(Z565,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z566<>0,VLOOKUP(Z566,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Rectum: histopathology, non-neoplastic findings terminal kill animals: lymphoid hyperplasia in 2/28 and 0/23 males at 0 and 10000 ppm and in 0/34, 1/34, 1/30 and 4/30 females at 0, 100, 1000 and 10000 ppm, lower than histoircal control data, considered to be incidental",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z566<>0,VLOOKUP(Z566,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ histopathology","Thymus histopathology",{"$f":"IF(Z567<>0,VLOOKUP(Z567,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross pathology, dead/moribund animals: enlarged in 0/22, 1/20, 0/22 and 3/27 males and 0/16, 3/16, 1/20 and 2/20 females at 0, 100, 1000 and 10000 ppm, associated with neoplasms of the hemolymphoreticular system, no dose relation\nhistopathology, non-neoplastic findings terminal kill animals: involution in 13/28 and 6/23 males and in 6/34 and 7/30 females at 0 and 10000 ppm, no involution in 9/28 and 9/23 males and in 20/34 and 14/30 females at 0 and 10000 ppm, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z567<>0,VLOOKUP(Z567,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",19,"1559.CARCI-M","OECD 451 (1981)","DAR",null,2001,"Mouse","Swiss albino (HsdOla: MF1)",50,"M + F","> 95","Oral","Feed","100; 1000; 10000",100,10000,"ppm",18,"Months","Adult","M + F",">10000","Organ histopathology","Lung histopathology",{"$f":"IF(Z568<>0,VLOOKUP(Z568,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, neoplastic findings: 11 tumors observed, mostly bronchioalveolar adenomas, no treatment relation",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z568<>0,VLOOKUP(Z568,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","In life observation","Mortality",{"$f":"IF(Z569<>0,VLOOKUP(Z569,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related findings, mortality rate was highest in males at 5000 ppm and lowest in females at 5000 ppm (survival up to terminal kill: 39/51, 41/51, 39/51 and 35/51 males and 37/51, 38/51, 38/51 and 40/51 females at 0, 500, 1500 and 5000 ppm)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z569<>0,VLOOKUP(Z569,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","In life observation","Clinical signs",{"$f":"IF(Z570<>0,VLOOKUP(Z570,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related findings. Wounds, scab formation, loss of whiskers, fur loss and limb swelling occasionally observed, consequence of intra-cage aggression",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z570<>0,VLOOKUP(Z570,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","In life observation","Body weight",{"$f":"IF(Z571<>0,VLOOKUP(Z571,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",5000,">5000","ppm",{"$f":"IF(Z571<>0,VLOOKUP(Z571,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","In life observation","Food consumption",{"$f":"IF(Z572<>0,VLOOKUP(Z572,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: no treatment-related findings\nFood efficiency: reduced in females of all dose levels in weeks 1 and 2, reduced in males at 5000 ppm in week 4 to 5, considered as an isolated event and not treatment-related",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z572<>0,VLOOKUP(Z572,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z573<>0,VLOOKUP(Z573,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology (differential white blood cell count performed only ): no treatment-related findings\nClinical chemistry: not performed\nUrinalysis: not performed",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z573<>0,VLOOKUP(Z573,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M",">5000","Organ Weight","Epididymis weight",{"$f":"IF(Z574<>0,VLOOKUP(Z574,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",5000,">5000","ppm",{"$f":"IF(Z574<>0,VLOOKUP(Z574,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ Weight","Liver weight",{"$f":"IF(Z575<>0,VLOOKUP(Z575,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",5000,">5000","ppm",{"$f":"IF(Z575<>0,VLOOKUP(Z575,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ Weight","Kidney weight",{"$f":"IF(Z576<>0,VLOOKUP(Z576,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",5000,">5000","ppm",{"$f":"IF(Z576<>0,VLOOKUP(Z576,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","F",">5000","Organ Weight","Ovary weight",{"$f":"IF(Z577<>0,VLOOKUP(Z577,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",5000,">5000","ppm",{"$f":"IF(Z577<>0,VLOOKUP(Z577,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M",">5000","Organ Weight","Testis weight",{"$f":"IF(Z578<>0,VLOOKUP(Z578,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",5000,">5000","ppm",{"$f":"IF(Z578<>0,VLOOKUP(Z578,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ Weight","Adrenals weight",{"$f":"IF(Z579<>0,VLOOKUP(Z579,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",5000,">5000","ppm",{"$f":"IF(Z579<>0,VLOOKUP(Z579,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ Weight","Brain weight",{"$f":"IF(Z580<>0,VLOOKUP(Z580,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",5000,">5000","ppm",{"$f":"IF(Z580<>0,VLOOKUP(Z580,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M",">5000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z581<>0,VLOOKUP(Z581,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings: no treatment-related findings (reduced spermatozoal content, spermatocoel and spermatocoel granuloma formation, eosinophilic contents, interstitial mononuclear cells and fibrosis, distention of ducts observed with low incidences, age-related)\nhistopathology, neoplastic findings: no neoplastic changes",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z581<>0,VLOOKUP(Z581,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","F",">5000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z582<>0,VLOOKUP(Z582,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings: no treatment-related findings (secretory distention of ducts frequently observed, age-related; glandular hyperplasia occasionally observed, age-related; instances of subcutaneous cyst formation)\nhistopathology, neoplastic findings: no treatment-related findings (adenocarcinomas or adenosquamous carcinomas in 2/51, 3/51 and 1/51 females at 500, 1500 and 5000 ppm)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z582<>0,VLOOKUP(Z582,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M",">5000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z583<>0,VLOOKUP(Z583,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"(only two animals examined)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z583<>0,VLOOKUP(Z583,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","F",">5000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z584<>0,VLOOKUP(Z584,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings: no treatment-related findings (follicular and non-follicular cysts frequently observed, age-related; cystic and haemorrhagic follicles or corpora lutea in several control and high dose animals; interstitial cell hyperplasia, vasculitis, rete cyst formation, cystic distention of the oviducts, haemorrhagic cyst formation, necrosis and interstitial haemorrhage occasionally observed)\nhistopathology, neoplastic findings: no treatment-related findings (tumours in 1/51 control and 5/51 females at 5000 ppm (9 treated females in total affected), diversity of tumor type did not suggest a treatment relation)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z584<>0,VLOOKUP(Z584,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M",">5000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z585<>0,VLOOKUP(Z585,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings: no treatment-related findings (focal epithelial hyperplastic and atrophic changes frequently observed, age-related; mononuclear cell foci, mixed inflammatory cell infiltrates, interstitial fibrosis and abscess formation occasionally ore rarely observed)\nhistopathology, neoplastic findings: no neoplastic lesions observed",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z585<>0,VLOOKUP(Z585,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M",">5000","Organ histopathology","Coagulating gland histopathology",{"$f":"IF(Z586<>0,VLOOKUP(Z586,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings: no treatment-related findings (focal epithelial hyperplastic and atrophic changes frequently observed, age-related; mononuclear cell foci, mixed inflammatory cell infiltrates, interstitial fibrosis and abscess formation occasionally ore rarely observed)\nhistopathology, neoplastic findings: no neoplastic lesions observed",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z586<>0,VLOOKUP(Z586,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M",">5000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z587<>0,VLOOKUP(Z587,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings: no treatment-related findings (variations in secretory content, instances of cystic distention, focal hyperplasia of the epithelial lining of the vesicles, mononuclear cell foci, mixed inflammatory cell infiltrates, fibrous thickening, atrophy and abscess formation; hyperplasia of the coagulating gland in 1/51 males at 5000 ppm)\nhistopathology, neoplastic findings: no treatment-related findings (adenoma of the vesicular epithelium in 2/51 control males and leiomyosarcoma in 1/51 high dose males)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z587<>0,VLOOKUP(Z587,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M",">5000","Organ histopathology","Testis histopathology",{"$f":"IF(Z588<>0,VLOOKUP(Z588,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"histopathology, non-neoplastic findings: bilateral testicular atrophy, statistically significant in males at 5000 ppm, considered not toxicologically significant; interstitial (Leydig) cell hyperplasia in most animals, age-related; incidental findings included spermatocoel formation, focal mineralisation of tubules, focal hyperplasia of the rete tubular epithelium, cyst formation)\nhistopathology, neoplastic findings: no treatment-related findings (benign interstitial (Leydig) cell tumours in 2/51 control males)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z588<>0,VLOOKUP(Z588,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z589<>0,VLOOKUP(Z589,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings: no treatment-related findings (distention and coalescence of follicles, focal follicular cell hyperplasia, focal C-cell hyperplasia, vasculitis, focal inflammation, follicular cell hypertrophy and mononuclear cell foci occasionally observed)\nhistopathology, neoplastic findings: no tumours observed",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z589<>0,VLOOKUP(Z589,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","F",">5000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z590<>0,VLOOKUP(Z590,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings: no treatment-related findings (cystic endometrial hyperplasia in most mice and uterine atrophy, age-related; instances of vasculitis, lymphoid foci, haemorrhagic cyst formation and angiectasis)\nhistopathology, neoplastic findings: no treatment-related findings (tumours observed in 20 mice, but group distribution was unrelated to treatment, 6 different tumour types; most frequently observed tumour was endometrial stromal polyp; histiocytic sarcomas in 5 animals)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z590<>0,VLOOKUP(Z590,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","F",">5000","Organ histopathology","Vagina histopathology",{"$f":"IF(Z591<>0,VLOOKUP(Z591,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings: no treatment-related findings (epithelial keratinisation as normal cyclical change; one case of peripheral lymphocyte infiltration)\nhistopathology, neoplastic findings: no neoplastic changes",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z591<>0,VLOOKUP(Z591,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z592<>0,VLOOKUP(Z592,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Histopathology, non-neoplastic findings: no treatment-related findings (focal hyperplasia of subcapsular cortical cells and focal hyperplasia of medullary cells in both sexes among all groups and focal cortical hypertrophy in males, age-related findings; focal hyperplasia of cortical cells and cortical atrophy were rarely observed)\nhistopathology, neoplastic findings: no treatment-related findings (cortical adenoma in 3/51 and 3/51 males at 0 and 5000 ppm, cortical carcinoma in 1/51 control males)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z592<>0,VLOOKUP(Z592,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Aorta histopathology",{"$f":"IF(Z593<>0,VLOOKUP(Z593,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (few observations without toxicological significance)\nhistopathology, neoplastic findings: no neoplastic lesions observed",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z593<>0,VLOOKUP(Z593,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Bone histopathology",{"$f":"IF(Z594<>0,VLOOKUP(Z594,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (hyperostosis in 1/51 control females)\nhistopathology, neoplastic findings: no treatment-related findings (benign osteoma of the sternum in 1/51 control females)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z594<>0,VLOOKUP(Z594,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z595<>0,VLOOKUP(Z595,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Histopathology, non-neoplastic findings: no treatment-related findings (isolated instances of dilatation of the lateral ventricles, crystalline clefts/ granuloma formation, focal mineralisation, vacuolation of the cerebral cortex and mononuclear cell foci; extensive abscess formation with areas of necrosis in 1/51 control males)\nhistopathology, neoplastic findings: no treatment-related findings (meningeal sarcoma in 1/51 males at 5000 ppm, oligodenroglioma in 1/51 and 1/51 control male and control female mice)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z595<>0,VLOOKUP(Z595,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Eyes histopathology",{"$f":"IF(Z596<>0,VLOOKUP(Z596,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Eyes: Histopathology, non-neoplastic findings: no treatment-related findings (spontaneous lesions such as retinal atrophy, retinal disruption, corneal ulceration, focal mineralisation of cornea/iris, keratitis, thickening of the iris and inflammation of the anterior chamber; lenticular degeneration more frenquently observed, considered as common background change)\nhistopathology, neoplastic findings: no neoplastic changes observed\nHarderian gland: histopathology, non-neoplastic findings: mononuclear cell foci and foci areas of atrophy, age related; instances of epithelial hyperplasia and generalised distention of the glands, not treatment-related\nhistopathology, neoplastic findings: Harderian gland adenomas in 4/51 males and 4/51 females at 0 and 5000 ppm each; carcinoma in 2/51 control females, not treatment-related\nLacrimal gland: histopathology, non-neoplastic findings: mononuclear cell foci and isolated instances of periductal/interstitial fibrosis, not treatment-related\n",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z596<>0,VLOOKUP(Z596,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Bone marrow histopathology",{"$f":"IF(Z597<>0,VLOOKUP(Z597,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (adipose infiltration observed in most animals of both sexes, no dose relation on frequency and severity; myeloid hyperplasia in a few mice of either sex, no treatment-related group distribution; fibroplasia, angiectasis and foci/areas of necrosis occasionally observed)\nhistopathology, neoplastic findings: no treatment-related findings (myeloid leukaemia in 1/51 males at 500 ppm and in 1/51 females at 1500 ppm, lipoma in the marrow cavity of the sternum in 1/51 females at 5000 ppm)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z597<>0,VLOOKUP(Z597,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Heart histopathology",{"$f":"IF(Z598<>0,VLOOKUP(Z598,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (myocarditis/fibrosis and vacuolisation of myocardial fibres commonly observed in males of all groups, no dose-related incidence or serverity; atrial thrombus formation, distention/thinning of the ventricular wall, vasculitis, focal ossification, focal mineralisation, atrial inflammation or fibrosis, atrial distention, pericardial inflammatory or fibrous thickening, focal necrosis/haemorrhage, mononuclear cell foci occasionally observed)\nhistopathology, neoplastic findings: no primary neoplastic lesions observed",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z598<>0,VLOOKUP(Z598,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z599<>0,VLOOKUP(Z599,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Intestinal tract: histopathology, non-neoplastic findings: no treatment-related findings (isolated instances of mucosal hypertrophy, mucosal hyperplasia, focal mucosal ulceration, submucosal oedema and inflammatory cell infiltration at various levels)\n histopathology, neoplastic findings: no treatment-related findings (benign adenoma in 1/51 control females)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z599<>0,VLOOKUP(Z599,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z600<>0,VLOOKUP(Z600,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (groups of basophilic tubules, mononuclear cell foci, distention of isolated tubules or glomerula spaces frequently observed in both sexes among all groups; chronic nephropathy occasionally observed, tubular vacuolation or dilatation, focal mineralisation, vasculitis, cortical scarring, hydronephrosis, papillary necrosis, focal haemorrhage or necrosis, hyperplasia of the papillary/pelvic epithelium, amyloid deposition and pigment accumulation, no dose relation regarding incidence or severity)\nhistopathology, neoplastic findings: no treatment-related findings (haemangiosarcoma in 1/51 females at 1500 ppm)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z600<>0,VLOOKUP(Z600,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Urinary bladder histopathology",{"$f":"IF(Z601<>0,VLOOKUP(Z601,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (epithelial/subepithelial or peripheral inflammatory cell infiltrates, epithelial ulceration, subepithelial haemorrhage, acute inflammatory cells in the lumen and amorphous contents occasionally observed)\nhistopathology, neoplastic findings: no neoplasms observed",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z601<>0,VLOOKUP(Z601,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Liver histopathology",{"$f":"IF(Z602<>0,VLOOKUP(Z602,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (centrilobular hepatocyte vacuolation, periportal hepatocyte vacuolation, focal or centrilobular hepatocyte necrosis, areas or nodules of necrosis, lobular necrosis, thrombus formation, non-neoplastic cyst formation, granulocytic or myelopoietic foci, scattered lipid vacuolation of hepatocytes, higher grades of severity of pigment accumulation, focal hepatocyte hypertrophy, and proliferation of sinusoid lining cells occasionally observed; foci of altered hepatocytes in 4/51, 2/51, 2/51 and 1/51 males at 0, 500, 1500 and 5000 ppm and in 1/51 females at 5000 ppm)\nhistopathology, neoplastic findings: no treatment-related findings (total hepatocellular tumours in 7/51, 12/51, 11/51 and 6/51 males at 0, 500, 1500 and 5000 ppm and in 1/51 females at 500 ppm; adenoma in 2/12 interim dead males at 1500 ppm, carcinoma in 1/16 interim dead males at 5000 ppm; adenoma in 1/39, 1/41, 2/39 and 2/35 terminal kill males at 0, 500, 1500 and 5000 ppm, carcinoma in 6/39, 11/41, 7/39 and 3/35 terminal kill males at 0, 500, 1500 and 5000 ppm and in 1/38 terminal kill females at 500 ppm)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z602<>0,VLOOKUP(Z602,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Gall bladder histopathology",{"$f":"IF(Z603<>0,VLOOKUP(Z603,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (focal epithelial cell hyperplasia, amorphous bodies in the lumen, vasculitis, cystic distention, focal necrosis, thickening of the wall and epithelial ulceration occasionally observed)\nhistopathology, neoplastic findings: no neoplasms observed",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z603<>0,VLOOKUP(Z603,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z604<>0,VLOOKUP(Z604,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (myelopoiesis, lymphoid hyperplasia, histiocytosis and angiectasis occasionally observed, age-related)\nhistopathology, neoplastic findings: no treatment-related findings (malignant lymphoma in 0/51, 1/51, 2/51 and 5/51 males and 11/51, 8/51, 10/51 and 11/51 females at 0, 500, 1500 and 5000 ppm; histiocystic sarcoma in a few females observed)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z604<>0,VLOOKUP(Z604,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Thymus histopathology",{"$f":"IF(Z605<>0,VLOOKUP(Z605,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (lymphoid hyperplasia, atrophy and peripheral inflammatory cells occasionally observed upon all groups, more prevalent in females, age-related ;one incidence of histiocytic sarcoma in 1/7 examined females at 1500 ppm at terminal kill)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z605<>0,VLOOKUP(Z605,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Lung histopathology",{"$f":"IF(Z606<>0,VLOOKUP(Z606,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (accumulation of perivascular/peribronchiolar lymphocytes, accumulation of alveolar macrophages, associated with pulmonary neoplasia, focal pneumonitis, focal fibrosis, hyperplasia of the bronchioloar epithelium, focal pleural thickening, foci/area of haemorrhage, granulomatous foci, thrombus formation, perivascular acute inflammatory cells occasionally observed; cuboidal cell metaplasia of the alveolar in few animals, pre-neoplastic change)\nhistopathology, neoplastic findings: no treatment-related findings (adenoma in 2/12 interim dead males at 1500 ppm, in 9/39, 7/41, 7/39 and 4/35 terminal kill males  and 2/37, 4/38, 2/38 and 2/40 terminal kill females at 0, 500, 1500 and 5000 ppm; adenocarcinoma in 2/12, 1/10, 2/12 and 2/16 interim dead males and in 3/39, 4/41, 5/39 and 9/35 terminal kill males and in 5/37, 2/38, 2/38 and 3/40 terminal kill females at 0, 500, 1500 and 5000 ppm)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z606<>0,VLOOKUP(Z606,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Oesophagus histopathology",{"$f":"IF(Z607<>0,VLOOKUP(Z607,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (background inflammatory lesions in a few animals)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z607<>0,VLOOKUP(Z607,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","[Not in list]",{"$f":"IF(Z608<>0,VLOOKUP(Z608,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Nasal cavities: no treatment-related findings (focal epithelial hyperplasia in both sexes frequently observed, epithelial inflammation, exudate overlaying the epithelium, dilatation of subepithelial glands, focal epithelial ulceration, prominent fibroplasia and resorption of bone occasionally observed; dental dysplasia and dental erosion/abscess formation in a few control and treated males)\nPharynx: no treatment-related findings (mononuclear cell infiltrates, exudate overlaying the epithelium, focal epithelial hyperplasia in a few animals, extensive inflammation and abscess formation in the supra-pharyngeal tissues in one control mouse)\nLarynx: no treatment-related findings (dilatation of subepithelial glands and epithelial/subepithelial inflammatory cell infiltrates, incidental)\nTrachea: no treatment-related findings (dilatation of subepithelial glands frequently observed in both sexes, isolated instances of inflammation)\nTongue: no treatment-related findings (focal inflammation, fibrosis, ulceration, vasculitis and abscess formation occasionally observed)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z608<>0,VLOOKUP(Z608,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z609<>0,VLOOKUP(Z609,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (exocrine atrophy, exocrine cell hyperplasia, areas of necrosis, interstitial fibrosis, prominent lymphoid foci occasionally seen; islet cell hyperplasia in a few mice)\nhistopathology, neoplastic findings: no treatment-related findings (islet cell adenocarcinoma in 1/51 control females)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z609<>0,VLOOKUP(Z609,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Peripheral nerve histopathology",{"$f":"IF(Z610<>0,VLOOKUP(Z610,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (fibre degeneration in several control and treated females; isolated instances of focal mineralisation and neuritis)\nhistopathology, neoplastic findings: no neoplasms observed",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z610<>0,VLOOKUP(Z610,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z611<>0,VLOOKUP(Z611,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Histopathology, non-neoplastic findings: no treatment-related findings (isolated instances of focal hyperplasia, developmental cysts or mononuclear cell foci, no toxicological significance)\nhistopathology, neoplastic findings: no treatment-related findings (three adenomas in females, no dose relation)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z611<>0,VLOOKUP(Z611,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Accessory sex organs histopathology",{"$f":"IF(Z612<>0,VLOOKUP(Z612,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Preputial gland: no treatment-related findings (inflammatory and atrophic lesions, age-related; abscess formation occasionally observed, one instance of keratin cyst formation)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z612<>0,VLOOKUP(Z612,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z613<>0,VLOOKUP(Z613,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (secretory depletion of the submandibular gland was frequently observed and more prevalent in females, no treatment related distribution; isolated instances if lymphocyte infiltration, distention of ducts, atropy, abscess formation, hypertrophy of mucous acini and peripheral inflammation)\nhistopathology, neoplastic findings: no neoplastic lesions",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z613<>0,VLOOKUP(Z613,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Skin histopathology",{"$f":"IF(Z614<>0,VLOOKUP(Z614,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (several spontaneous lesions: epidermal ulceration, scab formation, inflammatory lesions, abscess formation, focal acanthosis, focal mineralisation, focal dermal thickening, focal necrosis occasionally observed; few instances of ectasia, atrophy or inflammation of unidentified subcutaneous glandular tissue)\nhistopathology, neoplastic findings: no treatment-related findings (dermal/subcutaneous fibrosarcoma in 6 males among all treatment-groups; haemangiosarcoma in 1/51 females at 500 ppm)\nTail: no treaetment-related findings (subcutaneous keratin cyst in a few mice of either sex; isolated instances of focal hyperostosis of bone, focal acanthosis and hyperkeratosis, focal inflammation)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z614<>0,VLOOKUP(Z614,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Skeletal muscle histopathology",{"$f":"IF(Z615<>0,VLOOKUP(Z615,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (isolated instances of mononuclear cell foci, vasculitis and focal mineralisation, spontaneous changes)\nhistopathology, neoplastic findings: no neoplastic changes",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z615<>0,VLOOKUP(Z615,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z616<>0,VLOOKUP(Z616,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (higher grades of severity of extramedullary haematopoesis frequently observed in mice of either sex; lymphoid hyperplsaia, atrophy of lymphoid tissue and of the red pulp, background changes)\nhistopathology, neoplastic findings: no treatment-related findings (haemangioma in 1/51 control males, haemangiosarcoma in 1/51 and 1/51 females at 0 and 5000 ppm)",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z616<>0,VLOOKUP(Z616,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",20,null,"OECD 451 (1981), JMAFF 12 Nohsan No 8147 (2005), US EPA OPPTS 870.4200 (1996)","DAR",null,2009,"Mouse","Crl: CD-1 (ICR) BR",51,"M + F",95.7,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",18,"Months","Adult","M + F",">5000","Organ histopathology","Stomach histopathology",{"$f":"IF(Z617<>0,VLOOKUP(Z617,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (mucosal hyperplasia commonly observed, age-related; acanthosis and hypokeratosis of the forestomach frequently observed in both sexes, no toxicological significance, subepithelial and mucosal inflammation, epithelial ulceration, mineralisation of the muscularis, diverticulum formation and focal mucosal necrosis occasionally observed)\nhistopathology, neoplastic findings: no gastric neoplasia observed",null,"No effect",5000,">5000","ppm",{"$f":"IF(Z617<>0,VLOOKUP(Z617,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","In life observation","Mortality",{"$f":"IF(Z618<>0,VLOOKUP(Z618,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No significant differences between groups. Cumulative mortality was 24/50, 16/50, 23/50 and 21/50 in males and 18/50, 14/50, 10/50 and 15/50 in females at 0, 1600, 8000 and 40000 ppm",null,"No effect",40000,">40000","ppm",{"$f":"IF(Z618<>0,VLOOKUP(Z618,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","In life observation","Clinical signs",{"$f":"IF(Z619<>0,VLOOKUP(Z619,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related findings (increased loss of tactile hair loss in males at 40000 ppm and in females at 1600 ppm, masses in the anus (associated with neoplastic changes) and pale coloured skin in males at 40000 ppm, hairloss in males at 8000 ppm, loose stool in both sexes from week 20/21 onwards at 40000 ppm)",null,"No effect",40000,">40000","ppm",{"$f":"IF(Z619<>0,VLOOKUP(Z619,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",8000,"In life observation","Body weight",{"$f":"IF(Z620<>0,VLOOKUP(Z620,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Occasional decreases among groups at 8000 and 40000 ppm throughout the treatment in both sexes, reduction in females at 8000 during weeks 6, 9 and 24 were considered to be treatment-related, body weight gain was comparable to those of controls at study termination",null,"Decrease",1600,8000,"ppm",{"$f":"IF(Z620<>0,VLOOKUP(Z620,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",8000,"In life observation","Food consumption",{"$f":"IF(Z621<>0,VLOOKUP(Z621,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: statistically significantly depressed (-6% overall) in males at 40000 ppm at weeks 1 and 68 and in females (-7% overall) at 40000 ppm at weeks 1, 4, 8, 12, 20, 28, 40, 48 and 68, treatment-related\nFood efficiency: decreased in both sexes at 40000 ppm (-9% and -24% in males and femeles, respectively) and in females at 8000 ppm  throughout the study period (-16% overall), treatment-related",null,"Decrease",1600,8000,"ppm",{"$f":"IF(Z621<>0,VLOOKUP(Z621,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M",8000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z622<>0,VLOOKUP(Z622,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology (differential white blood cell count only): no treatment-related findings, increased lymphocytes in males and decreased neutrophils in males killed in extremis at 40000 ppm and increased lymphocytes in females at week 78, findings were attributed to skin lesions of high grade in moribund animals of the control group, which had high values of leukocytes and reduced values of lymphocytes, considered to be of sporadic nature\nClinical Chemistry: not performed\nUrinalysis: decreased pH in males at ≥ 8000 ppm, treatment-related but considered to be without toxicological significance as no histopathological findings were seen",null,"Change",1600,8000,"ppm",{"$f":"IF(Z622<>0,VLOOKUP(Z622,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","Organ Weight","Adrenals weight",{"$f":"IF(Z623<>0,VLOOKUP(Z623,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z623<>0,VLOOKUP(Z623,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","Organ Weight","Brain weight",{"$f":"IF(Z624<>0,VLOOKUP(Z624,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z624<>0,VLOOKUP(Z624,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","Organ Weight","Liver weight",{"$f":"IF(Z625<>0,VLOOKUP(Z625,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z625<>0,VLOOKUP(Z625,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M",">40000","Organ Weight","Testis weight",{"$f":"IF(Z626<>0,VLOOKUP(Z626,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z626<>0,VLOOKUP(Z626,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",40000,"Organ Weight","[Not in list]",{"$f":"IF(Z627<>0,VLOOKUP(Z627,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Caecum: abs+rel weight stat. signif. increased in both sexes at 40000 ppm, treatment-related, no macroscopic lesions at histopathology but occurence of anal prolapse as a change related to loose stool",null,"Increase",8000,40000,"ppm",{"$f":"IF(Z627<>0,VLOOKUP(Z627,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",40000,"Organ Weight","Kidney weight",{"$f":"IF(Z628<>0,VLOOKUP(Z628,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Rel weight stat. sign. increased in females at 40000 ppm, no treatment-relation as histopathology revealed no abnormalities",null,"Increase",8000,40000,"ppm",{"$f":"IF(Z628<>0,VLOOKUP(Z628,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","F",">40000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z629<>0,VLOOKUP(Z629,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z629<>0,VLOOKUP(Z629,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M",">40000","Organ histopathology","Coagulating gland histopathology",{"$f":"IF(Z630<>0,VLOOKUP(Z630,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z630<>0,VLOOKUP(Z630,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M",">40000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z631<>0,VLOOKUP(Z631,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z631<>0,VLOOKUP(Z631,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z632<>0,VLOOKUP(Z632,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross pathology: reduced incidence in swelling of spleen in males at 1600 ppm and in females at 1600 and 8000 ppm, no dose relation\nHistopathology, non-neoplastic findings: no treatment-related findings (decreased incidences of extramedullary haematopoesis in  both sexes at 8000 ppm; amyloid deposition in females at ≥ 1600 ppm, attributed to decreased occurence of skin lesions in the treated groups)\nHistopathology, neoplastic findings: no treatment-related findings",null,"No effect",40000,">40000","ppm",{"$f":"IF(Z632<>0,VLOOKUP(Z632,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","Organ histopathology","Liver histopathology",{"$f":"IF(Z633<>0,VLOOKUP(Z633,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: no treatment-related findings (decreased incidences of microgranuloma in females of groups found dead/killed in extremis and at terminal kill at 40000 ppm and decreased incidences of amyloid deposition in males at 40000 ppm and in females at ≥ 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups)\nHistopathology, neoplastic findings: no treatment-related findings",null,"No effect",40000,">40000","ppm",{"$f":"IF(Z633<>0,VLOOKUP(Z633,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z634<>0,VLOOKUP(Z634,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross pathology: reduced incidence of pale color and corse surface in females at 8000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings (reduced incidences of cortical cysts in both sexes at 40000 ppm; reduced incidences of glomerula amyoidosis in females at 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups)\nHistopathology, neoplastic findings: no treatment-related findings",null,"No effect",40000,">40000","ppm",{"$f":"IF(Z634<>0,VLOOKUP(Z634,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","Organ histopathology","Bone marrow histopathology",{"$f":"IF(Z635<>0,VLOOKUP(Z635,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology, non-neoplastic findings: femur: decreased incidences of haematopoesis in females at ≥ 1600 ppm, not treatment-related; sternum and vertebra:  decreased incidences of haematopoesis in females at ≥ 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups\nHistopathology, neoplastic findings: haematopoetic and lymphatic system, malignant lymphoma in 2/29 terminal kill males at 40000 ppm and in 4/32, 0/36, 5/40 and 3/35 terminal kill females at 0, 1600, 8000 and 40000 ppm, considered to be incidental",null,"No effect",40000,">40000","ppm",{"$f":"IF(Z635<>0,VLOOKUP(Z635,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z636<>0,VLOOKUP(Z636,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross pathology: swelling of cervical lymph nodes, reduced incidence in females at 8000 ppm, increased incidence swelling of mesenteric lymph nodes in males at  40000ppm (0/50 in control, 6/50 at 40000 ppm with 5/6 in animals found dead/killed in extrmis), increased incidence of swollen lymph nodes in females found dead/killed in extremis at ≥ 8000 ppm\nHistopathology, non-neoplastic findings: no treatment-related findings (decreased incidence of plasma cell hyperplasia in females at ≥ 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups; decreased incidences of myeloid cell aggregation in males at 1600 ppm)\nHistopathology, neoplastic findings: haematopoetic and lymphatic system, malignant lymphoma in 2/29 terminal kill males at 40000 ppm and in 4/32, 0/36, 5/40 and 3/35 terminal kill females at 0, 1600, 8000 and 40000 ppm, considered to be incidental",null,"No effect",40000,">40000","ppm",{"$f":"IF(Z636<>0,VLOOKUP(Z636,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",40000,"Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z637<>0,VLOOKUP(Z637,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross pathology: Caecum distention in males (28%) and females (36%) at 40000 ppm (14/50 males and 18/50 females at 40000 ppm, findings predominantly observed in terminal kill animals (11/29 males, 16/35 females), no animals of other groups, treatment-related); anal prolaps in the anus of 5/50 males at 40000 ppm, no findings in any other group, related to findings of loose stool; reduced incidence of amyloid deposition in the small intestine of females at 1600 and 8000 ppm, not treatment-related; small intestine: reduced incidence of amyloid deposition in females at 1600 and 8000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings\nHistopathology, neoplastic findings: no treatment-related findings",null,"Change",8000,40000,"ppm",{"$f":"IF(Z637<>0,VLOOKUP(Z637,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z638<>0,VLOOKUP(Z638,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology, non-neoplastic findings: no treatment-related findings (reduced incidences of amyloid deposition in thyroid and parathyroid at 1600 and 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups)\nHistopathology, neoplastic findings: no treatment-related findings",null,"No effect",40000,">40000","ppm",{"$f":"IF(Z638<>0,VLOOKUP(Z638,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","Organ histopathology","Skin histopathology",{"$f":"IF(Z639<>0,VLOOKUP(Z639,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross pathology: no treatment-related findings (loss of hair increased in males at 8000 ppm and decreased in females at 40000 ppm, reduced incidences of wounds in males at 40000 ppm and reduced incidences of ulcer/erosion in females at ≥ 8000 ppm, reduced incidences of swelling in males at 1600 and 40000 ppm, no dose relation)\nHistopathology, non-neoplastic findings: no treatment-related findings\nHistopathology, neoplastic findings: no treatment-related findings",null,"No effect",40000,">40000","ppm",{"$f":"IF(Z639<>0,VLOOKUP(Z639,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","Organ histopathology","Lung histopathology",{"$f":"IF(Z640<>0,VLOOKUP(Z640,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross pathology: masses in 9/50, 14/50, 17/50 and 15/50 males and in 10/50, 8/50, 20/50 and 11/50 females at 0, 1600, 8000 and 40000 ppm, findings predominantly observed at terminal kill, no dose relation\nHistopathology, non-neoplastic findings: no treatment-related findings (increased alveolar epithelial cell hyperplasia in males at 1600 ppm, no dose-response relationship)\nHistopathology, neoplastic findings: no treatment-related findings",null,"No effect",40000,">40000","ppm",{"$f":"IF(Z640<>0,VLOOKUP(Z640,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","F",">40000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z641<>0,VLOOKUP(Z641,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gross pathology: reduced incidence of cysts in females (found dead/killed in extremis and at terminal kill) at 40000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings (reduced incidences of amyloid deposition at 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups)\nHistopathology, neoplastic findings: no treatment-related findings",null,"No effect",40000,">40000","ppm",{"$f":"IF(Z641<>0,VLOOKUP(Z641,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","F",">40000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z642<>0,VLOOKUP(Z642,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z642<>0,VLOOKUP(Z642,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","F",">40000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z643<>0,VLOOKUP(Z643,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z643<>0,VLOOKUP(Z643,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M",">40000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z644<>0,VLOOKUP(Z644,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z644<>0,VLOOKUP(Z644,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M",">40000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z645<>0,VLOOKUP(Z645,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z645<>0,VLOOKUP(Z645,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M",">40000","Organ histopathology","Testis histopathology",{"$f":"IF(Z646<>0,VLOOKUP(Z646,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gross pathology: reduced incidence of atrophy at 40000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings\nHistopathology, neoplastic findings: no treatment-related findings",null,"No effect",40000,">40000","ppm",{"$f":"IF(Z646<>0,VLOOKUP(Z646,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","F",">40000","Organ histopathology","Vagina histopathology",{"$f":"IF(Z647<>0,VLOOKUP(Z647,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z647<>0,VLOOKUP(Z647,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z648<>0,VLOOKUP(Z648,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z648<>0,VLOOKUP(Z648,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z649<>0,VLOOKUP(Z649,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",40000,">40000","ppm",{"$f":"IF(Z649<>0,VLOOKUP(Z649,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Carcinogenicity",21,null,"US EPA 82-1 (1984)","DAR",null,1997,"Mouse","ICR (Crj:CD-1)",50,"M + F","97.56 and 94.61","Oral","Feed","1600; 8000; 40000",1600,40000,"ppm",18,"Months","Adult","M + F",">40000","Organ histopathology","Eyes histopathology",{"$f":"IF(Z650<>0,VLOOKUP(Z650,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross pathology: reduced incidence of opacity in females at 8000 and 40000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings\nHistopathology, neoplastic findings: no treatment-related findings",null,"No effect",40000,">40000","ppm",{"$f":"IF(Z650<>0,VLOOKUP(Z650,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","In life observation","Mortality",{"$f":"IF(Z651<>0,VLOOKUP(Z651,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related deaths; 1/28 P0 males at 1500 ppm was killed for humane reasons, 1/28 P0 females at 15000 ppm was found dead, 1/28 P0 females at 5000 ppm was killed in extremis; 1/24 control F1 females was killed for humane reasons",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z651<>0,VLOOKUP(Z651,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","In life observation","Clinical signs",{"$f":"IF(Z652<>0,VLOOKUP(Z652,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related findings (findings considered unrelated to treatment: incidences of red/brown staining of the external body surface, generalised fur loss, scab formation and red/brown staining on cage tray-liners in treated and control F0 + F1 animals, abrasion to the dorsal/cranial regions in males at 0 and 15000 ppm, physical injury to the tail apex in 1/28 females at 1500 ppm, red swollen ears in 1/28 and 1/28 females at 5000 and 15000 ppm; red stained urine, exophthalmia and piloerection each in one high dose group male or female, considered to be incidental; presence of mass in single animals, age-related; blood around the vagina in 1/28 females each at 0 and 5000 ppm; one control female showed lethargy, piloerection, hunched posture and staining around ano-genital region and was killed in extremis, incidence of protruding sternums in F1 females of control and treaetment groups, related to lactation phase)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z652<>0,VLOOKUP(Z652,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",15000,"In life observation","Body weight",{"$f":"IF(Z653<>0,VLOOKUP(Z653,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No adverse effect of bodyweight change was evident for treated animals in comparison to controls throughout the treatment period for both the F0 and F1 generations except for post-partum females treated with 15000 ppm. During the final week of lactation, both the F0 and F1 generations showed statistically significant less bodyweight loss in comparison to controls.",null,"Decrease",15000,">15000","ppm",{"$f":"IF(Z653<>0,VLOOKUP(Z653,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","In life observation","Food consumption",{"$f":"IF(Z654<>0,VLOOKUP(Z654,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z654<>0,VLOOKUP(Z654,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",">15000","Reproductive","Estrus cyclicity",{"$f":"IF(Z655<>0,VLOOKUP(Z655,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Higher number of irregular cycles in F1 females at ≥ 5000 ppm, not reflected in pre-coital intervals, considered to be incidental and to be of no toxicological significance",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z655<>0,VLOOKUP(Z655,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Reproductive","Fertility (mammals)",{"$f":"IF(Z656<>0,VLOOKUP(Z656,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No treatment-related findings (the following females failed to achieve pregnancy: 1/28 F0 control, 1/28 F0 1500 ppm, 1/24 and 1/24 F1 control and F1 at 1500 ppm, 1/24 F1 at 15000 ppm, no dose relation, normal variation)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z656<>0,VLOOKUP(Z656,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",">15000","Reproductive","Gestation length",{"$f":"IF(Z657<>0,VLOOKUP(Z657,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z657<>0,VLOOKUP(Z657,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Reproductive","Time to mating",{"$f":"IF(Z658<>0,VLOOKUP(Z658,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z658<>0,VLOOKUP(Z658,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",">15000","Reproductive","Reproduction",{"$f":"IF(Z659<>0,VLOOKUP(Z659,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"From the F0 generation, 26/28, 27/28, 27/28 and 26/28 females and from the F1 generation 22/24, 23/24, 24/24 and 23/24 females successfully gave birth at 0, 1500, 5000 and 15000 ppm",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z659<>0,VLOOKUP(Z659,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",">15000","Reproductive","Number of ovarian follicles",{"$f":"IF(Z660<>0,VLOOKUP(Z660,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"}," increased number of large follicles in F1 females at 15000 ppm, in the absence of supporting data from uterine examination and any differences in the number of offspring the increase was indicative of normal biological variation, toxicologically not important",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z660<>0,VLOOKUP(Z660,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Offspring (F1+F2)","F",">15000","Reproductive","Litter size",{"$f":"IF(Z661<>0,VLOOKUP(Z661,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z661<>0,VLOOKUP(Z661,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",">15000","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z662<>0,VLOOKUP(Z662,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z662<>0,VLOOKUP(Z662,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",">15000","Reproductive","Number of live births",{"$f":"IF(Z663<>0,VLOOKUP(Z663,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z663<>0,VLOOKUP(Z663,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",">15000","Reproductive","Post implantation loss",{"$f":"IF(Z664<>0,VLOOKUP(Z664,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z664<>0,VLOOKUP(Z664,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",">15000","Reproductive","Pre implantation loss",{"$f":"IF(Z665<>0,VLOOKUP(Z665,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z665<>0,VLOOKUP(Z665,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M",">15000","Organ Weight","Epididymis weight",{"$f":"IF(Z666<>0,VLOOKUP(Z666,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z666<>0,VLOOKUP(Z666,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",15000,"Organ Weight","Liver weight",{"$f":"IF(Z667<>0,VLOOKUP(Z667,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute and relative weight increased in F0 and F1 females only at 15000 ppm without any histopathological findings. Therefore, increased organ weight is considered to be adaptive and non-adverse.",null,"Increase",5000,15000,"ppm",{"$f":"IF(Z667<>0,VLOOKUP(Z667,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Organ Weight","Kidney weight",{"$f":"IF(Z668<>0,VLOOKUP(Z668,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Abs.+rel. weight increased in F0 females at 15000 ppm, abs. weight increased in F1 females at 5000 ppm, no histopathological findings, considered to be adaptive in nature and non-adverse, no effect in males",null,"No effect",5000,15000,"ppm",{"$f":"IF(Z668<>0,VLOOKUP(Z668,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Organ Weight","Spleen weight",{"$f":"IF(Z669<>0,VLOOKUP(Z669,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Abs. weight reduced in F1 males at 15000 ppm, considered to be incidental",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z669<>0,VLOOKUP(Z669,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",">15000","Organ Weight","Ovary weight",{"$f":"IF(Z670<>0,VLOOKUP(Z670,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z670<>0,VLOOKUP(Z670,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M",">15000","Organ Weight","Prostate weight",{"$f":"IF(Z671<>0,VLOOKUP(Z671,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z671<>0,VLOOKUP(Z671,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M",">15000","Organ Weight","Seminal vesicles weight",{"$f":"IF(Z672<>0,VLOOKUP(Z672,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z672<>0,VLOOKUP(Z672,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M",">15000","Organ Weight","Testis weight",{"$f":"IF(Z673<>0,VLOOKUP(Z673,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z673<>0,VLOOKUP(Z673,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Organ Weight","Thyroid weight",{"$f":"IF(Z674<>0,VLOOKUP(Z674,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute thyroid weight was increased in F0 females at 5000 ppm. Relative thyroid weight was decreased in F0 males at 1500 and 5000 ppm. Both changes were not considered treatment-related and no dose-reponse-relationship was deduced.",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z674<>0,VLOOKUP(Z674,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",">15000","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z675<>0,VLOOKUP(Z675,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z675<>0,VLOOKUP(Z675,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Organ Weight","Adrenals weight",{"$f":"IF(Z676<>0,VLOOKUP(Z676,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z676<>0,VLOOKUP(Z676,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Organ Weight","Brain weight",{"$f":"IF(Z677<>0,VLOOKUP(Z677,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Abs. weight reduced in F1 males at 15000 ppm, considered to be incidental",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z677<>0,VLOOKUP(Z677,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Organ Weight","Pituitary weight",{"$f":"IF(Z678<>0,VLOOKUP(Z678,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z678<>0,VLOOKUP(Z678,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M",">15000","Organ Weight","Coagulating gland weight",{"$f":"IF(Z679<>0,VLOOKUP(Z679,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z679<>0,VLOOKUP(Z679,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",">15000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z680<>0,VLOOKUP(Z680,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z680<>0,VLOOKUP(Z680,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M",">15000","Organ histopathology","Coagulating gland histopathology",{"$f":"IF(Z681<>0,VLOOKUP(Z681,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z681<>0,VLOOKUP(Z681,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M",">15000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z682<>0,VLOOKUP(Z682,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gross necropsy: no treatment-related findings (low incidence of small epididymides in terminal kill animals of F1 generation)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z682<>0,VLOOKUP(Z682,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",">15000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z683<>0,VLOOKUP(Z683,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z683<>0,VLOOKUP(Z683,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M",">15000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z684<>0,VLOOKUP(Z684,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathology: no treatment-related findings (interstitial chronic inflammatory cell infiltrates, common background finding)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z684<>0,VLOOKUP(Z684,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M",">15000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z685<>0,VLOOKUP(Z685,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z685<>0,VLOOKUP(Z685,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M",">15000","Organ histopathology","Testis histopathology",{"$f":"IF(Z686<>0,VLOOKUP(Z686,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gross necropsy: no treatment-related findings (low incidence of small testes in terminal kill animals of the F0 and F1 generation)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z686<>0,VLOOKUP(Z686,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",">15000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z687<>0,VLOOKUP(Z687,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gross necropsy: no treatment-related findings (red fluid filled in the dead F0 female at 15000 ppm containing under-developed and late death fetuses, dead fetuses in 1/28 F0 females at 5000 ppm killed in extremis and dead fetuses and placentae in 1/24 F1 females of the control group killed in extremis; discolouration of the horn in terminal kill F0 females)\nHistopathology: no treatment-related findings (focal haemorrhage, foam cell accumulations and haemosiderin pigment deposition in the peripheral uterine tissue of pregnant rats, commonly encountered consequences of pregnancy and parturition)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z687<>0,VLOOKUP(Z687,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",">15000","Organ histopathology","Vagina histopathology",{"$f":"IF(Z688<>0,VLOOKUP(Z688,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gross necropsy: no treatment-related findings (blood around the vagina in 1/28 F0 females at 5000 ppm killed in extremis)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z688<>0,VLOOKUP(Z688,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","F",">15000","Organ histopathology","Vaginal smears",{"$f":"IF(Z689<>0,VLOOKUP(Z689,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z689<>0,VLOOKUP(Z689,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Organ histopathology","Liver histopathology",{"$f":"IF(Z690<>0,VLOOKUP(Z690,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: no treatment-related findings (pallor in the dead F0 female at 15000 ppm, mottled appearence in the interim dead F1 control female)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z690<>0,VLOOKUP(Z690,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z691<>0,VLOOKUP(Z691,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: no treatment-related findings (pallor in one F0 female found dead at 15000 ppm; dark kidneys in the interim dead control female of the F1 generation; mottled appearance, enlargement and increased renal pelvic cavitation in terminal kill animals of the F0 and F1 generation)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z691<>0,VLOOKUP(Z691,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z692<>0,VLOOKUP(Z692,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Histopathology: lower incidence of vacoulation in all F1 male treated rats, treatment relation cannot be excluded, non-adverse, abscence of a dose response suggests that the background range of the controls was high and caused the effect (not treatment-related findings: bilateral extensice necrosis of the renal cortex in the single dead F1 control female)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z692<>0,VLOOKUP(Z692,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z693<>0,VLOOKUP(Z693,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: No treatment-related findings.",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z693<>0,VLOOKUP(Z693,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Organ histopathology","Thymus histopathology",{"$f":"IF(Z694<>0,VLOOKUP(Z694,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: no treatment-related findings (low incidence of small thymus in terminal kill animals of the F0 generation)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z694<>0,VLOOKUP(Z694,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z695<>0,VLOOKUP(Z695,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: no treatment-related findings (enlarged and fluid-filled in the dead control female of the F1 generation)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z695<>0,VLOOKUP(Z695,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z696<>0,VLOOKUP(Z696,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z696<>0,VLOOKUP(Z696,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z697<>0,VLOOKUP(Z697,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Gross necropsy: no treatment-related findings (pallor in the dead F0 female at 15000 ppm, pallor of the medulla at low incidences in terminal kill animals of the F1 generation)",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z697<>0,VLOOKUP(Z697,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females; organ histopathology performed on 0 and 15000 ppm dose group only","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M",">15000","Reproductive","Sperm morphology",{"$f":"IF(Z698<>0,VLOOKUP(Z698,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z698<>0,VLOOKUP(Z698,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M",">15000","Reproductive","Sperm motility",{"$f":"IF(Z699<>0,VLOOKUP(Z699,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z699<>0,VLOOKUP(Z699,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M",">15000","Reproductive","Sperm numbers",{"$f":"IF(Z700<>0,VLOOKUP(Z700,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"decreased",null,"No effect",5000,15000,"ppm",{"$f":"IF(Z700<>0,VLOOKUP(Z700,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Adult (F0+F1)","M + F",">15000","Abnormalities","Genital abnormalities",{"$f":"IF(Z701<>0,VLOOKUP(Z701,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z701<>0,VLOOKUP(Z701,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Offspring (F1)","M",15000,"Reproductive","Age at balanopreputial separation",{"$f":"IF(Z702<>0,VLOOKUP(Z702,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Preputial separation (PPS) was statistically significantly delayed at 15000 ppm  (about 1000 mg/kg bw/d), which is similar to the limit dose of the test system. The age at PPS was increased to  45.9 ± 3.1 days versus 43.0 ± 2.3 days in control group with no further signs of developmental retardation, hence, a higher mean bodyweight was noted at attainment of PPS. The delay of PPS is of marginal magnitude and considered to be based on biological variation.",null,"Increase",5000,15000,"ppm",{"$f":"IF(Z702<>0,VLOOKUP(Z702,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Offspring (F1+F2)","F",">15000","Reproductive","Age at Vaginal opening",{"$f":"IF(Z703<>0,VLOOKUP(Z703,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z703<>0,VLOOKUP(Z703,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Offspring (F1+F2)","M + F",">15000","Abnormalities","Ano-Genital distance",{"$f":"IF(Z704<>0,VLOOKUP(Z704,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z704<>0,VLOOKUP(Z704,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Offspring (F1+F2)","M + F",">15000","Developmental","Litter/pup weight",{"$f":"IF(Z705<>0,VLOOKUP(Z705,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z705<>0,VLOOKUP(Z705,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Offspring (F1+F2)","M + F",">15000","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z706<>0,VLOOKUP(Z706,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Macroscopical abnormalities detected were considered to be normal low incidence findings in offspring of the age and strain",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z706<>0,VLOOKUP(Z706,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Offspring (F1+F2)","M + F",">15000","Developmental","Functional observation battery",{"$f":"IF(Z707<>0,VLOOKUP(Z707,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Surface righting reflex were unaffected and all offspring displayed normal auditory and visual responses. The mid-air righting for F2 litters in the low-, mid- and high dose group were significantly reduced compared to the control group in a non-dose responsive manner, and this finding does not have implication of substance related involvement.",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z707<>0,VLOOKUP(Z707,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Offspring (F1+F2)","M + F",">15000","Developmental","Pup development",{"$f":"IF(Z708<>0,VLOOKUP(Z708,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z708<>0,VLOOKUP(Z708,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Offspring (F1+F2)","M + F",">15000","Reproductive","Sex ratio",{"$f":"IF(Z709<>0,VLOOKUP(Z709,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z709<>0,VLOOKUP(Z709,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Offspring (F1+F2)","M + F",">15000","Reproductive","Litter viability",{"$f":"IF(Z710<>0,VLOOKUP(Z710,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z710<>0,VLOOKUP(Z710,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Offspring (F1+F2)","M + F",">15000","Organ Weight","Brain weight",{"$f":"IF(Z711<>0,VLOOKUP(Z711,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z711<>0,VLOOKUP(Z711,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Offspring (F1+F2)","M + F",">15000","Organ Weight","Spleen weight",{"$f":"IF(Z712<>0,VLOOKUP(Z712,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z712<>0,VLOOKUP(Z712,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Offspring (F1+F2)","M + F",">15000","Organ Weight","Thymus weight",{"$f":"IF(Z713<>0,VLOOKUP(Z713,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Abs. weight reduced in F2 males at 15000 ppm, considered to be without toxicological significance",null,"No effect",15000,">15000","ppm",{"$f":"IF(Z713<>0,VLOOKUP(Z713,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Offspring (F1+F2)","F",">15000","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z714<>0,VLOOKUP(Z714,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z714<>0,VLOOKUP(Z714,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",22,"2060-0013","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","DAR",null,2007,"Rat","Sprague-Dawley","F0 generation: 28\nF1 generation: 24","M + F",95.7,"Oral","Feed","1500; 5000; 15000",1500,15000,"ppm",10,"Weeks","Offspring (F1+F2)","M + F",">15000","In life observation","Clinical signs",{"$f":"IF(Z715<>0,VLOOKUP(Z715,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",15000,">15000","ppm",{"$f":"IF(Z715<>0,VLOOKUP(Z715,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M + F",">10000","In life observation","Mortality",{"$f":"IF(Z716<>0,VLOOKUP(Z716,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related findings ",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z716<>0,VLOOKUP(Z716,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M + F",">10000","In life observation","Clinical signs",{"$f":"IF(Z717<>0,VLOOKUP(Z717,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related findings. Annular constrictions in tails of the F0 and F1 males and females during pre-mating, almost all males and half of the females affected in all groups, considered to be incidental",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z717<>0,VLOOKUP(Z717,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",10000,"In life observation","Body weight",{"$f":"IF(Z718<>0,VLOOKUP(Z718,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased body weight in F1 males at 10000 ppm during week 1, decreased body weight gain in F1 males at 10000 ppm from weeks 2 to 8, treatment-related (there were no effects in females during maturation, gestation and lactation)",null,"Decrease",1000,10000,"ppm",{"$f":"IF(Z718<>0,VLOOKUP(Z718,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",10000,"In life observation","Food consumption",{"$f":"IF(Z719<>0,VLOOKUP(Z719,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: decreased in F1 males at 10000 ppm during pre-mating, treatment-related \nFood efficiency: increased in F1 males at 10000 ppm during weeks 5-8, treatment-related",null,"Decrease",10000,">10000","ppm",{"$f":"IF(Z719<>0,VLOOKUP(Z719,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","F",">10000","Reproductive","Estrus cyclicity",{"$f":"IF(Z720<>0,VLOOKUP(Z720,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Higher number of cycles in F0 females at 10000 ppm, lower cycle length in F1 females at 10000 ppm, marginal and inconsistent finding, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z720<>0,VLOOKUP(Z720,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M + F",">10000","Reproductive","Fertility (mammals)",{"$f":"IF(Z721<>0,VLOOKUP(Z721,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"There was no effect on pre-coital interval or the proportion of successful matings.",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z721<>0,VLOOKUP(Z721,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","F",">10000","Reproductive","Gestation length",{"$f":"IF(Z722<>0,VLOOKUP(Z722,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z722<>0,VLOOKUP(Z722,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","F",">10000","Reproductive","Time to mating",{"$f":"IF(Z723<>0,VLOOKUP(Z723,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z723<>0,VLOOKUP(Z723,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","F",">10000","Reproductive","Number of ovarian follicles",{"$f":"IF(Z724<>0,VLOOKUP(Z724,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z724<>0,VLOOKUP(Z724,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Offspring (F1+F2)","F",">10000","Reproductive","Litter size",{"$f":"IF(Z725<>0,VLOOKUP(Z725,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z725<>0,VLOOKUP(Z725,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Offspring (F1+F2)","M + F",">10000","Reproductive","Litter viability",{"$f":"IF(Z726<>0,VLOOKUP(Z726,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Slightly increased in F1 and F2 pups of all treated groups (16/23, 15/22, 19/22 and 18/24 in F1 and 16/22, 17/23, 20/21 and 21/25 in F2 litters with all pups born at 0, 1000, 3000 and 10000 ppm), not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z726<>0,VLOOKUP(Z726,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","F",">10000","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z727<>0,VLOOKUP(Z727,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z727<>0,VLOOKUP(Z727,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Offspring (F1+F2)","F",">10000","Reproductive","Number of live births",{"$f":"IF(Z728<>0,VLOOKUP(Z728,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Slightly higher in F1 and F2 pups in the test item treated groups, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z728<>0,VLOOKUP(Z728,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","F",">10000","Reproductive","Post implantation loss",{"$f":"IF(Z729<>0,VLOOKUP(Z729,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z729<>0,VLOOKUP(Z729,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","F",">10000","Organ Weight","Spleen weight",{"$f":"IF(Z730<>0,VLOOKUP(Z730,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z730<>0,VLOOKUP(Z730,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Organ Weight","Epididymis weight",{"$f":"IF(Z731<>0,VLOOKUP(Z731,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z731<>0,VLOOKUP(Z731,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M + F",">10000","Organ Weight","Liver weight",{"$f":"IF(Z732<>0,VLOOKUP(Z732,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Rel. weight increased in F0 males at 10000 ppm, abs. values comparable to control group,  considered to be incidental",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z732<>0,VLOOKUP(Z732,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","F",">10000","Organ Weight","Ovary weight",{"$f":"IF(Z733<>0,VLOOKUP(Z733,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z733<>0,VLOOKUP(Z733,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Organ Weight","Prostate weight",{"$f":"IF(Z734<>0,VLOOKUP(Z734,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z734<>0,VLOOKUP(Z734,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Organ Weight","Seminal vesicles weight",{"$f":"IF(Z735<>0,VLOOKUP(Z735,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z735<>0,VLOOKUP(Z735,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Organ Weight","Testis weight",{"$f":"IF(Z736<>0,VLOOKUP(Z736,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z736<>0,VLOOKUP(Z736,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","F",">10000","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z737<>0,VLOOKUP(Z737,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z737<>0,VLOOKUP(Z737,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M + F",">10000","Organ Weight","Adrenals weight",{"$f":"IF(Z738<>0,VLOOKUP(Z738,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z738<>0,VLOOKUP(Z738,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M + F",">10000","Organ Weight","Brain weight",{"$f":"IF(Z739<>0,VLOOKUP(Z739,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Rel. weight increased in F0 males at ≥ 3000 ppm, abs. weight comparable to control group, considered to be incidental",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z739<>0,VLOOKUP(Z739,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M + F",">10000","Organ Weight","Pituitary weight",{"$f":"IF(Z740<>0,VLOOKUP(Z740,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z740<>0,VLOOKUP(Z740,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M + F",">10000","Organ Weight","Kidney weight",{"$f":"IF(Z741<>0,VLOOKUP(Z741,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Rel. weight increased in F0 males at 10000 ppm, abs. values comparable to control group,  considered to be incidental",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z741<>0,VLOOKUP(Z741,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Reproductive","Sperm morphology",{"$f":"IF(Z742<>0,VLOOKUP(Z742,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z742<>0,VLOOKUP(Z742,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Reproductive","Sperm motility",{"$f":"IF(Z743<>0,VLOOKUP(Z743,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z743<>0,VLOOKUP(Z743,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Reproductive","Sperm numbers",{"$f":"IF(Z744<>0,VLOOKUP(Z744,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z744<>0,VLOOKUP(Z744,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Offspring (F1+F2)","M",">10000","Reproductive","Age at balanopreputial separation",{"$f":"IF(Z745<>0,VLOOKUP(Z745,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z745<>0,VLOOKUP(Z745,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Offspring (F1+F2)","F",">10000","Reproductive","Age at Vaginal opening",{"$f":"IF(Z746<>0,VLOOKUP(Z746,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z746<>0,VLOOKUP(Z746,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Organ Weight","Coagulating gland weight",{"$f":"IF(Z747<>0,VLOOKUP(Z747,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z747<>0,VLOOKUP(Z747,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Coagulating gland was weighed together with prostate and seminal vesicles. Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z748<>0,VLOOKUP(Z748,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z748<>0,VLOOKUP(Z748,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z749<>0,VLOOKUP(Z749,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z749<>0,VLOOKUP(Z749,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Liver histopathology",{"$f":"IF(Z750<>0,VLOOKUP(Z750,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z750<>0,VLOOKUP(Z750,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z751<>0,VLOOKUP(Z751,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z751<>0,VLOOKUP(Z751,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","F",">10000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z752<>0,VLOOKUP(Z752,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z752<>0,VLOOKUP(Z752,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Coagulating gland histopathology",{"$f":"IF(Z753<>0,VLOOKUP(Z753,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z753<>0,VLOOKUP(Z753,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z754<>0,VLOOKUP(Z754,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z754<>0,VLOOKUP(Z754,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","F",">10000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z755<>0,VLOOKUP(Z755,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z755<>0,VLOOKUP(Z755,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z756<>0,VLOOKUP(Z756,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z756<>0,VLOOKUP(Z756,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z757<>0,VLOOKUP(Z757,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z757<>0,VLOOKUP(Z757,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Testis histopathology",{"$f":"IF(Z758<>0,VLOOKUP(Z758,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z758<>0,VLOOKUP(Z758,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","F",">10000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z759<>0,VLOOKUP(Z759,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z759<>0,VLOOKUP(Z759,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","F",">10000","Organ histopathology","Vagina histopathology",{"$f":"IF(Z760<>0,VLOOKUP(Z760,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z760<>0,VLOOKUP(Z760,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Adult (F0+F1)","F",">10000","Organ histopathology","Vaginal smears",{"$f":"IF(Z761<>0,VLOOKUP(Z761,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z761<>0,VLOOKUP(Z761,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Offspring (F1+F2)","M + F",">10000","In life observation","Clinical signs",{"$f":"IF(Z762<>0,VLOOKUP(Z762,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z762<>0,VLOOKUP(Z762,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Offspring (F1+F2)","M + F",10000,"Developmental","Litter/pup weight",{"$f":"IF(Z763<>0,VLOOKUP(Z763,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Decreased in F1 pups of the 10000 ppm group from day 8 to day 29 in males and from day 5 to day 29 in females",null,"Decrease",3000,10000,"ppm",{"$f":"IF(Z763<>0,VLOOKUP(Z763,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Offspring (F1+F2)","M + F",">10000","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z764<>0,VLOOKUP(Z764,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Increased pelvis dilatation in F2A females at 10000 ppm (3/58, 1/59, 2/57 and 9/69 at 0, 1000, 3000 and 10000 ppm), common spontaneous change, considered to be incidental",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z764<>0,VLOOKUP(Z764,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Offspring (F1+F2)","M + F",">10000","Reproductive","Sex ratio",{"$f":"IF(Z765<>0,VLOOKUP(Z765,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z765<>0,VLOOKUP(Z765,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Offspring (F1+F2)","M + F",">10000","Organ Weight","Brain weight",{"$f":"IF(Z766<>0,VLOOKUP(Z766,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z766<>0,VLOOKUP(Z766,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Offspring (F1+F2)","M + F",">10000","Organ Weight","Spleen weight",{"$f":"IF(Z767<>0,VLOOKUP(Z767,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z767<>0,VLOOKUP(Z767,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",23,null,"OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","DAR",null,2000,"Rat","Alpk:APfSD (Wistar derived)",26,"M + F",97.6,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 (pre-mating)","Weeks","Offspring (F1+F2)","M + F",">10000","Organ Weight","Thymus weight",{"$f":"IF(Z768<>0,VLOOKUP(Z768,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z768<>0,VLOOKUP(Z768,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M + F",">30000","In life observation","Mortality",{"$f":"IF(Z769<>0,VLOOKUP(Z769,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z769<>0,VLOOKUP(Z769,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M + F",30000,"In life observation","Clinical signs",{"$f":"IF(Z770<>0,VLOOKUP(Z770,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Loose stool in F1 males during pre-mating and in F0 + F1 females during pre-mating and lactation at 30000 ppm, treatment-related (not treatment-related findings: hairloss in F0 males at ≥ 1200 ppm, considered to be incidental, malocclusion of the incisors, respiratory wheezing and red sebum in 1/24 F0 control males, 1/24 F0 control females and 1/24 F0 males at 6000 ppm and in 1/24 F1 males at 1200 ppm; distention of the abdomen in 1/24 F0 males at 6000 ppm)",null,"Increase",6000,30000,"ppm",{"$f":"IF(Z770<>0,VLOOKUP(Z770,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M",30000,"In life observation","Body weight",{"$f":"IF(Z771<>0,VLOOKUP(Z771,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased in F0 and F1 males at 30000 ppm from treatment week 1 until necropsy, treatment-related (no treatment-related findings in females, increased mean body weight in F1 females at 30000 ppm on lactation day 0)",null,"Decrease",30000,">30000","ppm",{"$f":"IF(Z771<>0,VLOOKUP(Z771,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M + F",">30000","In life observation","Food consumption",{"$f":"IF(Z772<>0,VLOOKUP(Z772,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related findings (increased in F0 males at 1200 ppm in week 13; reduced in F1 males at 30000 ppm in week 4; increased in F0 females at 30000 ppm in weeks 2-4 and reduced in the same group on lactation days 7-14, no clear treatment-relation; increased in F1 females at 1200 and 6000 ppm on laction days 14-21, no dose relation, considered to be incidental)",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z772<>0,VLOOKUP(Z772,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","F",">30000","Reproductive","Estrus cyclicity",{"$f":"IF(Z773<>0,VLOOKUP(Z773,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z773<>0,VLOOKUP(Z773,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M + F",30000,"Reproductive","Fertility (mammals)",{"$f":"IF(Z774<>0,VLOOKUP(Z774,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Fertility indices in F1 animals were 95.8% (23/24), 95.8% (23/24), 87.5% (21/24) and 79.2% (23/24) at 0, 1200, 6000 and 30000 ppm. Slight reduction at 30000 ppm was considered to be incidental because normal reproduction results were obtained after re-mating with untreated animals. Moreover, general systemic toxicity was observed at this dose level.",null,"No effect",6000,30000,"ppm",{"$f":"IF(Z774<>0,VLOOKUP(Z774,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","F",">30000","Reproductive","Gestation length",{"$f":"IF(Z775<>0,VLOOKUP(Z775,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z775<>0,VLOOKUP(Z775,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M + F",">30000","Abnormalities","Genital abnormalities",{"$f":"IF(Z776<>0,VLOOKUP(Z776,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z776<>0,VLOOKUP(Z776,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Offspring (F1+F2)","F",">30000","Reproductive","Litter size",{"$f":"IF(Z777<>0,VLOOKUP(Z777,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z777<>0,VLOOKUP(Z777,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Offspring (F1+F2)","F",">30000","Reproductive","Number of live births",{"$f":"IF(Z778<>0,VLOOKUP(Z778,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z778<>0,VLOOKUP(Z778,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","F",">30000","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z779<>0,VLOOKUP(Z779,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Increased in F1 females at 1200 ppm, not treatment-related, no dose relation",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z779<>0,VLOOKUP(Z779,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M + F",30000,"Organ Weight","Liver weight",{"$f":"IF(Z780<>0,VLOOKUP(Z780,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Rel. weight increased in F0+F1 males and females at 30000 ppm, treatment-related",null,"Increase",6000,30000,"ppm",{"$f":"IF(Z780<>0,VLOOKUP(Z780,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Organs weights were collected from each 10 randomly assigned males and females per group. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M + F",30000,"Organ Weight","Kidney weight",{"$f":"IF(Z781<>0,VLOOKUP(Z781,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Rel. weight increased in F0+F1 males and females at 30000 ppm, treatment-related (abs. weight increased in females at 6000 ppm, considered to be not treatment-related)",null,"Increase",6000,30000,"ppm",{"$f":"IF(Z781<>0,VLOOKUP(Z781,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Organs weights were collected from each 10 randomly assigned males and females per group. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F1)","M",30000,"Organ Weight","Prostate weight",{"$f":"IF(Z782<>0,VLOOKUP(Z782,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Statistically significant abs.+rel. prostate weight decreased in F1 males at 30000 ppm, treatment-related. No effects in F0 males.",null,"Decrease",6000,30000,"ppm",{"$f":"IF(Z782<>0,VLOOKUP(Z782,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Organs weights were collected from each 10 randomly assigned males and females per group. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","F",">30000","Organ Weight","Ovary weight",{"$f":"IF(Z783<>0,VLOOKUP(Z783,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Rel. weight decreased in F1 females at 1200 ppm, not treatment-related, considered to be incidental",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z783<>0,VLOOKUP(Z783,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Organs weights were collected from each 10 randomly assigned males and females per group. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M",">30000","Organ Weight","Epididymis weight",{"$f":"IF(Z784<>0,VLOOKUP(Z784,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z784<>0,VLOOKUP(Z784,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Organs weights were collected from each 10 randomly assigned males and females per group. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M",">30000","Organ Weight","Seminal vesicles weight",{"$f":"IF(Z785<>0,VLOOKUP(Z785,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z785<>0,VLOOKUP(Z785,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Organs weights were collected from each 10 randomly assigned males and females per group. Seminal vesicle weights were collected together with coagulating glands. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M",">30000","Organ Weight","Testis weight",{"$f":"IF(Z786<>0,VLOOKUP(Z786,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z786<>0,VLOOKUP(Z786,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Organs weights were collected from each 10 randomly assigned males and females per group. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","F",">30000","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z787<>0,VLOOKUP(Z787,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z787<>0,VLOOKUP(Z787,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Organs weights were collected from each 10 randomly assigned males and females per group. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M + F",">30000","Organ Weight","Adrenals weight",{"$f":"IF(Z788<>0,VLOOKUP(Z788,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z788<>0,VLOOKUP(Z788,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Organs weights were collected from each 10 randomly assigned males and females per group. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M",30000,"Organ Weight","Brain weight",{"$f":"IF(Z789<>0,VLOOKUP(Z789,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Rel. weight increased in F0 males at 30000 ppm, considered to be a change associated with low body weight in this group",null,"Increase",6000,30000,"ppm",{"$f":"IF(Z789<>0,VLOOKUP(Z789,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Organs weights were collected from each 10 randomly assigned males and females per group. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M + F",">30000","Organ Weight","Pituitary weight",{"$f":"IF(Z790<>0,VLOOKUP(Z790,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z790<>0,VLOOKUP(Z790,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Organs weights were collected from each 10 randomly assigned males and females per group. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M + F",">30000","Organ histopathology","Liver histopathology",{"$f":"IF(Z791<>0,VLOOKUP(Z791,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z791<>0,VLOOKUP(Z791,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M + F",">30000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z792<>0,VLOOKUP(Z792,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z792<>0,VLOOKUP(Z792,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed in control and high dose group only. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","F",">30000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z793<>0,VLOOKUP(Z793,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z793<>0,VLOOKUP(Z793,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M",">30000","Organ histopathology","Coagulating gland histopathology",{"$f":"IF(Z794<>0,VLOOKUP(Z794,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z794<>0,VLOOKUP(Z794,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed in control and high dose group only. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M",">30000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z795<>0,VLOOKUP(Z795,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z795<>0,VLOOKUP(Z795,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed in control and high dose group only. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","F",">30000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z796<>0,VLOOKUP(Z796,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z796<>0,VLOOKUP(Z796,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed in control and high dose group only. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","F",">30000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z797<>0,VLOOKUP(Z797,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z797<>0,VLOOKUP(Z797,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Histopathology was performed in control and high dose group only. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M",">30000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z798<>0,VLOOKUP(Z798,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z798<>0,VLOOKUP(Z798,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed in control and high dose group only. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M",">30000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z799<>0,VLOOKUP(Z799,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z799<>0,VLOOKUP(Z799,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed in control and high dose group only. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M",">30000","Organ histopathology","Testis histopathology",{"$f":"IF(Z800<>0,VLOOKUP(Z800,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z800<>0,VLOOKUP(Z800,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed in control and high dose group only. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","F",">30000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z801<>0,VLOOKUP(Z801,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z801<>0,VLOOKUP(Z801,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed in control and high dose group only. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","F",">30000","Organ histopathology","Vagina histopathology",{"$f":"IF(Z802<>0,VLOOKUP(Z802,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z802<>0,VLOOKUP(Z802,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed in control and high dose group only. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","F",">30000","Organ histopathology","Vaginal smears",{"$f":"IF(Z803<>0,VLOOKUP(Z803,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z803<>0,VLOOKUP(Z803,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","M + F",30000,"Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z804<>0,VLOOKUP(Z804,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Distention of the caecum in F0 and F1 males and females at 30000 ppm, treatment-related",null,"Change",6000,30000,"ppm",{"$f":"IF(Z804<>0,VLOOKUP(Z804,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)",null,">30000","Reproductive","Sperm morphology",{"$f":"IF(Z805<>0,VLOOKUP(Z805,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z805<>0,VLOOKUP(Z805,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)",null,">30000","Reproductive","Sperm motility",{"$f":"IF(Z806<>0,VLOOKUP(Z806,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z806<>0,VLOOKUP(Z806,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)",null,">30000","Reproductive","Sperm numbers",{"$f":"IF(Z807<>0,VLOOKUP(Z807,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z807<>0,VLOOKUP(Z807,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)",null,">30000","Reproductive","Dystocia",{"$f":"IF(Z808<>0,VLOOKUP(Z808,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z808<>0,VLOOKUP(Z808,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Offspring (F1+F2)",null,30000,"Developmental","Litter/pup weight",{"$f":"IF(Z809<>0,VLOOKUP(Z809,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Decreased in F1 and F2 pups of both sexes at 30000 ppm, treatment-related",null,"Decrease",6000,30000,"ppm",{"$f":"IF(Z809<>0,VLOOKUP(Z809,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Offspring (F1+F2)",null,30000,"Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z810<>0,VLOOKUP(Z810,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Distention of the caecum in F1 and F2 weeanlings at 30000 ppm, treatment-related",null,"Increase",6000,30000,"ppm",{"$f":"IF(Z810<>0,VLOOKUP(Z810,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Offspring (F1+F2)",null,">30000","Reproductive","Pup survival index",{"$f":"IF(Z811<>0,VLOOKUP(Z811,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z811<>0,VLOOKUP(Z811,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Offspring (F1+F2)",null,">30000","Reproductive","Sex ratio",{"$f":"IF(Z812<>0,VLOOKUP(Z812,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z812<>0,VLOOKUP(Z812,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Offspring (F1+F2)",null,">30000","Reproductive","Litter viability",{"$f":"IF(Z813<>0,VLOOKUP(Z813,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z813<>0,VLOOKUP(Z813,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",24,null,"OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","DAR",null,1997,"Rat","Sprague-Dawley",24,"M + F",94.61,"Oral","Feed","1200; 6000; 30000",1200,30000,"ppm","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Offspring (F1+F2)",null,">30000","In life observation","Clinical signs",{"$f":"IF(Z814<>0,VLOOKUP(Z814,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No effects in offspring observed",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z814<>0,VLOOKUP(Z814,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","M + F",">10000","In life observation","Mortality",{"$f":"IF(Z815<>0,VLOOKUP(Z815,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related deaths; 2/30 F0 females at 100 pppm (one distocia and one suppurative pneumonia), 1/30 F0 females at 10000 ppm (death not ascertained) and 1/30 F1 females at 100 ppm died",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z815<>0,VLOOKUP(Z815,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","M + F",">10000","In life observation","Clinical signs",{"$f":"IF(Z816<>0,VLOOKUP(Z816,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related findings (nasal discharge and snuffling in both sexes of all treatment and control groups; rare instances of soft stool, biting injuries, urine incontinence and alopecia in single F0 and/or F1 animals; circling disease in 2/30 F1 females at 10000 ppm)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z816<>0,VLOOKUP(Z816,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","M + F",">10000","In life observation","Body weight",{"$f":"IF(Z817<>0,VLOOKUP(Z817,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related findings (Initial bw of F0 males in treatment groups was higher than in control group, the trend continued during the entire treatment period but terminal body weight gain was comparable for all groups; increased bw in F1 males at 1000 ppm prior to and during treatment; decreased bw in F1 males at 10000 ppm at week 2 and 3; increased in females of all F1 treatment groups at selection and at 1000 and 10000 ppm up to week 10; increased in F1 females at 1000 ppm on Days 1 and 4 and in F1 females at 10000 ppm during the whole lactation period; reduced in F1 females at 1000 ppm during the lactation period)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z817<>0,VLOOKUP(Z817,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F1)","M + F",10000,"In life observation","Food consumption",{"$f":"IF(Z818<>0,VLOOKUP(Z818,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased in F1 males at ≥ 1000 ppm during weeks 0-2; increased in F1 females at 10000 ppm during gestation (not treatment-related findings: decreased in F0 females at 100 and 1000 ppm and in F1 females at 100 ppm during lactation; increased in F0 females at 10000 ppm during lactation)",null,"Change",10000,">10000","ppm",{"$f":"IF(Z818<>0,VLOOKUP(Z818,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","F",">10000","Reproductive","Time to mating",{"$f":"IF(Z819<>0,VLOOKUP(Z819,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z819<>0,VLOOKUP(Z819,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","M + F",">10000","Reproductive","Fertility (mammals)",{"$f":"IF(Z820<>0,VLOOKUP(Z820,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Increased male fertility index in F0 animals at 100 and 10000 ppm, no dose relation, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z820<>0,VLOOKUP(Z820,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","F",">10000","Reproductive","Gestation length",{"$f":"IF(Z821<>0,VLOOKUP(Z821,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z821<>0,VLOOKUP(Z821,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","F",">10000","Reproductive","Reproduction",{"$f":"IF(Z822<>0,VLOOKUP(Z822,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z822<>0,VLOOKUP(Z822,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Offspring (F1+F2)","F",">10000","Reproductive","Litter size",{"$f":"IF(Z823<>0,VLOOKUP(Z823,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Mean number of F1 and F2 pups delivered and mean litter sizes in the 100, 1000 and 10000 ppm groups were comparable to the controls.",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z823<>0,VLOOKUP(Z823,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Offspring (F1+F2)","F",">10000","Reproductive","Litter viability",{"$f":"IF(Z824<>0,VLOOKUP(Z824,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The number of live pups on day 1 was reduced in F1 pups at 100 ppm,reduced in F2 pups at 1000 ppm and increased in F2 pups at 10000 ppm, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z824<>0,VLOOKUP(Z824,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Offspring (F1+F2)","M + F",">10000","Developmental","Litter/pup weight",{"$f":"IF(Z825<>0,VLOOKUP(Z825,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No treatment-related findings (F1 pups: increased litter weight of combined sex and female pups on days 1 and 4, decreased litter weight of combined sex and males at 100 ppm on day 7, increased litter weight of combined sex and males at 10000 ppm on day 7, increased in complete litter and individual sex on day 21 at 1000 ppm, no dose-relation; F2 pups: increased litter weight of combined sex and female pups on days 1 and 4, increased combined sex litter weight at 100 and 1000 ppm and of males and females at 1000 ppm on day 4, decreased in males at 10000 ppm on days 14 and 21, no dose-relation)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z825<>0,VLOOKUP(Z825,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","F",">10000","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z826<>0,VLOOKUP(Z826,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Decreased no of implantations in F2 dams at 100 and 1000 ppm, considered to be incidental",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z826<>0,VLOOKUP(Z826,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Offspring (F1+F2)","F",">10000","Reproductive","Number of live births",{"$f":"IF(Z827<>0,VLOOKUP(Z827,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"live-birth index increased in F1 pups at 1000 ppm, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z827<>0,VLOOKUP(Z827,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Offspring (F1+F2)","M + F",1000,"Developmental","Pup development",{"$f":"IF(Z828<>0,VLOOKUP(Z828,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No treatment and dose related consistent effects on number of pups born (combined and individual sex) and their growth were observed.",null,"No effect",1000,10000,"ppm",{"$f":"IF(Z828<>0,VLOOKUP(Z828,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Offspring (F1+F2)","M + F",">10000","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z829<>0,VLOOKUP(Z829,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No treatment-related findings (a few incidences of minor developmental abnormalities like kinky tail, rudimentary tail in F1 pups and of kidney hydronephrosis and dilated pelvis in F1 and F2 pups, no dose- or treatment-relationship)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z829<>0,VLOOKUP(Z829,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Offspring (F1+F2)","M + F",">10000","Reproductive","Pup survival index",{"$f":"IF(Z830<>0,VLOOKUP(Z830,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No treatment-related findings (F1 pups: decreased survival at 100 ppm on days 4, 14 and 21, decreased at 1000 ppm on day 4 and increased at 1000 ppm on day 14, increased at 10000 ppm on days 14 and 21; F2 pups: no significant intergroup differences)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z830<>0,VLOOKUP(Z830,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Offspring (F1+F2)","M + F",">10000","In life observation","Clinical signs",{"$f":"IF(Z831<>0,VLOOKUP(Z831,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z831<>0,VLOOKUP(Z831,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","F",">10000","Reproductive","Dystocia",{"$f":"IF(Z832<>0,VLOOKUP(Z832,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"1/30 F0 females and 1/30 F1 females at 100 ppm died due to dystocia, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z832<>0,VLOOKUP(Z832,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","M + F",">10000","Organ histopathology","Lung histopathology",{"$f":"IF(Z833<>0,VLOOKUP(Z833,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross pathology: Low incidences of consolidation, ecchymoses, collapse and/or emphysema in F0 and F1 adults, not dose- or treatment-related, 1/30 F0 females at 100 ppm died because of suppurative pneumonia",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z833<>0,VLOOKUP(Z833,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","M + F",">10000","Organ histopathology","Liver histopathology",{"$f":"IF(Z834<>0,VLOOKUP(Z834,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z834<>0,VLOOKUP(Z834,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","M + F",">10000","Organ histopathology","Kidney histopathology",null,"Low incidences of cysts, dilated pelvis in F0 adults and low incidences of hydronephrosis in 2/60 F1 adults, considered to be incidental, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z835<>0,VLOOKUP(Z835,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Testis histopathology",{"$f":"IF(Z836<>0,VLOOKUP(Z836,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gross necropsy findings: low incidences in hyperplasia/unilateral hyperplasia in 1/30 F0 control and 2/30 F0 males at 1000 ppm and in each 1/30 F1 males at 100 and 1000 ppm, not treatment-related\nHistopathology, F0 adults: degenerative changes in the seminiferous tubules in each 1/30  males at 100 and 10000 ppm, unequal in size at 1000 ppm, considered to be incidental and not related to treatment\nhistopathology, F1 adults: unilateral degenerative changes and giant cell formation in the seminiferous tubulus and chronic inflammation in each 1/30 F1 males at 100 and 1000 ppm, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z836<>0,VLOOKUP(Z836,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Coagulating gland histopathology",{"$f":"IF(Z837<>0,VLOOKUP(Z837,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z837<>0,VLOOKUP(Z837,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z838<>0,VLOOKUP(Z838,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z838<>0,VLOOKUP(Z838,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","F",">10000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z839<>0,VLOOKUP(Z839,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z839<>0,VLOOKUP(Z839,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z840<>0,VLOOKUP(Z840,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z840<>0,VLOOKUP(Z840,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z841<>0,VLOOKUP(Z841,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z841<>0,VLOOKUP(Z841,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","F",">10000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z842<>0,VLOOKUP(Z842,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z842<>0,VLOOKUP(Z842,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","F",">10000","Organ histopathology","Vagina histopathology",{"$f":"IF(Z843<>0,VLOOKUP(Z843,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z843<>0,VLOOKUP(Z843,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",25,"885-RP-G2","OECD 416 (1983)","DAR",null,1993,"Rat","Wistar",30,"M + F",96.8,"Oral","Feed","100; 1000; 10000",100,10000,"ppm","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","F",">10000","Organ histopathology","Vaginal smears",{"$f":"IF(Z844<>0,VLOOKUP(Z844,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z844<>0,VLOOKUP(Z844,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",">10000","In life observation","Mortality",{"$f":"IF(Z845<>0,VLOOKUP(Z845,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related findings (mortalities observed: 1/28 F0 males at 0 ppm sacrificed, 1/28 F0 females at 1000 ppm sacrificed, 2/28 F0 males at 10000 ppm found dead/sacrificed, 1/24 F1 females at 1000 ppm sacrificed, 1/24 F1 males at 3000 ppm found dead, 1/24 F1 females at 10000 ppm found dead and 1/24 F1 males at 10000 ppm sacrificed)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z845<>0,VLOOKUP(Z845,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",">10000","In life observation","Clinical signs",{"$f":"IF(Z846<>0,VLOOKUP(Z846,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related findings (occasional observations of skin ulceration, hair loss/scabbing, brown staining of the coat, red/brown eye discharge, dental abnormalities and soft faeces in F0 and F1 rats, no treatment relation)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z846<>0,VLOOKUP(Z846,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",10000,"In life observation","Body weight",{"$f":"IF(Z847<>0,VLOOKUP(Z847,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Absolute weight reduced in F1 males at 10000 ppm apparent at selection, overall weight gain was comparable to control, treatment-related (no clear adverse effects on bw gain during pregnancy and lactation, during the first mate of each generation bw gains during the initial stages of pregnancy were slightly lower than control at all dosage groups, no consistent dose-response)",null,"Decrease",10000,">10000","ppm",{"$f":"IF(Z847<>0,VLOOKUP(Z847,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F1)","M + F",10000,"In life observation","Food consumption",{"$f":"IF(Z848<>0,VLOOKUP(Z848,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: slightly increased in F1 females at 10000 ppm during the latter stage of the first pre-mating period, not statistically significant\nFood efficiency: no clear consistent adverse effects observed across both generations\nWater consumption: slightly increased in F1 females at 10000 ppm with statistical significance in week 16",null,"Increase",10000,">10000","ppm",{"$f":"IF(Z848<>0,VLOOKUP(Z848,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",">10000","Reproductive","Fertility (mammals)",{"$f":"IF(Z849<>0,VLOOKUP(Z849,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No treatment-related findings (males failing to induce pregnangy were 1/28 at 10000 ppm in F0 males and 3/24, 1/24, 3/24 and 3/24 at 0, 1000, 3000 and 10000 ppm, histopathological findings only in 2/24 F1 males at 3000 ppm; females failing to mate: 1/28, 2/28, 0/28 and 1/28 in F0 females and 3/24, 3/24, 7/24 and 3/24 F1 females at 0, 1000, 3000 and 10000 ppm, explained by histopathological findings without treatment-relation)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z849<>0,VLOOKUP(Z849,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","F",">10000","Reproductive","Gestation length",{"$f":"IF(Z850<>0,VLOOKUP(Z850,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z850<>0,VLOOKUP(Z850,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",">10000","Reproductive","Reproduction",{"$f":"IF(Z851<>0,VLOOKUP(Z851,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"In F1 generation, the pregnancy rate in all groups wass less than expected  (mate 1: 83%, 75%, 58% and 79%, mate 2: 67%, 78%, 67% and 74% at 0, 1000, 3000 and 10000 ppm, no dosage relationship)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z851<>0,VLOOKUP(Z851,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",">10000","Organ Weight","Liver weight",{"$f":"IF(Z852<>0,VLOOKUP(Z852,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z852<>0,VLOOKUP(Z852,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","F",">10000","Organ Weight","Ovary weight",{"$f":"IF(Z853<>0,VLOOKUP(Z853,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z853<>0,VLOOKUP(Z853,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M",">10000","Organ Weight","Prostate weight",{"$f":"IF(Z854<>0,VLOOKUP(Z854,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z854<>0,VLOOKUP(Z854,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Weighed together with seminal vesicles and coagulating gland\nMean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M",">10000","Organ Weight","Testis weight",{"$f":"IF(Z855<>0,VLOOKUP(Z855,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z855<>0,VLOOKUP(Z855,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Weighed together with epididymides.\nMean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",">10000","Organ Weight","Adrenals weight",{"$f":"IF(Z856<>0,VLOOKUP(Z856,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z856<>0,VLOOKUP(Z856,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",">10000","Organ Weight","Brain weight",{"$f":"IF(Z857<>0,VLOOKUP(Z857,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z857<>0,VLOOKUP(Z857,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",">10000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z858<>0,VLOOKUP(Z858,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Pale and oedematous pancreas in 1/28 F0 males at 10000 ppm which died during the course of the study, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z858<>0,VLOOKUP(Z858,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",">10000","Organ histopathology","Liver histopathology",{"$f":"IF(Z859<>0,VLOOKUP(Z859,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z859<>0,VLOOKUP(Z859,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",">10000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z860<>0,VLOOKUP(Z860,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Pale tissue overlaying cranium and congested thickening meninges in one male at 10000 ppm which was sacrificed during week 23, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z860<>0,VLOOKUP(Z860,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",">10000","Organ histopathology","Spinal cord histopathology",{"$f":"IF(Z861<>0,VLOOKUP(Z861,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z861<>0,VLOOKUP(Z861,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",">10000","Organ histopathology","Stomach histopathology",{"$f":"IF(Z862<>0,VLOOKUP(Z862,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Thickened forestomach, invaginated stomach and abnormal contents in the gastrointestinal tract in one F0 female at 1000 ppm which was sacrificed on Day 2 post-partum, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z862<>0,VLOOKUP(Z862,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",">10000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z863<>0,VLOOKUP(Z863,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Enlarged  in one female at 10000 ppm found dead in week 23, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z863<>0,VLOOKUP(Z863,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",3000,"Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z864<>0,VLOOKUP(Z864,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Hypertrophy of acinar cells with prominent granular cytoplasms in the parotid salivary gland in F0 and F1 males and females at ≥ 3000 ppm and in the submaxillary salivary gland in F0 females at ≥ 3000 ppm, treatment-related (parotid: 2/27, 2/28, 3/28 and 12/26 F0 males and 1/24, 0/24, 4/23 and 10/23 F1 males and in 0/28, 2/27, 5/28 and 17/28 F0 females and 0/24, 0/23, 4/24 and 9/23 F1 females at 0, 1000, 3000 and 10000 ppm; submaxillary: 0/28, 1/27, 4/28 and 14/28 F0 females and 0/24, 0/23, 0/28 and 3/23 F1 females at 0, 1000, 3000 and 10000 ppm)\nhypertrophy of acinar cells with prominent granular cytoplasms in the submaxillary salivary gland in females at ≥ 3000 ppm, treatment-related (0/28, 1/27, 4/28 and 14/28 F0 females and in 0/24, 0/23, 0/24 and 3/23 F1 females at 0, 1000, 3000 and 10000 ppm)",null,"Change",1000,3000,"ppm",{"$f":"IF(Z864<>0,VLOOKUP(Z864,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","F",">10000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z865<>0,VLOOKUP(Z865,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z865<>0,VLOOKUP(Z865,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Coagulating gland histopathology",{"$f":"IF(Z866<>0,VLOOKUP(Z866,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z866<>0,VLOOKUP(Z866,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z867<>0,VLOOKUP(Z867,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z867<>0,VLOOKUP(Z867,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M + F",">10000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z868<>0,VLOOKUP(Z868,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z868<>0,VLOOKUP(Z868,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","F",">10000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z869<>0,VLOOKUP(Z869,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No treatment-related findings (1/2 infertile F0 females at 1000 ppm had follicular cysts on ovaries, 1/3, 1/3, 1/7 and 0/3 infertile F1 females at 0, 1000, 3000 and 10000 ppm had no or a reduced number of corpora lutea in the ovaries)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z869<>0,VLOOKUP(Z869,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z870<>0,VLOOKUP(Z870,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z870<>0,VLOOKUP(Z870,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z871<>0,VLOOKUP(Z871,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z871<>0,VLOOKUP(Z871,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","M",">10000","Organ histopathology","Testis histopathology",{"$f":"IF(Z872<>0,VLOOKUP(Z872,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z872<>0,VLOOKUP(Z872,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","F",">10000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z873<>0,VLOOKUP(Z873,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No treatment-related findings (luminal dilatation of the uterus in 2/3 infertile control females of the F1 generation)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z873<>0,VLOOKUP(Z873,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","F",">10000","Organ histopathology","Vagina histopathology",{"$f":"IF(Z874<>0,VLOOKUP(Z874,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z874<>0,VLOOKUP(Z874,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","F",">10000","Organ histopathology","Vaginal smears",{"$f":"IF(Z875<>0,VLOOKUP(Z875,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z875<>0,VLOOKUP(Z875,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","F",">10000","Reproductive","Estrus cyclicity",{"$f":"IF(Z876<>0,VLOOKUP(Z876,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z876<>0,VLOOKUP(Z876,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","F",">10000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z877<>0,VLOOKUP(Z877,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No treatment-related findings (1/3 infertile F1 females at 1000 ppm had cysts in pars anterior of the pituitary)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z877<>0,VLOOKUP(Z877,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Offspring (F1+F2)","M + F",">10000","Reproductive","Litter size",{"$f":"IF(Z878<>0,VLOOKUP(Z878,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Reduced at 10000 ppm (consistently but not significant) across all four matings and remained lower at day 4 in 3/4 matings, not conclusively attributable to treatment as the mean litter size at birth whithin each mating was not always the lowest litter size recorded",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z878<>0,VLOOKUP(Z878,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Offspring (F1+F2)","M + F",">10000","Reproductive","Litter viability",{"$f":"IF(Z879<>0,VLOOKUP(Z879,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Total litter loss was 2, 3, 1 and 1 at 0, 1000, 3000 and 10000 ppm across the four mates on the study, not treatment-related",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z879<>0,VLOOKUP(Z879,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Offspring (F1+F2)","M + F",">10000","Developmental","Pup development",{"$f":"IF(Z880<>0,VLOOKUP(Z880,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z880<>0,VLOOKUP(Z880,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Offspring (F1+F2)","M + F",">10000","Reproductive","Pup survival index",{"$f":"IF(Z881<>0,VLOOKUP(Z881,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z881<>0,VLOOKUP(Z881,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Offspring (F1+F2)","M + F",">10000","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z882<>0,VLOOKUP(Z882,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z882<>0,VLOOKUP(Z882,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Offspring (F1+F2)","M + F",">10000","Reproductive","Sex ratio",{"$f":"IF(Z883<>0,VLOOKUP(Z883,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z883<>0,VLOOKUP(Z883,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Offspring (F1+F2)","M + F",">10000","Reproductive","Time to mating",{"$f":"IF(Z884<>0,VLOOKUP(Z884,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z884<>0,VLOOKUP(Z884,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Offspring (F1+F2)","M + F",">10000","Developmental","Litter/pup weight",{"$f":"IF(Z885<>0,VLOOKUP(Z885,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No treatment-related findings (litter weights were reduced in all treated groups first mating F0 generation from Day 16 post-partum with mean pup weights being lower from Day 8 post-partum, no dose-response, no findings in the 2nd mating of the F0 generation or in both matings of the F1 generation, considered unlikely to be  treatment-related)",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z885<>0,VLOOKUP(Z885,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Offspring (F1+F2)","M + F",">10000","Reproductive","Number of live births",{"$f":"IF(Z886<>0,VLOOKUP(Z886,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z886<>0,VLOOKUP(Z886,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Offspring (F1+F2)","M",">10000","Reproductive","Age at balanopreputial separation",{"$f":"IF(Z887<>0,VLOOKUP(Z887,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z887<>0,VLOOKUP(Z887,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Offspring (F1+F2)","F",">10000","Reproductive","Age at Vaginal opening",{"$f":"IF(Z888<>0,VLOOKUP(Z888,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10000,">10000","ppm",{"$f":"IF(Z888<>0,VLOOKUP(Z888,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",26,null,"OECD 416 (1983), US EPA 83-4 (1982)","DAR",null,1992,"Rat","Crl: CD (SD) BR VAF/Plus","F0 generation: 28\nF1 generation: 24","M + F",99.2,"Oral","Feed","1000; 3000; 10000",1000,10000,"ppm","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","F",">10000","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z889<>0,VLOOKUP(Z889,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No treatment-related effect was observed on number of corpora lutea.",null,"No effect",10000,">10000","ppm",{"$f":"IF(Z889<>0,VLOOKUP(Z889,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","M + F",">30000","In life observation","Mortality",{"$f":"IF(Z890<>0,VLOOKUP(Z890,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related findings (one F0 female died before treatment, 2 F1a males and one F1a female died, one F1a female was sacrificed in extremis, causes of death were not due to toxicity of the test item)",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z890<>0,VLOOKUP(Z890,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","M + F",30000,"In life observation","Clinical signs",{"$f":"IF(Z891<>0,VLOOKUP(Z891,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Soft stool at 30000 ppm in F0 and F1 animals of both sexes, treatment-related (not treatment-related findings: red ocular discharge, result of overgrown / maloccluded teeth in both sexes, no dose-relation)",null,"Increase",10000,30000,"ppm",{"$f":"IF(Z891<>0,VLOOKUP(Z891,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","M + F",30000,"In life observation","Body weight",{"$f":"IF(Z892<>0,VLOOKUP(Z892,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Reduced in both sexes (F0+F1) at 30000 ppm throughout the study, treatment-related (F0: -8% and F1 -10% during pre-mating) (Not treatment-related findings: during gestation and lactation maternal bw at 30000 ppm tended to be lower than controls although bw gain was comparable to those of controls)",null,"Decrease",10000,30000,"ppm",{"$f":"IF(Z892<>0,VLOOKUP(Z892,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","M + F",30000,"In life observation","Food consumption",{"$f":"IF(Z893<>0,VLOOKUP(Z893,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: slightly decreased at 30000 ppm in F0 and F1 males and females during the first week of treatment and in F0 dams at 30000 ppm during the last week of lactation. However, in general food intake was not substantially affected during the study period.",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z893<>0,VLOOKUP(Z893,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","F",">30000","Reproductive","Gestation length",{"$f":"IF(Z894<>0,VLOOKUP(Z894,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Gestation length was not affected in the F0 and F1 generation, including the second mating of the F1 generation.",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z894<>0,VLOOKUP(Z894,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","M",">30000","Organ Weight","Epididymis weight",{"$f":"IF(Z895<>0,VLOOKUP(Z895,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z895<>0,VLOOKUP(Z895,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","F",">30000","Organ Weight","Ovary weight",{"$f":"IF(Z896<>0,VLOOKUP(Z896,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z896<>0,VLOOKUP(Z896,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","M",">30000","Organ Weight","Testis weight",{"$f":"IF(Z897<>0,VLOOKUP(Z897,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on testes weight with epididymides was observed, except for a statistically significant increase in relative organ weight change in F1a adults of the high dose group which was attributed to the observed lower terminal body weight.",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z897<>0,VLOOKUP(Z897,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","M + F",">30000","Reproductive","Time to mating",{"$f":"IF(Z898<>0,VLOOKUP(Z898,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z898<>0,VLOOKUP(Z898,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","M + F",">30000","Reproductive","Fertility (mammals)",{"$f":"IF(Z899<>0,VLOOKUP(Z899,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Mating rates for F0 and F1a treated dams were comparable and in some cases greater than for the control group. No adverse effect on precoital length were noted.",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z899<>0,VLOOKUP(Z899,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","M",">30000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z900<>0,VLOOKUP(Z900,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z900<>0,VLOOKUP(Z900,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","F",">30000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z901<>0,VLOOKUP(Z901,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z901<>0,VLOOKUP(Z901,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","M",">30000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z902<>0,VLOOKUP(Z902,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z902<>0,VLOOKUP(Z902,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","M",">30000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z903<>0,VLOOKUP(Z903,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z903<>0,VLOOKUP(Z903,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","M",">30000","Organ histopathology","Testis histopathology",{"$f":"IF(Z904<>0,VLOOKUP(Z904,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z904<>0,VLOOKUP(Z904,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","F",">30000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z905<>0,VLOOKUP(Z905,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z905<>0,VLOOKUP(Z905,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","F",">30000","Organ histopathology","Vagina histopathology",{"$f":"IF(Z906<>0,VLOOKUP(Z906,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z906<>0,VLOOKUP(Z906,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F1)","M + F",">30000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z907<>0,VLOOKUP(Z907,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z907<>0,VLOOKUP(Z907,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","M + F",">30000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z908<>0,VLOOKUP(Z908,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z908<>0,VLOOKUP(Z908,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","M",">30000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z909<>0,VLOOKUP(Z909,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z909<>0,VLOOKUP(Z909,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","F",">30000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z910<>0,VLOOKUP(Z910,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z910<>0,VLOOKUP(Z910,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Offspring (F1+F2)","M + F",">30000","Reproductive","Number of live births",{"$f":"IF(Z911<>0,VLOOKUP(Z911,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z911<>0,VLOOKUP(Z911,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Offspring (F1+F2)","M + F",30000,"Reproductive","Litter size",{"$f":"IF(Z912<>0,VLOOKUP(Z912,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Slightly reduced (not statistically significant) in F1 pups and F2a pups at 30000 ppm, not reproduced in F2b pups, treatment relation equivocal",null,"Decrease",10000,30000,"ppm",{"$f":"IF(Z912<>0,VLOOKUP(Z912,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Offspring (F1+F2)","M + F",">30000","Reproductive","Litter viability",{"$f":"IF(Z913<>0,VLOOKUP(Z913,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z913<>0,VLOOKUP(Z913,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Offspring (F1+F2)","M + F",30000,"Developmental","Litter/pup weight",{"$f":"IF(Z914<>0,VLOOKUP(Z914,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Reduced (> -10%) by lactation Day 21 at 30000 ppm in F1, in F2 pups the effect appeared to occur earlier (Day 14 of lactctaion), consumption of prepared diet was considered responsibel for bw effect, treatment-related (Not treatment-related: slightly reduced at weaning in the 10000 ppm group, transient, not consistent for both sexes in all generations, toxicological relevance questionable)",null,"Decrease",10000,30000,"ppm",{"$f":"IF(Z914<>0,VLOOKUP(Z914,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Offspring (F1+F2)","M + F",">30000","Developmental","Pup development",{"$f":"IF(Z915<>0,VLOOKUP(Z915,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z915<>0,VLOOKUP(Z915,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Offspring (F1+F2)","M + F",">30000","Reproductive","Pup survival index",{"$f":"IF(Z916<>0,VLOOKUP(Z916,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z916<>0,VLOOKUP(Z916,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Offspring (F1+F2)","M + F",">30000","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z917<>0,VLOOKUP(Z917,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z917<>0,VLOOKUP(Z917,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Offspring (F1+F2)","M + F",">30000","In life observation","Mortality",{"$f":"IF(Z918<>0,VLOOKUP(Z918,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z918<>0,VLOOKUP(Z918,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",27,null,"similar to OECD 416 ","DAR",null,1990,"Rat","Sprague-Dawley",30,"M + F",97.67,"Oral","Feed","2000; 10000; 30000",2000,30000,"ppm","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Offspring (F1+F2)","M + F",">30000","In life observation","Clinical signs",{"$f":"IF(Z919<>0,VLOOKUP(Z919,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",30000,">30000","ppm",{"$f":"IF(Z919<>0,VLOOKUP(Z919,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",28,null,"similar to OECD 414","DAR",null,"1996 (Amendment 2002)","Rat","Alpk:APfSD ",24,"F",95.6,"Oral","Gavage/Intubation","250; 500; 1000",250,1000,"mg/kg bw/day","10 (GD 7-16)","Days","Adult","F",">1000","In life observation","Mortality",{"$f":"IF(Z920<>0,VLOOKUP(Z920,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"One control animal was killed on Day 7 as a result of being misdosed, not treatment-related",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z920<>0,VLOOKUP(Z920,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-16, caesarian section on gestation day 22, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",28,null,"similar to OECD 414","DAR",null,"1996 (Amendment 2002)","Rat","Alpk:APfSD ",24,"F",95.6,"Oral","Gavage/Intubation","250; 500; 1000",250,1000,"mg/kg bw/day","10 (GD 7-16)","Days","Adult","F",">1000","In life observation","Clinical signs",{"$f":"IF(Z921<>0,VLOOKUP(Z921,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z921<>0,VLOOKUP(Z921,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-16, caesarian section on gestation day 22, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",28,null,"similar to OECD 414","DAR",null,"1996 (Amendment 2002)","Rat","Alpk:APfSD ",24,"F",95.6,"Oral","Gavage/Intubation","250; 500; 1000",250,1000,"mg/kg bw/day","10 (GD 7-16)","Days","Adult","F",">1000","In life observation","Body weight",{"$f":"IF(Z922<>0,VLOOKUP(Z922,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z922<>0,VLOOKUP(Z922,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-16, caesarian section on gestation day 22, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",28,null,"similar to OECD 414","DAR",null,"1996 (Amendment 2002)","Rat","Alpk:APfSD ",24,"F",95.6,"Oral","Gavage/Intubation","250; 500; 1000",250,1000,"mg/kg bw/day","10 (GD 7-16)","Days","Adult","F",">1000","In life observation","Food consumption",{"$f":"IF(Z923<>0,VLOOKUP(Z923,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: marginally reduced at 1000 mg/kg bw/day during dosing period, differences were not statistically significant",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z923<>0,VLOOKUP(Z923,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-16, caesarian section on gestation day 22, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",28,null,"similar to OECD 414","DAR",null,"1996 (Amendment 2002)","Rat","Alpk:APfSD ",24,"F",95.6,"Oral","Gavage/Intubation","250; 500; 1000",250,1000,"mg/kg bw/day","10 (GD 7-16)","Days","Adult","F",">1000","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z924<>0,VLOOKUP(Z924,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gravid uterus weight was not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z924<>0,VLOOKUP(Z924,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment on gestation days 7-16, caesarian section on gestation day 22, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",28,null,"similar to OECD 414","DAR",null,"1996 (Amendment 2002)","Rat","Alpk:APfSD ",24,"F",95.6,"Oral","Gavage/Intubation","250; 500; 1000",250,1000,"mg/kg bw/day","10 (GD 7-16)","Days","Adult","F",">1000","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z925<>0,VLOOKUP(Z925,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Neither number of implantations nor corpora lutea was affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z925<>0,VLOOKUP(Z925,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-16, caesarian section on gestation day 22, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",28,null,"similar to OECD 414","DAR",null,"1996 (Amendment 2002)","Rat","Alpk:APfSD ",24,"F",95.6,"Oral","Gavage/Intubation","250; 500; 1000",250,1000,"mg/kg bw/day","10 (GD 7-16)","Days","Fetus","M + F",">1000","Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z926<>0,VLOOKUP(Z926,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Neither early nor late intrauterine deaths were observed.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z926<>0,VLOOKUP(Z926,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-16, caesarian section on gestation day 22, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",28,null,"similar to OECD 414","DAR",null,"1996 (Amendment 2002)","Rat","Alpk:APfSD ",24,"F",95.6,"Oral","Gavage/Intubation","250; 500; 1000",250,1000,"mg/kg bw/day","10 (GD 7-16)","Days","Adult","F",">1000","Reproductive","Pre implantation loss",{"$f":"IF(Z927<>0,VLOOKUP(Z927,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z927<>0,VLOOKUP(Z927,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-16, caesarian section on gestation day 22, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",28,null,"similar to OECD 414","DAR",null,"1996 (Amendment 2002)","Rat","Alpk:APfSD ",24,"F",95.6,"Oral","Gavage/Intubation","250; 500; 1000",250,1000,"mg/kg bw/day","10 (GD 7-16)","Days","Adult","F",">1000","Reproductive","Post implantation loss",{"$f":"IF(Z928<>0,VLOOKUP(Z928,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z928<>0,VLOOKUP(Z928,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-16, caesarian section on gestation day 22, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",28,null,"similar to OECD 414","DAR",null,"1996 (Amendment 2002)","Rat","Alpk:APfSD ",24,"F",95.6,"Oral","Gavage/Intubation","250; 500; 1000",250,1000,"mg/kg bw/day","10 (GD 7-16)","Days","Fetus","M + F",">1000","Developmental","Litter/pup weight",{"$f":"IF(Z929<>0,VLOOKUP(Z929,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Mean litter as well as foetal weight were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z929<>0,VLOOKUP(Z929,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-16, caesarian section on gestation day 22, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",28,null,"similar to OECD 414","DAR",null,"1996 (Amendment 2002)","Rat","Alpk:APfSD ",24,"F",95.6,"Oral","Gavage/Intubation","250; 500; 1000",250,1000,"mg/kg bw/day","10 (GD 7-16)","Days","Fetus","M + F",">1000","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z930<>0,VLOOKUP(Z930,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The incidence of fetuses with major defects was 1/284, 1/297, 1/301 and 2/296 at 0, 250, 500 and 1000 mg/kg bw/day, type or incidence gave no evidence for a treatment-related effect. The amount of fetuses with external/visceral variants and with skeletal variants were lower in the test item treated groups than in the controls.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z930<>0,VLOOKUP(Z930,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-16, caesarian section on gestation day 22, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",28,null,"similar to OECD 414","DAR",null,"1996 (Amendment 2002)","Rat","Alpk:APfSD ",24,"F",95.6,"Oral","Gavage/Intubation","250; 500; 1000",250,1000,"mg/kg bw/day","10 (GD 7-16)","Days","Fetus","M + F",">1000","Reproductive","Sex ratio",{"$f":"IF(Z931<>0,VLOOKUP(Z931,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z931<>0,VLOOKUP(Z931,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-16, caesarian section on gestation day 22, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",28,null,"similar to OECD 414","DAR",null,"1996 (Amendment 2002)","Rat","Alpk:APfSD ",24,"F",95.6,"Oral","Gavage/Intubation","250; 500; 1000",250,1000,"mg/kg bw/day","10 (GD 7-16)","Days","Fetus","M + F",">1000","Developmental","Fetal development",{"$f":"IF(Z932<>0,VLOOKUP(Z932,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z932<>0,VLOOKUP(Z932,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-16, caesarian section on gestation day 20, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",29,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rat","Crj:CD (SD)",24,"F",95.68,"Oral","Gavage/Intubation","30; 300; 1000",30,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","In life observation","Mortality",{"$f":"IF(Z933<>0,VLOOKUP(Z933,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z933<>0,VLOOKUP(Z933,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-16, caesarian section on gestation day 20, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",29,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rat","Crj:CD (SD)",24,"F",95.68,"Oral","Gavage/Intubation","30; 300; 1000",30,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",1000,"In life observation","Clinical signs",{"$f":"IF(Z934<>0,VLOOKUP(Z934,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Loose stool in 20/22 pregnant females at 1000 mg/kg bw/day during the dosing period and in 9/20 females one day after treatment (gestation day 16) (not treatment-related findings: hair loss or scabs in maternal rats at 30 and 300 mg/kg bw/day during the dosing period, within historical control data, hairloss in 1-2 maternal rats per group in each treated group)",null,"Increase",300,1000,"mg/kg bw/day",{"$f":"IF(Z934<>0,VLOOKUP(Z934,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-16, caesarian section on gestation day 20, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",29,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rat","Crj:CD (SD)",24,"F",95.68,"Oral","Gavage/Intubation","30; 300; 1000",30,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","In life observation","Body weight",{"$f":"IF(Z935<>0,VLOOKUP(Z935,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z935<>0,VLOOKUP(Z935,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-16, caesarian section on gestation day 20, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",29,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rat","Crj:CD (SD)",24,"F",95.68,"Oral","Gavage/Intubation","30; 300; 1000",30,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",1000,"In life observation","Food consumption",{"$f":"IF(Z936<>0,VLOOKUP(Z936,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased at 1000 mg/kg bw/day on gestation days 6-9, treatment-related (increase at 1000 mg/kg bw/day on gestation days 15-20 was considered to be due to the rebound effect against the reduced food consumption during the dosing period)",null,"Decrease",300,1000,"mg/kg bw/day",{"$f":"IF(Z936<>0,VLOOKUP(Z936,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-16, caesarian section on gestation day 20, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",29,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rat","Crj:CD (SD)",24,"F",95.68,"Oral","Gavage/Intubation","30; 300; 1000",30,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z937<>0,VLOOKUP(Z937,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gravid uterus weight as well as placental weight were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z937<>0,VLOOKUP(Z937,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment on gestation days 7-16, caesarian section on gestation day 20, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",29,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rat","Crj:CD (SD)",24,"F",95.68,"Oral","Gavage/Intubation","30; 300; 1000",30,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z938<>0,VLOOKUP(Z938,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z938<>0,VLOOKUP(Z938,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-16, caesarian section on gestation day 20, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",29,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rat","Crj:CD (SD)",24,"F",95.68,"Oral","Gavage/Intubation","30; 300; 1000",30,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","Organ histopathology","Skin histopathology",{"$f":"IF(Z939<>0,VLOOKUP(Z939,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Hair loss in 1/10 control females, not treatment-related",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z939<>0,VLOOKUP(Z939,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-16, caesarian section on gestation day 20, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",29,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rat","Crj:CD (SD)",24,"F",95.68,"Oral","Gavage/Intubation","30; 300; 1000",30,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z940<>0,VLOOKUP(Z940,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"}," Gross necropsy: No treatment-related findings. ",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z940<>0,VLOOKUP(Z940,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-16, caesarian section on gestation day 20, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",29,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rat","Crj:CD (SD)",24,"F",95.68,"Oral","Gavage/Intubation","30; 300; 1000",30,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Fetus","M + F",">1000","Developmental","Litter/pup weight",{"$f":"IF(Z941<>0,VLOOKUP(Z941,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z941<>0,VLOOKUP(Z941,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-16, caesarian section on gestation day 20, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",29,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rat","Crj:CD (SD)",24,"F",95.68,"Oral","Gavage/Intubation","30; 300; 1000",30,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Fetus","M + F",">1000","Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z942<>0,VLOOKUP(Z942,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect on mean number of live fetuses, fetal deaths and resorptions was observed.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z942<>0,VLOOKUP(Z942,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-16, caesarian section on gestation day 20, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",29,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rat","Crj:CD (SD)",24,"F",95.68,"Oral","Gavage/Intubation","30; 300; 1000",30,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Fetus","M + F",">1000","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z943<>0,VLOOKUP(Z943,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"External malformations: no treatment-related findings (short tail in 1/361 fetus at 30 mg/kg bw/day, microphthalmia in 1/339 fetus at 1000 mg/kg bw/day)\nVisceral malformations: no treatment-related findings (right aortic arch in 1/173 fetus at 300 mg/kg bw/day, ventricular septical defects in 1/173 and in 1/164 fetuses each at 300 and 1000 mg/kg bw/day, considered to be incidental due to the low incidence; malformations such as thymic remnant in the neck, dilatation of the renal pelvis and left umbilical artery among all groups: 21/150, 28/174, 28/173 and 19/164 fetuses at 0, 30, 300 and 1000 mg/kg bw/day, not treatment-related)\nSkeletal malformations: no treatment-related findings (splitting of the ossification centers of the thoracic vertebral bodies in 2/164, 1/185 and 2/175 fetuses at 0, 300 and 1000 mg/kg bw/day; asymmetry of the sternebrae with sterno-costal joint displacement in 1/185 fetuses at 300 mg/kg bw/day, fusion of the sternebrae in 1/175 fetuses at 1000 mg/kg bw/day; malformations such as cervical ribs shortening, lumber ribs, sacralisation of the lumbar vertebra were observed in all groups: 9/164, 6/187, 11/185 and 14/175 fetuses at 0, 30, 300 and 1000 mg/kg bw/day)",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z943<>0,VLOOKUP(Z943,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-16, caesarian section on gestation day 20, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",29,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rat","Crj:CD (SD)",24,"F",95.68,"Oral","Gavage/Intubation","30; 300; 1000",30,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Fetus","M + F",">1000","Reproductive","Sex ratio",{"$f":"IF(Z944<>0,VLOOKUP(Z944,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z944<>0,VLOOKUP(Z944,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-16, caesarian section on gestation day 20, no quantification of T3, T4, TSH hormones performed","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",30,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rabbit","Japanese White (Kbl:JW)",18,"F",97.56,"Oral","Gavage/Intubation","10; 100; 300",10,300,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F",300,"In life observation","Mortality",{"$f":"IF(Z945<>0,VLOOKUP(Z945,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"1/18 females died at 300 mg/kg bw/day, histopathology revealed pale color in the liver and ascites in the abdomnial cavity, treatment relation could not be entirely denied (not treatment-related findings: 1/18 females at 10 mg/kg bw/day died, necropsy revealed no abnormalities)",null,"Increase",100,300,"mg/kg bw/day",{"$f":"IF(Z945<>0,VLOOKUP(Z945,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 6-18, caesarian section on gestation day 27","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",30,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rabbit","Japanese White (Kbl:JW)",18,"F",97.56,"Oral","Gavage/Intubation","10; 100; 300",10,300,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F",300,"In life observation","Clinical signs",{"$f":"IF(Z946<>0,VLOOKUP(Z946,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Loose stool in 4/17 females during the dosing period at 300 mg/kg bw/day  and soiled fur in the perianal region in 2 of them, loose stool remained in 2/4 affected females of this group after dosing, one of the affected does aborted on gestation day 26 and the other one prematurely delivered on gestation day 27, treatment-related (not treatment-related findings: hair loss in 1/17 and 1/16 females at 10 and 100 mg/kg bw/day during dosing and in  1/17 and 1/16 females at 10 and 100 mg/kg bw/day post-dosing, loose stool and red material on the tray in 2/18 control females after dosing, loose stool in 1/17 females at 10 mg/kg bw/day post-dosing)",null,"Increase",100,300,"mg/kg bw/day",{"$f":"IF(Z946<>0,VLOOKUP(Z946,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 6-18, caesarian section on gestation day 27","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",30,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rabbit","Japanese White (Kbl:JW)",18,"F",97.56,"Oral","Gavage/Intubation","10; 100; 300",10,300,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F",300,"In life observation","Body weight",{"$f":"IF(Z947<>0,VLOOKUP(Z947,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased bw at 300 mg/kg bw/day on gestation days 16-24, not statistically significant; decreased bw gain at 300 mg/kg bw/day during gestation days 0-16 and 0-24",null,"Decrease",100,300,"mg/kg bw/day",{"$f":"IF(Z947<>0,VLOOKUP(Z947,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 6-18, caesarian section on gestation day 27","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",30,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rabbit","Japanese White (Kbl:JW)",18,"F",97.56,"Oral","Gavage/Intubation","10; 100; 300",10,300,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F",">300","In life observation","Food consumption",{"$f":"IF(Z948<>0,VLOOKUP(Z948,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",300,"> 300","mg/kg bw/day",{"$f":"IF(Z948<>0,VLOOKUP(Z948,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 6-18, caesarian section on gestation day 27","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",30,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rabbit","Japanese White (Kbl:JW)",18,"F",97.56,"Oral","Gavage/Intubation","10; 100; 300",10,300,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F",">300","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z949<>0,VLOOKUP(Z949,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gravid uterus weight was not affected.",null,"No effect",300,"> 300","mg/kg bw/day",{"$f":"IF(Z949<>0,VLOOKUP(Z949,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment on gestation days 6-18, caesarian section on gestation day 27","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",30,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rabbit","Japanese White (Kbl:JW)",18,"F",97.56,"Oral","Gavage/Intubation","10; 100; 300",10,300,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F",">300","Organ Weight","Ovary weight",{"$f":"IF(Z950<>0,VLOOKUP(Z950,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",300,"> 300","mg/kg bw/day",{"$f":"IF(Z950<>0,VLOOKUP(Z950,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment on gestation days 6-18, caesarian section on gestation day 27","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",30,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rabbit","Japanese White (Kbl:JW)",18,"F",97.56,"Oral","Gavage/Intubation","10; 100; 300",10,300,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F",">300","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z951<>0,VLOOKUP(Z951,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",300,"> 300","mg/kg bw/day",{"$f":"IF(Z951<>0,VLOOKUP(Z951,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 6-18, caesarian section on gestation day 27","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",30,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rabbit","Japanese White (Kbl:JW)",18,"F",97.56,"Oral","Gavage/Intubation","10; 100; 300",10,300,"mg/kg bw/day","13 (GD 6-18)","Days","Fetus","M + F",">300","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z952<>0,VLOOKUP(Z952,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"High incidence of maternal rabbits with fetuses with any malformation at 300 mg/kg bw/day, malformations were of inconsistent type and comprised external, visceral and skeletal malformations in single animals, considered to be sporadic",null,"No effect",300,"> 300","mg/kg bw/day",{"$f":"IF(Z952<>0,VLOOKUP(Z952,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 6-18, caesarian section on gestation day 27","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",30,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rabbit","Japanese White (Kbl:JW)",18,"F",97.56,"Oral","Gavage/Intubation","10; 100; 300",10,300,"mg/kg bw/day","13 (GD 6-18)","Days","Fetus","M + F",">300","Developmental","Litter/pup weight",{"$f":"IF(Z953<>0,VLOOKUP(Z953,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",300,"> 300","mg/kg bw/day",{"$f":"IF(Z953<>0,VLOOKUP(Z953,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 6-18, caesarian section on gestation day 27","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",30,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rabbit","Japanese White (Kbl:JW)",18,"F",97.56,"Oral","Gavage/Intubation","10; 100; 300",10,300,"mg/kg bw/day","13 (GD 6-18)","Days","Fetus","M + F",">300","Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z954<>0,VLOOKUP(Z954,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",300,"> 300","mg/kg bw/day",{"$f":"IF(Z954<>0,VLOOKUP(Z954,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 6-18, caesarian section on gestation day 27","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",30,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rabbit","Japanese White (Kbl:JW)",18,"F",97.56,"Oral","Gavage/Intubation","10; 100; 300",10,300,"mg/kg bw/day","13 (GD 6-18)","Days","Fetus","M + F",">300","Reproductive","Sex ratio",{"$f":"IF(Z955<>0,VLOOKUP(Z955,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",300,"> 300","mg/kg bw/day",{"$f":"IF(Z955<>0,VLOOKUP(Z955,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 6-18, caesarian section on gestation day 27","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",30,null,"OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1995,"Rabbit","Japanese White (Kbl:JW)",18,"F",97.56,"Oral","Gavage/Intubation","10; 100; 300",10,300,"mg/kg bw/day","13 (GD 6-18)","Days","Fetus","M + F",">300","Developmental","Fetal development",{"$f":"IF(Z956<>0,VLOOKUP(Z956,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",300,"> 300","mg/kg bw/day",{"$f":"IF(Z956<>0,VLOOKUP(Z956,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 6-18, caesarian section on gestation day 27","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",31,"434/020","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1996,"Rabbit","New Zealand White",18,"F",95.3,"Oral","Gavage/Intubation","50; 200; 400",50,400,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F",400,"In life observation","Mortality",{"$f":"IF(Z957<>0,VLOOKUP(Z957,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Intercurrent deaths in 2/18 females at 400 mg/kg bw/day (one died on gestation day 19, one was sacrificed in extremis on day 20, histopathological findings of the stomach and intestine in the animal found dead, treatment-related (further mortalities, not treatment-related: each 1/18 females at 0 and 200 mg/kg bw/day, mal-dosing)",null,"Increase",200,400,"mg/kg bw/day",{"$f":"IF(Z957<>0,VLOOKUP(Z957,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",31,"434/020","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1996,"Rabbit","New Zealand White",18,"F",95.3,"Oral","Gavage/Intubation","50; 200; 400",50,400,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F",400,"In life observation","Clinical signs",{"$f":"IF(Z958<>0,VLOOKUP(Z958,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Scours (16/18 does), reduced faecal output (6/18 does) and diarrhoea (10/18 does) at 400 mg/kg bw/day, treatment-related (lethargy, ptosis, hunched posture, hypothermia and blood on tray in 1/18 females at 400 mg/kg bw/day killed in extremis) (not treatment-related: vaginal bleeding in 1/18 females at 200 mg/kg bw/day, no dose-relation, not evaluated as toxicological effect, scours in 5/18, 10/18 and 7/18 females at 0, 50 and 200 mg/kg bw/day)",null,"Increase",200,400,"mg/kg bw/day",{"$f":"IF(Z958<>0,VLOOKUP(Z958,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",31,"434/020","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1996,"Rabbit","New Zealand White",18,"F",95.3,"Oral","Gavage/Intubation","50; 200; 400",50,400,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F",200,"In life observation","Body weight",{"$f":"IF(Z959<>0,VLOOKUP(Z959,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Reduced bw gain at ≥ 200 mg/kg bw/day from days 9-29 of gestation, treatment-related. Statistical significance was observed for body weight gain in the high dose group only from Days 13-29 post coitum.",null,"Decrease",50,200,"mg/kg bw/day",{"$f":"IF(Z959<>0,VLOOKUP(Z959,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-19, caesarian section on gestation day 30","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",31,"434/020","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1996,"Rabbit","New Zealand White",18,"F",95.3,"Oral","Gavage/Intubation","50; 200; 400",50,400,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F",400,"In life observation","Food consumption",{"$f":"IF(Z960<>0,VLOOKUP(Z960,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption: Reduced at 400 mg/kg bw/day during the dosing period, treatment-related",null,"Decrease",200,400,"mg/kg bw/day",{"$f":"IF(Z960<>0,VLOOKUP(Z960,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-19, caesarian section on gestation day 31","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",31,"434/020","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1996,"Rabbit","New Zealand White",18,"F",95.3,"Oral","Gavage/Intubation","50; 200; 400",50,400,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F","> 400","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z961<>0,VLOOKUP(Z961,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",400,"> 400","mg/kg bw/day",{"$f":"IF(Z961<>0,VLOOKUP(Z961,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 34","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",31,"434/020","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1996,"Rabbit","New Zealand White",18,"F",95.3,"Oral","Gavage/Intubation","50; 200; 400",50,400,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F",400,"Reproductive","Post implantation loss",{"$f":"IF(Z962<>0,VLOOKUP(Z962,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Increased at 400 mg/kg bw/day due to 1/18 females with nine late deaths (69.2%), not treatment-related; increased at 200 mg/kg bw/day due to early fetal deaths, no dose relation, considered to be not treatment-related",null,"No effect",400,"> 400","mg/kg bw/day",{"$f":"IF(Z962<>0,VLOOKUP(Z962,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 35","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",31,"434/020","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1996,"Rabbit","New Zealand White",18,"F",95.3,"Oral","Gavage/Intubation","50; 200; 400",50,400,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F","> 400","Reproductive","Pre implantation loss",{"$f":"IF(Z963<>0,VLOOKUP(Z963,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",400,"> 400","mg/kg bw/day",{"$f":"IF(Z963<>0,VLOOKUP(Z963,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 36","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",31,"434/020","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1996,"Rabbit","New Zealand White",18,"F",95.3,"Oral","Gavage/Intubation","50; 200; 400",50,400,"mg/kg bw/day","13 (GD 7-19)","Days","Fetus","M + F","> 400","Developmental","Fetal development",{"$f":"IF(Z964<>0,VLOOKUP(Z964,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",400,"> 400","mg/kg bw/day",{"$f":"IF(Z964<>0,VLOOKUP(Z964,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 37","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",31,"434/020","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1996,"Rabbit","New Zealand White",18,"F",95.3,"Oral","Gavage/Intubation","50; 200; 400",50,400,"mg/kg bw/day","13 (GD 7-19)","Days","Fetus","M + F","> 400","Developmental","Litter/pup weight",{"$f":"IF(Z965<>0,VLOOKUP(Z965,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",400,"> 400","mg/kg bw/day",{"$f":"IF(Z965<>0,VLOOKUP(Z965,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 38","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",31,"434/020","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1996,"Rabbit","New Zealand White",18,"F",95.3,"Oral","Gavage/Intubation","50; 200; 400",50,400,"mg/kg bw/day","13 (GD 7-19)","Days","Fetus","M + F",200,"Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z966<>0,VLOOKUP(Z966,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Dead fetuses in 1/2 dead females at 400 mg/kg bw/day, treatment-related. Slight increase in late fetal death at 400 mg/kg bw/day leading to an increase of total fetal deaths, attributed to one animal with nine late deaths resulting a post-implatation loss of 69.2%, not treatment-related; increased early fetal death leading to an increase in total fetal death at 200 mg/kg bw/day, no dose relation, considered to be unrelated to treatment",null,"Increase",200,400,"mg/kg bw/day",{"$f":"IF(Z966<>0,VLOOKUP(Z966,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 39","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",31,"434/020","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1996,"Rabbit","New Zealand White",18,"F",95.3,"Oral","Gavage/Intubation","50; 200; 400",50,400,"mg/kg bw/day","13 (GD 7-19)","Days","Fetus","M + F","> 400","Reproductive","Sex ratio",{"$f":"IF(Z967<>0,VLOOKUP(Z967,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",400,"> 400","mg/kg bw/day",{"$f":"IF(Z967<>0,VLOOKUP(Z967,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 40","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",31,"434/020","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1996,"Rabbit","New Zealand White",18,"F",95.3,"Oral","Gavage/Intubation","50; 200; 400",50,400,"mg/kg bw/day","13 (GD 7-19)","Days","Fetus","M + F","> 400","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z968<>0,VLOOKUP(Z968,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No treatment-related findings. Incidences of external and visceral malformations observed in single animals, no dose relation. Incidences of skeletal malformations of different types were higher but comparable between treatment and control animals and therefore not attributed to treatment.",null,"No effect",400,"> 400","mg/kg bw/day",{"$f":"IF(Z968<>0,VLOOKUP(Z968,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 41","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",31,"434/020","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1996,"Rabbit","New Zealand White",18,"F",95.3,"Oral","Gavage/Intubation","50; 200; 400",50,400,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F",400,"Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z969<>0,VLOOKUP(Z969,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gross necropsy: blood and dead fetuses in 1/2 dead females at 400 mg/kg bw/day, treatment-related (there were no histopathological findings)",null,"No effect",200,400,"mg/kg bw/day",{"$f":"IF(Z969<>0,VLOOKUP(Z969,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment on gestation days 7-19, caesarian section on gestation day 42","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",31,"434/020","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1996,"Rabbit","New Zealand White",18,"F",95.3,"Oral","Gavage/Intubation","50; 200; 400",50,400,"mg/kg bw/day","13 (GD 7-19)","Days","Fetus","F",">400","Reproductive","Litter size",{"$f":"IF(Z970<>0,VLOOKUP(Z970,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",400,"> 400","mg/kg bw/day",{"$f":"IF(Z970<>0,VLOOKUP(Z970,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 43","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",31,"434/020","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","DAR",null,1996,"Rabbit","New Zealand White",18,"F",95.3,"Oral","Gavage/Intubation","50; 200; 400",50,400,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F",400,"Organ histopathology","Stomach histopathology",{"$f":"IF(Z971<>0,VLOOKUP(Z971,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Macroscopic findings in 2/4 females at 400 mg/kg bw/day that died/were killed in extremis, treatment-related (fluid-filled large intestines, haemorrhage, ulceration and sloughing of the stomach, duodenum, congestion and colon, rectum and appendix gas distended; the animal killed in extremis had blood and dead fetuses in the uterus)",null,"Change",200,400,"mg/kg bw/day",{"$f":"IF(Z971<>0,VLOOKUP(Z971,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-19, caesarian section on gestation day 43","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",32,null,"OECD 414 (1981); 87/302/EEC, OJEC L133 24-26 (1988); US EPA 83-3","DAR",null,1996,"Rabbit","New Zealand White",20,"F",95.6,"Oral","Gavage/Intubation","100; 175; 300",100,300,"mg/kg bw/day","13 (GD 8-20)","Days","Adult","F",175,"In life observation","Clinical signs",{"$f":"IF(Z972<>0,VLOOKUP(Z972,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Sings of diarrhoea; reduction in faecal output; staining in the genital area (300 mg/kg bw/day group); not significant for all groups",null,"Increase",100,175,"mg/kg bw/day",{"$f":"IF(Z972<>0,VLOOKUP(Z972,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 8-20, caesarian section on gestation day 30","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",32,null,"OECD 414 (1981); 87/302/EEC, OJEC L133 24-26 (1988); US EPA 83-3","DAR",null,1996,"Rabbit","New Zealand White",20,"F",95.6,"Oral","Gavage/Intubation","100; 175; 300",100,300,"mg/kg bw/day","13 (GD 8-20)","Days","Adult","F",175,"In life observation","Food consumption",{"$f":"IF(Z973<>0,VLOOKUP(Z973,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Statistically significant",null,"Decrease",100,175,"mg/kg bw/day",{"$f":"IF(Z973<>0,VLOOKUP(Z973,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 8-20, caesarian section on gestation day 30","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",32,null,"OECD 414 (1981); 87/302/EEC, OJEC L133 24-26 (1988); US EPA 83-3","DAR",null,1996,"Rabbit","New Zealand White",20,"F",95.6,"Oral","Gavage/Intubation","100; 175; 300",100,300,"mg/kg bw/day","13 (GD 8-20)","Days","Adult","F",175,"In life observation","Body weight",{"$f":"IF(Z974<>0,VLOOKUP(Z974,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Body weight; statiscially significant; all animals except one showed recovery in the post dosing period",null,"Decrease",100,175,"mg/kg bw/day",{"$f":"IF(Z974<>0,VLOOKUP(Z974,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 8-20, caesarian section on gestation day 30","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",32,null,"OECD 414 (1981); 87/302/EEC, OJEC L133 24-26 (1988); US EPA 83-3","DAR",null,1996,"Rabbit","New Zealand White",20,"F",95.6,"Oral","Gavage/Intubation","100; 175; 300",100,300,"mg/kg bw/day","13 (GD 8-20)","Days","Adult","F","> 300","In life observation","Mortality",{"$f":"IF(Z975<>0,VLOOKUP(Z975,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"1/20; 2/20; 2/20; 2/20 in the control, 100, 175 and 300 mg/kg bw/day group, respectively. The mortality was not considered to be treatment-related.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z975<>0,VLOOKUP(Z975,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 8-20, caesarian section on gestation day 30","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",32,null,"OECD 414 (1981); 87/302/EEC, OJEC L133 24-26 (1988); US EPA 83-3","DAR",null,1996,"Rabbit","New Zealand White",20,"F",95.6,"Oral","Gavage/Intubation","100; 175; 300",100,300,"mg/kg bw/day","13 (GD 8-20)","Days","Adult","F","> 300","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z976<>0,VLOOKUP(Z976,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute gravid uterine weight",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z976<>0,VLOOKUP(Z976,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment on gestation days 8-20, caesarian section on gestation day 30","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",32,null,"OECD 414 (1981); 87/302/EEC, OJEC L133 24-26 (1988); US EPA 83-3","DAR",null,1996,"Rabbit","New Zealand White",20,"F",95.6,"Oral","Gavage/Intubation","100; 175; 300",100,300,"mg/kg bw/day","13 (GD 8-20)","Days","Adult","F",300,"Developmental","Litter/pup weight",{"$f":"IF(Z977<>0,VLOOKUP(Z977,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Mean fetal weight was reduced, which was attributed to 2 litters with particularly low fetal weight.",null,"Decrease",175,300,"mg/kg bw/day",{"$f":"IF(Z977<>0,VLOOKUP(Z977,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 8-20, caesarian section on gestation day 30","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",32,null,"OECD 414 (1981); 87/302/EEC, OJEC L133 24-26 (1988); US EPA 83-3","DAR",null,1996,"Rabbit","New Zealand White",20,"F",95.6,"Oral","Gavage/Intubation","100; 175; 300",100,300,"mg/kg bw/day","13 (GD 8-20)","Days","Adult","F","> 300","Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z978<>0,VLOOKUP(Z978,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"viable foetuses; number of intra-uterine deaths early+late, ",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z978<>0,VLOOKUP(Z978,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 8-20, caesarian section on gestation day 30","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",32,null,"OECD 414 (1981); 87/302/EEC, OJEC L133 24-26 (1988); US EPA 83-3","DAR",null,1996,"Rabbit","New Zealand White",20,"F",95.6,"Oral","Gavage/Intubation","100; 175; 300",100,300,"mg/kg bw/day","13 (GD 8-20)","Days","Adult","F","> 300","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z979<>0,VLOOKUP(Z979,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z979<>0,VLOOKUP(Z979,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 8-20, caesarian section on gestation day 30","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",32,null,"OECD 414 (1981); 87/302/EEC, OJEC L133 24-26 (1988); US EPA 83-3","DAR",null,1996,"Rabbit","New Zealand White",20,"F",95.6,"Oral","Gavage/Intubation","100; 175; 300",100,300,"mg/kg bw/day","13 (GD 8-20)","Days","Adult","F","> 300","Reproductive","Post implantation loss",{"$f":"IF(Z980<>0,VLOOKUP(Z980,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z980<>0,VLOOKUP(Z980,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 8-20, caesarian section on gestation day 30","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",32,null,"OECD 414 (1981); 87/302/EEC, OJEC L133 24-26 (1988); US EPA 83-3","DAR",null,1996,"Rabbit","New Zealand White",20,"F",95.6,"Oral","Gavage/Intubation","100; 175; 300",100,300,"mg/kg bw/day","13 (GD 8-20)","Days","Adult","F","> 300","Reproductive","Pre implantation loss",{"$f":"IF(Z981<>0,VLOOKUP(Z981,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z981<>0,VLOOKUP(Z981,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 8-20, caesarian section on gestation day 30","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",32,null,"OECD 414 (1981); 87/302/EEC, OJEC L133 24-26 (1988); US EPA 83-3","DAR",null,1996,"Rabbit","New Zealand White",20,"F",95.6,"Oral","Gavage/Intubation","100; 175; 300",100,300,"mg/kg bw/day","13 (GD 8-20)","Days","Fetus","M + F","> 300","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z982<>0,VLOOKUP(Z982,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Only very minor changes in ossification were observed in the 300 mg/kg bw/day group but not considered treatment-related but due to lower bodyweight of the foetuses",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z982<>0,VLOOKUP(Z982,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 8-20, caesarian section on gestation day 30","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",32,null,"OECD 414 (1981); 87/302/EEC, OJEC L133 24-26 (1988); US EPA 83-3","DAR",null,1996,"Rabbit","New Zealand White",20,"F",95.6,"Oral","Gavage/Intubation","100; 175; 300",100,300,"mg/kg bw/day","13 (GD 8-20)","Days","Adult","F","> 300","Reproductive","Sex ratio",{"$f":"IF(Z983<>0,VLOOKUP(Z983,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The proportion of male fetuses was increased in the 175 mg/kg bw/day group. This was not considered treatment-related since no dose-response was observed.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z983<>0,VLOOKUP(Z983,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 8-20, caesarian section on gestation day 30","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",33,null,"pre-Guideline; in general compliance with OECD 414 or US EPA 83-3","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",175,"In life observation","Clinical signs",{"$f":"IF(Z984<>0,VLOOKUP(Z984,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Increase in soft stool and diarrhea (from 175 mg/kg bw/d); nasal discharge (350 mg/kg bw/day group only)",null,"Increase",75,175,"mg/kg bw/day",{"$f":"IF(Z984<>0,VLOOKUP(Z984,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 6-27, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",33,null,"pre-Guideline; in general compliance with OECD 414 or US EPA 83-3","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",350,"In life observation","Mortality",{"$f":"IF(Z985<>0,VLOOKUP(Z985,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"11/16 animals died in the high dose group; 2/16, 1/16 and 3/16 animals died in the control, 75 and 175 mg/kg bw/day group, respectively. Reasons for mortality were: pneumonia, gastroenteritis, enteritis, respiratory disease, gastroenteritis and caecal ulcerations",null,"Increase",175,300,"mg/kg bw/day",{"$f":"IF(Z985<>0,VLOOKUP(Z985,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 6-27, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",33,null,"pre-Guideline; in general compliance with OECD 414 or US EPA 83-3","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F","> 350","In life observation","Body weight",{"$f":"IF(Z986<>0,VLOOKUP(Z986,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Mean maternal body weight gain was not affected.",null,"No effect",350,"> 350","mg/kg bw/day",{"$f":"IF(Z986<>0,VLOOKUP(Z986,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 6-27, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",33,null,"pre-Guideline; in general compliance with OECD 414 or US EPA 83-3","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F","> 350","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z987<>0,VLOOKUP(Z987,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",350,"> 350","mg/kg bw/day",{"$f":"IF(Z987<>0,VLOOKUP(Z987,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 6-27, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",33,null,"pre-Guideline; in general compliance with OECD 414 or US EPA 83-3","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F","> 350","Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z988<>0,VLOOKUP(Z988,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"An increase in the mean number of viable foetuses in the 75 mg/kg bw/day was considered as not toxicologically relevant.",null,"No effect",350,"> 350","mg/kg bw/day",{"$f":"IF(Z988<>0,VLOOKUP(Z988,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 6-27, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",33,null,"pre-Guideline; in general compliance with OECD 414 or US EPA 83-3","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F","> 350","Reproductive","Post implantation loss",{"$f":"IF(Z989<>0,VLOOKUP(Z989,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",350,"> 350","mg/kg bw/day",{"$f":"IF(Z989<>0,VLOOKUP(Z989,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 6-27, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",33,null,"pre-Guideline; in general compliance with OECD 414 or US EPA 83-3","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F","> 350","Reproductive","Sex ratio",{"$f":"IF(Z990<>0,VLOOKUP(Z990,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",350,"> 350","mg/kg bw/day",{"$f":"IF(Z990<>0,VLOOKUP(Z990,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 6-27, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",33,null,"pre-Guideline; in general compliance with OECD 414 or US EPA 83-3","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F","> 350","Developmental","Litter/pup weight",{"$f":"IF(Z991<>0,VLOOKUP(Z991,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"A slight decrease in mean fetal body weight was observed in all treatment groups which was comparable to historical control data.",null,"No effect",350,"> 350","mg/kg bw/day",{"$f":"IF(Z991<>0,VLOOKUP(Z991,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 6-27, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",33,null,"pre-Guideline; in general compliance with OECD 414 or US EPA 83-3","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Fetus","M + F","> 350","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z992<>0,VLOOKUP(Z992,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Malformations were noted only in treatment groups but not considered to be treatment-related due to a lack of a dose-related pattern and because the frequency did not exceed the historical control data; not increased due to control",null,"No effect",350,"> 350","mg/kg bw/day",{"$f":"IF(Z992<>0,VLOOKUP(Z992,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 6-27, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",34,"884-TER-RB","OECD 414 (1981)","DAR",null,1993,"Rabbit","New Zealand White","at least 12","F",96.8,"Oral","Gavage/Intubation","20; 100; 500",20,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F",500,"In life observation","Clinical signs",{"$f":"IF(Z993<>0,VLOOKUP(Z993,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"toxic syntoms of the respiratory and the gastrointestinal tract (rales, dyspnoea, diaahoea/soft stool and weakness)",null,"Increase",100,500,"mg/kg bw/day",{"$f":"IF(Z993<>0,VLOOKUP(Z993,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",34,"884-TER-RB","OECD 414 (1981)","DAR",null,1993,"Rabbit","New Zealand White","at least 12","F",96.8,"Oral","Gavage/Intubation","20; 100; 500",20,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F",500,"In life observation","Mortality",{"$f":"IF(Z994<>0,VLOOKUP(Z994,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"4/16 and 8/15 animals died in the 100 and 500 mg/kg bw/day group, respectively.",null,"Increase",20,100,"mg/kg bw/day",{"$f":"IF(Z994<>0,VLOOKUP(Z994,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",34,"884-TER-RB","OECD 414 (1981)","DAR",null,1993,"Rabbit","New Zealand White","at least 12","F",96.8,"Oral","Gavage/Intubation","20; 100; 500",20,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","In life observation","Body weight",{"$f":"IF(Z995<>0,VLOOKUP(Z995,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Lower body weight was observed at differnet stages of the study, but due to lower initial body weight the effect is not considered treatment-related; body weight gain is unaffected",null,"No effect",100,500,"mg/kg bw/day",{"$f":"IF(Z995<>0,VLOOKUP(Z995,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",34,"884-TER-RB","OECD 414 (1981)","DAR",null,1993,"Rabbit","New Zealand White","at least 12","F",96.8,"Oral","Gavage/Intubation","20; 100; 500",20,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","In life observation","Food consumption",{"$f":"IF(Z996<>0,VLOOKUP(Z996,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Feed intake was decreased during the dosing period",null,"No effect",100,500,"mg/kg bw/day",{"$f":"IF(Z996<>0,VLOOKUP(Z996,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",34,"884-TER-RB","OECD 414 (1981)","DAR",null,1993,"Rabbit","New Zealand White","at least 12","F",96.8,"Oral","Gavage/Intubation","20; 100; 500",20,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z997<>0,VLOOKUP(Z997,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",500,"> 500","mg/kg bw/day",{"$f":"IF(Z997<>0,VLOOKUP(Z997,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",34,"884-TER-RB","OECD 414 (1981)","DAR",null,1993,"Rabbit","New Zealand White","at least 12","F",96.8,"Oral","Gavage/Intubation","20; 100; 500",20,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","Reproductive","Post implantation loss",{"$f":"IF(Z998<>0,VLOOKUP(Z998,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",500,"> 500","mg/kg bw/day",{"$f":"IF(Z998<>0,VLOOKUP(Z998,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",34,"884-TER-RB","OECD 414 (1981)","DAR",null,1993,"Rabbit","New Zealand White","at least 12","F",96.8,"Oral","Gavage/Intubation","20; 100; 500",20,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","Reproductive","Pre implantation loss",{"$f":"IF(Z999<>0,VLOOKUP(Z999,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",500,"> 500","mg/kg bw/day",{"$f":"IF(Z999<>0,VLOOKUP(Z999,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",34,"884-TER-RB","OECD 414 (1981)","DAR",null,1993,"Rabbit","New Zealand White","at least 12","F",96.8,"Oral","Gavage/Intubation","20; 100; 500",20,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z1000<>0,VLOOKUP(Z1000,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"resorptions: one dam of the high dose group showed complete resorptions;  no dose-relationship in the incidence of resorptions among the treatment groups and control group",null,"No effect",500,"> 500","mg/kg bw/day",{"$f":"IF(Z1000<>0,VLOOKUP(Z1000,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",34,"884-TER-RB","OECD 414 (1981)","DAR",null,1993,"Rabbit","New Zealand White","at least 12","F",96.8,"Oral","Gavage/Intubation","20; 100; 500",20,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","Reproductive","Litter size",{"$f":"IF(Z1001<>0,VLOOKUP(Z1001,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",500,"> 500","mg/kg bw/day",{"$f":"IF(Z1001<>0,VLOOKUP(Z1001,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",34,"884-TER-RB","OECD 414 (1981)","DAR",null,1993,"Rabbit","New Zealand White","at least 12","F",96.8,"Oral","Gavage/Intubation","20; 100; 500",20,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","Reproductive","Sex ratio",{"$f":"IF(Z1002<>0,VLOOKUP(Z1002,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",500,"> 500","mg/kg bw/day",{"$f":"IF(Z1002<>0,VLOOKUP(Z1002,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",34,"884-TER-RB","OECD 414 (1981)","DAR",null,1993,"Rabbit","New Zealand White","at least 12","F",96.8,"Oral","Gavage/Intubation","20; 100; 500",20,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z1003<>0,VLOOKUP(Z1003,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",500,"> 500","mg/kg bw/day",{"$f":"IF(Z1003<>0,VLOOKUP(Z1003,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",34,"884-TER-RB","OECD 414 (1981)","DAR",null,1993,"Rabbit","New Zealand White","at least 12","F",96.8,"Oral","Gavage/Intubation","20; 100; 500",20,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F",20,"Developmental","Litter/pup weight",{"$f":"IF(Z1004<>0,VLOOKUP(Z1004,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Litter weight was statistically significant higher in the low and mid dose group, but not in the high dose group",null,"Increase","< 20",20,"mg/kg bw/day",{"$f":"IF(Z1004<>0,VLOOKUP(Z1004,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",34,"884-TER-RB","OECD 414 (1981)","DAR",null,1993,"Rabbit","New Zealand White","at least 12","F",96.8,"Oral","Gavage/Intubation","20; 100; 500",20,500,"mg/kg bw/day","13 (GD 6-18)","Days","Fetus","M + F",20,"Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z1005<>0,VLOOKUP(Z1005,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"A significant increase in dilated heart was observed in all treatment groups while other incidences of visceral malformations were not considered treatment-related; no treatment and dose-related significant major skeletal malformations; no significant or dose-relationship of the incidences of external malformations",null,"Increase","< 20",20,"mg/kg bw/day",{"$f":"IF(Z1005<>0,VLOOKUP(Z1005,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",34,"884-TER-RB","OECD 414 (1981)","DAR",null,1993,"Rabbit","New Zealand White","at least 12","F",96.8,"Oral","Gavage/Intubation","20; 100; 500",20,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z1006<>0,VLOOKUP(Z1006,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,"absolute","No effect",500,"> 500","mg/kg bw/day",{"$f":"IF(Z1006<>0,VLOOKUP(Z1006,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",35,1086,"OECD 414 (1981)","DAR",null,1989,"Rabbit","New Zealand White",15,"F",95,"Oral","Gavage/Intubation","125; 250; 500",125,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F",500,"In life observation","Body weight",{"$f":"IF(Z1007<>0,VLOOKUP(Z1007,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Reduced body weight was observed in the high dose group.",null,"Decrease",250,500,"mg/kg bw/day",{"$f":"IF(Z1007<>0,VLOOKUP(Z1007,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",35,1086,"OECD 414 (1981)","DAR",null,1989,"Rabbit","New Zealand White",15,"F",95,"Oral","Gavage/Intubation","125; 250; 500",125,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F",500,"In life observation","Food consumption",{"$f":"IF(Z1008<>0,VLOOKUP(Z1008,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"Decrease",250,500,"mg/kg bw/day",{"$f":"IF(Z1008<>0,VLOOKUP(Z1008,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",35,1086,"OECD 414 (1981)","DAR",null,1989,"Rabbit","New Zealand White",15,"F",95,"Oral","Gavage/Intubation","125; 250; 500",125,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","In life observation","Clinical signs",{"$f":"IF(Z1009<>0,VLOOKUP(Z1009,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",500,"> 500","mg/kg bw/day",{"$f":"IF(Z1009<>0,VLOOKUP(Z1009,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",35,1086,"OECD 414 (1981)","DAR",null,1989,"Rabbit","New Zealand White",15,"F",95,"Oral","Gavage/Intubation","125; 250; 500",125,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F",500,"Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z1010<>0,VLOOKUP(Z1010,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Two animals of the high dose group aborted which is considered secondary to maternal toxicity. ",null,"Decrease",250,500,"mg/kg bw/day",{"$f":"IF(Z1010<>0,VLOOKUP(Z1010,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",35,1086,"OECD 414 (1981)","DAR",null,1989,"Rabbit","New Zealand White",15,"F",95,"Oral","Gavage/Intubation","125; 250; 500",125,500,"mg/kg bw/day","13 (GD 6-18)","Days","Fetus","F",500,"Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z1011<>0,VLOOKUP(Z1011,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"External: Tail abnormal, low-set ears; Visceral: ventricular septal defect, postvacal lung lobe absent, kidneys absent; skeletal: Rudimentary rib on lumbar arch",null,"Decrease","<250",500,"mg/kg bw/day",{"$f":"IF(Z1011<>0,VLOOKUP(Z1011,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",35,1086,"OECD 414 (1981)","DAR",null,1989,"Rabbit","New Zealand White",15,"F",95,"Oral","Gavage/Intubation","125; 250; 500",125,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z1012<>0,VLOOKUP(Z1012,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect on corpora lutea was observed. Low number of viable implants and increase in non-viable implants in high dose group (not statistically significant). ",null,"No effect",500,"> 500","mg/kg bw/day",{"$f":"IF(Z1012<>0,VLOOKUP(Z1012,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",35,1086,"OECD 414 (1981)","DAR",null,1989,"Rabbit","New Zealand White",15,"F",95,"Oral","Gavage/Intubation","125; 250; 500",125,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z1013<>0,VLOOKUP(Z1013,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,"absolute","No effect",500,"> 500","mg/kg bw/day",{"$f":"IF(Z1013<>0,VLOOKUP(Z1013,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",35,1086,"OECD 414 (1981)","DAR",null,1989,"Rabbit","New Zealand White",15,"F",95,"Oral","Gavage/Intubation","125; 250; 500",125,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","Reproductive","Pre implantation loss",{"$f":"IF(Z1014<>0,VLOOKUP(Z1014,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",500,"> 500","mg/kg bw/day",{"$f":"IF(Z1014<>0,VLOOKUP(Z1014,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",35,1086,"OECD 414 (1981)","DAR",null,1989,"Rabbit","New Zealand White",15,"F",95,"Oral","Gavage/Intubation","125; 250; 500",125,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","Reproductive","Post implantation loss",{"$f":"IF(Z1015<>0,VLOOKUP(Z1015,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",500,"> 500","mg/kg bw/day",{"$f":"IF(Z1015<>0,VLOOKUP(Z1015,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",35,1086,"OECD 414 (1981)","DAR",null,1989,"Rabbit","New Zealand White",15,"F",95,"Oral","Gavage/Intubation","125; 250; 500",125,500,"mg/kg bw/day","13 (GD 6-18)","Days","Fetus","M + F","> 500","Developmental","Litter/pup weight",{"$f":"IF(Z1016<>0,VLOOKUP(Z1016,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Fetal body weight per litter was not affected.",null,"No effect",500,"> 500","mg/kg bw/day",{"$f":"IF(Z1016<>0,VLOOKUP(Z1016,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",35,1086,"OECD 414 (1981)","DAR",null,1989,"Rabbit","New Zealand White",15,"F",95,"Oral","Gavage/Intubation","125; 250; 500",125,500,"mg/kg bw/day","13 (GD 6-18)","Days","Adult","F","> 500","Reproductive","Litter size",{"$f":"IF(Z1017<>0,VLOOKUP(Z1017,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",500,"> 500","mg/kg bw/day",{"$f":"IF(Z1017<>0,VLOOKUP(Z1017,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",36,null,"OPPTS 870.7800","DAR",null,2012,"Mouse","B6C3F1/Crl",10,"F",95.11,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",28,"Days","Adult","F","> 5000","In life observation","Clinical signs",{"$f":"IF(Z1018<>0,VLOOKUP(Z1018,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",5000,"> 5000","ppm",{"$f":"IF(Z1018<>0,VLOOKUP(Z1018,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Doses are equivalent to 150.1, 449.1, 1447.5 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",36,null,"OPPTS 870.7800","DAR",null,2012,"Mouse","B6C3F1/Crl",10,"F",95.11,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",28,"Days","Adult","F","> 5000","In life observation","Mortality",{"$f":"IF(Z1019<>0,VLOOKUP(Z1019,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",5000,"> 5000","ppm",{"$f":"IF(Z1019<>0,VLOOKUP(Z1019,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Doses are equivalent to 150.1, 449.1, 1447.5 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",36,null,"OPPTS 870.7800","DAR",null,2012,"Mouse","B6C3F1/Crl",10,"F",95.11,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",28,"Days","Adult","F","> 5000","In life observation","Food consumption",{"$f":"IF(Z1020<>0,VLOOKUP(Z1020,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",5000,"> 5000","ppm",{"$f":"IF(Z1020<>0,VLOOKUP(Z1020,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Doses are equivalent to 150.1, 449.1, 1447.5 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",36,null,"OPPTS 870.7800","DAR",null,2012,"Mouse","B6C3F1/Crl",10,"F",95.11,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",28,"Days","Adult","F","> 5000","In life observation","Body weight",{"$f":"IF(Z1021<>0,VLOOKUP(Z1021,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",5000,"> 5000","ppm",{"$f":"IF(Z1021<>0,VLOOKUP(Z1021,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Doses are equivalent to 150.1, 449.1, 1447.5 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",36,null,"OPPTS 870.7800","DAR",null,2012,"Mouse","B6C3F1/Crl",10,"F",95.11,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",28,"Days","Adult","F","> 5000","Organ Weight","Spleen weight",{"$f":"IF(Z1022<>0,VLOOKUP(Z1022,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,"absolute/relaitve","No effect",5000,"> 5000","ppm",{"$f":"IF(Z1022<>0,VLOOKUP(Z1022,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Doses are equivalent to 150.1, 449.1, 1447.5 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",36,null,"OPPTS 870.7800","DAR",null,2012,"Mouse","B6C3F1/Crl",10,"F",95.11,"Oral","Feed","500; 1500; 5000",500,5000,"ppm",28,"Days","Adult","F","> 5000","Organ Weight","Thymus weight",{"$f":"IF(Z1023<>0,VLOOKUP(Z1023,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,"absolute/relaitve","No effect",5000,"> 5000","ppm",{"$f":"IF(Z1023<>0,VLOOKUP(Z1023,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Doses are equivalent to 150.1, 449.1, 1447.5 mg/kg bw/day","Yes","Yes"]
["InVitroEstrogen","ER Binding Assay",37,"6500V-100334ERB","OPPTS 890.1250 (2009)","DAR",null,2012,"Rat, Sprague-Dawley, cytosol from uterus",null,null,null,"95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Uptake from the medium (in vitro)",null,"10-10; 10-9; 10-8; 10-7; 10-6; 10-5; 10-4; 10-3"," 10 -10"," 10 -03","Molar","16-20","Hours",null,null,">  10-03","Receptor binding","Estrogen receptor",{"$f":"IF(Z1024<>0,VLOOKUP(Z1024,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Glyphosate demonstrated no evidence for ER binding in the estrogen receptor binding (rat uterine cytosol) screening assay since the test substance was identified as \"non-interacting\" in three valid independent runs.",null,"No effect"," 10-03",">  10-03","Molar",{"$f":"IF(Z1024<>0,VLOOKUP(Z1024,Interpretation!$C:$E,3,FALSE),\"\")","v":"E"},null,"Yes","Yes"]
["InVitroEstrogen","Stably Transfected Human ERα Transcriptional Activation Assay (ER STTA)",38,"6500V-100334ERTA","OPPTS 890.1300 (2009); OECD 455 (2009)","DAR",null,2012,"Human cell line (HeLa-9903)",null,null,null,"95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Uptake from the medium (in vitro)",null,"10-10; 10-9, 10-8; 10-7; 10-6; 10-5; 10-4; 10-3"," 10 -10"," 10 -03","Molar",24,"Hours",null,null,">  10-03","Receptor (trans)activation","Estrogen receptor",{"$f":"IF(Z1025<>0,VLOOKUP(Z1025,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Based on the results of the two valid transcriptional activation assays, it can be concluded glyphosate is not an agonist of human estrogen receptor alpha (hERα) over the concentration range (maximum concentration 10-3 M) tested in the HeLa-9903 model system.",null,"No effect"," 10-03",">  10-03","Molar",{"$f":"IF(Z1025<>0,VLOOKUP(Z1025,Interpretation!$C:$E,3,FALSE),\"\")","v":"E"},null,"Yes","Yes"]
["InVitroAndrogen","AR Binding Assay",39,"6500V-100334ARB","OPPTS 890.1150 (2009)","DAR",null,2012,"Rat, Sprague-Dawley, cytosol from prostate",null,null,null,"95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Uptake from the medium (in vitro)",null,"10-10; 10-9; 10-8; 10-7; 10-6; 10-5; 10-4; 10-3"," 10 -10"," 10 -03","Molar","16-20","Hours",null,null,">  10-03","Receptor binding","Androgen receptor",{"$f":"IF(Z1026<>0,VLOOKUP(Z1026,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Glyphosate demonstrated no evidence for AR binding in the androgen receptor binding (rat prostate cytosol) screening assay since the test substance was identified as \"non-binder\" in three valid independent runs.",null,"No effect"," 10-03",">  10-03","Molar",{"$f":"IF(Z1026<>0,VLOOKUP(Z1026,Interpretation!$C:$E,3,FALSE),\"\")","v":"A"},null,"Yes","Yes"]
["InVitroSteroidogenesis","Aromatase Assay",40,"6500V-100334AROM","OPPTS 890.1200","DAR",null,2012,"Human (CYP19 (aromatase) and P450 reductase Supersomes TM)","in vitro",null,null,"95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Uptake from the medium (in vitro)",null,"10-10; 10-9; 10-8; 10-7; 10-6; 10-5; 10-4; 10-3"," 10 -10"," 10 -03","Molar",15,"Minutes",null,null,">  10-03","Enzyme inhibition","CYP19",{"$f":"IF(Z1027<>0,VLOOKUP(Z1027,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Based on 3 independent assay runs, glyphosate is classified as a \"non-inhibitor\" of aromatase activity in the human recombinant aromatase assay.",null,"No effect"," 10-03",">  10-03","Molar",{"$f":"IF(Z1027<>0,VLOOKUP(Z1027,Interpretation!$C:$E,3,FALSE),\"\")","v":"S"},null,"Yes","Yes"]
["InVitroSteroidogenesis","H295R steroidogenesis assay",41,"DOI 10.1007/s11356-010-0396-x","OCSPP 890.1550, OECD 456","DAR",null,2011,"Human cell line (H295R)",null,null,null,"95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Uptake from the medium (in vitro)",null," 10 -10 - 10-3"," 10 -10"," 10 -04","Molar",48,"Hours",null,null,">  10-04","Steroidogenesis","Steroidogenesis (genes/enzyme changes) (in vitro)",{"$f":"IF(Z1028<>0,VLOOKUP(Z1028,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Glyphosate did not alter 17ß-estradiol and testosterone production in the H295R steroidogenesis assay.",null,"No effect"," 10-04",">  10-04","Molar",{"$f":"IF(Z1028<>0,VLOOKUP(Z1028,Interpretation!$C:$E,3,FALSE),\"\")","v":"S"},null,"Yes","Yes"]
["Mammals","Uterotrophic assay",42,null,"OCSPP 890.1600, OECD 440","DAR",null,2012,"Rat","Crl:CD(SD)",6,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day",3,"Days","Adult","F","> 1000","In life observation","Clinical signs",{"$f":"IF(Z1029<>0,VLOOKUP(Z1029,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Glyphosate was negative indicating lack of estrogenic activity. A single occurrence of red material around the nose in one animal of the 300 ppm group. ",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1029<>0,VLOOKUP(Z1029,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Uterotrophic assay",42,null,"OCSPP 890.1600, OECD 440","DAR",null,2012,"Rat","Crl:CD(SD)",6,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day",3,"Days","Adult","F","> 1000","In life observation","Mortality",{"$f":"IF(Z1030<>0,VLOOKUP(Z1030,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1030<>0,VLOOKUP(Z1030,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Uterotrophic assay",42,null,"OCSPP 890.1600, OECD 440","DAR",null,2012,"Rat","Crl:CD(SD)",6,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day",3,"Days","Adult","F","> 1000","In life observation","Body weight",{"$f":"IF(Z1031<>0,VLOOKUP(Z1031,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Mean body weights and body weight gains were not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1031<>0,VLOOKUP(Z1031,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Uterotrophic assay",42,null,"OCSPP 890.1600, OECD 440","DAR",null,2012,"Rat","Crl:CD(SD)",6,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day",3,"Days","Adult","F","> 1000","Organ Weight","Uterus weight (UT assay)",{"$f":"IF(Z1032<>0,VLOOKUP(Z1032,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"Mean uterine weights (wet and blotted, including luminal fluid) were not affetced.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1032<>0,VLOOKUP(Z1032,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A"},null,"Yes","Yes"]
["Mammals","Hershberger assay",43,null,"OCSPP 890.1400, OECD 441","DAR",null,2012,"Rat","Crl:CD(SD)",6,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day",10,"Days","Adult","M","> 1000","In life observation","Clinical signs",{"$f":"IF(Z1033<>0,VLOOKUP(Z1033,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1033<>0,VLOOKUP(Z1033,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Hershberger assay",43,null,"OCSPP 890.1400, OECD 441","DAR",null,2012,"Rat","Crl:CD(SD)",6,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day",10,"Days","Adult","M","> 1000","In life observation","Mortality",{"$f":"IF(Z1034<>0,VLOOKUP(Z1034,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1034<>0,VLOOKUP(Z1034,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Hershberger assay",43,null,"OCSPP 890.1400, OECD 441","DAR",null,2012,"Rat","Crl:CD(SD)",6,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day",10,"Days","Adult","M","> 1000","In life observation","Body weight",{"$f":"IF(Z1035<>0,VLOOKUP(Z1035,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1035<>0,VLOOKUP(Z1035,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Hershberger assay",43,null,"OCSPP 890.1400, OECD 441","DAR",null,2012,"Rat","Crl:CD(SD)",6,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day",10,"Days","Adult","M","> 1000","Organ Weight","Prostate weight (Hershberger)",{"$f":"IF(Z1036<>0,VLOOKUP(Z1036,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"In the androgen agonist assay, the CV of the ventral prostate low dose (100 mg/kg/day) treated animals was slightly higher (43.74%) than the OECD CD value (40%); not considered significant.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1036<>0,VLOOKUP(Z1036,Interpretation!$C:$E,3,FALSE),\"\")","v":"A"},null,"Yes","Yes"]
["Mammals","Hershberger assay",43,null,"OCSPP 890.1400, OECD 441","DAR",null,2012,"Rat","Crl:CD(SD)",6,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day",10,"Days","Adult","M","> 1000","Organ Weight","Glans penis weight  (Hershberger)",{"$f":"IF(Z1037<>0,VLOOKUP(Z1037,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"In the androgen agonist assay, the CV of the glans penis (19.44%) was slightly higher than the OECD CD of 17%; not considered significant.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1037<>0,VLOOKUP(Z1037,Interpretation!$C:$E,3,FALSE),\"\")","v":"A"},null,"Yes","Yes"]
["Mammals","Hershberger assay",43,null,"OCSPP 890.1400, OECD 441","DAR",null,2012,"Rat","Crl:CD(SD)",6,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day",10,"Days","Adult","M","> 1000","Organ Weight","Seminal vesicles weight (Hershberger)",{"$f":"IF(Z1038<>0,VLOOKUP(Z1038,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"All coefficient of variance (CV) values for the control and high-dose groups in this study are within the acceptable range.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1038<>0,VLOOKUP(Z1038,Interpretation!$C:$E,3,FALSE),\"\")","v":"A"},null,"Yes","Yes"]
["Mammals","Hershberger assay",43,null,"OCSPP 890.1400, OECD 441","DAR",null,2012,"Rat","Crl:CD(SD)",6,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day",10,"Days","Adult","M","> 1000","Organ Weight","Coagulating gland weight",{"$f":"IF(Z1039<>0,VLOOKUP(Z1039,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"All coefficient of variance (CV) values for the control and high-dose groups in this study are within the acceptable range.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1039<>0,VLOOKUP(Z1039,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Hershberger assay",43,null,"OCSPP 890.1400, OECD 441","DAR",null,2012,"Rat","Crl:CD(SD)",6,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day",10,"Days","Adult","M","> 1000","Organ Weight","Cowpers glands weight (Hershberger)",{"$f":"IF(Z1040<>0,VLOOKUP(Z1040,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"All coefficient of variance (CV) values for the control and high-dose groups in this study are within the acceptable range.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1040<>0,VLOOKUP(Z1040,Interpretation!$C:$E,3,FALSE),\"\")","v":"A"},null,"Yes","Yes"]
["Mammals","Hershberger assay",43,null,"OCSPP 890.1400, OECD 441","DAR",null,2012,"Rat","Crl:CD(SD)",6,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day",10,"Days","Adult","M","> 1000","Organ Weight","LABC weight (Hershberger)",{"$f":"IF(Z1041<>0,VLOOKUP(Z1041,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"All coefficient of variance (CV) values for the control and high-dose groups in this study are within the acceptable range.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1041<>0,VLOOKUP(Z1041,Interpretation!$C:$E,3,FALSE),\"\")","v":"A"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F",300,"In life observation","Clinical signs",{"$f":"IF(Z1042<>0,VLOOKUP(Z1042,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Dose dependent rales were noted in 4/15 animals in the 300 mg/kg bw/day group and 13/15 animals in the 1000 mg/kg bw/day group.",null,"Increase",100,300,"mg/kg bw/day",{"$f":"IF(Z1042<>0,VLOOKUP(Z1042,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","In life observation","Mortality",{"$f":"IF(Z1043<>0,VLOOKUP(Z1043,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1043<>0,VLOOKUP(Z1043,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","In life observation","Body weight",{"$f":"IF(Z1044<>0,VLOOKUP(Z1044,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1044<>0,VLOOKUP(Z1044,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Reproductive","Age at Vaginal opening",{"$f":"IF(Z1045<>0,VLOOKUP(Z1045,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Control group (PND 36.4) was higher than the acceptable range of values in the performance criteria (30.67 days to 35.62 days; OPPTS 890.1450). However, the coefficient of variation (CV) value (6.52) fell within the acceptable range (0.00-6.52).",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1045<>0,VLOOKUP(Z1045,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Reproductive","Age at first estrus",{"$f":"IF(Z1046<>0,VLOOKUP(Z1046,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1046<>0,VLOOKUP(Z1046,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Reproductive","Estrus cyclicity",{"$f":"IF(Z1047<>0,VLOOKUP(Z1047,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Mean estrus cycle lengths were not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1047<>0,VLOOKUP(Z1047,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Clinical chemistry/hormones","T3 and T4 level",{"$f":"IF(Z1048<>0,VLOOKUP(Z1048,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"T4 levels were not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1048<>0,VLOOKUP(Z1048,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Clinical chemistry/hormones","Thyroid-stimulating hormone level (TSH)",{"$f":"IF(Z1049<>0,VLOOKUP(Z1049,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"TSH levels were not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1049<>0,VLOOKUP(Z1049,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1050<>0,VLOOKUP(Z1050,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Lower AST in all three dose groups, lower potassium in the 100 and 300 mg/kg/day groups, higher chloride and ALP in the 1000 mg/kg/day group, and lower phosphorus in the 100 mg/kg/day group.  Since no histopathological changes were observed, the changes in clinical chemistry parameters were considered not toxicologically relevant.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1050<>0,VLOOKUP(Z1050,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Organ Weight","Ovary weight",{"$f":"IF(Z1051<>0,VLOOKUP(Z1051,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No evidence of glyphosate-related estrogenic or anti-estrogenic effects or effects on pubertal development or thyroid function .","absolute","No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1051<>0,VLOOKUP(Z1051,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z1052<>0,VLOOKUP(Z1052,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on uterus weight wet (with luminal fluid) and blotted was observed.","absolute","No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1052<>0,VLOOKUP(Z1052,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Organ Weight","Thyroid weight",{"$f":"IF(Z1053<>0,VLOOKUP(Z1053,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,"absolute","No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1053<>0,VLOOKUP(Z1053,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Organ Weight","Liver weight",{"$f":"IF(Z1054<>0,VLOOKUP(Z1054,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,"absolute","No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1054<>0,VLOOKUP(Z1054,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Organ Weight","Kidney weight",{"$f":"IF(Z1055<>0,VLOOKUP(Z1055,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,"absolute","No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1055<>0,VLOOKUP(Z1055,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Organ Weight","Pituitary weight",{"$f":"IF(Z1056<>0,VLOOKUP(Z1056,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,"absolute","No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1056<>0,VLOOKUP(Z1056,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Organ Weight","Adrenals weight",{"$f":"IF(Z1057<>0,VLOOKUP(Z1057,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,"absolute","No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1057<>0,VLOOKUP(Z1057,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1058<>0,VLOOKUP(Z1058,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1058<>0,VLOOKUP(Z1058,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1059<>0,VLOOKUP(Z1059,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1059<>0,VLOOKUP(Z1059,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1060<>0,VLOOKUP(Z1060,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1060<>0,VLOOKUP(Z1060,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Female pubertal assay (PP Female Assay)",44,null,"OPPTS 890.1450","DAR",null,2012,"Rat","Crl:CD(SD)",15,"F","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","21 (PND 22-42)","Days","Juvenile","F","> 1000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1061<>0,VLOOKUP(Z1061,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1061<>0,VLOOKUP(Z1061,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M",300,"In life observation","Clinical signs",{"$f":"IF(Z1062<>0,VLOOKUP(Z1062,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Rales were noted in 9/15 animals in the 300 mg/kg bw/day group and 14/14 animals in the 1000 mg/kg bw/day group throughout the treatment period approximately 4 hours following dose administration.",null,"Increase",100,300,"mg/kg bw/day",{"$f":"IF(Z1062<>0,VLOOKUP(Z1062,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M",1000,"In life observation","Mortality",{"$f":"IF(Z1063<>0,VLOOKUP(Z1063,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"One male in the 1000 mg/kg/day group was found dead prior to dose administration on PND 24.",null,"Increase",300,1000,"mg/kg bw/day",{"$f":"IF(Z1063<>0,VLOOKUP(Z1063,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M",300,"In life observation","Body weight",{"$f":"IF(Z1064<>0,VLOOKUP(Z1064,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Mean body weight gains for the 300 and 1000 mg/kg/day groups were decreased (7.5% and 12.4%, respectively) when the overall treatment period (PND 23-53) was evaluated, reaching statistical significance for the high dose group. Mean body weights for the 300 mg/kg/day group were 5.07% - 8.08% lower than the control group towards the end of the treatment period (PND 44-53), whereas mean body weights for the 1000 mg/kg/day group were 5.09% - 11.06% lower generally throughout the entire treatment period (PND 24-53). Final body weight was statistically significantly decreased by 12.4% and 7.5% for high and mid dose, respectively.  ",null,"Decrease",100,300,"mg/kg bw/day",{"$f":"IF(Z1064<>0,VLOOKUP(Z1064,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M",1000,"Reproductive","Age at balanopreputial separation",{"$f":"IF(Z1065<>0,VLOOKUP(Z1065,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"A statistically non-significant delay in the mean age at attainment of balanopreputial separation was observed in the high dose group (48.0 days). However, the body weight on the day of attainment of complete balanopreputial separation in the 1000 mg/kg/day group was similar to the control group. Thus, the delay of BPS is considered an effect secondary to reduced body weight gain. Moreover, when adjusting the day of attainment for those males with three or more consecutive days of incomplete separation (persistent threads), no statistically significant delay in the mean age of attainment of preputial separation was noted for the 1000 mg/kg bw/day dose group when compared to the control group. There were 6, 11, 9, and 9 males in the control, 100, 300, and 1000 mg/kg bw/day dose group, respectively, with incomplete PSS for more than three days. No test substance related effects were observed at doses ≤300 mg/kg bw/day.\n",null,"Increase",300,1000,"mg/kg bw/day",{"$f":"IF(Z1065<>0,VLOOKUP(Z1065,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M","> 1000","Clinical chemistry/hormones","Thyroid-stimulating hormone level (TSH)",{"$f":"IF(Z1066<>0,VLOOKUP(Z1066,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"Mean serum hormone level (TSH) were decreased from 100 mg/kg bw/day. However, the trend was not statistically significant. Moreover, no histological changes were observed in thyroid and thus, the observed decreasing trend is not considered toxicologically relevant.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1066<>0,VLOOKUP(Z1066,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M","> 1000","Clinical chemistry/hormones","T3 and T4 level",{"$f":"IF(Z1067<>0,VLOOKUP(Z1067,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"Mean serum hormone level (T4) were decreased from 100 mg/kg bw/day. However, the trend was not statistically significant. Moreover, no histological changes were observed in thyroid and thus, the observed decreasing trend is not considered toxicologically relevant.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1067<>0,VLOOKUP(Z1067,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M","> 1000","Clinical chemistry/hormones","Testosterone level",{"$f":"IF(Z1068<>0,VLOOKUP(Z1068,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"Mean serum hormone level was not statistically significantly decreased at 1000 mg/kg bw/day; a dose showing overt toxicity (1 mortality, rales, body weight gain decrease >10%). No dose-response was observed and no histological changes were observed in testes.  Therefore, the decrease is considered not treatment-related. ",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1068<>0,VLOOKUP(Z1068,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M","> 1000","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1069<>0,VLOOKUP(Z1069,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Higher mean alanine aminotransferase (ALT) and sodium levels were noted in the 300 and 1000 mg/kg/day groups, respectively; higher mean albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), chloride, phosphorus, and total protein levels and a lower urea nitrogen level were noted in the 1000 mg/kg/day group compared to the control group. These effects are reported as toxicologically not significant.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1069<>0,VLOOKUP(Z1069,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M","> 1000","Organ Weight","Thyroid weight",{"$f":"IF(Z1070<>0,VLOOKUP(Z1070,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1070<>0,VLOOKUP(Z1070,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M",300,"Organ Weight","Adrenals weight",{"$f":"IF(Z1071<>0,VLOOKUP(Z1071,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Lower mean absolute adrenal gland (9.2%, 8.6% for 1000 and 300 mg/kg bw/day dose group, respectively) weight was observed (not statistically significant). The effect was considered secondary to body weight changes.","absolute","Decrease",100,300,"mg/kg bw/day",{"$f":"IF(Z1071<>0,VLOOKUP(Z1071,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M",300,"Organ Weight","Epididymis weight",{"$f":"IF(Z1072<>0,VLOOKUP(Z1072,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Lower mean absolute left and right epididymis weight (9.5-9.9% and 3.8-7.1% for 1000 and 300 mg/kg bw/day dose group, respectively) was observed (not statistically significant). The effect was considered secondary to body weight changes.","absolute","Decrease",100,300,"mg/kg bw/day",{"$f":"IF(Z1072<>0,VLOOKUP(Z1072,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M",300,"Organ Weight","Kidney weight",{"$f":"IF(Z1073<>0,VLOOKUP(Z1073,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1073<>0,VLOOKUP(Z1073,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M",300,"Organ Weight","Liver weight",{"$f":"IF(Z1074<>0,VLOOKUP(Z1074,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Statistically significantly lower mean absolute liver weight (15.1% and 9.8% for 1000 and 300 mg/kg bw/day dose group, respectively) were observed. The effect was considered secondary to body weight changes.","absolute","Decrease",100,300,"mg/kg bw/day",{"$f":"IF(Z1074<>0,VLOOKUP(Z1074,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M",1000,"Organ Weight","Pituitary weight",{"$f":"IF(Z1075<>0,VLOOKUP(Z1075,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Statistically significantly lower mean absolute pituitary weight (15.6%) was observed. The effect was considered secondary to body weight changes.","absolute","Decrease",300,1000,"mg/kg bw/day",{"$f":"IF(Z1075<>0,VLOOKUP(Z1075,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M",1000,"Organ Weight","LABC weight",{"$f":"IF(Z1076<>0,VLOOKUP(Z1076,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Statistically significantly lower mean absolute LABC weight (15.9%) were observed. The effect was considered secondary to body weight changes.","absolute","Decrease",300,1000,"mg/kg bw/day",{"$f":"IF(Z1076<>0,VLOOKUP(Z1076,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M",1000,"Organ Weight","Prostate weight",{"$f":"IF(Z1077<>0,VLOOKUP(Z1077,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Statistically significantly lower mean absolute ventral prostate weight (22.6%) were observed. The effect was considered secondary to body weight changes.","absolute","Decrease",300,1000,"mg/kg bw/day",{"$f":"IF(Z1077<>0,VLOOKUP(Z1077,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M",1000,"Organ Weight","Seminal vesicles weight",{"$f":"IF(Z1078<>0,VLOOKUP(Z1078,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Statistically significantly lower mean absolute seminal vesicle (with coagulating gland and fluid 18.5% and without 16.4%) weight were observed in the 1000 mg/kg/day group. The effect is considered to be a consequence of the lower mean body weights in this group. The effect was considered secondary to body weight changes.","absolute","Decrease",300,1000,"mg/kg bw/day",{"$f":"IF(Z1078<>0,VLOOKUP(Z1078,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M","> 1000","Organ Weight","Testis weight",{"$f":"IF(Z1079<>0,VLOOKUP(Z1079,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",300,1000,"mg/kg bw/day",{"$f":"IF(Z1079<>0,VLOOKUP(Z1079,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M","> 1000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1080<>0,VLOOKUP(Z1080,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1080<>0,VLOOKUP(Z1080,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M","> 1000","Organ histopathology","Testis histopathology",{"$f":"IF(Z1081<>0,VLOOKUP(Z1081,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1081<>0,VLOOKUP(Z1081,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M","> 1000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1082<>0,VLOOKUP(Z1082,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1082<>0,VLOOKUP(Z1082,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Male pubertal assay (PP Male Assay)",45,null,"OPPTS 890.1500","DAR",null,2012,"Rat","Crl:CD(SD)",15,"M","95.93 (glyphosate acid); 85.14 (calculated glyphosate content)","Oral","Gavage/Intubation","100; 300; 1000",100,1000,"mg/kg bw/day","31 (PND 23-53)","Days","Juvenile","M","> 1000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1083<>0,VLOOKUP(Z1083,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1083<>0,VLOOKUP(Z1083,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",46,null,"EPA FIFRA 83-3; OECD 414","DAR",null,1991,"Rabbit","New Zealand White","16-20","F",98.6,"Oral","Gavage/Intubation","50; 150; 450",50,450,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F",50,"In life observation","Clinical signs",{"$f":"IF(Z1084<>0,VLOOKUP(Z1084,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Light increase in females with gastro-intestinal disturbances (from 50 mg/kg bw/day), dose-related increase in the incidence of females showing soft/liquid faeces; sings of inappetence (150 mg/kg bw/day group and higher dose groups)",null,"Increase","< 50",50,"mg/kg bw/day",{"$f":"IF(Z1084<>0,VLOOKUP(Z1084,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",46,null,"EPA FIFRA 83-3; OECD 414","DAR",null,1991,"Rabbit","New Zealand White","16-20","F",98.6,"Oral","Gavage/Intubation","50; 150; 450",50,450,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F",150,"In life observation","Food consumption",{"$f":"IF(Z1085<>0,VLOOKUP(Z1085,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption was decreased throughout the treatment period.",null,"Decrease",50,150,"mg/kg bw/day",{"$f":"IF(Z1085<>0,VLOOKUP(Z1085,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",46,null,"EPA FIFRA 83-3; OECD 414","DAR",null,1991,"Rabbit","New Zealand White","16-20","F",98.6,"Oral","Gavage/Intubation","50; 150; 450",50,450,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F",150,"In life observation","Body weight",{"$f":"IF(Z1086<>0,VLOOKUP(Z1086,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Body weight gain was slightly reduced from 150 mg/kg bw (GD11-19)",null,"Decrease",50,150,"mg/kg bw/day",{"$f":"IF(Z1086<>0,VLOOKUP(Z1086,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",46,null,"EPA FIFRA 83-3; OECD 414","DAR",null,1991,"Rabbit","New Zealand White","16-20","F",98.6,"Oral","Gavage/Intubation","50; 150; 450",50,450,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F",450,"In life observation","Mortality",{"$f":"IF(Z1087<>0,VLOOKUP(Z1087,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"1/20 animals of the high dose group died after abortion: gastro-intestinal disturbances; heart and kidneys pale; a few haemorrhagic depressions in the stomach (concurrent severe reduction in food intake; body weight loss)",null,"Increase",150,450,"mg/kg bw/day",{"$f":"IF(Z1087<>0,VLOOKUP(Z1087,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",46,null,"EPA FIFRA 83-3; OECD 414","DAR",null,1991,"Rabbit","New Zealand White","16-20","F",98.6,"Oral","Gavage/Intubation","50; 150; 450",50,450,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F","> 450","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z1088<>0,VLOOKUP(Z1088,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect on corpora lutea or implantation rate were observed (established parameters prior to treatment). ",null,"No effect",450,"> 450","mg/kg bw/day",{"$f":"IF(Z1088<>0,VLOOKUP(Z1088,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",46,null,"EPA FIFRA 83-3; OECD 414","DAR",null,1991,"Rabbit","New Zealand White","16-20","F",98.6,"Oral","Gavage/Intubation","50; 150; 450",50,450,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F","> 450","Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z1089<>0,VLOOKUP(Z1089,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect on abortions was observed. Number of embryonic deaths was in treated groups was increased compared to concurrent control. However, this effect is not considered treatment-related since the concurrent control values were atypically low and observed incidences in treatment groups were within the  range of historic control data. Consequently viable fetuses at GD 29 and weight were reduced in treated groups. (A total of 18, 12, 15 and 13 pregnant females (and 163, 104, 112 and 95 foetuses) in control, 50, 150, 450 mg/kg bw/d group, respectively have been included in assessment.)",null,"No effect",450,"> 450","mg/kg bw/day",{"$f":"IF(Z1089<>0,VLOOKUP(Z1089,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",46,null,"EPA FIFRA 83-3; OECD 414","DAR",null,1991,"Rabbit","New Zealand White","16-20","F",98.6,"Oral","Gavage/Intubation","50; 150; 450",50,450,"mg/kg bw/day","13 (GD 7-19)","Days","Fetus","M + F","> 450","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z1090<>0,VLOOKUP(Z1090,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Increases in fetuses with heart malformations (from 150 mg/kg bw/d) were not considered treatment-related when compared to historic control data of 13 studies performed the same year. Group mean incidences of anomalies and malformations showed no significant differences compared to the control group.",null,"No effect",150,450,"mg/kg bw/day",{"$f":"IF(Z1090<>0,VLOOKUP(Z1090,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",46,null,"EPA FIFRA 83-3; OECD 414","DAR",null,1991,"Rabbit","New Zealand White","16-20","F",98.6,"Oral","Gavage/Intubation","50; 150; 450",50,450,"mg/kg bw/day","13 (GD 7-19)","Days","Fetus","M + F","> 450","Developmental","Litter/pup weight",{"$f":"IF(Z1091<>0,VLOOKUP(Z1091,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Litter weight was similarly reduced at all dose-levels, reflecting the differences in the litter size. However, no change on mean fetal weight was observed.",null,"No effect",450,"> 450","mg/kg bw/day",{"$f":"IF(Z1091<>0,VLOOKUP(Z1091,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",46,null,"EPA FIFRA 83-3; OECD 414","DAR",null,1991,"Rabbit","New Zealand White","16-20","F",98.6,"Oral","Gavage/Intubation","50; 150; 450",50,450,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F","> 450","Reproductive","Post implantation loss",{"$f":"IF(Z1092<>0,VLOOKUP(Z1092,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"An increase compared to concurrent control group was observed based on the increase of embryonic deaths. However, this effect was considered not treatment-related since the concurrent control group values were very low, no dose-related effect was observed, and incidence was only slightly above the historic control.",null,"No effect",150,450,"mg/kg bw/day",{"$f":"IF(Z1092<>0,VLOOKUP(Z1092,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",46,null,"EPA FIFRA 83-3; OECD 414","DAR",null,1991,"Rabbit","New Zealand White","16-20","F",98.6,"Oral","Gavage/Intubation","50; 150; 450",50,450,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F","> 450","Reproductive","Pre implantation loss",{"$f":"IF(Z1093<>0,VLOOKUP(Z1093,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect on pre-implantation loss was observed. However, treatment was started after implantation.",null,"No effect",450,"> 450","mg/kg bw/day",{"$f":"IF(Z1093<>0,VLOOKUP(Z1093,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",46,null,"EPA FIFRA 83-3; OECD 414","DAR",null,1991,"Rabbit","New Zealand White","16-20","F",98.6,"Oral","Gavage/Intubation","50; 150; 450",50,450,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F","> 450","Reproductive","Sex ratio",{"$f":"IF(Z1094<>0,VLOOKUP(Z1094,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",450,"> 450","mg/kg bw/day",{"$f":"IF(Z1094<>0,VLOOKUP(Z1094,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",47,null,"in general compliance to: EPA FIFRA 83-3; OECD 414 (preliminary study)","DAR",null,1991,"Rabbit","New Zealand White",6,"F",98.6,"Oral","Gavage/Intubation","100; 250; 625",100,625,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F",100,"In life observation","Clinical signs",{"$f":"IF(Z1095<>0,VLOOKUP(Z1095,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Signs of gastro-intestinal disturbances and inappetence were observed in all dose groups.",null,"Increase","< 100",100,"mg/kg bw/day",{"$f":"IF(Z1095<>0,VLOOKUP(Z1095,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",47,null,"in general compliance to: EPA FIFRA 83-3; OECD 414 (preliminary study)","DAR",null,1991,"Rabbit","New Zealand White",6,"F",98.6,"Oral","Gavage/Intubation","100; 250; 625",100,625,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F",100,"In life observation","Body weight",{"$f":"IF(Z1096<>0,VLOOKUP(Z1096,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Transient body weight gain reductions were observed in the low and mid dose group and throughout the treatment period for the high dose group. ",null,"Decrease","< 100",100,"mg/kg bw/day",{"$f":"IF(Z1096<>0,VLOOKUP(Z1096,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",47,null,"in general compliance to: EPA FIFRA 83-3; OECD 414 (preliminary study)","DAR",null,1991,"Rabbit","New Zealand White",6,"F",98.6,"Oral","Gavage/Intubation","100; 250; 625",100,625,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F",100,"In life observation","Food consumption",{"$f":"IF(Z1097<>0,VLOOKUP(Z1097,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"A marked reduction was observed in the high dose group and slight or transient reductions in the low and mid-dose group.",null,"Decrease","< 100",100,"mg/kg bw/day",{"$f":"IF(Z1097<>0,VLOOKUP(Z1097,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",47,null,"in general compliance to: EPA FIFRA 83-3; OECD 414 (preliminary study)","DAR",null,1991,"Rabbit","New Zealand White",6,"F",98.6,"Oral","Gavage/Intubation","100; 250; 625",100,625,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F",625,"In life observation","Mortality",{"$f":"IF(Z1098<>0,VLOOKUP(Z1098,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"2/6 animals died in the high dose group (following marked body weight loss, inappetence, complete litter loss).",null,"Increase",250,625,"mg/kg bw/day",{"$f":"IF(Z1098<>0,VLOOKUP(Z1098,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",47,null,"in general compliance to: EPA FIFRA 83-3; OECD 414 (preliminary study)","DAR",null,1991,"Rabbit","New Zealand White",6,"F",98.6,"Oral","Gavage/Intubation","100; 250; 625",100,625,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F","> 625","Reproductive","Litter size",{"$f":"IF(Z1099<>0,VLOOKUP(Z1099,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",625,"> 625","mg/kg bw/day",{"$f":"IF(Z1099<>0,VLOOKUP(Z1099,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",47,null,"in general compliance to: EPA FIFRA 83-3; OECD 414 (preliminary study)","DAR",null,1991,"Rabbit","New Zealand White",6,"F",98.6,"Oral","Gavage/Intubation","100; 250; 625",100,625,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F","> 625","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z1100<>0,VLOOKUP(Z1100,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"There were no treatment-related effects on corpora lutea count, implantation rate (all established prior to treatment).",null,"No effect",625,"> 625","mg/kg bw/day",{"$f":"IF(Z1100<>0,VLOOKUP(Z1100,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",47,null,"in general compliance to: EPA FIFRA 83-3; OECD 414 (preliminary study)","DAR",null,1991,"Rabbit","New Zealand White",6,"F",98.6,"Oral","Gavage/Intubation","100; 250; 625",100,625,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F","> 625","Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z1101<>0,VLOOKUP(Z1101,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect on embryonic deaths was observed.",null,"No effect",625,"> 625","mg/kg bw/day",{"$f":"IF(Z1101<>0,VLOOKUP(Z1101,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",47,null,"in general compliance to: EPA FIFRA 83-3; OECD 414 (preliminary study)","DAR",null,1991,"Rabbit","New Zealand White",6,"F",98.6,"Oral","Gavage/Intubation","100; 250; 625",100,625,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F","> 625","Reproductive","Pre implantation loss",{"$f":"IF(Z1102<>0,VLOOKUP(Z1102,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",625,"> 625","mg/kg bw/day",{"$f":"IF(Z1102<>0,VLOOKUP(Z1102,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",47,null,"in general compliance to: EPA FIFRA 83-3; OECD 414 (preliminary study)","DAR",null,1991,"Rabbit","New Zealand White",6,"F",98.6,"Oral","Gavage/Intubation","100; 250; 625",100,625,"mg/kg bw/day","13 (GD 7-19)","Days","Adult","F","> 625","Reproductive","Post implantation loss",{"$f":"IF(Z1103<>0,VLOOKUP(Z1103,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",625,"> 625","mg/kg bw/day",{"$f":"IF(Z1103<>0,VLOOKUP(Z1103,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",47,null,"in general compliance to: EPA FIFRA 83-3; OECD 414 (preliminary study)","DAR",null,1991,"Rabbit","New Zealand White",6,"F",98.6,"Oral","Gavage/Intubation","100; 250; 625",100,625,"mg/kg bw/day","13 (GD 7-19)","Days","Fetus","M + F","> 625","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z1104<>0,VLOOKUP(Z1104,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",625,"> 625","mg/kg bw/day",{"$f":"IF(Z1104<>0,VLOOKUP(Z1104,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",47,null,"in general compliance to: EPA FIFRA 83-3; OECD 414 (preliminary study)","DAR",null,1991,"Rabbit","New Zealand White",6,"F",98.6,"Oral","Gavage/Intubation","100; 250; 625",100,625,"mg/kg bw/day","13 (GD 7-19)","Days","Fetus","M + F","> 625","Developmental","Litter/pup weight",{"$f":"IF(Z1105<>0,VLOOKUP(Z1105,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",625,"> 625","mg/kg bw/day",{"$f":"IF(Z1105<>0,VLOOKUP(Z1105,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",47,null,"in general compliance to: EPA FIFRA 83-3; OECD 414 (preliminary study)","DAR",null,1991,"Rabbit","New Zealand White",6,"F",98.6,"Oral","Gavage/Intubation","100; 250; 625",100,625,"mg/kg bw/day","13 (GD 7-19)","Days","Fetus","M + F","> 625","Reproductive","Sex ratio",{"$f":"IF(Z1106<>0,VLOOKUP(Z1106,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",625,"> 625","mg/kg bw/day",{"$f":"IF(Z1106<>0,VLOOKUP(Z1106,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",48,null," dose range finding study for maximum tolerated dose in the rabbit","DAR",null,1991,"Rabbit","New Zealand White",2,"F",98.6,"Oral","Gavage/Intubation","500; 750; 1000",500,1000,"mg/kg bw/day"," 7 (high dose) -13 (mid and low dose)","Days","Adult","F",500,"In life observation","Clinical signs",{"$f":"IF(Z1107<>0,VLOOKUP(Z1107,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Soft feces (from 500 mg/kg bw/day); gastro-intestinal disturbances (from 750 mg/kg bw/day); haemorrhagic depressions of the stomach and damp/stained fur of the tail (1000 mg/kg bw/day).",null,"Increase","< 500",500,"mg/kg bw/day",{"$f":"IF(Z1107<>0,VLOOKUP(Z1107,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",48,null," dose range finding study for maximum tolerated dose in the rabbit","DAR",null,1991,"Rabbit","New Zealand White",2,"F",98.6,"Oral","Gavage/Intubation","500; 750; 1000",500,1000,"mg/kg bw/day"," 7 (high dose) -13 (mid and low dose)","Days","Adult","F",750,"In life observation","Body weight",{"$f":"IF(Z1108<>0,VLOOKUP(Z1108,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Marked weight loss was observed from 750 mg/kg bw/day (not significant).",null,"Decrease",500,750,"mg/kg bw/day",{"$f":"IF(Z1108<>0,VLOOKUP(Z1108,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",48,null," dose range finding study for maximum tolerated dose in the rabbit","DAR",null,1991,"Rabbit","New Zealand White",2,"F",98.6,"Oral","Gavage/Intubation","500; 750; 1000",500,1000,"mg/kg bw/day"," 7 (high dose) -13 (mid and low dose)","Days","Adult","F",1000,"In life observation","Food consumption",{"$f":"IF(Z1109<>0,VLOOKUP(Z1109,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption?",null,"Decrease",500,750,"mg/kg bw/day",{"$f":"IF(Z1109<>0,VLOOKUP(Z1109,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","In life observation","Mortality",{"$f":"IF(Z1110<>0,VLOOKUP(Z1110,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1110<>0,VLOOKUP(Z1110,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","In life observation","Clinical signs",{"$f":"IF(Z1111<>0,VLOOKUP(Z1111,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related findings. (A few incidences of urine incontinence were observed at 2000 ppm (2/5 males) and 20000 ppm (2/5 females), but not in 20000 ppm recovery animals, therefore the findings wer considered to be incidental)",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1111<>0,VLOOKUP(Z1111,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","In life observation","Body weight",{"$f":"IF(Z1112<>0,VLOOKUP(Z1112,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1112<>0,VLOOKUP(Z1112,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","In life observation","Food consumption",{"$f":"IF(Z1113<>0,VLOOKUP(Z1113,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1113<>0,VLOOKUP(Z1113,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",20000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1114<>0,VLOOKUP(Z1114,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: No treatment-related findings. (Statistically significant decrease in haemoglobin in the high dose recovery animals; as the animals of the main group were not affected the effect was considered to be incidental.)\nClinical chemistry: Statistically significant increase in GPT and BUN at 20000 ppm in both sexes, which is reversible after 14 days of recovery (Non-treatment-related findings: statistically significant increase in BUN at 200 ppm, considered to be incidental due to the lack of a dose-relationship NOEAL for changes in BUN and GPT is 2000 mg/kg bw/d equivalent to 100 mg/kg bw; incidental decrease in Ca2+ at 200 ppm, increase in Ca2+ in 20000 ppm recovery group but not in the main group)",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1114<>0,VLOOKUP(Z1114,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ Weight","Liver weight",{"$f":"IF(Z1115<>0,VLOOKUP(Z1115,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Neither absolute nor relative organ weight was affected.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1115<>0,VLOOKUP(Z1115,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ Weight","Kidney weight",{"$f":"IF(Z1116<>0,VLOOKUP(Z1116,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Neither absolute nor relative organ weight was affected.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1116<>0,VLOOKUP(Z1116,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","F",">20000","Organ Weight","Ovary weight",{"$f":"IF(Z1117<>0,VLOOKUP(Z1117,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Neither absolute nor relative organ weight was affected.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1117<>0,VLOOKUP(Z1117,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Urinalysis was not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M",">20000","Organ Weight","Testis weight",{"$f":"IF(Z1118<>0,VLOOKUP(Z1118,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Neither absolute nor relative organ weight was affected.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1118<>0,VLOOKUP(Z1118,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Urinalysis was not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ Weight","Adrenals weight",{"$f":"IF(Z1119<>0,VLOOKUP(Z1119,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1119<>0,VLOOKUP(Z1119,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Urinalysis was not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M",">20000","Organ histopathology","Coagulating gland histopathology",{"$f":"IF(Z1120<>0,VLOOKUP(Z1120,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1120<>0,VLOOKUP(Z1120,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","F",">20000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1121<>0,VLOOKUP(Z1121,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1121<>0,VLOOKUP(Z1121,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M",">20000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1122<>0,VLOOKUP(Z1122,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1122<>0,VLOOKUP(Z1122,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M",">20000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z1123<>0,VLOOKUP(Z1123,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1123<>0,VLOOKUP(Z1123,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M",">20000","Organ histopathology","Testis histopathology",{"$f":"IF(Z1124<>0,VLOOKUP(Z1124,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1124<>0,VLOOKUP(Z1124,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1125<>0,VLOOKUP(Z1125,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1125<>0,VLOOKUP(Z1125,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","F",">20000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1126<>0,VLOOKUP(Z1126,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1126<>0,VLOOKUP(Z1126,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1127<>0,VLOOKUP(Z1127,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1127<>0,VLOOKUP(Z1127,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1128<>0,VLOOKUP(Z1128,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1128<>0,VLOOKUP(Z1128,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ histopathology","Heart histopathology",{"$f":"IF(Z1129<>0,VLOOKUP(Z1129,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1129<>0,VLOOKUP(Z1129,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ histopathology","Eyes histopathology",{"$f":"IF(Z1130<>0,VLOOKUP(Z1130,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1130<>0,VLOOKUP(Z1130,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z1131<>0,VLOOKUP(Z1131,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1131<>0,VLOOKUP(Z1131,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ histopathology","Liver histopathology",{"$f":"IF(Z1132<>0,VLOOKUP(Z1132,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1132<>0,VLOOKUP(Z1132,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1133<>0,VLOOKUP(Z1133,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1133<>0,VLOOKUP(Z1133,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1134<>0,VLOOKUP(Z1134,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1134<>0,VLOOKUP(Z1134,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1135<>0,VLOOKUP(Z1135,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1135<>0,VLOOKUP(Z1135,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ histopathology","Lung histopathology",{"$f":"IF(Z1136<>0,VLOOKUP(Z1136,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: Petechiae in 1/5 males and 2/5 recovery males at 20000 ppm, ecchymosis in 1/5 males at 20000 ppm, focal congestion in 1/5 males and 1/5 females at 20000 ppm; all findings were considered to be incidental\nHistopathology: Lymphoid hyperplasia in 1/5 and 5/5 males and in 2/5 and 1/5 females at 0 and 20000 ppm, considered to be incidental as the severity was not increased in the high dose group (increased incidences of congestion, atelectasis, interstitial pneumonia, perivascular leucocytic infiltration and perivascular lymphocytic aggregation were comparable between treated and control animals)",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1136<>0,VLOOKUP(Z1136,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z1137<>0,VLOOKUP(Z1137,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology colon: lymphoid hyperplasia in 1/5 and 2/5 females at 0 and 20000 ppm, considered to be incidental as the severitiy was not increased in the high dose group",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1137<>0,VLOOKUP(Z1137,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",49,null,"OECD 407 (1981)","DAR",null,"1991 (Amendment 1994)","Rat","Wistar",5,"M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",28,"Days","Adult","M + F",">20000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1138<>0,VLOOKUP(Z1138,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: thickening of capsule in 1/5 females at 20000 ppm in the recovery group, considered to be incidental as histopathological findings were absent",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1138<>0,VLOOKUP(Z1138,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Urinalysis was not performed, histopathology was performed for control and high dose group animals only","Yes","Yes"]
["Mammals","Subacute oral in rodent ",50,5626,"OECD 407 (1981)","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",99.5,"Oral","Feed","50; 250; 1000; 2500",50,2500,"mg/kg bw/day",28,"Days","Adult","M + F",">2500","In life observation","Mortality",{"$f":"IF(Z1139<>0,VLOOKUP(Z1139,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",2500,">2500","mg/kg bw/day",{"$f":"IF(Z1139<>0,VLOOKUP(Z1139,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses: 49 ± 5.8, 255 ± 9.6, 1034 ± 58.2 and 2592 ± 226.9 mg/kg bw/day in males and 55 ± 7.9, 277 ± 17.1, 1047 ± 86.4 and 2614 ± 318.4 mg/kg bw/day in females; no recovery animals included, urinarlysis not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",50,5626,"OECD 407 (1981)","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",99.5,"Oral","Feed","50; 250; 1000; 2500",50,2500,"mg/kg bw/day",28,"Days","Adult","M + F",2500,"In life observation","Clinical signs",{"$f":"IF(Z1140<>0,VLOOKUP(Z1140,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Soft faeces in 3/5 males at 2500 mg/kg bw/day during weeks 3 and 4, treatment-related",null,"Increase",1000,2500,"mg/kg bw/day",{"$f":"IF(Z1140<>0,VLOOKUP(Z1140,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses: 49 ± 5.8, 255 ± 9.6, 1034 ± 58.2 and 2592 ± 226.9 mg/kg bw/day in males and 55 ± 7.9, 277 ± 17.1, 1047 ± 86.4 and 2614 ± 318.4 mg/kg bw/day in females; no recovery animals included, urinarlysis not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",50,5626,"OECD 407 (1981)","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",99.5,"Oral","Feed","50; 250; 1000; 2500",50,2500,"mg/kg bw/day",28,"Days","Adult","M + F",2500,"In life observation","Body weight",{"$f":"IF(Z1141<>0,VLOOKUP(Z1141,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Reduced total body weight gain at 2500 mg/kg bw/day in males (-9%) and females (-11%) throughout the dosing period, statistically not significant, not considered treatment-related",null,"No effect",2500,">2500","mg/kg bw/day",{"$f":"IF(Z1141<>0,VLOOKUP(Z1141,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses: 49 ± 5.8, 255 ± 9.6, 1034 ± 58.2 and 2592 ± 226.9 mg/kg bw/day in males and 55 ± 7.9, 277 ± 17.1, 1047 ± 86.4 and 2614 ± 318.4 mg/kg bw/day in females; no recovery animals included, urinarlysis not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",50,5626,"OECD 407 (1981)","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",99.5,"Oral","Feed","50; 250; 1000; 2500",50,2500,"mg/kg bw/day",28,"Days","Adult","M + F",">2500","In life observation","Food consumption",{"$f":"IF(Z1142<>0,VLOOKUP(Z1142,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Neither an efect on food not on water consumption was observed.",null,"No effect",2500,">2500","mg/kg bw/day",{"$f":"IF(Z1142<>0,VLOOKUP(Z1142,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses: 49 ± 5.8, 255 ± 9.6, 1034 ± 58.2 and 2592 ± 226.9 mg/kg bw/day in males and 55 ± 7.9, 277 ± 17.1, 1047 ± 86.4 and 2614 ± 318.4 mg/kg bw/day in females; no recovery animals included, urinarlysis not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",50,5626,"OECD 407 (1981)","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",99.5,"Oral","Feed","50; 250; 1000; 2500",50,2500,"mg/kg bw/day",28,"Days","Adult","M + F",250,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1143<>0,VLOOKUP(Z1143,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: No treatment-related findings (statistically significantly decreased MCHC (-2%) in males at 50 mg/kg bw/day was considered to be incidental)\nClinical chemistry: statistically significantly increased ALT in males at ≥ 250 mg/kg bw/day and in females at 2500 mg/kg bw/day, increased ALP in males at ≥ 250 mg/kg bw/day (statistically significant at 250 and 2500 mg/kg bw/day) and in females at ≥ 1000 mg/kg bw/day (not significant) and bilirubin were regarded as normal responses to increased liver activity; increased phosphate levels in males at ≥ 1000 mg/kg bw/day, treatment-related (slightly increased Na in females at 50, 1000 and 2500 mg/kg bw/day and slighly decreased Cl in females at 50 mg/kg bw/day were considered to be incidental)",null,"Change",50,250,"mg/kg bw/day",{"$f":"IF(Z1143<>0,VLOOKUP(Z1143,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses: 49 ± 5.8, 255 ± 9.6, 1034 ± 58.2 and 2592 ± 226.9 mg/kg bw/day in males and 55 ± 7.9, 277 ± 17.1, 1047 ± 86.4 and 2614 ± 318.4 mg/kg bw/day in females; no recovery animals included, urinarlysis not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",50,5626,"OECD 407 (1981)","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",99.5,"Oral","Feed","50; 250; 1000; 2500",50,2500,"mg/kg bw/day",28,"Days","Adult","M + F",">2500","Organ Weight","Liver weight",{"$f":"IF(Z1144<>0,VLOOKUP(Z1144,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",2500,">2500","mg/kg bw/day",{"$f":"IF(Z1144<>0,VLOOKUP(Z1144,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses: 49 ± 5.8, 255 ± 9.6, 1034 ± 58.2 and 2592 ± 226.9 mg/kg bw/day in males and 55 ± 7.9, 277 ± 17.1, 1047 ± 86.4 and 2614 ± 318.4 mg/kg bw/day in females; no recovery animals included, urinarlysis not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",50,5626,"OECD 407 (1981)","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",99.5,"Oral","Feed","50; 250; 1000; 2500",50,2500,"mg/kg bw/day",28,"Days","Adult","M",">2500","Organ Weight","Testis weight",{"$f":"IF(Z1145<>0,VLOOKUP(Z1145,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on testes weight was observed (weighted together with epididymis).",null,"No effect",2500,">2500","mg/kg bw/day",{"$f":"IF(Z1145<>0,VLOOKUP(Z1145,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved doses: 49 ± 5.8, 255 ± 9.6, 1034 ± 58.2 and 2592 ± 226.9 mg/kg bw/day in males and 55 ± 7.9, 277 ± 17.1, 1047 ± 86.4 and 2614 ± 318.4 mg/kg bw/day in females; weighed together with epididymides; no recovery animals included, urinarlysis not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",50,5626,"OECD 407 (1981)","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",99.5,"Oral","Feed","50; 250; 1000; 2500",50,2500,"mg/kg bw/day",28,"Days","Adult","M + F",">2500","Organ Weight","Adrenals weight",{"$f":"IF(Z1146<>0,VLOOKUP(Z1146,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",2500,">2500","mg/kg bw/day",{"$f":"IF(Z1146<>0,VLOOKUP(Z1146,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved doses: 49 ± 5.8, 255 ± 9.6, 1034 ± 58.2 and 2592 ± 226.9 mg/kg bw/day in males and 55 ± 7.9, 277 ± 17.1, 1047 ± 86.4 and 2614 ± 318.4 mg/kg bw/day in females; no recovery animals included, urinarlysis not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",50,5626,"OECD 407 (1981)","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",99.5,"Oral","Feed","50; 250; 1000; 2500",50,2500,"mg/kg bw/day",28,"Days","Adult","M + F",">2500","Organ Weight","Kidney weight",{"$f":"IF(Z1147<>0,VLOOKUP(Z1147,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",2500,">2500","mg/kg bw/day",{"$f":"IF(Z1147<>0,VLOOKUP(Z1147,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses: 49 ± 5.8, 255 ± 9.6, 1034 ± 58.2 and 2592 ± 226.9 mg/kg bw/day in males and 55 ± 7.9, 277 ± 17.1, 1047 ± 86.4 and 2614 ± 318.4 mg/kg bw/day in females; no recovery animals included, urinarlysis not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",50,5626,"OECD 407 (1981)","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",99.5,"Oral","Feed","50; 250; 1000; 2500",50,2500,"mg/kg bw/day",28,"Days","Adult","M + F",">2500","Organ histopathology","Liver histopathology",{"$f":"IF(Z1148<>0,VLOOKUP(Z1148,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",2500,">2500","mg/kg bw/day",{"$f":"IF(Z1148<>0,VLOOKUP(Z1148,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses: 49 ± 5.8, 255 ± 9.6, 1034 ± 58.2 and 2592 ± 226.9 mg/kg bw/day in males and 55 ± 7.9, 277 ± 17.1, 1047 ± 86.4 and 2614 ± 318.4 mg/kg bw/day in females; no recovery animals included, urinarlysis not performed; Histopathology was performed in control and high dose groups.","Yes","Yes"]
["Mammals","Subacute oral in rodent ",50,5626,"OECD 407 (1981)","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",99.5,"Oral","Feed","50; 250; 1000; 2500",50,2500,"mg/kg bw/day",28,"Days","Adult","M + F",">2500","Organ histopathology","Heart histopathology",{"$f":"IF(Z1149<>0,VLOOKUP(Z1149,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",2500,">2500","mg/kg bw/day",{"$f":"IF(Z1149<>0,VLOOKUP(Z1149,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses: 49 ± 5.8, 255 ± 9.6, 1034 ± 58.2 and 2592 ± 226.9 mg/kg bw/day in males and 55 ± 7.9, 277 ± 17.1, 1047 ± 86.4 and 2614 ± 318.4 mg/kg bw/day in females; no recovery animals included, urinarlysis not performed; Histopathology was performed in control and high dose groups.","Yes","Yes"]
["Mammals","Subacute oral in rodent ",50,5626,"OECD 407 (1981)","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",99.5,"Oral","Feed","50; 250; 1000; 2500",50,2500,"mg/kg bw/day",28,"Days","Adult","F",250,"Organ histopathology","Kidney histopathology",{"$f":"IF(Z1150<>0,VLOOKUP(Z1150,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Nephrocalcinosis (mineral deposition) in 2/5, 2/5 and 4/5 females at 250, 1000 and 2500 mg/kg bw/day, treatment-related",null,"Change",50,250,"mg/kg bw/day",{"$f":"IF(Z1150<>0,VLOOKUP(Z1150,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses: 49 ± 5.8, 255 ± 9.6, 1034 ± 58.2 and 2592 ± 226.9 mg/kg bw/day in males and 55 ± 7.9, 277 ± 17.1, 1047 ± 86.4 and 2614 ± 318.4 mg/kg bw/day in females; no recovery animals included, urinarlysis not performed","Yes","Yes"]
["Mammals","Subacute oral in rodent ",50,5626,"OECD 407 (1981)","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",99.5,"Oral","Feed","50; 250; 1000; 2500",50,2500,"mg/kg bw/day",28,"Days","Adult","M + F",">2500","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1151<>0,VLOOKUP(Z1151,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",2500,">2500","mg/kg bw/day",{"$f":"IF(Z1151<>0,VLOOKUP(Z1151,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses: 49 ± 5.8, 255 ± 9.6, 1034 ± 58.2 and 2592 ± 226.9 mg/kg bw/day in males and 55 ± 7.9, 277 ± 17.1, 1047 ± 86.4 and 2614 ± 318.4 mg/kg bw/day in females; no recovery animals included, urinarlysis not performed; Histopathology was performed in control and high dose groups.","Yes","Yes"]
["Mammals","Subacute oral in rodent ",50,5626,"OECD 407 (1981)","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",99.5,"Oral","Feed","50; 250; 1000; 2500",50,2500,"mg/kg bw/day",28,"Days","Adult","M + F",">2500","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1152<>0,VLOOKUP(Z1152,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",2500,">2500","mg/kg bw/day",{"$f":"IF(Z1152<>0,VLOOKUP(Z1152,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved doses: 49 ± 5.8, 255 ± 9.6, 1034 ± 58.2 and 2592 ± 226.9 mg/kg bw/day in males and 55 ± 7.9, 277 ± 17.1, 1047 ± 86.4 and 2614 ± 318.4 mg/kg bw/day in females; no recovery animals included, urinarlysis not performed; Histopathology was performed in control and high dose groups.","Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",51,5660,"dose-range finding study for maximum tolerated dose","DAR",null,1989,"Dog","Beagle",1,"M + F",99.5,"Oral","Capsule","100; 300; 1000 *see remarks",100,1000,"mg/kg bw/day","Study part A: 21\nStudy Part B: 14","Days","Adult","M + F",">1000","In life observation","Mortality",{"$f":"IF(Z1153<>0,VLOOKUP(Z1153,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1153<>0,VLOOKUP(Z1153,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"* The study was separated in parts A and B. For each part each one male and one female dog were used.\nStudy part A: the male and the female dog were treated at all dose levels: 100 mg/kg bw/day in study Days 1-7, 300 mg/kg bw/day in study Days 8-14 and 1000 mg/kg bw/day in study Days 15-21\nStudy part B: both dogs were treated at 1000 mg/kg bw/day for 14 days","Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",51,5660,"dose-range finding study for maximum tolerated dose","DAR",null,1989,"Dog","Beagle",1,"M + F",99.5,"Oral","Capsule","100; 300; 1000 *see remarks",100,1000,"mg/kg bw/day","Study part A: 21\nStudy Part B: 14","Days","Adult","M + F",">1000","In life observation","Clinical signs",{"$f":"IF(Z1154<>0,VLOOKUP(Z1154,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Study part A (21 days of treatment): No abnormal findings were observed.\nStudy part B (14 days of treatment): the female dog showed loose faeces during the course of the treatment period, findings were not attributed to treatment",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1154<>0,VLOOKUP(Z1154,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"* The study was separated in parts A and B. For each part each one male and one female dog were used.\nStudy part A: the male and the female dog were treated at all dose levels: 100 mg/kg bw/day in study Days 1-7, 300 mg/kg bw/day in study Days 8-14 and 1000 mg/kg bw/day in study Days 15-21\nStudy part B: both dogs were treated at 1000 mg/kg bw/day for 14 days","Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",51,5660,"dose-range finding study for maximum tolerated dose","DAR",null,1989,"Dog","Beagle",1,"M + F",99.5,"Oral","Capsule","100; 300; 1000 *see remarks",100,1000,"mg/kg bw/day","Study part A: 21\nStudy Part B: 14","Days","Adult","M + F",">1000","In life observation","Body weight",{"$f":"IF(Z1155<>0,VLOOKUP(Z1155,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1155<>0,VLOOKUP(Z1155,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"* The study was separated in parts A and B. For each part each one male and one female dog were used.\nStudy part A: the male and the female dog were treated at all dose levels: 100 mg/kg bw/day in study Days 1-7, 300 mg/kg bw/day in study Days 8-14 and 1000 mg/kg bw/day in study Days 15-21\nStudy part B: both dogs were treated at 1000 mg/kg bw/day for 14 days","Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",51,5660,"dose-range finding study for maximum tolerated dose","DAR",null,1989,"Dog","Beagle",1,"M + F",99.5,"Oral","Capsule","100; 300; 1000 *see remarks",100,1000,"mg/kg bw/day","Study part A: 21\nStudy Part B: 14","Days","Adult","M + F",">1000","In life observation","Food consumption",{"$f":"IF(Z1156<>0,VLOOKUP(Z1156,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1156<>0,VLOOKUP(Z1156,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"* The study was separated in parts A and B. For each part each one male and one female dog were used.\nStudy part A: the male and the female dog were treated at all dose levels: 100 mg/kg bw/day in study Days 1-7, 300 mg/kg bw/day in study Days 8-14 and 1000 mg/kg bw/day in study Days 15-21\nStudy part B: both dogs were treated at 1000 mg/kg bw/day for 14 days","Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",51,5660,"dose-range finding study for maximum tolerated dose","DAR",null,1989,"Dog","Beagle",1,"M + F",99.5,"Oral","Capsule","100; 300; 1000 *see remarks",100,1000,"mg/kg bw/day","Study part A: 21\nStudy Part B: 14","Days","Adult","M + F",1000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1157<>0,VLOOKUP(Z1157,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: \nStudy part A (21 days treatment): the male dog showed a reduced Hb and a mild increase in reticulocytes on Day 22 (treatment period 1000 mg/kg bw/day), not treatment-related, attributed to repeated blood sampling\nStudy part B (14 days treatment): no treatment-related findings\nClinical chemistry: \nStudy part A (21 days treatment): mild increase in ALT in the male dog and reduced cholesterol in the male and the female dog over the whole treatment period, considered to be not treatment-related\nStudy part B (14 days treatment): mild increase in ALT in the male dog, considered to be not treatment-related\nUrinalysis (available for study part B only, 14 days treatment): no adverse effects observed\nFaecal occult blood: no adverse effects observed",null,"Change",300,1000,"mg/kg bw/day",{"$f":"IF(Z1157<>0,VLOOKUP(Z1157,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"* The study was separated in parts A and B. For each part each one male and one female dog were used.\nStudy part A: the male and the female dog were treated at all dose levels: 100 mg/kg bw/day in study Days 1-7, 300 mg/kg bw/day in study Days 8-14 and 1000 mg/kg bw/day in study Days 15-21\nStudy part B: both dogs were treated at 1000 mg/kg bw/day for 14 days","Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",51,5660,"dose-range finding study for maximum tolerated dose","DAR",null,1989,"Dog","Beagle",1,"M + F",99.5,"Oral","Capsule","100; 300; 1000 *see remarks",100,1000,"mg/kg bw/day","Study part A: 21\nStudy Part B: 14","Days","Adult","M + F",">1000","Organ Weight","Kidney weight",{"$f":"IF(Z1158<>0,VLOOKUP(Z1158,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Relative and absolute organ weight were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1158<>0,VLOOKUP(Z1158,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"* The study was separated in parts A and B. For each part each one male and one female dog were used.\nStudy part A: the male and the female dog were treated at all dose levels: 100 mg/kg bw/day in study Days 1-7, 300 mg/kg bw/day in study Days 8-14 and 1000 mg/kg bw/day in study Days 15-21\nStudy part B: both dogs were treated at 1000 mg/kg bw/day for 14 days","Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",51,5660,"dose-range finding study for maximum tolerated dose","DAR",null,1989,"Dog","Beagle",1,"M + F",99.5,"Oral","Capsule","100; 300; 1000 *see remarks",100,1000,"mg/kg bw/day","Study part A: 21\nStudy Part B: 14","Days","Adult","M + F",">1000","Organ Weight","Heart weight",{"$f":"IF(Z1159<>0,VLOOKUP(Z1159,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Relative and absolute organ weight were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1159<>0,VLOOKUP(Z1159,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"* The study was separated in parts A and B. For each part each one male and one female dog were used.\nStudy part A: the male and the female dog were treated at all dose levels: 100 mg/kg bw/day in study Days 1-7, 300 mg/kg bw/day in study Days 8-14 and 1000 mg/kg bw/day in study Days 15-21\nStudy part B: both dogs were treated at 1000 mg/kg bw/day for 14 days","Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",51,5660,"dose-range finding study for maximum tolerated dose","DAR",null,1989,"Dog","Beagle",1,"M + F",99.5,"Oral","Capsule","100; 300; 1000 *see remarks",100,1000,"mg/kg bw/day","Study part A: 21\nStudy Part B: 14","Days","Adult","F",100,"Organ Weight","Spleen weight",{"$f":"IF(Z1160<>0,VLOOKUP(Z1160,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Study part A (21 days of treatment): Absolute and relative spleen weight were considered reduced in the female animal.\nStudy part B (14 days of treatment): no abnormalities observed",null,"Decrease",">100",100,"mg/kg bw/day",{"$f":"IF(Z1160<>0,VLOOKUP(Z1160,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"* The study was separated in parts A and B. For each part each one male and one female dog were used.\nStudy part A: the male and the female dog were treated at all dose levels: 100 mg/kg bw/day in study Days 1-7, 300 mg/kg bw/day in study Days 8-14 and 1000 mg/kg bw/day in study Days 15-21\nStudy part B: both dogs were treated at 1000 mg/kg bw/day for 14 days","Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",51,5660,"dose-range finding study for maximum tolerated dose","DAR",null,1989,"Dog","Beagle",1,"M + F",99.5,"Oral","Capsule","100; 300; 1000 *see remarks",100,1000,"mg/kg bw/day","Study part A: 21\nStudy Part B: 14","Days","Adult","M + F",">1000","Organ Weight","Liver weight",{"$f":"IF(Z1161<>0,VLOOKUP(Z1161,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1161<>0,VLOOKUP(Z1161,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"* The study was separated in parts A and B. For each part each one male and one female dog were used.\nStudy part A: the male and the female dog were treated at all dose levels: 100 mg/kg bw/day in study Days 1-7, 300 mg/kg bw/day in study Days 8-14 and 1000 mg/kg bw/day in study Days 15-21\nStudy part B: both dogs were treated at 1000 mg/kg bw/day for 14 days","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","In life observation","Mortality",{"$f":"IF(Z1162<>0,VLOOKUP(Z1162,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1162<>0,VLOOKUP(Z1162,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","In life observation","Clinical signs",{"$f":"IF(Z1163<>0,VLOOKUP(Z1163,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1163<>0,VLOOKUP(Z1163,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","In life observation","Body weight",{"$f":"IF(Z1164<>0,VLOOKUP(Z1164,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1164<>0,VLOOKUP(Z1164,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","In life observation","Food consumption",{"$f":"IF(Z1165<>0,VLOOKUP(Z1165,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1165<>0,VLOOKUP(Z1165,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",1000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1166<>0,VLOOKUP(Z1166,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: statistically significant increase in eosinophils in males at 300 mg/kg bw/day, no dose relation, considered to be incidental\nClinical chemistry: statistically significantly increased glucose (11%), total protein (9%), albumin (9%) and creatinine (8%) in females at 1000 mg/kg bw/day, treatment-related (statistically significantly increased ALP in males (28%) at 300 mg/kg bw/day was considered to be incidental as it was not observed at the higher dose)\nUrinalysis: reduced pH in males at 1000 mg/kg bw/day, treatment-related",null,"Change",300,1000,"mg/kg bw/day",{"$f":"IF(Z1166<>0,VLOOKUP(Z1166,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ Weight","Heart weight",{"$f":"IF(Z1167<>0,VLOOKUP(Z1167,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1167<>0,VLOOKUP(Z1167,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ Weight","Kidney weight",{"$f":"IF(Z1168<>0,VLOOKUP(Z1168,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1168<>0,VLOOKUP(Z1168,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ Weight","Thymus weight",{"$f":"IF(Z1169<>0,VLOOKUP(Z1169,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1169<>0,VLOOKUP(Z1169,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ Weight","Spleen weight",{"$f":"IF(Z1170<>0,VLOOKUP(Z1170,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1170<>0,VLOOKUP(Z1170,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ Weight","[Not in list]",{"$f":"IF(Z1171<>0,VLOOKUP(Z1171,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Salivary gland weights were weighed.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1171<>0,VLOOKUP(Z1171,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ Weight","Liver weight",{"$f":"IF(Z1172<>0,VLOOKUP(Z1172,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1172<>0,VLOOKUP(Z1172,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","F",">1000","Organ Weight","Ovary weight",{"$f":"IF(Z1173<>0,VLOOKUP(Z1173,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1173<>0,VLOOKUP(Z1173,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M",">1000","Organ Weight","Prostate weight",{"$f":"IF(Z1174<>0,VLOOKUP(Z1174,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1174<>0,VLOOKUP(Z1174,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M",">1000","Organ Weight","Testis weight",{"$f":"IF(Z1175<>0,VLOOKUP(Z1175,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Testes and epididymis were weighed together.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1175<>0,VLOOKUP(Z1175,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Testis were weighed together with epididymides; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","F",">1000","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z1176<>0,VLOOKUP(Z1176,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1176<>0,VLOOKUP(Z1176,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ Weight","Adrenals weight",{"$f":"IF(Z1177<>0,VLOOKUP(Z1177,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1177<>0,VLOOKUP(Z1177,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ Weight","Brain weight",{"$f":"IF(Z1178<>0,VLOOKUP(Z1178,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1178<>0,VLOOKUP(Z1178,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ Weight","Pituitary weight",{"$f":"IF(Z1179<>0,VLOOKUP(Z1179,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1179<>0,VLOOKUP(Z1179,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ histopathology","Liver histopathology",{"$f":"IF(Z1180<>0,VLOOKUP(Z1180,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1180<>0,VLOOKUP(Z1180,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1181<>0,VLOOKUP(Z1181,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1181<>0,VLOOKUP(Z1181,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ histopathology","Lung histopathology",{"$f":"IF(Z1182<>0,VLOOKUP(Z1182,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1182<>0,VLOOKUP(Z1182,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",30,"Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z1183<>0,VLOOKUP(Z1183,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increased incidence of cellular alteration in the parotid salivary glands in both sexes at 30, 300 and 1000 mg/kg bw/day and increased severity of cellular alteration in the parotid salivary glands in both sexes at 1000 mg/kg bw/day and in males at 300 mg/kg bw/day, treatment-related, toxicological significance unclear",null,"Change","<30",30,"mg/kg bw/day",{"$f":"IF(Z1183<>0,VLOOKUP(Z1183,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1184<>0,VLOOKUP(Z1184,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1184<>0,VLOOKUP(Z1184,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1185<>0,VLOOKUP(Z1185,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1185<>0,VLOOKUP(Z1185,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ histopathology","Heart histopathology",{"$f":"IF(Z1186<>0,VLOOKUP(Z1186,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1186<>0,VLOOKUP(Z1186,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z1187<>0,VLOOKUP(Z1187,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Mesenteric lymph nodes",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1187<>0,VLOOKUP(Z1187,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1188<>0,VLOOKUP(Z1188,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1188<>0,VLOOKUP(Z1188,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ histopathology","Thymus histopathology",{"$f":"IF(Z1189<>0,VLOOKUP(Z1189,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1189<>0,VLOOKUP(Z1189,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1190<>0,VLOOKUP(Z1190,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1190<>0,VLOOKUP(Z1190,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1191<>0,VLOOKUP(Z1191,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1191<>0,VLOOKUP(Z1191,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M",">1000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1192<>0,VLOOKUP(Z1192,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1192<>0,VLOOKUP(Z1192,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","F",">1000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z1193<>0,VLOOKUP(Z1193,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1193<>0,VLOOKUP(Z1193,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M",">1000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z1194<>0,VLOOKUP(Z1194,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1194<>0,VLOOKUP(Z1194,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","F",">1000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1195<>0,VLOOKUP(Z1195,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"With fallopian tubes",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1195<>0,VLOOKUP(Z1195,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M",">1000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1196<>0,VLOOKUP(Z1196,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1196<>0,VLOOKUP(Z1196,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M",">1000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z1197<>0,VLOOKUP(Z1197,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1197<>0,VLOOKUP(Z1197,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M",">1000","Organ histopathology","Testis histopathology",{"$f":"IF(Z1198<>0,VLOOKUP(Z1198,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1198<>0,VLOOKUP(Z1198,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","M + F",">1000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1199<>0,VLOOKUP(Z1199,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1199<>0,VLOOKUP(Z1199,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",52,7136,"OECD 408 (1998), FIFRA 82-1","DAR",null,1991,"Rat","Sprague-Dawley",10,"M + F",98.6,"Oral","Feed","30; 300; 1000",30,1000,"mg/kg bw/day",90,"Days","Adult","F",">1000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1200<>0,VLOOKUP(Z1200,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1200<>0,VLOOKUP(Z1200,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histophathology was performed on control and high dose group only; no recovery group included","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","In life observation","Mortality",{"$f":"IF(Z1201<>0,VLOOKUP(Z1201,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1201<>0,VLOOKUP(Z1201,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",20000,"In life observation","Clinical signs",{"$f":"IF(Z1202<>0,VLOOKUP(Z1202,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Diarrhea in 10/10 males and 9/10 females at 20000 ppm, treatment-related \nOphthalmic examinations: persistent pupillary membrane in the right eye of 1/10 control males and numerous corneal deposits in the right eye of 1/10 males at 20000 ppm, not treatment-related",null,"Increase",6000,20000,"ppm",{"$f":"IF(Z1202<>0,VLOOKUP(Z1202,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","In life observation","Body weight",{"$f":"IF(Z1203<>0,VLOOKUP(Z1203,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"The total mean body weight gain was similar for all groups.  However, decreased bwg at wk 50 and 85 in both sexes\nStatistically sign. increased mean body weight gains in males on Day 43 at 6000 and 20000 ppm were attributed to decreased weight gain in the control group. Statistically signif. decreased body weight  at 20000 ppm in both sexes on Day 50 and in males on Day 85. ",null,"Decrease",6000,20000,"ppm",{"$f":"IF(Z1203<>0,VLOOKUP(Z1203,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","In life observation","Food consumption",{"$f":"IF(Z1204<>0,VLOOKUP(Z1204,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1204<>0,VLOOKUP(Z1204,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",6000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1205<>0,VLOOKUP(Z1205,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: No changes in haematological parameters observed.\nClinical chemistry: No treatment-related effects observed. (K was statistically signif. reduced in males at 2000 ppm, which was considered to be incidental because a dose-response relationship was lacking. Reduced ALT and increased bilirubin in males at 20000 ppm were considered to be without toxicological significance)\nUrinalysis: Treatment-related increase in RBC and detection of blood in females at ≥ 6000 ppm and in all treatment groups in males. Findings in males were not unequivocally attributed to treatment, as a mild elevation of RBC is commonly observed in male rats",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1205<>0,VLOOKUP(Z1205,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",6000,"Organ Weight","Liver weight",{"$f":"IF(Z1206<>0,VLOOKUP(Z1206,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No changes",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1206<>0,VLOOKUP(Z1206,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","F",">20000","Organ Weight","Ovary weight",{"$f":"IF(Z1207<>0,VLOOKUP(Z1207,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1207<>0,VLOOKUP(Z1207,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M",">20000","Organ Weight","Testis weight",{"$f":"IF(Z1208<>0,VLOOKUP(Z1208,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Testes and epididymis were weighed together.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1208<>0,VLOOKUP(Z1208,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; weighed together with epididymides","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M",">20000","Organ Weight","Epididymis weight",{"$f":"IF(Z1209<>0,VLOOKUP(Z1209,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Testes and epididymis were weighed together.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1209<>0,VLOOKUP(Z1209,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; weighed together with testes","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M",">20000","Organ Weight","Seminal vesicles weight",{"$f":"IF(Z1210<>0,VLOOKUP(Z1210,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1210<>0,VLOOKUP(Z1210,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; weighed together with testes","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ Weight","Brain weight",{"$f":"IF(Z1211<>0,VLOOKUP(Z1211,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1211<>0,VLOOKUP(Z1211,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",20000,"Organ Weight","Adrenals weight",{"$f":"IF(Z1212<>0,VLOOKUP(Z1212,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Abs. weight statistically signif. decreased in males at 2000 and 20000 ppm; as an effect at 6000 ppm was lacking the finding was questionable as toxicological effect, no findings in females\nrel. weight (to brain and body weight) statistically significantly decreased in high dose group in males.",null,"Decrease",6000,20000,"ppm",{"$f":"IF(Z1212<>0,VLOOKUP(Z1212,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ Weight","Kidney weight",{"$f":"IF(Z1213<>0,VLOOKUP(Z1213,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1213<>0,VLOOKUP(Z1213,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",20000,"Organ Weight","Spleen weight",{"$f":"IF(Z1214<>0,VLOOKUP(Z1214,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Abs. weight increased in females only in all treatment groups (reaching statistical significance in high dose group only), rel. weight to body weight statistically signif. increased for the high dose group only; spleen weight increased relative to brain weight not statistically significant. However, no effect was observed during macroscopic and microscopic examination.",null,"Increase",6000,20000,"ppm",{"$f":"IF(Z1214<>0,VLOOKUP(Z1214,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Heart histopathology",{"$f":"IF(Z1215<>0,VLOOKUP(Z1215,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Heart and aorta were subject to histopathology.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1215<>0,VLOOKUP(Z1215,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z1216<>0,VLOOKUP(Z1216,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Esophagus and stomach were also analysed.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1216<>0,VLOOKUP(Z1216,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z1217<>0,VLOOKUP(Z1217,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1217<>0,VLOOKUP(Z1217,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Liver histopathology",{"$f":"IF(Z1218<>0,VLOOKUP(Z1218,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Minimal focal subacute inflammation in both sexes of all groups, common finding among laboratory rats, not attributed to treatment",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1218<>0,VLOOKUP(Z1218,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Lung histopathology",{"$f":"IF(Z1219<>0,VLOOKUP(Z1219,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Focal mineralisation of the vascular intima was commonly observed in both sexes of all groups, general finding among laboratory rats, not regarded as treatment-related\nTrachea was analysed as well and no changes were observed.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1219<>0,VLOOKUP(Z1219,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","F",">20000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z1220<>0,VLOOKUP(Z1220,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Cervix, uterus and vagina were fixed together. ",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1220<>0,VLOOKUP(Z1220,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1221<>0,VLOOKUP(Z1221,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1221<>0,VLOOKUP(Z1221,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","F",">20000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z1222<>0,VLOOKUP(Z1222,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1222<>0,VLOOKUP(Z1222,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z1223<>0,VLOOKUP(Z1223,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1223<>0,VLOOKUP(Z1223,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","F",">20000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1224<>0,VLOOKUP(Z1224,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1224<>0,VLOOKUP(Z1224,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1225<>0,VLOOKUP(Z1225,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1225<>0,VLOOKUP(Z1225,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Testis histopathology",{"$f":"IF(Z1226<>0,VLOOKUP(Z1226,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1226<>0,VLOOKUP(Z1226,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1227<>0,VLOOKUP(Z1227,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1227<>0,VLOOKUP(Z1227,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","F",">20000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1228<>0,VLOOKUP(Z1228,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Cervix, uterus and vagina were fixed together. ",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1228<>0,VLOOKUP(Z1228,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","F",">20000","Organ histopathology","Vagina histopathology",{"$f":"IF(Z1229<>0,VLOOKUP(Z1229,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Cervix, uterus and vagina were fixed together. ",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1229<>0,VLOOKUP(Z1229,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1230<>0,VLOOKUP(Z1230,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1230<>0,VLOOKUP(Z1230,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1231<>0,VLOOKUP(Z1231,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Urinary bladder histopathology was performed as well.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1231<>0,VLOOKUP(Z1231,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Thymus histopathology",{"$f":"IF(Z1232<>0,VLOOKUP(Z1232,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1232<>0,VLOOKUP(Z1232,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1233<>0,VLOOKUP(Z1233,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1233<>0,VLOOKUP(Z1233,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1234<>0,VLOOKUP(Z1234,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Minimal to mild cytoplasmic vacuolization of adrenal cortical cells was noted in 5/10 (50%) of the male rats included in the control group.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1234<>0,VLOOKUP(Z1234,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",53,"011-0001","US EPA 82-1, OECD 408 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",10,"M + F",97.5,"Oral","Feed","2000; 6000; 20000",2000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1235<>0,VLOOKUP(Z1235,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1235<>0,VLOOKUP(Z1235,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females; histopathology was performed in control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","In life observation","Mortality",{"$f":"IF(Z1236<>0,VLOOKUP(Z1236,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1236<>0,VLOOKUP(Z1236,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",200,"In life observation","Clinical signs",{"$f":"IF(Z1237<>0,VLOOKUP(Z1237,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Higher incidences of respiratory affections (nasal discharge, snuffling) in both sexes in all test item treated groups, persistent in males after recovery period, treatment-related",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1237<>0,VLOOKUP(Z1237,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","F",20000,"In life observation","Body weight",{"$f":"IF(Z1238<>0,VLOOKUP(Z1238,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Reduced body weight gain in females at 20000 ppm during study weeks 3-6 and thereafter, statistically signif. reduced body weight throughout the treatment period, treatment-related. Findings were restricted to females and were not evident in the high dose recovery group during the exposure period",null,"Decrease",2000,20000,"ppm",{"$f":"IF(Z1238<>0,VLOOKUP(Z1238,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","In life observation","Food consumption",{"$f":"IF(Z1239<>0,VLOOKUP(Z1239,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1239<>0,VLOOKUP(Z1239,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",200,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1240<>0,VLOOKUP(Z1240,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Clinical chemistry: statistically signif. increase in ALP in males at 20000 ppm which remained high (not statistically signif.) and increased glucose levels in females at 20000 ppm treatment-related",null,"Change",2000,20000,"ppm",{"$f":"IF(Z1240<>0,VLOOKUP(Z1240,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ Weight","Kidney weight",{"$f":"IF(Z1241<>0,VLOOKUP(Z1241,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effect on absolute and relative organ weight was observed.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1241<>0,VLOOKUP(Z1241,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ Weight","Liver weight",{"$f":"IF(Z1242<>0,VLOOKUP(Z1242,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effect on absolute and relative organ weight was observed.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1242<>0,VLOOKUP(Z1242,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","F",">20000","Organ Weight","Ovary weight",{"$f":"IF(Z1243<>0,VLOOKUP(Z1243,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on absolute and relative organ weight was observed.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1243<>0,VLOOKUP(Z1243,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M",">20000","Organ Weight","Testis weight",{"$f":"IF(Z1244<>0,VLOOKUP(Z1244,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on absolute and relative organ weight was observed.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1244<>0,VLOOKUP(Z1244,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ Weight","Adrenals weight",{"$f":"IF(Z1245<>0,VLOOKUP(Z1245,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect on absolute and relative organ weight was observed.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1245<>0,VLOOKUP(Z1245,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1246<>0,VLOOKUP(Z1246,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1246<>0,VLOOKUP(Z1246,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1247<>0,VLOOKUP(Z1247,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1247<>0,VLOOKUP(Z1247,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Liver histopathology",{"$f":"IF(Z1248<>0,VLOOKUP(Z1248,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"A few gross lesions were observed at comparable incidences among all groups, no dose- or treatment-relation; focal chronic hepatitis in 1/10 males at 20000ppm, considered to be incidental",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1248<>0,VLOOKUP(Z1248,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Lung histopathology",{"$f":"IF(Z1249<>0,VLOOKUP(Z1249,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"A few gross and histopathological lesions were observed at comparable incidences among all groups, no dose- or treatment-relation",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1249<>0,VLOOKUP(Z1249,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females; histopathology performed on control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z1250<>0,VLOOKUP(Z1250,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Intestine: hyperplasia of lymphoid nodules in the submucosa of the duodenum, ileum and colon with varying frequencies and severity were considered as spontaneous lesions; No effect was observed on stomach.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1250<>0,VLOOKUP(Z1250,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females; histopathology performed on control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1251<>0,VLOOKUP(Z1251,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1251<>0,VLOOKUP(Z1251,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females; histopathology performed on control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Thymus histopathology",{"$f":"IF(Z1252<>0,VLOOKUP(Z1252,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Thymus histopahtological examination not performed",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1252<>0,VLOOKUP(Z1252,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females; histopathology performed on control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Coagulating gland histopathology",{"$f":"IF(Z1253<>0,VLOOKUP(Z1253,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1253<>0,VLOOKUP(Z1253,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females; histopathology performed on control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","F",">20000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1254<>0,VLOOKUP(Z1254,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1254<>0,VLOOKUP(Z1254,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females; histopathology performed on control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1255<>0,VLOOKUP(Z1255,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Prostrate histopathological examination not performed",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1255<>0,VLOOKUP(Z1255,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females; histopathology performed on control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z1256<>0,VLOOKUP(Z1256,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1256<>0,VLOOKUP(Z1256,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females; histopathology performed on control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Testis histopathology",{"$f":"IF(Z1257<>0,VLOOKUP(Z1257,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1257<>0,VLOOKUP(Z1257,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females; histopathology performed on control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1258<>0,VLOOKUP(Z1258,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on thyroid (including parathyroids) was observed.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1258<>0,VLOOKUP(Z1258,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females; histopathology performed on control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","F",">20000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1259<>0,VLOOKUP(Z1259,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1259<>0,VLOOKUP(Z1259,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females; histopathology performed on control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1260<>0,VLOOKUP(Z1260,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1260<>0,VLOOKUP(Z1260,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females; histopathology performed on control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1261<>0,VLOOKUP(Z1261,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1261<>0,VLOOKUP(Z1261,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females; histopathology performed on control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",54,null,"OECD 408 (1981)","DAR",null,1992,"Rat","Wistar","Main: 10\nRecovery: 10 (only high dose)","M + F",96.8,"Oral","Feed","200; 2000; 20000",200,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1262<>0,VLOOKUP(Z1262,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1262<>0,VLOOKUP(Z1262,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females; histopathology performed on control and high dose group animals only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","In life observation","Mortality",{"$f":"IF(Z1263<>0,VLOOKUP(Z1263,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1263<>0,VLOOKUP(Z1263,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","In life observation","Clinical signs",{"$f":"IF(Z1264<>0,VLOOKUP(Z1264,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1264<>0,VLOOKUP(Z1264,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","In life observation","Body weight",{"$f":"IF(Z1265<>0,VLOOKUP(Z1265,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1265<>0,VLOOKUP(Z1265,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","In life observation","Food consumption",{"$f":"IF(Z1266<>0,VLOOKUP(Z1266,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1266<>0,VLOOKUP(Z1266,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1267<>0,VLOOKUP(Z1267,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: No adverse effects observed.\nClinical chemistry: No treatment-related findings. \n(Statistically significant increases in lymphocytes in males at 1000 and 5000 ppm and increased WBC in males at 5000 ppm were not dose-related and therefore not attributed to treatment; statistically signif. increased P and K in both sexes in all test item-treated groups and statistically signif. increased glucose levels in males at 5000 and 20000 ppm showed no dose-relation and/or where within or close to the upper levels of normal values and therefore considered to be without toxicological significance; increased BUN and AP (not siginificant) was attributed to extreme values of one rat)\nUrinalysis: Statistically signif. changes in specific gravity and pH at 5000 ppm in males were not considered to be related to treatment",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1267<>0,VLOOKUP(Z1267,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",">20000","Organ Weight","Epididymis weight",{"$f":"IF(Z1268<>0,VLOOKUP(Z1268,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Epididymides were weighed together with testes.",null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1268<>0,VLOOKUP(Z1268,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; weighed collected together with testes","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",">20000","Organ Weight","Testis weight",{"$f":"IF(Z1269<>0,VLOOKUP(Z1269,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1269<>0,VLOOKUP(Z1269,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; weight collected together with epididymides","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ Weight","Kidney weight",{"$f":"IF(Z1270<>0,VLOOKUP(Z1270,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1270<>0,VLOOKUP(Z1270,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; weight collected together with epididymides","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ Weight","Liver weight",{"$f":"IF(Z1271<>0,VLOOKUP(Z1271,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1271<>0,VLOOKUP(Z1271,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; weight collected together with epididymides","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1272<>0,VLOOKUP(Z1272,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1272<>0,VLOOKUP(Z1272,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Heart histopathology",{"$f":"IF(Z1273<>0,VLOOKUP(Z1273,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1273<>0,VLOOKUP(Z1273,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z1274<>0,VLOOKUP(Z1274,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1274<>0,VLOOKUP(Z1274,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Stomach histopathology",{"$f":"IF(Z1275<>0,VLOOKUP(Z1275,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1275<>0,VLOOKUP(Z1275,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Bone marrow histopathology",{"$f":"IF(Z1276<>0,VLOOKUP(Z1276,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1276<>0,VLOOKUP(Z1276,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z1277<>0,VLOOKUP(Z1277,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1277<>0,VLOOKUP(Z1277,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Peripheral nerve histopathology",{"$f":"IF(Z1278<>0,VLOOKUP(Z1278,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1278<>0,VLOOKUP(Z1278,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Spinal cord histopathology",{"$f":"IF(Z1279<>0,VLOOKUP(Z1279,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1279<>0,VLOOKUP(Z1279,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1280<>0,VLOOKUP(Z1280,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1280<>0,VLOOKUP(Z1280,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Thymus histopathology",{"$f":"IF(Z1281<>0,VLOOKUP(Z1281,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1281<>0,VLOOKUP(Z1281,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1282<>0,VLOOKUP(Z1282,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1282<>0,VLOOKUP(Z1282,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Urinary bladder histopathology",{"$f":"IF(Z1283<>0,VLOOKUP(Z1283,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1283<>0,VLOOKUP(Z1283,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Liver histopathology",{"$f":"IF(Z1284<>0,VLOOKUP(Z1284,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1284<>0,VLOOKUP(Z1284,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Lung histopathology",{"$f":"IF(Z1285<>0,VLOOKUP(Z1285,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1285<>0,VLOOKUP(Z1285,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Trachea histopathology",{"$f":"IF(Z1286<>0,VLOOKUP(Z1286,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1286<>0,VLOOKUP(Z1286,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","F",">20000","Organ histopathology","Cervix histopathology",{"$f":"IF(Z1287<>0,VLOOKUP(Z1287,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1287<>0,VLOOKUP(Z1287,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1288<>0,VLOOKUP(Z1288,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1288<>0,VLOOKUP(Z1288,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","F",">20000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z1289<>0,VLOOKUP(Z1289,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1289<>0,VLOOKUP(Z1289,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z1290<>0,VLOOKUP(Z1290,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1290<>0,VLOOKUP(Z1290,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","F",">20000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1291<>0,VLOOKUP(Z1291,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1291<>0,VLOOKUP(Z1291,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1292<>0,VLOOKUP(Z1292,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1292<>0,VLOOKUP(Z1292,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z1293<>0,VLOOKUP(Z1293,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1293<>0,VLOOKUP(Z1293,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Testis histopathology",{"$f":"IF(Z1294<>0,VLOOKUP(Z1294,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1294<>0,VLOOKUP(Z1294,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1295<>0,VLOOKUP(Z1295,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1295<>0,VLOOKUP(Z1295,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1296<>0,VLOOKUP(Z1296,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1296<>0,VLOOKUP(Z1296,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M + F",">20000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1297<>0,VLOOKUP(Z1297,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1297<>0,VLOOKUP(Z1297,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","F",">20000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1298<>0,VLOOKUP(Z1298,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1298<>0,VLOOKUP(Z1298,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",55,null,"similar to OECD 408","DAR",null,1987,"Rat","Sprague-Dawley",12,"M + F",95.21,"Oral","Feed","1000; 5000; 20000",1000,20000,"ppm",90,"Days","Adult","M",">20000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1299<>0,VLOOKUP(Z1299,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",20000,">20000","ppm",{"$f":"IF(Z1299<>0,VLOOKUP(Z1299,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females; Histopathology was performed for control and high dose group animals only.","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","In life observation","Mortality",{"$f":"IF(Z1300<>0,VLOOKUP(Z1300,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1300<>0,VLOOKUP(Z1300,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","In life observation","Body weight",{"$f":"IF(Z1301<>0,VLOOKUP(Z1301,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1301<>0,VLOOKUP(Z1301,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","In life observation","Food consumption",{"$f":"IF(Z1302<>0,VLOOKUP(Z1302,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Neither food nor water consumtion were affected.",null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1302<>0,VLOOKUP(Z1302,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","In life observation","Clinical signs",{"$f":"IF(Z1303<>0,VLOOKUP(Z1303,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1303<>0,VLOOKUP(Z1303,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1304<>0,VLOOKUP(Z1304,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: No toxicologically relevant finding was observed. (Prothrombin time statist. signif. increased in females at 200 mg/kg bw/day, no dose-relation, considered to be incidental)\nClinical chemistry:  No toxicologically relevant finding was observed. (Dose-related increase in glucose levels in males over all test item treated groups, statistically not signifant; increase in  plasma cholinesterase and AP and decrease of K in males over all dose groups, not dose-related, toxicological significance of this finding is unclear; slightly increased glucose and AP levels in females in all test item treated groups, statistically not significant, no dose-response relationship)\nUrinalysis: Not performed",null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1304<>0,VLOOKUP(Z1304,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M",">4500","Organ Weight","Testis weight",{"$f":"IF(Z1305<>0,VLOOKUP(Z1305,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Statistically signif. increased abs + rel weight at 200 and 1000 mg/kg bw/day, no dose-relation, considered to be by chance",null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1305<>0,VLOOKUP(Z1305,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Weighed together with epididymides","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ Weight","Thymus weight",{"$f":"IF(Z1306<>0,VLOOKUP(Z1306,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Statistically signif. increased abs.+rel. weight in males only at the mid dose group (1000 mg/kg bw/day) was considered to be incidental, since no dose-response was observed.",null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1306<>0,VLOOKUP(Z1306,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M",">4500","Organ Weight","Prostate weight",{"$f":"IF(Z1307<>0,VLOOKUP(Z1307,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Increased abs. weight (statistically not significant) and statist. signif. increased rel. weight at 1000 mg/kg bw/day, were considered incidental since no effect was observed in the high dose group. Moreover, no histopathological changes were observed.",null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1307<>0,VLOOKUP(Z1307,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ Weight","Pituitary weight",{"$f":"IF(Z1308<>0,VLOOKUP(Z1308,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Statistically signif. increased abs. weight in females only at 4500 mg/kg bw/day, considered incidental due to the lack of a dose-response relationship and the variability seen in the other dose groups. Moreover, no histopathological changes were observed.",null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1308<>0,VLOOKUP(Z1308,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M",">4500","Organ Weight","Epididymis weight",{"$f":"IF(Z1309<>0,VLOOKUP(Z1309,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Epididymides weight was examined together with testes.",null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1309<>0,VLOOKUP(Z1309,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Weighed together with testes","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ Weight","Liver weight",{"$f":"IF(Z1310<>0,VLOOKUP(Z1310,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Liver was weighed together with gall bladder.",null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1310<>0,VLOOKUP(Z1310,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","F",">4500","Organ Weight","Ovary weight",{"$f":"IF(Z1311<>0,VLOOKUP(Z1311,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1311<>0,VLOOKUP(Z1311,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","F",">4500","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z1312<>0,VLOOKUP(Z1312,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1312<>0,VLOOKUP(Z1312,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ Weight","Adrenals weight",{"$f":"IF(Z1313<>0,VLOOKUP(Z1313,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1313<>0,VLOOKUP(Z1313,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ Weight","Brain weight",{"$f":"IF(Z1314<>0,VLOOKUP(Z1314,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1314<>0,VLOOKUP(Z1314,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ Weight","Heart weight",{"$f":"IF(Z1315<>0,VLOOKUP(Z1315,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1315<>0,VLOOKUP(Z1315,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"}]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ Weight","Kidney weight",{"$f":"IF(Z1316<>0,VLOOKUP(Z1316,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1316<>0,VLOOKUP(Z1316,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"}]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ Weight","Spleen weight",{"$f":"IF(Z1317<>0,VLOOKUP(Z1317,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1317<>0,VLOOKUP(Z1317,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"}]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ Weight","[Not in list]",{"$f":"IF(Z1318<>0,VLOOKUP(Z1318,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Lung weight was not affected.",null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1318<>0,VLOOKUP(Z1318,Interpretation!$C:$E,3,FALSE),\"\")","v":0}]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","F",">4500","Organ histopathology","Cervix histopathology",{"$f":"IF(Z1319<>0,VLOOKUP(Z1319,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1319<>0,VLOOKUP(Z1319,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed for high dose and control group only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M",">4500","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1320<>0,VLOOKUP(Z1320,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1320<>0,VLOOKUP(Z1320,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed for high dose and control group only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","F",">4500","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z1321<>0,VLOOKUP(Z1321,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1321<>0,VLOOKUP(Z1321,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed for high dose and control group only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M",">4500","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z1322<>0,VLOOKUP(Z1322,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1322<>0,VLOOKUP(Z1322,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed for high dose and control group only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","F",">4500","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1323<>0,VLOOKUP(Z1323,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1323<>0,VLOOKUP(Z1323,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed for high dose and control group only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M",">4500","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1324<>0,VLOOKUP(Z1324,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1324<>0,VLOOKUP(Z1324,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed for high dose and control group only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M",">4500","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z1325<>0,VLOOKUP(Z1325,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1325<>0,VLOOKUP(Z1325,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed for high dose and control group only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M",">4500","Organ histopathology","Testis histopathology",{"$f":"IF(Z1326<>0,VLOOKUP(Z1326,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1326<>0,VLOOKUP(Z1326,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed for high dose and control group only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1327<>0,VLOOKUP(Z1327,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1327<>0,VLOOKUP(Z1327,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Histopathology was performed for high dose and control group only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1328<>0,VLOOKUP(Z1328,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1328<>0,VLOOKUP(Z1328,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Histopathology was performed for high dose and control group only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","F",">4500","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1329<>0,VLOOKUP(Z1329,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1329<>0,VLOOKUP(Z1329,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed for high dose and control group only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1330<>0,VLOOKUP(Z1330,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1330<>0,VLOOKUP(Z1330,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Histopathology was performed for high dose and control group only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ histopathology","Lung histopathology",{"$f":"IF(Z1331<>0,VLOOKUP(Z1331,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1331<>0,VLOOKUP(Z1331,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ histopathology","Liver histopathology",{"$f":"IF(Z1332<>0,VLOOKUP(Z1332,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1332<>0,VLOOKUP(Z1332,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed on all dose groups","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1333<>0,VLOOKUP(Z1333,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increased incidence of cortical tubular epithelial hypertrophy in 1/10, 2/10 and 5/10 females and in 2/10, 0/10 and 2/10 males at 0, 200 and 1000 mg/kg bw/day, no findings in the high dose group. Due to lacking dose-response, the effect is not considered treatment-related (probably early stage in the development of nephropathy).",null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1333<>0,VLOOKUP(Z1333,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed on all dose groups","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",56,7024,"OECD 408 (1981), FIFRA 82-1","DAR",null,1991,"Mouse","CD-1",10,"M + F","1st batch: 99.5, 2nd batch: 98.0","Oral","Feed","200; 1000; 4500",200,4500,"mg/kg bw/day",90,"Days","Adult","M + F",">4500","Organ histopathology","Thymus histopathology",{"$f":"IF(Z1334<>0,VLOOKUP(Z1334,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",4500,">4500","mg/kg bw/day",{"$f":"IF(Z1334<>0,VLOOKUP(Z1334,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed for high dose and control group only","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","In life observation","Mortality",{"$f":"IF(Z1335<>0,VLOOKUP(Z1335,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1335<>0,VLOOKUP(Z1335,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study was performed for 6 month instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","In life observation","Clinical signs",{"$f":"IF(Z1336<>0,VLOOKUP(Z1336,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1336<>0,VLOOKUP(Z1336,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study was performed for 6 month instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","In life observation","Body weight",{"$f":"IF(Z1337<>0,VLOOKUP(Z1337,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Beginning midway through the study, the body weights (also final body weights) of males in the high-dose group were slightly decreased (-4-6%) beginning from the mid of the study (not statistically significant). Body weight of females was not affected.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1337<>0,VLOOKUP(Z1337,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study was performed for 6 month instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","In life observation","Food consumption",{"$f":"IF(Z1338<>0,VLOOKUP(Z1338,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1338<>0,VLOOKUP(Z1338,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study was performed for 6 month instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",300,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1339<>0,VLOOKUP(Z1339,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: Statistically significantly increased MCHC in both sexes at different sampling time points, no dose-relation, within normal range, not related to treatment\nClinical chemistry: A dose-related increase in alkaline phosphatase activity was observed in males and females at all doses (statistically significant in high-dose males (month 5) only) and total lactic dehydrogenase levels statist. signif. decreased in males at 60 and 300 mg/kg bw/day after 4 months of treatment until study termination. As no gross or microscopic liver lesions were observed, biological relevance equivocal and parameter not considered T-related\nUrinalysis: No treatment-related effects observed.",null,"Change",60,300,"mg/kg bw/day",{"$f":"IF(Z1339<>0,VLOOKUP(Z1339,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study was performed for 6 month instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ Weight","Adrenals weight",{"$f":"IF(Z1340<>0,VLOOKUP(Z1340,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect on relative and absolute organ weight was observed.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1340<>0,VLOOKUP(Z1340,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Study was performed for 6 month instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ Weight","Brain weight",{"$f":"IF(Z1341<>0,VLOOKUP(Z1341,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect on relative and absolute organ weight was observed.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1341<>0,VLOOKUP(Z1341,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Study was performed for 6 month instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ Weight","Pituitary weight",{"$f":"IF(Z1342<>0,VLOOKUP(Z1342,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect on relative and absolute organ weight was observed.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1342<>0,VLOOKUP(Z1342,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Study was performed for 6 month instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ Weight","Liver weight",{"$f":"IF(Z1343<>0,VLOOKUP(Z1343,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effect on relative and absolute organ weight was observed.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1343<>0,VLOOKUP(Z1343,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study was performed for 6 month instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ Weight","Ovary weight",{"$f":"IF(Z1344<>0,VLOOKUP(Z1344,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on relative and absolute organ weight was observed.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1344<>0,VLOOKUP(Z1344,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Study was performed for 6 month instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M",">300","Organ Weight","Testis weight",{"$f":"IF(Z1345<>0,VLOOKUP(Z1345,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Non-statistically significant increase in absolute organ weight at 300 mg/kg bw/day which was attributed to one animal. No histopathological changes were observed and thus, the increase is considered not treatment-related.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1345<>0,VLOOKUP(Z1345,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Weighed together with epididymides; study was performed for 6 instead of 6 months","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M",">300","Organ Weight","Thyroid weight",{"$f":"IF(Z1346<>0,VLOOKUP(Z1346,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute weight was statistically significantly decreased in males at 60 mg/kg bw/day, relative weight was increased in females at 10 mg/kg bw/day (statistically not significant). No dose-response and no effect in thyroid histopathology were observed.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1346<>0,VLOOKUP(Z1346,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Study was performed for 6 month instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ Weight","Kidney weight",{"$f":"IF(Z1347<>0,VLOOKUP(Z1347,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effect on relative and absolute organ weight was observed.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1347<>0,VLOOKUP(Z1347,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study was performed for 6 month instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ Weight","Heart weight",{"$f":"IF(Z1348<>0,VLOOKUP(Z1348,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Rel. weight increased in females at 60 mg/kg bw/day (statist. not signif.), no dose-relation, not treatment-related",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1348<>0,VLOOKUP(Z1348,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study was performed for 6 month instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Heart histopathology",{"$f":"IF(Z1349<>0,VLOOKUP(Z1349,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Heart and aorta were subject to histopathology.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1349<>0,VLOOKUP(Z1349,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z1350<>0,VLOOKUP(Z1350,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Mandibular salivary glands were investigated.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1350<>0,VLOOKUP(Z1350,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z1351<>0,VLOOKUP(Z1351,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1351<>0,VLOOKUP(Z1351,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1352<>0,VLOOKUP(Z1352,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1352<>0,VLOOKUP(Z1352,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1353<>0,VLOOKUP(Z1353,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Urinary bladder was examined as well.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1353<>0,VLOOKUP(Z1353,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1354<>0,VLOOKUP(Z1354,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1354<>0,VLOOKUP(Z1354,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Liver histopathology",{"$f":"IF(Z1355<>0,VLOOKUP(Z1355,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1355<>0,VLOOKUP(Z1355,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Lung histopathology",{"$f":"IF(Z1356<>0,VLOOKUP(Z1356,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1356<>0,VLOOKUP(Z1356,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z1357<>0,VLOOKUP(Z1357,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1357<>0,VLOOKUP(Z1357,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1358<>0,VLOOKUP(Z1358,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1358<>0,VLOOKUP(Z1358,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Thymus histopathology",{"$f":"IF(Z1359<>0,VLOOKUP(Z1359,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1359<>0,VLOOKUP(Z1359,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Stomach histopathology",{"$f":"IF(Z1360<>0,VLOOKUP(Z1360,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Stomach and esophagus were histopathologically examined.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1360<>0,VLOOKUP(Z1360,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Peripheral nerve histopathology",{"$f":"IF(Z1361<>0,VLOOKUP(Z1361,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"The sciatic nerve was examined.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1361<>0,VLOOKUP(Z1361,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1362<>0,VLOOKUP(Z1362,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1362<>0,VLOOKUP(Z1362,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M",">300","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1363<>0,VLOOKUP(Z1363,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Examined together with testes.",null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1363<>0,VLOOKUP(Z1363,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","F",">300","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z1364<>0,VLOOKUP(Z1364,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1364<>0,VLOOKUP(Z1364,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M",">300","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z1365<>0,VLOOKUP(Z1365,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1365<>0,VLOOKUP(Z1365,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","F",">300","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1366<>0,VLOOKUP(Z1366,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1366<>0,VLOOKUP(Z1366,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M",">300","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1367<>0,VLOOKUP(Z1367,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1367<>0,VLOOKUP(Z1367,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M",">300","Organ histopathology","Testis histopathology",{"$f":"IF(Z1368<>0,VLOOKUP(Z1368,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1368<>0,VLOOKUP(Z1368,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","F",">300","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1369<>0,VLOOKUP(Z1369,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1369<>0,VLOOKUP(Z1369,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1370<>0,VLOOKUP(Z1370,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1370<>0,VLOOKUP(Z1370,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Mammals Not il list",57,null,"similar to OECD 409","DAR",null,1983,"Dog","Beagle",6,"M + F","62.49% aqueous solution of the isopropylamine salt of glyphosate","Oral","Capsule","10; 60; 300",10,300,"mg/kg bw/day",6,"Months","Adult","M + F",">300","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1371<>0,VLOOKUP(Z1371,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",300,">300","mg/kg bw/day",{"$f":"IF(Z1371<>0,VLOOKUP(Z1371,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Histopathology was performed on control and high dose group animals only, study was performed for 6 months instead of 3 months (90 days)","Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","In life observation","Mortality",{"$f":"IF(Z1372<>0,VLOOKUP(Z1372,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1372<>0,VLOOKUP(Z1372,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",20,"In life observation","Clinical signs",{"$f":"IF(Z1373<>0,VLOOKUP(Z1373,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Increased incidences of abnormal excrement (bloody stool, yellow mucoid stool, diarrhea, emesis) were observed in a few females at 20 and 500 mg/kg bw/day; most observations were attributed to 1 female of each group (1/6), no findings at 100 mg/kg bw/day females or in males (all dose groups), considered to be not dose-related and of questionable biological significance; skin redness with slight alopecia in 1/6 females at 100 and in 1/6 females at 500 mg/kg bw/day, treatment-related \nOphthalmoscopy: no treatment-related findings",null,"Increase","<20",20,"mg/kg bw/day",{"$f":"IF(Z1373<>0,VLOOKUP(Z1373,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","In life observation","Body weight",{"$f":"IF(Z1374<>0,VLOOKUP(Z1374,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1374<>0,VLOOKUP(Z1374,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","In life observation","Food consumption",{"$f":"IF(Z1375<>0,VLOOKUP(Z1375,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1375<>0,VLOOKUP(Z1375,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1376<>0,VLOOKUP(Z1376,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: No treatment related findings (mild elevations in RBC, HGB and HCT in females at 20 mg/kg bw/day, not dose-related and within normal range; mild changes in MCHC in males at 100 mg/kg bw/day after 12 months and in females at 10 and 100 mg/kg bw/day after 3 and 12 month, not dose-related).\nClinical chemistry: No treatment-related findings (statistically significant decrease in P and changes in SGPT, Na, K, Ca, Gluc and Alb were transient and within normal ranges and therefore not related to treatment).\nUrinalysis: No adverse effects observed.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1376<>0,VLOOKUP(Z1376,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M",">500","Organ Weight","Epididymis weight",{"$f":"IF(Z1377<>0,VLOOKUP(Z1377,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Epididymides were weighed together with testes. Absolute and relative organ weights were not affected.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1377<>0,VLOOKUP(Z1377,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Weighed together with testes","Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M",">500","Organ Weight","Testis weight",{"$f":"IF(Z1378<>0,VLOOKUP(Z1378,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute and relative organ weights were not affected.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1378<>0,VLOOKUP(Z1378,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Weighed together with epididymides","Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ Weight","Liver weight",{"$f":"IF(Z1379<>0,VLOOKUP(Z1379,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute and relative organ weights were not affected.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1379<>0,VLOOKUP(Z1379,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","F",">500","Organ Weight","Ovary weight",{"$f":"IF(Z1380<>0,VLOOKUP(Z1380,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute and relative organ weights were not affected.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1380<>0,VLOOKUP(Z1380,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ Weight","Adrenals weight",{"$f":"IF(Z1381<>0,VLOOKUP(Z1381,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Absolute and relative organ weights were not affected.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1381<>0,VLOOKUP(Z1381,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ Weight","Thyroid weight",{"$f":"IF(Z1382<>0,VLOOKUP(Z1382,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute and relative organ weights were not affected.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1382<>0,VLOOKUP(Z1382,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ Weight","Heart weight",{"$f":"IF(Z1383<>0,VLOOKUP(Z1383,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute and relative organ weights were not affected.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1383<>0,VLOOKUP(Z1383,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ Weight","Kidney weight",{"$f":"IF(Z1384<>0,VLOOKUP(Z1384,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute and relative organ weights were not affected.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1384<>0,VLOOKUP(Z1384,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ Weight","Brain weight",{"$f":"IF(Z1385<>0,VLOOKUP(Z1385,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Abs. weight statist. signif. decreased in males at 100 mg/kg bw/day, not dose-related and therefore not attributed to treatment. Moreover, no microscopic changes observed.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1385<>0,VLOOKUP(Z1385,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",100,"Organ Weight","Pituitary weight",{"$f":"IF(Z1386<>0,VLOOKUP(Z1386,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Abs. + rel. weight statist. signif. decreased in males only at 100 and 500 mg/kg bw/day, treatment-related but no microscopical abnormalities observed.",null,"Decrease",20,100,"mg/kg bw/day",{"$f":"IF(Z1386<>0,VLOOKUP(Z1386,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","F",">500","Organ histopathology","Cervix histopathology",{"$f":"IF(Z1387<>0,VLOOKUP(Z1387,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Cervix examined together with uterus. ",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1387<>0,VLOOKUP(Z1387,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M",">500","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1388<>0,VLOOKUP(Z1388,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1388<>0,VLOOKUP(Z1388,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","F",">500","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z1389<>0,VLOOKUP(Z1389,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1389<>0,VLOOKUP(Z1389,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M",">500","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z1390<>0,VLOOKUP(Z1390,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1390<>0,VLOOKUP(Z1390,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","F",">500","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1391<>0,VLOOKUP(Z1391,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1391<>0,VLOOKUP(Z1391,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M",">500","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1392<>0,VLOOKUP(Z1392,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1392<>0,VLOOKUP(Z1392,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M",">500","Organ histopathology","Testis histopathology",{"$f":"IF(Z1393<>0,VLOOKUP(Z1393,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1393<>0,VLOOKUP(Z1393,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1394<>0,VLOOKUP(Z1394,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1394<>0,VLOOKUP(Z1394,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","F",">500","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1395<>0,VLOOKUP(Z1395,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1395<>0,VLOOKUP(Z1395,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Heart histopathology",{"$f":"IF(Z1396<>0,VLOOKUP(Z1396,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology was performed for heart and aorta.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1396<>0,VLOOKUP(Z1396,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1397<>0,VLOOKUP(Z1397,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Kidney, ureter and urinary bladder were examined.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1397<>0,VLOOKUP(Z1397,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Liver histopathology",{"$f":"IF(Z1398<>0,VLOOKUP(Z1398,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1398<>0,VLOOKUP(Z1398,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Stomach histopathology",{"$f":"IF(Z1399<>0,VLOOKUP(Z1399,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1399<>0,VLOOKUP(Z1399,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z1400<>0,VLOOKUP(Z1400,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1400<>0,VLOOKUP(Z1400,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Lung histopathology",{"$f":"IF(Z1401<>0,VLOOKUP(Z1401,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Lung and trachea were examined.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1401<>0,VLOOKUP(Z1401,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z1402<>0,VLOOKUP(Z1402,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Mesenteric lymph nodes were examined.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1402<>0,VLOOKUP(Z1402,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Peripheral nerve histopathology",{"$f":"IF(Z1403<>0,VLOOKUP(Z1403,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"The sciatic nerve was examined.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1403<>0,VLOOKUP(Z1403,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1404<>0,VLOOKUP(Z1404,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1404<>0,VLOOKUP(Z1404,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z1405<>0,VLOOKUP(Z1405,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"The mandibular salivary glands were examined.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1405<>0,VLOOKUP(Z1405,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Spinal cord histopathology",{"$f":"IF(Z1406<>0,VLOOKUP(Z1406,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"The cervical, midthoracic and lumbar sections were examined.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1406<>0,VLOOKUP(Z1406,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1407<>0,VLOOKUP(Z1407,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1407<>0,VLOOKUP(Z1407,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Thymus histopathology",{"$f":"IF(Z1408<>0,VLOOKUP(Z1408,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1408<>0,VLOOKUP(Z1408,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1409<>0,VLOOKUP(Z1409,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1409<>0,VLOOKUP(Z1409,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",58,null,"similar to OECD 452 (1981)","DAR",null,1985,"Dog","Beagle",6,"M + F",96.17,"Oral","Capsule","20; 100; 500",20,500,"mg/kg bw/day",1,"Year","Adult","M + F",">500","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1410<>0,VLOOKUP(Z1410,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1410<>0,VLOOKUP(Z1410,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","In life observation","Mortality",{"$f":"IF(Z1411<>0,VLOOKUP(Z1411,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1411<>0,VLOOKUP(Z1411,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",1000,"In life observation","Clinical signs",{"$f":"IF(Z1412<>0,VLOOKUP(Z1412,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Increased incidences of changes in faecal consistency (soft, loose, liquid) were recorded more frequently at 1000 mg/kg bw/day, treatment-related (not treatment-related observations: vomiting, salivation, minor wound bites and conjunctivitis were infrequently observed, no dose or treatment relation)\nOphthalmoscopy: no treatment-related findings",null,"Increase",300,1000,"mg/kg bw/day",{"$f":"IF(Z1412<>0,VLOOKUP(Z1412,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",30,"In life observation","Body weight",{"$f":"IF(Z1413<>0,VLOOKUP(Z1413,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Reduced mean body weight gain in males at 30 (-17%), 300 (-25%) and 1000 mg/kg bw/day (-25%) and in females at 1000 mg/kg bw/day (-19%), statistically not significant, treatment-relation not clear. RMS: treatment-related and adverse effect in M and F at 1000 mg/kg bw/day.",null,"Decrease",300,1000,"mg/kg bw/day",{"$f":"IF(Z1413<>0,VLOOKUP(Z1413,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","In life observation","Food consumption",{"$f":"IF(Z1414<>0,VLOOKUP(Z1414,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1414<>0,VLOOKUP(Z1414,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1415<>0,VLOOKUP(Z1415,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: No treatment-related findings\nClinical chemistry: No treatment-related findings\nUrinalysis: No treatment-related findings\nFaeces: Occult blood determinations performed in faecal samples were negative for all animals throughout the study.\nBrain cholinesterase: No effect was observed.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1415<>0,VLOOKUP(Z1415,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M",">1000","Organ Weight","Epididymis weight",{"$f":"IF(Z1416<>0,VLOOKUP(Z1416,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Epididymides were weighed with testes. Absolute and relative organ weights were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1416<>0,VLOOKUP(Z1416,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Weighed together with testis","Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ Weight","Liver weight",{"$f":"IF(Z1417<>0,VLOOKUP(Z1417,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Liver and drained gall bladder were weighed. Absolute and relative organ weights were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1417<>0,VLOOKUP(Z1417,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","F",">1000","Organ Weight","Ovary weight",{"$f":"IF(Z1418<>0,VLOOKUP(Z1418,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute and relative organ weights were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1418<>0,VLOOKUP(Z1418,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M",">1000","Organ Weight","Prostate weight",{"$f":"IF(Z1419<>0,VLOOKUP(Z1419,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute and relative organ weights were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1419<>0,VLOOKUP(Z1419,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M",">1000","Organ Weight","Testis weight",{"$f":"IF(Z1420<>0,VLOOKUP(Z1420,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute and relative organ weights were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1420<>0,VLOOKUP(Z1420,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Weighed together with epididymides","Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ Weight","Thyroid weight",{"$f":"IF(Z1421<>0,VLOOKUP(Z1421,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute and relative organ weights were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1421<>0,VLOOKUP(Z1421,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","F",">1000","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z1422<>0,VLOOKUP(Z1422,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute and relative organ weights were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1422<>0,VLOOKUP(Z1422,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ Weight","Adrenals weight",{"$f":"IF(Z1423<>0,VLOOKUP(Z1423,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Absolute and relative organ weights were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1423<>0,VLOOKUP(Z1423,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ Weight","Brain weight",{"$f":"IF(Z1424<>0,VLOOKUP(Z1424,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Absolute and relative organ weights were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1424<>0,VLOOKUP(Z1424,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ Weight","Pituitary weight",{"$f":"IF(Z1425<>0,VLOOKUP(Z1425,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Absolute and relative organ weights were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1425<>0,VLOOKUP(Z1425,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ Weight","Heart weight",{"$f":"IF(Z1426<>0,VLOOKUP(Z1426,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute and relative organ weights were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1426<>0,VLOOKUP(Z1426,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ Weight","Kidney weight",{"$f":"IF(Z1427<>0,VLOOKUP(Z1427,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute and relative organ weights were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1427<>0,VLOOKUP(Z1427,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ Weight","Spleen weight",{"$f":"IF(Z1428<>0,VLOOKUP(Z1428,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute and relative organ weights were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1428<>0,VLOOKUP(Z1428,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ Weight","Thymus weight",{"$f":"IF(Z1429<>0,VLOOKUP(Z1429,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute and relative organ weights were not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1429<>0,VLOOKUP(Z1429,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ Weight","[Not in list]",{"$f":"IF(Z1430<>0,VLOOKUP(Z1430,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Relative and absolute pancreas weight was not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1430<>0,VLOOKUP(Z1430,Interpretation!$C:$E,3,FALSE),\"\")","v":0},null,"Yes","Yes"]
["Mammals","Chronic toxicity","59a",7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ Weight","[Not in list]",{"$f":"IF(Z1431<>0,VLOOKUP(Z1431,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Absolute and relative lung weight was not affected.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1431<>0,VLOOKUP(Z1431,Interpretation!$C:$E,3,FALSE),\"\")","v":0},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1432<>0,VLOOKUP(Z1432,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The brain was sectioned at 3 levels (cerebral cortex, mid-brain and cerebellum with medulla) for histopathological examination.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1432<>0,VLOOKUP(Z1432,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Heart histopathology",{"$f":"IF(Z1433<>0,VLOOKUP(Z1433,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Heart and aorta were examined.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1433<>0,VLOOKUP(Z1433,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1434<>0,VLOOKUP(Z1434,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1434<>0,VLOOKUP(Z1434,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1435<>0,VLOOKUP(Z1435,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1435<>0,VLOOKUP(Z1435,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Thymus histopathology",{"$f":"IF(Z1436<>0,VLOOKUP(Z1436,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1436<>0,VLOOKUP(Z1436,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z1437<>0,VLOOKUP(Z1437,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Submaxillary, sublingual, parotid salivary glands were examined.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1437<>0,VLOOKUP(Z1437,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Lung histopathology",{"$f":"IF(Z1438<>0,VLOOKUP(Z1438,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: Pale or dark patches were commonly observed among all groups, not treatment-related\nHistopathology: Performed for trachea and lung. Localised inflammatory lesions including small granulomas correlating with macroscopical findings in lung in 1/4, 3/4, 1/4 and 3/4 males and in 1/4, 1/4, 0/4 and 0/4 females at 0, 30, 300 and 1000 mg/kg bw/day, not treatment-related",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1438<>0,VLOOKUP(Z1438,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z1439<>0,VLOOKUP(Z1439,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1439<>0,VLOOKUP(Z1439,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z1440<>0,VLOOKUP(Z1440,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Submandibular and mesenteric lymph nodes were examined.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1440<>0,VLOOKUP(Z1440,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Stomach histopathology",{"$f":"IF(Z1441<>0,VLOOKUP(Z1441,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1441<>0,VLOOKUP(Z1441,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Peripheral nerve histopathology",{"$f":"IF(Z1442<>0,VLOOKUP(Z1442,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Sciatic nerve was examined.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1442<>0,VLOOKUP(Z1442,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Oesophagus histopathology",{"$f":"IF(Z1443<>0,VLOOKUP(Z1443,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1443<>0,VLOOKUP(Z1443,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Liver histopathology",{"$f":"IF(Z1444<>0,VLOOKUP(Z1444,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Prominent lobulation and pale patches at necropsy in animals of all groups, not treatment-related",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1444<>0,VLOOKUP(Z1444,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1445<>0,VLOOKUP(Z1445,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1445<>0,VLOOKUP(Z1445,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Urinary bladder histopathology",{"$f":"IF(Z1446<>0,VLOOKUP(Z1446,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Thickened wall in 1/4 males at 1000 mg/kg bw/day and in 1/4 females at 30 mg/kg bw/day, microscopically verified as muscular hypertrophy and in 2/4 females at 30 mg/kg bw/day, microscopically verified as lymphocyte infiltration, not treatment-related",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1446<>0,VLOOKUP(Z1446,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M",">1000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1447<>0,VLOOKUP(Z1447,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1447<>0,VLOOKUP(Z1447,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","F",">1000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z1448<>0,VLOOKUP(Z1448,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1448<>0,VLOOKUP(Z1448,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M",">1000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z1449<>0,VLOOKUP(Z1449,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1449<>0,VLOOKUP(Z1449,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","F",">1000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1450<>0,VLOOKUP(Z1450,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1450<>0,VLOOKUP(Z1450,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M",">1000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1451<>0,VLOOKUP(Z1451,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1451<>0,VLOOKUP(Z1451,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M",">1000","Organ histopathology","Testis histopathology",{"$f":"IF(Z1452<>0,VLOOKUP(Z1452,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1452<>0,VLOOKUP(Z1452,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1453<>0,VLOOKUP(Z1453,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1453<>0,VLOOKUP(Z1453,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","F",">1000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1454<>0,VLOOKUP(Z1454,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1454<>0,VLOOKUP(Z1454,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1455<>0,VLOOKUP(Z1455,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1455<>0,VLOOKUP(Z1455,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Chronic toxicity",59,7502,"similar to OECD 452 (1981)","DAR",null,1990,"Dog","Beagle",4,"M + F","1st batch: 99.5, 2nd batch: 98.9, 3rd batch: 98.6","Oral","Capsule","30; 300; 1000",30,1000,"mg/kg bw/day",1,"Year","Adult","M + F",">1000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1456<>0,VLOOKUP(Z1456,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1456<>0,VLOOKUP(Z1456,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",60,7839,"equivalent to OECD 410 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",5,"M + F","101.5 (vehicle diethylphthalate)","Dermal","Topical",1000,1000,1000,"mg/kg bw/day",21,"Days","Adult","M + F",">1000","In life observation","Mortality",{"$f":"IF(Z1457<>0,VLOOKUP(Z1457,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1457<>0,VLOOKUP(Z1457,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",60,7839,"equivalent to OECD 410 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",5,"M + F","101.5  (vehicle diethylphthalate)","Dermal","Topical",1000,1000,1000,"mg/kg bw/day",21,"Days","Adult","M + F",1000,"In life observation","Clinical signs",{"$f":"IF(Z1458<>0,VLOOKUP(Z1458,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Clinical signs of systemic toxicity: no adverse effects observed\nLocal skin reactions: 2/5 males and 3/5 females showed very slight erythema during Week 2, which remained apparent in 1/5 females in Week 3 at 1000 mg/kg bw/day, moderate to severe desquamation in 3/5 males and mild to severe desquamation in 5/5 females at 1000 mg/kg bw/day during Week2 and in 1/5 males and 1/5 females at 1000 mg/kg bw/day in Week 3, treatment-related",null,"Increase","<1000",1000,"mg/kg bw/day",{"$f":"IF(Z1458<>0,VLOOKUP(Z1458,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",60,7839,"equivalent to OECD 410 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",5,"M + F","101.5  (vehicle diethylphthalate)","Dermal","Topical",1000,1000,1000,"mg/kg bw/day",21,"Days","Adult","M + F",">1000","In life observation","Body weight",{"$f":"IF(Z1459<>0,VLOOKUP(Z1459,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Reduced body weight gain in males (-17%, statistically not significant) and statistically signifcant increased body weight gain in females (58%), due to the lack opf statistical significance, the wide variation between the sexes and the lack of similar observations in previous studies the changes were not attributed to treatment .",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1459<>0,VLOOKUP(Z1459,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",60,7839,"equivalent to OECD 410 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",5,"M + F","101.5  (vehicle diethylphthalate)","Dermal","Topical",1000,1000,1000,"mg/kg bw/day",21,"Days","Adult","M + F",1000,"In life observation","Food consumption",{"$f":"IF(Z1460<>0,VLOOKUP(Z1460,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Increased food consumption in females at 1000 mg/kg bw/day (14%), as findings in males and in previous studies were lacking the effect was considered to be by chance and not of toxicological importance",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1460<>0,VLOOKUP(Z1460,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",60,7839,"equivalent to OECD 410 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",5,"M + F","101.5  (vehicle diethylphthalate)","Dermal","Topical",1000,1000,1000,"mg/kg bw/day",21,"Days","Adult","F",1000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1461<>0,VLOOKUP(Z1461,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: statistically significant increase in MCH (4%) and MCV (4%) in females, reduced number of neutrophils (31%) in females. There was a decrease in monocytes (44%, P<0.05) and large unstained cells (62%, P<0.05) in the high dose males compared to\ncontrols. These findings have not been seen in previous studies and the decrease in monocytes may partly be due to higher values in concurrent control animals.\nClinical chemistry: no adverse effects observed\nUrinalysis: not performed",null,"Change","<1000",1000,"mg/kg bw/day",{"$f":"IF(Z1461<>0,VLOOKUP(Z1461,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",60,7839,"equivalent to OECD 410 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",5,"M + F","101.5  (vehicle diethylphthalate)","Dermal","Topical",1000,1000,1000,"mg/kg bw/day",21,"Days","Adult","M + F",">1000","Organ Weight","Kidney weight",{"$f":"IF(Z1462<>0,VLOOKUP(Z1462,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1462<>0,VLOOKUP(Z1462,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",60,7839,"equivalent to OECD 410 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",5,"M + F","101.5  (vehicle diethylphthalate)","Dermal","Topical",1000,1000,1000,"mg/kg bw/day",21,"Days","Adult","M + F",">1000","Organ Weight","Liver weight",{"$f":"IF(Z1463<>0,VLOOKUP(Z1463,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1463<>0,VLOOKUP(Z1463,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",60,7839,"equivalent to OECD 410 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",5,"M + F","101.5  (vehicle diethylphthalate)","Dermal","Topical",1000,1000,1000,"mg/kg bw/day",21,"Days","Adult","M",">1000","Organ Weight","Testis weight",{"$f":"IF(Z1464<>0,VLOOKUP(Z1464,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1464<>0,VLOOKUP(Z1464,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",60,7839,"equivalent to OECD 410 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",5,"M + F","101.5  (vehicle diethylphthalate)","Dermal","Topical",1000,1000,1000,"mg/kg bw/day",21,"Days","Adult","M + F",">1000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1465<>0,VLOOKUP(Z1465,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy: unilateral dilatation in 2/5 males at 1000 mg/kg bw/day, common finding in rats of this age, not considered related to treatment\nHistopathology: unilateral papillary necrosis in 1/5 males at 1000 mg/kg bw/day, urothelial hyperplasia in 2/5 males at 1000 mg/kg bw/day, pelvic dilatation in 3/5 males at 1000 mg/kg bw/day, common finding in rats of this age, not treatment-related",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1465<>0,VLOOKUP(Z1465,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",60,7839,"equivalent to OECD 410 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",5,"M + F","101.5  (vehicle diethylphthalate)","Dermal","Topical",1000,1000,1000,"mg/kg bw/day",21,"Days","Adult","M + F",1000,"Organ histopathology","Liver histopathology",{"$f":"IF(Z1466<>0,VLOOKUP(Z1466,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1466<>0,VLOOKUP(Z1466,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",60,7839,"equivalent to OECD 410 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",5,"M + F","101.5  (vehicle diethylphthalate)","Dermal","Topical",1000,1000,1000,"mg/kg bw/day",21,"Days","Adult","M",">1000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1467<>0,VLOOKUP(Z1467,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1467<>0,VLOOKUP(Z1467,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",60,7839,"equivalent to OECD 410 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",5,"M + F","101.5  (vehicle diethylphthalate)","Dermal","Topical",1000,1000,1000,"mg/kg bw/day",21,"Days","Adult","M",">1000","Organ histopathology","Testis histopathology",{"$f":"IF(Z1468<>0,VLOOKUP(Z1468,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1468<>0,VLOOKUP(Z1468,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",60,7839,"equivalent to OECD 410 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",5,"M + F","101.5  (vehicle diethylphthalate)","Dermal","Topical",1000,1000,1000,"mg/kg bw/day",21,"Days","Adult","F",">1000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1469<>0,VLOOKUP(Z1469,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1469<>0,VLOOKUP(Z1469,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",60,7839,"equivalent to OECD 410 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",5,"M + F","101.5  (vehicle diethylphthalate)","Dermal","Topical",1000,1000,1000,"mg/kg bw/day",21,"Days","Adult","M + F",">1000","Organ histopathology","Skin histopathology",{"$f":"IF(Z1470<>0,VLOOKUP(Z1470,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1470<>0,VLOOKUP(Z1470,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",60,7839,"equivalent to OECD 410 (1981)","DAR",null,1993,"Rat","Sprague-Dawley",5,"M + F","101.5  (vehicle diethylphthalate)","Dermal","Topical",1000,1000,1000,"mg/kg bw/day",21,"Days","Adult","M",">1000","Organ Weight","Epididymis weight",{"$f":"IF(Z1471<>0,VLOOKUP(Z1471,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1471<>0,VLOOKUP(Z1471,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Weighed together with testis, treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",61,null,"OECD 410 (1981)","DAR",null,1996,"Rat","Alpk: APfSD",5,"M + F",95.6,"Dermal","Topical","250; 500; 1000",250,1000,"mg/kg bw/day",21,"Days","Adult","M + F",">1000","In life observation","Mortality",{"$f":"IF(Z1472<>0,VLOOKUP(Z1472,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1472<>0,VLOOKUP(Z1472,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: area 7 cm x 7 cm, 6h/day for 5 days/week under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",61,null,"OECD 410 (1981)","DAR",null,1996,"Rat","Alpk: APfSD",5,"M + F",95.6,"Dermal","Topical","250; 500; 1000",250,1000,"mg/kg bw/day",21,"Days","Adult","M + F",">1000","In life observation","Clinical signs",{"$f":"IF(Z1473<>0,VLOOKUP(Z1473,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related signs of systemic toxicity or local skin reactions observed. 1/5 females at 500 mg/kg bw/day had desquamation during the latter part of the study, no dose-relation, toxicologically not significant",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1473<>0,VLOOKUP(Z1473,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: area 7 cm x 7 cm, 6h/day for 5 days/week under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",61,null,"OECD 410 (1981)","DAR",null,1996,"Rat","Alpk: APfSD",5,"M + F",95.6,"Dermal","Topical","250; 500; 1000",250,1000,"mg/kg bw/day",21,"Days","Adult","M + F",">1000","In life observation","Body weight",{"$f":"IF(Z1474<>0,VLOOKUP(Z1474,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1474<>0,VLOOKUP(Z1474,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: area 7 cm x 7 cm, 6h/day for 5 days/week under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",61,null,"OECD 410 (1981)","DAR",null,1996,"Rat","Alpk: APfSD",5,"M + F",95.6,"Dermal","Topical","250; 500; 1000",250,1000,"mg/kg bw/day",21,"Days","Adult","M + F",">1000","In life observation","Food consumption",{"$f":"IF(Z1475<>0,VLOOKUP(Z1475,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1475<>0,VLOOKUP(Z1475,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: area 7 cm x 7 cm, 6h/day for 5 days/week under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",61,null,"OECD 410 (1981)","DAR",null,1996,"Rat","Alpk: APfSD",5,"M + F",95.6,"Dermal","Topical","250; 500; 1000",250,1000,"mg/kg bw/day",21,"Days","Adult","M + F",1000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1476<>0,VLOOKUP(Z1476,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: statistically significant increase in Hb in females at 1000 mg/kg bw/day, treatment-related; statist. signif. decrease in RBC in females at 250 and 1000 mg/kg bw/day, considered not to be of tox. significance since no effect on the red cell parameters were observed\nClinical chemistry: statistically significant increase in plasma urea but not urea levels in females at 1000 mg/kg bw/day, considered to be not of tox significance; stat. signif. decrease in triglycerides in males at 500 mg/kg bw/day, no dose relation, considered to be not treatment-related\nUrinalysis: not performed",null,"Change","<1000",1000,"mg/kg bw/day",{"$f":"IF(Z1476<>0,VLOOKUP(Z1476,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: area 7 cm x 7 cm, 6h/day for 5 days/week under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",61,null,"OECD 410 (1981)","DAR",null,1996,"Rat","Alpk: APfSD",5,"M + F",95.6,"Dermal","Topical","250; 500; 1000",250,1000,"mg/kg bw/day",21,"Days","Adult","M + F",">1000","Organ Weight","Kidney weight",{"$f":"IF(Z1477<>0,VLOOKUP(Z1477,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1477<>0,VLOOKUP(Z1477,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"}]
["Mammals","Repeated dose dermal toxicity",61,null,"OECD 410 (1981)","DAR",null,1996,"Rat","Alpk: APfSD",5,"M + F",95.6,"Dermal","Topical","250; 500; 1000",250,1000,"mg/kg bw/day",21,"Days","Adult","M + F",">1000","Organ Weight","Adrenals weight",{"$f":"IF(Z1478<>0,VLOOKUP(Z1478,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1478<>0,VLOOKUP(Z1478,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment: area 7 cm x 7 cm, 6h/day for 5 days/week under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",61,null,"OECD 410 (1981)","DAR",null,1996,"Rat","Alpk: APfSD",5,"M + F",95.6,"Dermal","Topical","250; 500; 1000",250,1000,"mg/kg bw/day",21,"Days","Adult","M + F",">1000","Organ Weight","Liver weight",{"$f":"IF(Z1479<>0,VLOOKUP(Z1479,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1479<>0,VLOOKUP(Z1479,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: area 7 cm x 7 cm, 6h/day for 5 days/week under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",61,null,"OECD 410 (1981)","DAR",null,1996,"Rat","Alpk: APfSD",5,"M + F",95.6,"Dermal","Topical","250; 500; 1000",250,1000,"mg/kg bw/day",21,"Days","Adult","M",">1000","Organ Weight","Testis weight",{"$f":"IF(Z1480<>0,VLOOKUP(Z1480,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Decreased abs. weight at 500 mg/kg bw/day, findings attributed to one (single) animal showing reduced and flaccid testes, not treatment-related",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1480<>0,VLOOKUP(Z1480,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment: area 7 cm x 7 cm, 6h/day for 5 days/week under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",61,null,"OECD 410 (1981)","DAR",null,1996,"Rat","Alpk: APfSD",5,"M + F",95.6,"Dermal","Topical","250; 500; 1000",250,1000,"mg/kg bw/day",21,"Days","Adult","M",">1000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1481<>0,VLOOKUP(Z1481,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1481<>0,VLOOKUP(Z1481,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: area 7 cm x 7 cm, 6h/day for 5 days/week under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",61,null,"OECD 410 (1981)","DAR",null,1996,"Rat","Alpk: APfSD",5,"M + F",95.6,"Dermal","Topical","250; 500; 1000",250,1000,"mg/kg bw/day",21,"Days","Adult","M",">1000","Organ histopathology","Liver histopathology",{"$f":"IF(Z1482<>0,VLOOKUP(Z1482,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1482<>0,VLOOKUP(Z1482,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: area 7 cm x 7 cm, 6h/day for 5 days/week under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M + F",">5000","In life observation","Mortality",{"$f":"IF(Z1483<>0,VLOOKUP(Z1483,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1483<>0,VLOOKUP(Z1483,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M + F",">5000","In life observation","Clinical signs",{"$f":"IF(Z1484<>0,VLOOKUP(Z1484,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Clinical signs of systemic toxicity: soft stool, diarrhea and mucoid diarrhea and ocular and nasal discharge were observed in a few animals of both sexes among all groups, not treatment-related\nLocal skin reactions: doubtful or barely perceptible to very slight erythema at 5000 mg/kg bw/day in 3/5 males and 3/5 females with abraded skin and in 3/5 males and 2/5 females with intact skin, doubtful to barely perceptable edema at 5000 mg/kg bw/day in 2/5 males and 2/5 females with abraded skin and in 2/5 males and 2/5 females with intact skin, not considered biologically significant",null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1484<>0,VLOOKUP(Z1484,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M + F",">5000","In life observation","Body weight",{"$f":"IF(Z1485<>0,VLOOKUP(Z1485,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1485<>0,VLOOKUP(Z1485,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M + F",">5000","In life observation","Food consumption",{"$f":"IF(Z1486<>0,VLOOKUP(Z1486,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1486<>0,VLOOKUP(Z1486,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M + F",">5000","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1487<>0,VLOOKUP(Z1487,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: No treatment-related findings (statist. signif. increase in Hb and Hct in males at 100 mg/kg bw/day, no dose-relation)\nClinical chemistry: No treatment-related findings (statist. siginif. increase in Na in males at 5000 mg/kg bw/day, statist. signif. increase in glucose in females at 100 and 5000 mg/kg bw/day, statist. signif. decreased LDH in females at 5000 mg/kg bw/day were considered to be without biological significance)\nUrinalysis: not performed",null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1487<>0,VLOOKUP(Z1487,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M + F",">5000","Organ Weight","Adrenals weight",{"$f":"IF(Z1488<>0,VLOOKUP(Z1488,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1488<>0,VLOOKUP(Z1488,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M + F",">5000","Organ Weight","Kidney weight",{"$f":"IF(Z1489<>0,VLOOKUP(Z1489,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"A significant increase in mean relative organ weight was observed in females of the 5000 mg/kg bw/d group which was not considered toxicologically relevant since no histopathological effects were observed.",null,"Increase",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1489<>0,VLOOKUP(Z1489,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M + F",">5000","Organ Weight","Liver weight",{"$f":"IF(Z1490<>0,VLOOKUP(Z1490,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1490<>0,VLOOKUP(Z1490,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","F",">5000","Organ Weight","Ovary weight",{"$f":"IF(Z1491<>0,VLOOKUP(Z1491,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1491<>0,VLOOKUP(Z1491,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M",">5000","Organ Weight","Testis weight",{"$f":"IF(Z1492<>0,VLOOKUP(Z1492,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1492<>0,VLOOKUP(Z1492,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M + F",">5000","Organ Weight","Pituitary weight",{"$f":"IF(Z1493<>0,VLOOKUP(Z1493,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1493<>0,VLOOKUP(Z1493,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M + F",">5000","Organ Weight","Thyroid weight",{"$f":"IF(Z1494<>0,VLOOKUP(Z1494,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1494<>0,VLOOKUP(Z1494,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M + F",">5000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1495<>0,VLOOKUP(Z1495,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1495<>0,VLOOKUP(Z1495,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M + F",">5000","Organ histopathology","Liver histopathology",{"$f":"IF(Z1496<>0,VLOOKUP(Z1496,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1496<>0,VLOOKUP(Z1496,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M + F",">5000","Organ histopathology","Skin histopathology",{"$f":"IF(Z1497<>0,VLOOKUP(Z1497,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No treatment-related findings. Findings of inflammation evident as mild dermal inflammatory cell infiltrate was comparable for treated and untreated skin among all groups in both sexes. (inflammation of treated skin in 3/5, 4/5, 3/5 and 3/5 males and of untreated skin in 5/5, 4/5, 4/5 and 3/5 males; inflammation of treated skin in 4/5, 4/5, 5/5 and 5/5 females and of untreated skin in 4/5, 5/5, 4/5 and 5/5 females)",null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1497<>0,VLOOKUP(Z1497,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M",">5000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1498<>0,VLOOKUP(Z1498,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1498<>0,VLOOKUP(Z1498,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","F",">5000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1499<>0,VLOOKUP(Z1499,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1499<>0,VLOOKUP(Z1499,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M",">5000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1500<>0,VLOOKUP(Z1500,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1500<>0,VLOOKUP(Z1500,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M",">5000","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z1501<>0,VLOOKUP(Z1501,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1501<>0,VLOOKUP(Z1501,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","M",">5000","Organ histopathology","Testis histopathology",{"$f":"IF(Z1502<>0,VLOOKUP(Z1502,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Traces of mild degeneration of seminiferous tubules were observed in control and treartment groups which were attributed to non-specific stress caused by treatment procedures.\n",null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1502<>0,VLOOKUP(Z1502,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",62,null,"equivalent to OECD 410 (1981)","DAR",null,1982,"Rabbit","New Zealand White",10,"M + F",null,"Dermal","Topical","100; 1000; 5000",100,5000,"mg/kg bw/day",21,"Days","Adult","F",">5000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1503<>0,VLOOKUP(Z1503,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",5000,">5000","mg/kg bw/day",{"$f":"IF(Z1503<>0,VLOOKUP(Z1503,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M + F",">2000","In life observation","Mortality",{"$f":"IF(Z1504<>0,VLOOKUP(Z1504,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1504<>0,VLOOKUP(Z1504,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M + F",">2000","In life observation","Clinical signs",{"$f":"IF(Z1505<>0,VLOOKUP(Z1505,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Clinical signs of systemic toxicity: no adverse effects observed\nLocal skin reactions: very slight erythema in males at 2000 mg/kg bw/day through Days 7-20 and in females at 500 mg/kg bw/day lasting for 5 days were not attributed to treatment. No edema was observed.",null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1505<>0,VLOOKUP(Z1505,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M + F",">2000","In life observation","Body weight",{"$f":"IF(Z1506<>0,VLOOKUP(Z1506,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1506<>0,VLOOKUP(Z1506,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M + F",">2000","In life observation","Food consumption",{"$f":"IF(Z1507<>0,VLOOKUP(Z1507,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1507<>0,VLOOKUP(Z1507,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M + F",">2000","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1508<>0,VLOOKUP(Z1508,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: no treatment-related findings. Mean corpuscular volume of platelets and variation of platelet volume were statist. signif. decreased in females at 1000 and 2000 mg/kg bw/day were within normal limits and therefore not attributed to treatment.\nClinical chemistry: no treatment-related findings. Statist. signif. increased urea values in males at 2000 mg/kg bw/day were within normal limits and therefore not attributed to treatment.\nUrinalysis: not performed",null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1508<>0,VLOOKUP(Z1508,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M + F",">2000","Organ Weight","Liver weight",{"$f":"IF(Z1509<>0,VLOOKUP(Z1509,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute and organ weight relative to brain weight was assessed.",null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1509<>0,VLOOKUP(Z1509,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M + F",">2000","Organ Weight","Kidney weight",{"$f":"IF(Z1510<>0,VLOOKUP(Z1510,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute and organ weight relative to brain weight was assessed.",null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1510<>0,VLOOKUP(Z1510,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M",">2000","Organ Weight","Testis weight",{"$f":"IF(Z1511<>0,VLOOKUP(Z1511,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute and organ weight relative to brain weight was assessed.",null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1511<>0,VLOOKUP(Z1511,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M + F",">2000","Organ Weight","Adrenals weight",{"$f":"IF(Z1512<>0,VLOOKUP(Z1512,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Absolute and organ weight relative to brain weight was assessed.",null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1512<>0,VLOOKUP(Z1512,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M + F",">2000","Organ Weight","Brain weight",{"$f":"IF(Z1513<>0,VLOOKUP(Z1513,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Fresh brain weight was recorded.",null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1513<>0,VLOOKUP(Z1513,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","F",">2000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1514<>0,VLOOKUP(Z1514,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1514<>0,VLOOKUP(Z1514,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology performed for control and high dose group animals only. Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M",">2000","Organ histopathology","Testis histopathology",{"$f":"IF(Z1515<>0,VLOOKUP(Z1515,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1515<>0,VLOOKUP(Z1515,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathology performed for control and high dose group animals only. Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M + F",">2000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1516<>0,VLOOKUP(Z1516,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1516<>0,VLOOKUP(Z1516,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Histopathology performed for control and high dose group animals only. Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M + F",">2000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1517<>0,VLOOKUP(Z1517,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Atrophy, congestion and focal fatty degeneration in 1/5 and 1/5 males of control and high dose group, not treatment-related",null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1517<>0,VLOOKUP(Z1517,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Histopathology performed for control and high dose group animals only. Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M + F",">2000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1518<>0,VLOOKUP(Z1518,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1518<>0,VLOOKUP(Z1518,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Histopathology performed for control and high dose group animals only. Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M + F",">2000","Organ histopathology","Liver histopathology",{"$f":"IF(Z1519<>0,VLOOKUP(Z1519,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1519<>0,VLOOKUP(Z1519,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology performed for control and high dose group animals only. Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",63,null,"OECD 410 (1981)","DAR",null,1994,"Rabbit","New Zealand White",5,"M + F",99.6,"Dermal","Topical","500; 1000; 2000",500,2000,"mg/kg bw/day",28,"Days","Adult","M + F",">2000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1520<>0,VLOOKUP(Z1520,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",2000,">2000","mg/kg bw/day",{"$f":"IF(Z1520<>0,VLOOKUP(Z1520,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathology performed for control and high dose group animals only. Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",64,"43-90716","OECD 414, US EPA 83-3 (1982)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",25,"F",98.6,"Oral","Gavage/Intubation","300; 1000; 3500",300,3500,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",1000,"In life observation","Clinical signs",{"$f":"IF(Z1521<>0,VLOOKUP(Z1521,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"3500 mg/kg: respiratory distress (noisy respiration/gasping (15/25)), post-dose salivation (22/22), wet coats (13/22), loose faeces from GD7-GD16 (22/22). 1000 mg/kg: noisy respiration on one occasion (2/25). Hair loss/scabbing in occasional animals, including controls, not treatment related.",null,"Change",300,1000,"mg/kg bw/day",{"$f":"IF(Z1521<>0,VLOOKUP(Z1521,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Vehicle: 1% Methylcellulose; Pre-Study (study ID 41-90716) included in report, doses tested: 500; 1000; 3500 mg/kg bw/day","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",64,"43-90716","OECD 414, US EPA 83-3 (1982)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",25,"F",98.6,"Oral","Gavage/Intubation","300; 1000; 3500",300,3500,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",3500,"In life observation","Mortality",{"$f":"IF(Z1522<>0,VLOOKUP(Z1522,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"One female was sacrificed on GD10 immediately after dosing following a probable intubation error (white fluid was found in the thoracic cavity). A further two females were sacrificed on GD7 and GD13 respectively following signs of respiratory distress (noisy respiration/gasping). Post mortem observation did not reveal the cause of distress but the marked signs were a continuation of the signs representative for this group and these two deaths are considered to be related to treatment. There were no further deaths.",null,"Increase",1000,3500,"mg/kg bw/day",{"$f":"IF(Z1522<>0,VLOOKUP(Z1522,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Vehicle: 1% Methylcellulose; Pre-Study (study ID 41-90716) included in report, doses tested: 500; 1000; 3500 mg/kg bw/day","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",64,"43-90716","OECD 414, US EPA 83-3 (1982)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",25,"F",98.6,"Oral","Gavage/Intubation","300; 1000; 3500",300,3500,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",3500,"In life observation","Food consumption",{"$f":"IF(Z1523<>0,VLOOKUP(Z1523,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food: 3500 mg/kg: Food consumption was decreased throughout the treatment period, thereafter, food intake was comparable with controls to termination. At lower dosages, food consumption was comparable with controls throughout.\nWater: 3500 mg/kg: water consumption was increased following the start of treatment and continued to increase throughout the remainder of the treatment period. Thereafter, intake decreased, but was still slightly greater than controls at termination. At lower dosages, the pattern of water consumption did not indicate any clear effects, although at 1000 mg/kg/day, there was a suggestion of increased intake from Days 14 - 15 to termination, although at this stage no clear association with treatment can be made.\n",null,"Change",1000,3500,"mg/kg bw/day",{"$f":"IF(Z1523<>0,VLOOKUP(Z1523,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Vehicle: 1% Methylcellulose; Pre-Study (study ID 41-90716) included in report, doses tested: 500; 1000; 3500 mg/kg bw/day","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",64,"43-90716","OECD 414, US EPA 83-3 (1982)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",25,"F",98.6,"Oral","Gavage/Intubation","300; 1000; 3500",300,3500,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",3500,"In life observation","Body weight",{"$f":"IF(Z1524<>0,VLOOKUP(Z1524,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"At 3500 mg/kg/day, the rate of bodyweight gain was markedly reduced during the first two days of treatment when compared to the concurrent control values. Thereafter, apart from a slight reduction in the rate of bodyweight gain during Days 12 to 14 of pregnancy, the rate of bodyweight gain was comparable with the controls, although absolute parity with the control group was not attained by Day 20.\nAt 1000 mg/kg/day, there was a marginal reduction in the rate of bodyweight gain during the first two days of treatment when compared with the concurrent control group. Thereafter, the pattern of bodyweight change was similar to the controls.",null,"Decrease",1000,3500,"mg/kg bw/day",{"$f":"IF(Z1524<>0,VLOOKUP(Z1524,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Vehicle: 1% Methylcellulose; Pre-Study (study ID 41-90716) included in report, doses tested: 500; 1000; 3500 mg/kg bw/day","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",64,"43-90716","OECD 414, US EPA 83-3 (1982)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",25,"F",98.6,"Oral","Gavage/Intubation","300; 1000; 3500",300,3500,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">3500","Reproductive","Litter size",{"$f":"IF(Z1525<>0,VLOOKUP(Z1525,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"A total of 23, 23, 25 and 22 females had live young at Day 20 in control to high dose groups respectively. No treatment related effect on litter size.",null,"No effect",3500,">3500","mg/kg bw/day",{"$f":"IF(Z1525<>0,VLOOKUP(Z1525,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: 1% Methylcellulose; Pre-Study (study ID 41-90716) included in report, doses tested: 500; 1000; 3500 mg/kg bw/day","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",64,"43-90716","OECD 414, US EPA 83-3 (1982)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",25,"F",98.6,"Oral","Gavage/Intubation","300; 1000; 3500",300,3500,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">3500","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z1526<>0,VLOOKUP(Z1526,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No treatment-related effect on pre-treatment events (implantation rate, corpora lutea).",null,"No effect",3500,">3500","mg/kg bw/day",{"$f":"IF(Z1526<>0,VLOOKUP(Z1526,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: 1% Methylcellulose; Pre-Study (study ID 41-90716) included in report, doses tested: 500; 1000; 3500 mg/kg bw/day","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",64,"43-90716","OECD 414, US EPA 83-3 (1982)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",25,"F",98.6,"Oral","Gavage/Intubation","300; 1000; 3500",300,3500,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">3500","Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z1527<>0,VLOOKUP(Z1527,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No treatment-related effect on embryonic losses and mean number of live fetuses.",null,"No effect",3500,">3500","mg/kg bw/day",{"$f":"IF(Z1527<>0,VLOOKUP(Z1527,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: 1% Methylcellulose; Pre-Study (study ID 41-90716) included in report, doses tested: 500; 1000; 3500 mg/kg bw/day","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",64,"43-90716","OECD 414, US EPA 83-3 (1982)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",25,"F",98.6,"Oral","Gavage/Intubation","300; 1000; 3500",300,3500,"mg/kg bw/day","10 (GD 6-15)","Days","Fetus","M + F",">3500","Reproductive","Sex ratio",{"$f":"IF(Z1528<>0,VLOOKUP(Z1528,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No treatment-related effect on sex ratio.",null,"No effect",3500,">3500","mg/kg bw/day",{"$f":"IF(Z1528<>0,VLOOKUP(Z1528,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: 1% Methylcellulose; Pre-Study (study ID 41-90716) included in report, doses tested: 500; 1000; 3500 mg/kg bw/day","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",64,"43-90716","OECD 414, US EPA 83-3 (1982)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",25,"F",98.6,"Oral","Gavage/Intubation","300; 1000; 3500",300,3500,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",3500,"Reproductive","Pre implantation loss",{"$f":"IF(Z1529<>0,VLOOKUP(Z1529,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"A significant increase in pre-implantation loss at 3500 mg/kg/day was observed. However, since treatment commences after implantation, this is not considered to be treatment-related.",null,"No effect",1000,3500,"mg/kg bw/day",{"$f":"IF(Z1529<>0,VLOOKUP(Z1529,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: 1% Methylcellulose; Pre-Study (study ID 41-90716) included in report, doses tested: 500; 1000; 3500 mg/kg bw/day","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",64,"43-90716","OECD 414, US EPA 83-3 (1982)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",25,"F",98.6,"Oral","Gavage/Intubation","300; 1000; 3500",300,3500,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">3500","Reproductive","Post implantation loss",{"$f":"IF(Z1530<>0,VLOOKUP(Z1530,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No treatment-related effect on post-implantation loss.",null,"No effect",3500,">3500","mg/kg bw/day",{"$f":"IF(Z1530<>0,VLOOKUP(Z1530,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: 1% Methylcellulose; Pre-Study (study ID 41-90716) included in report, doses tested: 500; 1000; 3500 mg/kg bw/day","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",64,"43-90716","OECD 414, US EPA 83-3 (1982)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",25,"F",98.6,"Oral","Gavage/Intubation","300; 1000; 3500",300,3500,"mg/kg bw/day","10 (GD 6-15)","Days","Fetus","M + F",3500,"Developmental","Litter/pup weight",{"$f":"IF(Z1531<>0,VLOOKUP(Z1531,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"At 3500 mg/kg, both litter and mean foetal weights were reduced compared to control (statistically significant for mean foetal weight).",null,"Decrease",1000,3500,"mg/kg bw/day",{"$f":"IF(Z1531<>0,VLOOKUP(Z1531,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: 1% Methylcellulose; Pre-Study (study ID 41-90716) included in report, doses tested: 500; 1000; 3500 mg/kg bw/day","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",64,"43-90716","OECD 414, US EPA 83-3 (1982)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",25,"F",98.6,"Oral","Gavage/Intubation","300; 1000; 3500",300,3500,"mg/kg bw/day","10 (GD 6-15)","Days","Fetus","M + F",">3500","Abnormalities","Genital abnormalities",{"$f":"IF(Z1532<>0,VLOOKUP(Z1532,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No treatment-related effect on genitals was observed during sex determination, visceral examination, as well as gonadal inspection.",null,"No effect",3500,">3500","mg/kg bw/day",{"$f":"IF(Z1532<>0,VLOOKUP(Z1532,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Vehicle: 1% Methylcellulose; Pre-Study (study ID 41-90716) included in report, doses tested: 500; 1000; 3500 mg/kg bw/day","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",64,"43-90716","OECD 414, US EPA 83-3 (1982)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",25,"F",98.6,"Oral","Gavage/Intubation","300; 1000; 3500",300,3500,"mg/kg bw/day","10 (GD 6-15)","Days","Fetus","M + F",3500,"Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z1533<>0,VLOOKUP(Z1533,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Skeletal change: The incidence of rib distortion (wavy ribs) was markedly increased at 3500 mg/kg/day. The marginally higher incidence at 1000 mg/kg/day was of uncertain relationship to treatment.\nNo increase in incidence of malformed foetuses was observed (A total of 1, 2, 1 and 3 foetuses in control to high dose groups, respectively were malformed). Increased incidence of reduced ossification was observed in all treated groups compared to the concurrent control. However, compared to historical control data, the incidence of these skeletal changes at 3500 mg/kg/day was only slightly outside the range. Since no clear dosage-response was apparent, reduced ossification was not considered treatment-related.\nThe incidence of foetuses with visceral anomalies was low and did not indicate any adverse treatment-related effects.\n",null,"Increase",300,1000,"mg/kg bw/day",{"$f":"IF(Z1533<>0,VLOOKUP(Z1533,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: 1% Methylcellulose; Pre-Study (study ID 41-90716) included in report, doses tested: 500; 1000; 3500 mg/kg bw/day","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",65,null,"OECD 414 (1981)","DAR",null,1991,"Rat","Wistar",20,"F",96.8,"Oral","Gavage/Intubation",1000,1000,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","In life observation","Mortality",{"$f":"IF(Z1534<>0,VLOOKUP(Z1534,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No mortality was observed.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1534<>0,VLOOKUP(Z1534,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",65,null,"OECD 414 (1981)","DAR",null,1991,"Rat","Wistar",20,"F",96.8,"Oral","Gavage/Intubation",1000,1000,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","In life observation","Clinical signs",{"$f":"IF(Z1535<>0,VLOOKUP(Z1535,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related clinical signs were observed.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1535<>0,VLOOKUP(Z1535,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",65,null,"OECD 414 (1981)","DAR",null,1991,"Rat","Wistar",20,"F",96.8,"Oral","Gavage/Intubation",1000,1000,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z1536<>0,VLOOKUP(Z1536,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Gravid uterus weight along with ovaries was weighed. However, no further details were reported.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1536<>0,VLOOKUP(Z1536,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",65,null,"OECD 414 (1981)","DAR",null,1991,"Rat","Wistar",20,"F",96.8,"Oral","Gavage/Intubation",1000,1000,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","Organ histopathology","Lung histopathology",{"$f":"IF(Z1537<>0,VLOOKUP(Z1537,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology was not performed. During macroscopic examination (necropsy) no treatment-related findings were observed. ",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1537<>0,VLOOKUP(Z1537,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",65,null,"OECD 414 (1981)","DAR",null,1991,"Rat","Wistar",20,"F",96.8,"Oral","Gavage/Intubation",1000,1000,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","Organ histopathology","Liver histopathology",{"$f":"IF(Z1538<>0,VLOOKUP(Z1538,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathology was not performed. During macroscopic examination (necropsy) no treatment-related findings were observed. ",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1538<>0,VLOOKUP(Z1538,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",65,null,"OECD 414 (1981)","DAR",null,1991,"Rat","Wistar",20,"F",96.8,"Oral","Gavage/Intubation",1000,1000,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","In life observation","Food consumption",{"$f":"IF(Z1539<>0,VLOOKUP(Z1539,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"There was no intergroup differnce in feed intake between treatment and control group. ",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1539<>0,VLOOKUP(Z1539,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",65,null,"OECD 414 (1981)","DAR",null,1991,"Rat","Wistar",20,"F",96.8,"Oral","Gavage/Intubation",1000,1000,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","In life observation","Body weight",{"$f":"IF(Z1540<>0,VLOOKUP(Z1540,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"There were no significant intergroup differences in body weight at GD0; GD6; GD15; and GD20. The mean body weight gain during pre-treatment, treatment, post-treatment or overall gestation period did not show any statistical difference between the control and treatment groups. Similarly absolute body weight at the end of pregnancy had significantly (p=0.01) increased in both the study groups (control group and treatment group) as compared to GD0 weights.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1540<>0,VLOOKUP(Z1540,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",65,null,"OECD 414 (1981)","DAR",null,1991,"Rat","Wistar",20,"F",96.8,"Oral","Gavage/Intubation",1000,1000,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","Reproductive","Litter size",{"$f":"IF(Z1541<>0,VLOOKUP(Z1541,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The intergroup comparison of litter data regarding \"litter size\" between control group and treatment group has not shown any statistically significant (p=0.5) difference.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1541<>0,VLOOKUP(Z1541,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",65,null,"OECD 414 (1981)","DAR",null,1991,"Rat","Wistar",20,"F",96.8,"Oral","Gavage/Intubation",1000,1000,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Fetus","M + F",">1000","Developmental","Litter/pup weight",{"$f":"IF(Z1542<>0,VLOOKUP(Z1542,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The intergroup comparison of litter data regarding \"mean fetal weight\" (combined sex and sex wise) between control group and treatment group has not shown any statistically significant (p=0.5) difference.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1542<>0,VLOOKUP(Z1542,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",65,null,"OECD 414 (1981)","DAR",null,1991,"Rat","Wistar",20,"F",96.8,"Oral","Gavage/Intubation",1000,1000,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z1543<>0,VLOOKUP(Z1543,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The number of corpora lutea and implantations were similar in both control and treatment groups.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1543<>0,VLOOKUP(Z1543,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",65,null,"OECD 414 (1981)","DAR",null,1991,"Rat","Wistar",20,"F",96.8,"Oral","Gavage/Intubation",1000,1000,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Fetus","M + F",">1000","Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z1544<>0,VLOOKUP(Z1544,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The number of embryonic and fetal resorptions was similar in both control and treatment groups. The number of dams with any resorption tended to decrease in treatment group which appears to be an incidential finding. The intergroup comparison of litter data regarding \"total number of fetuses\" and \"number of abnormal, dead and live fetuses\" between control group and treatment group has not shown any statistically significant (p=0.5) difference.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1544<>0,VLOOKUP(Z1544,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",65,null,"OECD 414 (1981)","DAR",null,1991,"Rat","Wistar",20,"F",96.8,"Oral","Gavage/Intubation",1000,1000,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","Reproductive","Pre implantation loss",{"$f":"IF(Z1545<>0,VLOOKUP(Z1545,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The number of pre-implantation loss was similar in both control and treatment groups.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1545<>0,VLOOKUP(Z1545,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",65,null,"OECD 414 (1981)","DAR",null,1991,"Rat","Wistar",20,"F",96.8,"Oral","Gavage/Intubation",1000,1000,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Adult","F",">1000","Reproductive","Post implantation loss",{"$f":"IF(Z1546<>0,VLOOKUP(Z1546,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The number of post-implantation loss was similar in both control and treatment groups.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1546<>0,VLOOKUP(Z1546,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",65,null,"OECD 414 (1981)","DAR",null,1991,"Rat","Wistar",20,"F",96.8,"Oral","Gavage/Intubation",1000,1000,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Fetus","M + F",1000,"Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z1547<>0,VLOOKUP(Z1547,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The intergroup comparison of litter data regarding \"number of abnormal, dead and live fetuses\" between control group and treatment group has not shown any statistically significant (p=0.5) difference. \nEXTERNAL MALFORMATIONS: No incidence of major external malformations was seen in either of the study groups. VISCERAL MALFORMATION: There was no incidence of major visceral malformations. SKELETAL MALFORMATIONS:  Indidence of minor and major skeletal malformations, did not show any statistically significant intergroup difference. The incidence of delayed ossification of caudal vertebral arch, forelimb-proximal phalange and hindlimb-distal phalange was significantly higher in the treatment group than in control. However, the incidence of incomplete to partial ossification of parietal and interparietal of the skull was less in the treatment group.",null,"Increase","<1000",1000,"mg/kg bw/day",{"$f":"IF(Z1547<>0,VLOOKUP(Z1547,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"The pattern of ossification is unclear and difficult to assess in the absence of additional dose groups. Therefore it is not considered possible to set a NOAEL for developmental toxicity. "]
["Mammals","Prenatal developmental toxicity study",65,null,"OECD 414 (1981)","DAR",null,1991,"Rat","Wistar",20,"F",96.8,"Oral","Gavage/Intubation",1000,1000,1000,"mg/kg bw/day","10 (GD 6-15)","Days","Fetus","M + F",">1000","Reproductive","Sex ratio",{"$f":"IF(Z1549<>0,VLOOKUP(Z1549,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No statistically significant (p=0.5) effect on sex ration was observed.",null,"No effect",1000,">1000","mg/kg bw/day",{"$f":"IF(Z1549<>0,VLOOKUP(Z1549,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",66,null,"similar to OECD 414 (\"Teratology study in rabbits\")","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",350,"In life observation","Mortality",{"$f":"IF(Z1550<>0,VLOOKUP(Z1550,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Two rabbits in the control group aborted and were sacrificed (GD 22). One rabbit in the 75 mg/kg/day dosage group died on gestation day 26. In the 175 mg/kg/day dosage group, one rabbit aborted and was sacrificed on gestation day 27 and two rabbits died, one each on gestation days 22 and 25. One rabbit in the 350 mg/kg/day dosage group aborted and was sacrificed on gestation day 23 and 10 died by gestation day 21. One rabbit in this group died on gestation day 3. On the same day, a replacement female was selected and artificially inseminated.",null,"Increase",75,175,"mg/kg bw/day",{"$f":"IF(Z1550<>0,VLOOKUP(Z1550,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Vehicle: 0.5% aqueous Methocel","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",66,null,"similar to OECD 414 (\"Teratology study in rabbits\")","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",175,"In life observation","Clinical signs",{"$f":"IF(Z1551<>0,VLOOKUP(Z1551,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Soft stool and diarrhea were noted in all groups during the treatment period. A slight increase was noted, however, in the 175 mg/kg/day dosage group when compared to the control group and either soft stool, diarrhea or both were noted in each animal at least once during the treatment period in the 350 mg/kg/day dosage group. A definite increase in nasal discharge was also noted in the 350 mg/kg/day dosage group when compared to the control group.",null,"Change",75,175,"mg/kg bw/day",{"$f":"IF(Z1551<>0,VLOOKUP(Z1551,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Vehicle: 0.5% aqueous Methocel","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",66,null,"similar to OECD 414 (\"Teratology study in rabbits\")","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",">350","In life observation","Body weight",{"$f":"IF(Z1552<>0,VLOOKUP(Z1552,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"There were no relevant differences in mean maternal body weight gain in any of the treatment groups when compared to the control group throughout the entire gestation period.",null,"No effect",350,">350","mg/kg bw/day",{"$f":"IF(Z1552<>0,VLOOKUP(Z1552,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Vehicle: 0.5% aqueous Methocel","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",66,null,"similar to OECD 414 (\"Teratology study in rabbits\")","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Fetus","M + F",">350","Abnormalities","Genital abnormalities",{"$f":"IF(Z1553<>0,VLOOKUP(Z1553,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Each fetus was first examined for external malformations and variations and subsequently dissected, internally sexed, and examined for visceral malformations and variations. No genital abnormalities were reported.",null,"No effect",350,">350","mg/kg bw/day",{"$f":"IF(Z1553<>0,VLOOKUP(Z1553,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Vehicle: 0.5% aqueous Methocel","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",66,null,"similar to OECD 414 (\"Teratology study in rabbits\")","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Fetus","M + F",">350","Developmental","Litter/pup weight",{"$f":"IF(Z1554<>0,VLOOKUP(Z1554,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"There were no biologically relevant or statistically significant differences in mean fetal body weight in any of the treatment groups when compared to the control group. A slight decrease was noted in mean fetal body weight in all treated groups when compared to the control group, however, the parameter was comparable to the historical control.",null,"No effect",75,"<350","mg/kg bw/day",{"$f":"IF(Z1554<>0,VLOOKUP(Z1554,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: 0.5% aqueous Methocel","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",66,null,"similar to OECD 414 (\"Teratology study in rabbits\")","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",">350","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z1555<>0,VLOOKUP(Z1555,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"There were no biologically meaningful or statistically significant differences in the mean numbers of total implantations or corpora lutea in any of the treatment groups when compared to the control group.",null,"No effect",75,"<350","mg/kg bw/day",{"$f":"IF(Z1555<>0,VLOOKUP(Z1555,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: 0.5% aqueous Methocel","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",66,null,"similar to OECD 414 (\"Teratology study in rabbits\")","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",">350","Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z1556<>0,VLOOKUP(Z1556,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Non-viable fetuses were not present in any group and there were no biologically relevant or statistically significant differences in the mean numbers of early or late resorptions in any of the treatment groups when compared to the control group. A statistically significant, though not biologically relevant increase was noted in the mean number of viable fetuses in the 75 mg/kg/day dosage group which was considered incidental. There were no biologically relevant or statistically significant differences in the mean numbers of total implantations or corpora lutea in any of the treatment groups when compared to the control group.\nABORTIONS: Two rabbits in the control group aborted and were sacrificed, both on gestation day 22. In the 175 mg/kg/day dosage group, one rabbit aborted and was sacrificed on gestation day 27. One rabbit in the 350 mg/kg/day dosage group aborted and was sacrificed on gestation day 23. Therefore, no treatment-related increase in the incidence of abortions was noted.",null,"No effect",75,"<350","mg/kg bw/day",{"$f":"IF(Z1556<>0,VLOOKUP(Z1556,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: 0.5% aqueous Methocel","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",66,null,"similar to OECD 414 (\"Teratology study in rabbits\")","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",">350","Reproductive","Post implantation loss",{"$f":"IF(Z1557<>0,VLOOKUP(Z1557,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"There were no biologically relevant or statistically significant differences in the mean numbers of early or late resorptions in any of the treatment groups when compared to the control group.",null,"No effect",75,"<350","mg/kg bw/day",{"$f":"IF(Z1557<>0,VLOOKUP(Z1557,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: 0.5% aqueous Methocel","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",66,null,"similar to OECD 414 (\"Teratology study in rabbits\")","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Fetus","M + F",">350","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z1558<>0,VLOOKUP(Z1558,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"All fetuses were individually weighed and examined for external malformations and variations, including the palate and eyes. Each fetus was dissected, internally sexed and examined for visceral malformations and variations, including the brain by a mid-coronal slice. There were no statistically significant or biologically meaningful differences in the number of litters with malformations in any of the treatment groups when compared to the control group. Malformations were noted only in the treatment groups, however, this was not considered to be treatment-related as they did not occur in a dose-related pattern, were not similar in nature and the frequency did not exceed that of the historical control.",null,"No effect",75,"<350","mg/kg bw/day",{"$f":"IF(Z1558<>0,VLOOKUP(Z1558,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: 0.5% aqueous Methocel","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",66,null,"similar to OECD 414 (\"Teratology study in rabbits\")","DAR",null,1980,"Rabbit","Dutch Belted",16,"F",98.7,"Oral","Gavage/Intubation","75; 175; 350",75,350,"mg/kg bw/day","22 (GD 6-27)","Days","Fetus","M + F",">350","Reproductive","Sex ratio",{"$f":"IF(Z1559<>0,VLOOKUP(Z1559,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"There were no biologically meaningful or statistically significant differences in the mean numbers of fetal sex distribution in any of the treatment groups when compared to the control group.",null,"No effect",75,"<350","mg/kg bw/day",{"$f":"IF(Z1559<>0,VLOOKUP(Z1559,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Vehicle: 0.5% aqueous Methocel","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","In life observation","Mortality",{"$f":"IF(Z1560<>0,VLOOKUP(Z1560,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"There were 208 pre-terminal deaths throughout the study. There was no evidence to suggest that any of these deaths were treatment-related. ",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1560<>0,VLOOKUP(Z1560,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","In life observation","Clinical signs",{"$f":"IF(Z1561<>0,VLOOKUP(Z1561,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"There were no notable intergroup differences in either sex. There were no notable intergroup differences in the incidences of externally palpable masses.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1561<>0,VLOOKUP(Z1561,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","In life observation","Body weight",{"$f":"IF(Z1562<>0,VLOOKUP(Z1562,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Treatment groups showed a comparable weight gain compared to controls.\nA slight decrease in absolute body weight at Week 40 was evident in all groups of both sexes except control and intermediate dose females. This transient effect is not considered to be attributable to the test substance.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1562<>0,VLOOKUP(Z1562,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","In life observation","Food consumption",{"$f":"IF(Z1563<>0,VLOOKUP(Z1563,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No effect on food and water (visual assessment) consumption was observed.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1563<>0,VLOOKUP(Z1563,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1564<>0,VLOOKUP(Z1564,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: No effect on differential blood count was observed (weeks 52, 77, 102).",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1564<>0,VLOOKUP(Z1564,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Lung histopathology",{"$f":"IF(Z1565<>0,VLOOKUP(Z1565,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross pathology: Incidence of lung masses was slightly higher in the male high dose group (18/50) compared to control (10/50). No effect in females was observed. Moreover, there was little difference between the groups in the numbers of tumours after histological evaluation. Therefore, the necropsy finding is considered incidental.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1565<>0,VLOOKUP(Z1565,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F",300,"Organ Weight","Thymus weight",{"$f":"IF(Z1566<>0,VLOOKUP(Z1566,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Males: Absolute thymus weight was increased in the intermediate and high dose groups (P<0.01 and P<0.05 respectively) compared to control. Thymus weight was also increased in the intermediate and high dose groups after covariance analysis. The increase in high dose males was due to one animal which had an enlarged thymus infiltrated with lymphoma cells. Moreover, since no effect was observed at necropsy or histopathological examination, the increased thymus weight is considered not toxicologically relevant. \nFemales: No effect on organ weight was observed.",null,"Increase",100,300,"mg/kg bw/day",{"$f":"IF(Z1566<>0,VLOOKUP(Z1566,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Organ weight was investigated in 10 animals/sex of each dose at study termination.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ Weight","Adrenals weight",{"$f":"IF(Z1567<>0,VLOOKUP(Z1567,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Absolute organ weight was not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1567<>0,VLOOKUP(Z1567,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Organ weight was investigated in 10 animals/sex of each dose at study termination.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ Weight","Brain weight",{"$f":"IF(Z1568<>0,VLOOKUP(Z1568,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Absolute organ weight was not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1568<>0,VLOOKUP(Z1568,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Organ weight was investigated in 10 animals/sex of each dose at study termination.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ Weight","Heart weight",{"$f":"IF(Z1569<>0,VLOOKUP(Z1569,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute organ weight was not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1569<>0,VLOOKUP(Z1569,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Organ weight was investigated in 10 animals/sex of each dose at study termination.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ Weight","Kidney weight",{"$f":"IF(Z1570<>0,VLOOKUP(Z1570,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute organ weight was not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1570<>0,VLOOKUP(Z1570,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Organ weight was investigated in 10 animals/sex of each dose at study termination.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ Weight","Liver weight",{"$f":"IF(Z1571<>0,VLOOKUP(Z1571,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Liver with gall bladder was weighed. Absolute organ weight was not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1571<>0,VLOOKUP(Z1571,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Organ weight was investigated in 10 animals/sex of each dose at study termination.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","F","> 1000","Organ Weight","Ovary weight",{"$f":"IF(Z1572<>0,VLOOKUP(Z1572,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute organ weight was not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1572<>0,VLOOKUP(Z1572,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Organ weight was investigated in 10 animals/sex of each dose at study termination.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ Weight","Pituitary weight",{"$f":"IF(Z1573<>0,VLOOKUP(Z1573,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Absolute organ weight was not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1573<>0,VLOOKUP(Z1573,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Organ weight was investigated in 10 animals/sex of each dose at study termination.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M","> 1000","Organ Weight","Prostate weight",{"$f":"IF(Z1574<>0,VLOOKUP(Z1574,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute organ weight was not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1574<>0,VLOOKUP(Z1574,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Organ weight was investigated in 10 animals/sex of each dose at study termination.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ Weight","Spleen weight",{"$f":"IF(Z1575<>0,VLOOKUP(Z1575,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute organ weight was not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1575<>0,VLOOKUP(Z1575,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Organ weight was investigated in 10 animals/sex of each dose at study termination.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M","> 1000","Organ Weight","Testis weight",{"$f":"IF(Z1576<>0,VLOOKUP(Z1576,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Testes were weighed with epididymides. Absolute organ weight was not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1576<>0,VLOOKUP(Z1576,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Organ weight was investigated in 10 animals/sex of each dose at study termination.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M","> 1000","Organ Weight","Epididymis weight",{"$f":"IF(Z1577<>0,VLOOKUP(Z1577,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Epididymides were weighed together with testes. Absolute organ weight was not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1577<>0,VLOOKUP(Z1577,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Organ weight was investigated in 10 animals/sex of each dose at study termination.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","F","> 1000","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z1578<>0,VLOOKUP(Z1578,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute organ weight was not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1578<>0,VLOOKUP(Z1578,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Organ weight was investigated in 10 animals/sex of each dose at study termination.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ Weight","[Not in list]",{"$f":"IF(Z1579<>0,VLOOKUP(Z1579,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"No effect on absolute lung weight was observed. ",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1579<>0,VLOOKUP(Z1579,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"Organ weight was investigated in 10 animals/sex of each dose at study termination.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ Weight","[Not in list]",{"$f":"IF(Z1580<>0,VLOOKUP(Z1580,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Salivary glands (paratoid, sublingual and submaxillary): Absolute organ weight was not affected.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1580<>0,VLOOKUP(Z1580,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"Organ weight was investigated in 10 animals/sex of each dose at study termination.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F",1000,"Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1581<>0,VLOOKUP(Z1581,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Histopathological examination was performed for control and high dose group. The incidence of increased mineral deposits in the brain was higher in the high dose group (13/50, P<0.05) compared to control (4/49) in males only and is a common finding of mice of this strain and age. No effect was observed in females. Therefore, the effect is not considered toxicologically relevant.",null,"No effect",300,1000,"mg/kg bw/day",{"$f":"IF(Z1581<>0,VLOOKUP(Z1581,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1582<>0,VLOOKUP(Z1582,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1582<>0,VLOOKUP(Z1582,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Bone histopathology",{"$f":"IF(Z1583<>0,VLOOKUP(Z1583,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1583<>0,VLOOKUP(Z1583,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Urinary bladder histopathology",{"$f":"IF(Z1584<>0,VLOOKUP(Z1584,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1584<>0,VLOOKUP(Z1584,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z1585<>0,VLOOKUP(Z1585,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1585<>0,VLOOKUP(Z1585,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Heart histopathology",{"$f":"IF(Z1586<>0,VLOOKUP(Z1586,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Heart and aorta were investigated. Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1586<>0,VLOOKUP(Z1586,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1587<>0,VLOOKUP(Z1587,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1587<>0,VLOOKUP(Z1587,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Liver histopathology",{"$f":"IF(Z1588<>0,VLOOKUP(Z1588,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1588<>0,VLOOKUP(Z1588,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Gall bladder histopathology",{"$f":"IF(Z1589<>0,VLOOKUP(Z1589,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1589<>0,VLOOKUP(Z1589,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Lung histopathology",{"$f":"IF(Z1590<>0,VLOOKUP(Z1590,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1590<>0,VLOOKUP(Z1590,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","F","> 1000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z1591<>0,VLOOKUP(Z1591,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1591<>0,VLOOKUP(Z1591,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M","> 1000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z1592<>0,VLOOKUP(Z1592,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1592<>0,VLOOKUP(Z1592,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z1593<>0,VLOOKUP(Z1593,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Mesentric lymph nodes were investigated. Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1593<>0,VLOOKUP(Z1593,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Skeletal muscle histopathology",{"$f":"IF(Z1594<>0,VLOOKUP(Z1594,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Thigh was investigated. Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1594<>0,VLOOKUP(Z1594,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Oesophagus histopathology",{"$f":"IF(Z1595<>0,VLOOKUP(Z1595,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1595<>0,VLOOKUP(Z1595,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","F","> 1000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1596<>0,VLOOKUP(Z1596,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1596<>0,VLOOKUP(Z1596,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1597<>0,VLOOKUP(Z1597,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1597<>0,VLOOKUP(Z1597,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z1598<>0,VLOOKUP(Z1598,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Parotid, sublingual and submaxilliar salivary glands were investigated. Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1598<>0,VLOOKUP(Z1598,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1599<>0,VLOOKUP(Z1599,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1599<>0,VLOOKUP(Z1599,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M","> 1000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1600<>0,VLOOKUP(Z1600,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1600<>0,VLOOKUP(Z1600,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Peripheral nerve histopathology",{"$f":"IF(Z1601<>0,VLOOKUP(Z1601,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Sciatic nerve was investigated in control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1601<>0,VLOOKUP(Z1601,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Spinal cord histopathology",{"$f":"IF(Z1602<>0,VLOOKUP(Z1602,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Cervical, thoracic and lumbar parts of spinal cord were investigated of control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1602<>0,VLOOKUP(Z1602,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1603<>0,VLOOKUP(Z1603,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1603<>0,VLOOKUP(Z1603,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Stomach histopathology",{"$f":"IF(Z1604<>0,VLOOKUP(Z1604,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathological examination was performed for control and high dose group of the glandular and non-glandular stomach.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1604<>0,VLOOKUP(Z1604,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M","> 1000","Organ histopathology","Testis histopathology",{"$f":"IF(Z1605<>0,VLOOKUP(Z1605,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1605<>0,VLOOKUP(Z1605,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M","> 1000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1606<>0,VLOOKUP(Z1606,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1606<>0,VLOOKUP(Z1606,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Thymus histopathology",{"$f":"IF(Z1607<>0,VLOOKUP(Z1607,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1607<>0,VLOOKUP(Z1607,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1608<>0,VLOOKUP(Z1608,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathological examination was performed for control and high dose group. No effects were observed in thyroid and parathyroid.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1608<>0,VLOOKUP(Z1608,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","M + F","> 1000","Organ histopathology","Trachea histopathology",{"$f":"IF(Z1609<>0,VLOOKUP(Z1609,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1609<>0,VLOOKUP(Z1609,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","F","> 1000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1610<>0,VLOOKUP(Z1610,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Histopathological examination was performed for control and high dose group.",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1610<>0,VLOOKUP(Z1610,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Carcinogenicity",67,7793,"EPA F, 83-2 (1982) equivalent to OECD 451","DAR",null,1989,"Mouse","CD-1",50,"M + F","97.5 and 100.2","Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",2,"Years","Adult","F","> 1000","Organ histopathology","[Not in list]",{"$f":"IF(Z1611<>0,VLOOKUP(Z1611,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Neoplastic findings:  \nThere were no statistically significant increases in incidence of any tumour. The number of animals with tumours, both benign and malignant, was similar between the control and high dose groups (m+f).\nAnimals with multiple tumour types was slightly increased in the high dose group of both sexes (males: 16/50 and females: 11/50) compared to control (males: 11/50 and females: 6/50) causing a slight increase in the total number of tumours in the high dose group of both sexes (males: 60 and females: 43) compared to control (males: 49 and females: 36). \nHaemangiosarcoma was evident in 4/50 high dose males, 2/50 low dose females and 1/50 high dose females (not significant) compared to the respective controls (m+f: 0/50).\nHistiocytic sarcoma in the lymphoreticular/haemopoietic tissue was evident in 2 low and 2/50 high dose males and 3 low, 3 intermediate and 1/50 high dose females (not significant) compared to the respective controls (m+f: 0/50).\nThe incidences of haemangiosarcoma and histiocytic sarcoma were higher in all groups of both sexes exposed to the test substance. Similar incidences of haemangiosarcoma and histiocytic sarcoma have been seen in other studies using mice of a similar age and strain (historic control data). Due to the lack of a dose relationship, statistical significance and the incidences in this study falling within the historic control ranges, these changes are not considered to be due to test substance treatment.\n",null,"No effect",1000,"> 1000","mg/kg bw/day",{"$f":"IF(Z1611<>0,VLOOKUP(Z1611,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"Histopathological examination was performed for control and high dose group.","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","In life observation","Mortality",{"$f":"IF(Z1612<>0,VLOOKUP(Z1612,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"The incidence of mortality was considered to demonstrate no dose- or test substance-related adverse effect.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1612<>0,VLOOKUP(Z1612,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","In life observation","Clinical signs",{"$f":"IF(Z1613<>0,VLOOKUP(Z1613,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related clinical signs were observed.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1613<>0,VLOOKUP(Z1613,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F",30000,"In life observation","Body weight",{"$f":"IF(Z1614<>0,VLOOKUP(Z1614,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Mean body weights for the high-dose males were generally lower than control (-11% at Week 102) and were (mostly) statistically significant. Mean body weights for the high-dose females and the males and females at the low- and mid-dose levels were not affected. Mean fasted body weight at termination of the study was statistically significantly reduced for male high dose animals. Moreover, no effect on body weight gain was observed for all dose groups.",null,"Decrease",10000,30000,"ppm",{"$f":"IF(Z1614<>0,VLOOKUP(Z1614,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","In life observation","Food consumption",{"$f":"IF(Z1615<>0,VLOOKUP(Z1615,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No consistent effect on feed and water consumption was observed.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1615<>0,VLOOKUP(Z1615,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1616<>0,VLOOKUP(Z1616,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology (12, 18, 24 months): Differences observed (after 12 month) were not attributed to treatment. Moreover, morphologic evaluation of leukocytes and erytrocytes showed no effect.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1616<>0,VLOOKUP(Z1616,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M",30000,"Organ Weight","Testis weight",{"$f":"IF(Z1617<>0,VLOOKUP(Z1617,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"At terminal sacrifice, the mean absolute and relative weights (to brain and body weight) of the testes were elevated for the high-dose group. (Epididymis was not weighed.) No histopathological effects were observed.",null,"Increase",5000,30000,"ppm",{"$f":"IF(Z1617<>0,VLOOKUP(Z1617,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","F","> 30000","Organ Weight","Ovary weight",{"$f":"IF(Z1618<>0,VLOOKUP(Z1618,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"The mean absolute and relative (to body and brain weight) ovarian weights for the high-dose females were markedly elevated, although differences from control were not statistically significant. These differences were due to a single animal, whose ovarian weight was approximately six times the mean ovarian weight for the group when this value was excluded. Differences from control excluding this animal were not apparent.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1618<>0,VLOOKUP(Z1618,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ Weight","Adrenals weight",{"$f":"IF(Z1619<>0,VLOOKUP(Z1619,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The mean absolute and relative (to body and brain weight) adrenals weight were not affected.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1619<>0,VLOOKUP(Z1619,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ Weight","Brain weight",{"$f":"IF(Z1620<>0,VLOOKUP(Z1620,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The mean absolute and relative (to body and brain weight) brain weight were not affected.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1620<>0,VLOOKUP(Z1620,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ Weight","Heart weight",{"$f":"IF(Z1621<>0,VLOOKUP(Z1621,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"The mean absolute and relative (to body and brain weight) heart weight were not affected.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1621<>0,VLOOKUP(Z1621,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ Weight","Kidney weight",{"$f":"IF(Z1622<>0,VLOOKUP(Z1622,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"The mean absolute and relative (to body and brain weight) kidneys weight were not affected.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1622<>0,VLOOKUP(Z1622,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ Weight","Liver weight",{"$f":"IF(Z1623<>0,VLOOKUP(Z1623,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"The mean absolute and relative (to body and brain weight) liver weight were not affected.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1623<>0,VLOOKUP(Z1623,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ Weight","Spleen weight",{"$f":"IF(Z1624<>0,VLOOKUP(Z1624,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"The mean absolute and relative (to body and brain weight) spleen weight were not affected.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1624<>0,VLOOKUP(Z1624,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Urinary bladder histopathology",{"$f":"IF(Z1625<>0,VLOOKUP(Z1625,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"A slight-to-mild epithelial hyperplasia of the urinary bladder in males. The incidence was 6%, 6%, 20% and 16% controls through high-dose, respectively. Even though the increase at the mid- and high-dose was present, no test substance relationship was derived based on the missing dose-relationship.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1625<>0,VLOOKUP(Z1625,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1626<>0,VLOOKUP(Z1626,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1626<>0,VLOOKUP(Z1626,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Aorta histopathology",{"$f":"IF(Z1627<>0,VLOOKUP(Z1627,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1627<>0,VLOOKUP(Z1627,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Bone histopathology",{"$f":"IF(Z1628<>0,VLOOKUP(Z1628,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1628<>0,VLOOKUP(Z1628,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Bone marrow histopathology",{"$f":"IF(Z1629<>0,VLOOKUP(Z1629,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Bone marrow histopathology was performed of the costochondral juction).",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1629<>0,VLOOKUP(Z1629,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1630<>0,VLOOKUP(Z1630,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1630<>0,VLOOKUP(Z1630,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M","> 30000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1631<>0,VLOOKUP(Z1631,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1631<>0,VLOOKUP(Z1631,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Eyes histopathology",{"$f":"IF(Z1632<>0,VLOOKUP(Z1632,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Eyes were examined includong the optic nerve and contiguous Harderian glands.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1632<>0,VLOOKUP(Z1632,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Heart histopathology",{"$f":"IF(Z1633<>0,VLOOKUP(Z1633,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1633<>0,VLOOKUP(Z1633,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z1634<>0,VLOOKUP(Z1634,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1634<>0,VLOOKUP(Z1634,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1635<>0,VLOOKUP(Z1635,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1635<>0,VLOOKUP(Z1635,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Liver histopathology",{"$f":"IF(Z1636<>0,VLOOKUP(Z1636,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Centrilobular hepatocyte hypertrophy: 6%, 10%, 18% and 34% in control to high dose groups, respectively (no further neoplasms). This change may represent an adaptation to hepatocellular metabolism.",null,"Change",30000,"> 30000","ppm",{"$f":"IF(Z1636<>0,VLOOKUP(Z1636,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Gall bladder histopathology",{"$f":"IF(Z1637<>0,VLOOKUP(Z1637,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1637<>0,VLOOKUP(Z1637,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Lung histopathology",{"$f":"IF(Z1638<>0,VLOOKUP(Z1638,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1638<>0,VLOOKUP(Z1638,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z1639<>0,VLOOKUP(Z1639,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Mediastinal, mesenteric and regional lymph nodes were examined.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1639<>0,VLOOKUP(Z1639,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","F","> 30000","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z1640<>0,VLOOKUP(Z1640,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1640<>0,VLOOKUP(Z1640,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M","> 30000","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z1641<>0,VLOOKUP(Z1641,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1641<>0,VLOOKUP(Z1641,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Skeletal muscle histopathology",{"$f":"IF(Z1642<>0,VLOOKUP(Z1642,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"The biceps femoris was examined.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1642<>0,VLOOKUP(Z1642,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Oesophagus histopathology",{"$f":"IF(Z1643<>0,VLOOKUP(Z1643,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1643<>0,VLOOKUP(Z1643,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","F","> 30000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1644<>0,VLOOKUP(Z1644,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1644<>0,VLOOKUP(Z1644,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1645<>0,VLOOKUP(Z1645,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1645<>0,VLOOKUP(Z1645,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z1646<>0,VLOOKUP(Z1646,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"mandibular ",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1646<>0,VLOOKUP(Z1646,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1647<>0,VLOOKUP(Z1647,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1647<>0,VLOOKUP(Z1647,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M","> 30000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1648<>0,VLOOKUP(Z1648,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1648<>0,VLOOKUP(Z1648,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Peripheral nerve histopathology",{"$f":"IF(Z1649<>0,VLOOKUP(Z1649,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"The sciatic nerve was examined.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1649<>0,VLOOKUP(Z1649,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Spinal cord histopathology",{"$f":"IF(Z1650<>0,VLOOKUP(Z1650,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1650<>0,VLOOKUP(Z1650,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1651<>0,VLOOKUP(Z1651,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1651<>0,VLOOKUP(Z1651,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Stomach histopathology",{"$f":"IF(Z1652<>0,VLOOKUP(Z1652,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1652<>0,VLOOKUP(Z1652,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M","> 30000","Organ histopathology","Testis histopathology",{"$f":"IF(Z1653<>0,VLOOKUP(Z1653,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1653<>0,VLOOKUP(Z1653,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Thymus histopathology",{"$f":"IF(Z1654<>0,VLOOKUP(Z1654,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1654<>0,VLOOKUP(Z1654,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1655<>0,VLOOKUP(Z1655,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1655<>0,VLOOKUP(Z1655,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general similar to OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Trachea histopathology",{"$f":"IF(Z1656<>0,VLOOKUP(Z1656,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1656<>0,VLOOKUP(Z1656,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1657<>0,VLOOKUP(Z1657,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Uterus histopathology was performed including uterine horns and cervix.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1657<>0,VLOOKUP(Z1657,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","Chronic toxicity",68,null,"no guideline specified; in general compliance with OECD 451","DAR",null,1983,"Mouse","CD-1",50,"M + F",99.7,"Oral","Feed","1000; 5000; 30000",1000,30000,"ppm",2,"Years","Adult","M + F","> 30000","Organ histopathology","[Not in list]",{"$f":"IF(Z1658<>0,VLOOKUP(Z1658,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Neoplastic findings were those commonly encountered in mice: Bronchiolaralveolar tumors of the lungs, hepatocellular neoplasms, and tumors of the lymphoreticular system accounted for the majority encountered. There were no suspected test substance-associated trends in the incidence of these tumors or in any of the other spontaneously occurring neoplasms. Lymphoreticular tumors tended to be more frequent in treated animals, particularly the females. The numbers were relatively small and differences from the control failed to provide supportive evidence that the neoplasms had a test substance\nrelationship.\nThe other neoplasms that occurred with any frequency in treated mice only were renal tubule adenomas (males: 3 present at the high-dose; 1 at the mid-dose level). However, the distribution of this benign tumor was considered spurious and unrelated to treatment.\n\n\nRenal tubule adenomas (males only; 3 in high-dose and 1 in the mid-dose) -> spurious and unrelated to treatment due to the absence of other renal lesions.",null,"No effect",30000,"> 30000","ppm",{"$f":"IF(Z1658<>0,VLOOKUP(Z1658,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","5.5 (GD 3 till 21 days post partum)","Weeks","Adult (F0)","F",">30000","In life observation","Mortality",{"$f":"IF(Z1659<>0,VLOOKUP(Z1659,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"There were two mortalities. One at 3000 ppm was sacrificed Day 22 of pregnancy due to poor condition. Post mortem examination did not reveal any reason for the apparent dystocia. Since no similar mortalities were seen at higher levels, this death is not considered to be attributed to treatment.\nA second animal at 30000 ppm was found dead Day 21 post partum (Day 43 of study). Post mortem examination or signs prior to sacrifice did not reveal the cause of death; it is difficult to relate this death to treatment or not.",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z1659<>0,VLOOKUP(Z1659,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study not suitable for NOAEL setting. This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","5.5 (GD 3 till 21 days post partum)","Weeks","Adult (F0)","F",10000,"In life observation","Clinical signs",{"$f":"IF(Z1660<>0,VLOOKUP(Z1660,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Clinical signs  included soft faeces and yellow stained sawdust (considered to be caused by the urine) in both cages of animals at 10000 and 30000 ppm. Onset of these signs was earlier at 30000 ppm than at 10000 ppm (soft faeces occurred immediately dietary administration commenced at 30000 ppm but not until the third week post partum at 10000 ppm; yellow staining of the sawdust occurred on Day 26 post coitum at 30000 ppm but not until Day 28 post coitum at 10000 ppm), with signs still apparent in both groups at termination. There were no clinical signs at 3000 ppm considered to be attributable to treatment.",null,"Change",3000,10000,"ppm",{"$f":"IF(Z1660<>0,VLOOKUP(Z1660,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study not suitable for NOAEL setting. This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","5.5 (GD 3 till 21 days post partum)","Weeks","Adult (F0)","F",">30000","In life observation","Food consumption",{"$f":"IF(Z1661<>0,VLOOKUP(Z1661,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"WATER: At 30000 ppm, slight increases in water intake during gestation were apparent towards the end of pregnancy when compared with concurrent control values. At 3000 and 10000 ppm, no adverse effects on water consumption were observed.\nFOOD: Apart from a slight reduction in food intake during the first three days of treatment at 30000 ppm, food intake of all the treated groups was comparable with concurrent controls throughout pregnancy.",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z1661<>0,VLOOKUP(Z1661,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study not suitable for NOAEL setting. This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","5.5 (GD 3 till 21 days post partum)","Weeks","Adult (F0)","F",30000,"In life observation","Body weight",{"$f":"IF(Z1662<>0,VLOOKUP(Z1662,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"At 30000 ppm, the rate of bodyweight gain following the initiation of treatment was reduced to Day 14 of pregnancy: thereafter, the rate of bodyweight gain to Day 20 of pregnancy was similar to controls, however, absolute parity with controls at Day 20 was not achieved.\nAt both 3000 and 10000 ppm the pattern of bodyweight gain during pregnancy was essentially similar to controls throughout, although by Day 14 of pregnancy, bodyweights were slightly lower than controls.\nDuring the first week of lactation the pattern of bodyweight change in all groups was comparable. Thereafter, slight differences in the pattern of change were apparent to weaning at 10000 and 30000 ppm in so much as more weight loss occurred than in the control group. There were no further effects at 3000 ppm.",null,"Decrease",10000,30000,"ppm",{"$f":"IF(Z1662<>0,VLOOKUP(Z1662,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study not suitable for NOAEL setting. This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","5.5 (GD 3 till 21 days post partum)","Weeks","Adult (F0)","F",">30000","Reproductive","Gestation length",{"$f":"IF(Z1663<>0,VLOOKUP(Z1663,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The pregnancy rate was good, 90%, 100%, 100% and 90% in Groups 1 to 4 respectively. (Note, treatment started at GD 3.)\nThe duration of pregnancy was similar in all groups and not adversely affected by treatment.",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z1663<>0,VLOOKUP(Z1663,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Study not suitable for NOAEL setting. This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","5.5 (GD 3 till 21 days post partum)","Weeks","Adult (F0)","F",3000,"Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z1664<>0,VLOOKUP(Z1664,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Watery and/or dark contents in the gastro-intestinal tract were observed in 0, 2, 7 and 8 animals in Groups 1 to 4 respectively. Distended caecum was seen in 0, 0, 0 and 4 animals in Groups 1 to 4 respectively.These findings generally followed the trend noted in the clinical signs observed. No histopathology performed.",null,"Change","<3000",3000,"ppm",{"$f":"IF(Z1664<>0,VLOOKUP(Z1664,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study not suitable for NOAEL setting. This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","5.5 (GD 3 till 21 days post partum)","Weeks","Adult (F0)","F",3000,"Organ histopathology","Stomach histopathology",{"$f":"IF(Z1665<>0,VLOOKUP(Z1665,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Distended and/or congested stomach was seen in 0, 2, 5 and 4 animals in Groups 1 to 4 respectively. These findings generally followed the trend noted in the clinical signs observed. No histopathology performed.",null,"Change","<3000",3000,"ppm",{"$f":"IF(Z1665<>0,VLOOKUP(Z1665,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study not suitable for NOAEL setting. This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","5.5 (GD 3 till 21 days post partum)","Weeks","Adult (F0+F1)","F",3000,"Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z1666<>0,VLOOKUP(Z1666,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"F0: Macroscopic changes to the salivary glands (enlarged/firm/congested/swollen) were observed in 0, 2, 6 and 8 animals respectively in Groups 1 to 4 of F0 generation.\nDose-related incidence and degree of granular basophilic cytoplasm of acinar cells was seen with 0, 2, 0 and 0 animals showing minimal effects, 0, 0, 2 and 0 animals showing moderate effects and 0, 0, 8 and 9 animals showing marked effects in Groups 1 to 4, respectively. This change was associated with hypertrophy of acinar cells with 0, 2, 2 and 0 animals with minimal hypertrophy and 0, 0, 8 and 9 animals in Groups 1 to 4 respectively with moderate hypertrophy of the acinar cells. Prominent mitoses were also seen in 2 animals at 30000 ppm, but not in lower treatment levels or the controls.\nF1: Post mortem examination of F1 generation at PND 42 revealed swollen/enlarged parotid salivary glands in 5/10 males and 2/10 females at 30000 ppm, and in 1/10 males at 3000 ppm. No histopathological examinations were performed.",null,"Change","<3000",3000,"ppm",{"$f":"IF(Z1666<>0,VLOOKUP(Z1666,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study not suitable for NOAEL setting. This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","5.5 (GD 3 till 21 days post partum)","Weeks","Adult (F0)","F",">30000","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z1667<>0,VLOOKUP(Z1667,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The implantation rates in all treated groups were higher than the controls. Since pup losses, both pre-birth and from birth to weaning, were generally similar among the groups, litter size of all treated groups was, as a consequence, generally greater than controls throughout weaning. These findings are not, however, considered to be an adverse effect of treatment. ",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z1667<>0,VLOOKUP(Z1667,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Study not suitable for NOAEL setting. This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"M + F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","only secondary exposure through milk from PND 0-21","Weeks","Offspring (F1)","M + F",">30000","Reproductive","Litter viability",{"$f":"IF(Z1668<>0,VLOOKUP(Z1668,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Pup losses, both pre-birth and from birth to weaning, were generally similar among the groups.",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z1668<>0,VLOOKUP(Z1668,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Study not suitable for NOAEL setting. This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","5.5 (GD 3 till 21 days post partum)","Weeks","Adult (F0)","F",">30000","Reproductive","Litter size",{"$f":"IF(Z1669<>0,VLOOKUP(Z1669,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The implantation rates in all treated groups were higher than the controls. Since pup losses, both pre-birth and from birth to weaning, were generally similar among the groups, litter size of all treated groups was, as a consequence, generally greater than controls throughout weaning. These findings are not, however, considered to be an adverse effect of treatment. ",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z1669<>0,VLOOKUP(Z1669,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Study not suitable for NOAEL setting. This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"M + F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","only secondary exposure through milk from PND 0-21","Weeks","Offspring (F1)","M + F",">30000","Reproductive","Sex ratio",{"$f":"IF(Z1670<>0,VLOOKUP(Z1670,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Glyphosate did not selectively affect pups of one sex since, in all groups, sex ratios at birth and weaning were similar. ",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z1670<>0,VLOOKUP(Z1670,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Study not suitable for NOAEL setting. This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"M + F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","only secondary exposure through milk from PND 0-21","Weeks","Offspring (F1)","M + F",30000,"Developmental","Litter/pup weight",{"$f":"IF(Z1671<>0,VLOOKUP(Z1671,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"At birth, [total] litter weight of all treatment groups was increased compared to control - this is due to the increased litter sizes seen in the treatment groups.\nAt 30000 ppm litter weight converged towards control values to Day 8; thereafter litter weight became reduced and by Day 21 was only 78% of the concurrent control value. Mean pup weight was reduced at birth and diverged further away from controls through to Day 21 when mean pup weight at this level was only 62% of the controls.\nAt 3000 and 10000 ppm litter weight through to weaning was comparable with the controls even though litter size was increased. As a consequence mean pup weight diverged below control values to an extent that on Day 21 post partum mean pup weight at 3000 and 10000 ppm was 91% and 87% lower than the corresponding control value. These differences, however, can probably be attributed to the pivotal association between litter size, litter weight and mean pup weight and, at this stage, no conclusive treatment-related effects can be established.",null,"Decrease",10000,30000,"ppm",{"$f":"IF(Z1671<>0,VLOOKUP(Z1671,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Study not suitable for NOAEL setting. This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"M + F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","3 (PND 21-42)","Weeks","Adult (F1)","M + F",">30000","In life observation","Mortality",{"$f":"IF(Z1672<>0,VLOOKUP(Z1672,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"There were no mortalities.",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z1672<>0,VLOOKUP(Z1672,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study not suitable for NOAEL setting. Group achieved intakes of Glyphosate in Groups 2 to 4 respectively, recorded during Weeks 5 and 6, ranged from 368 - 390, 1291 - 1335 and 3918 - 4453 mg/kg/day for males and 355 - 402, 1191 - 1271 and 3961 - 4397 mg/kg/day for females.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"M + F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","3 (PND 21-42)","Weeks","Adult (F1)","M + F",30000,"In life observation","Clinical signs",{"$f":"IF(Z1673<>0,VLOOKUP(Z1673,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Soft faeces were observed for all animals at 30000 ppm from Week 4 through to sacrifice at Week 6. No other clinical signs were observed at this or lower dosages.",null,"Change",10000,30000,"ppm",{"$f":"IF(Z1673<>0,VLOOKUP(Z1673,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study not suitable for NOAEL setting. Group achieved intakes of Glyphosate in Groups 2 to 4 respectively, recorded during Weeks 5 and 6, ranged from 368 - 390, 1291 - 1335 and 3918 - 4453 mg/kg/day for males and 355 - 402, 1191 - 1271 and 3961 - 4397 mg/kg/day for females.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"M + F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","3 (PND 21-42)","Weeks","Adult (F1)","M + F",30000,"In life observation","Food consumption",{"$f":"IF(Z1674<>0,VLOOKUP(Z1674,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption at 30000 ppm was lower than controls during Weeks 5 and 6 (males only). There were no other effects considered attributable to treatment for males or females at any dosage.\nThe food conversion ratio for males at 30000 ppm was slightly greater when compared to controls (Week 6 only), indicating a slightly lower efficiency of food utilisatian into bodyweight gain.\nThere were no other effects on food conversion ratios.",null,"Decrease",10000,30000,"ppm",{"$f":"IF(Z1674<>0,VLOOKUP(Z1674,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study not suitable for NOAEL setting. Group achieved intakes of Glyphosate in Groups 2 to 4 respectively, recorded during Weeks 5 and 6, ranged from 368 - 390, 1291 - 1335 and 3918 - 4453 mg/kg/day for males and 355 - 402, 1191 - 1271 and 3961 - 4397 mg/kg/day for females.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)",null,null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",null,"M + F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","3 (PND 21-42)","Weeks","Adult (F1)","M",30000,"In life observation","Body weight",{"$f":"IF(Z1675<>0,VLOOKUP(Z1675,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"From weaning to termination (PND 21 - 42), males at 30000 ppm had a reduced rate of weight change. At lower dosages, and at all dosages among females, the rate of weight change was comparable with controls, however, differences inherent at weaning were still present by Week 6.",null,"Decrease",10000,30000,"ppm",{"$f":"IF(Z1675<>0,VLOOKUP(Z1675,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study not suitable for NOAEL setting. Group achieved intakes of Glyphosate in Groups 2 to 4 respectively, recorded during Weeks 5 and 6, ranged from 368 - 390, 1291 - 1335 and 3918 - 4453 mg/kg/day for males and 355 - 402, 1191 - 1271 and 3961 - 4397 mg/kg/day for females.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"M + F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","only secondary exposure through milk from PND 0-21","Weeks","Offspring (F1)","M + F",3000,"Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z1676<>0,VLOOKUP(Z1676,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Post mortem examination of weanlings at PND 21 revealed four pups with congested salivary glands at 10000 ppm and one pup with congested salivary glands at 3000 ppm. Since no similar findings were seen at 30000 ppm the significance of these incidences is unclear. No histopathological examinations were performed.",null,"Change","<3000",3000,"ppm",{"$f":"IF(Z1676<>0,VLOOKUP(Z1676,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study not suitable for NOAEL setting. Group achieved intakes of Glyphosate in Groups 2 to 4 respectively, recorded during Weeks 5 and 6, ranged from 368 - 390, 1291 - 1335 and 3918 - 4453 mg/kg/day for males and 355 - 402, 1191 - 1271 and 3961 - 4397 mg/kg/day for females.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)",null,null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",null,"M + F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","only secondary exposure through milk from PND 0-21","Weeks","Offspring (F1)","M + F",">30000","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z1677<>0,VLOOKUP(Z1677,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effect observed at necropsy.",null,"No effect",30000,">30000","ppm",{"$f":"IF(Z1677<>0,VLOOKUP(Z1677,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study not suitable for NOAEL setting. Group achieved intakes of Glyphosate in Groups 2 to 4 respectively, recorded during Weeks 5 and 6, ranged from 368 - 390, 1291 - 1335 and 3918 - 4453 mg/kg/day for males and 355 - 402, 1191 - 1271 and 3961 - 4397 mg/kg/day for females.","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",69,"42-90619","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","DAR",null,1991,"Rat","Crl:CD® (SD) BR VAF/Plus",10,"M + F",98.6,"Oral","Feed","3000; 10000; 30000",3000,30000,"ppm","3 (PND 21-42)","Weeks","Adult (F1)","M + F",30000,"Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z1678<>0,VLOOKUP(Z1678,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Post mortem examination revealed: Soft gastro-intestinal contents were noted in 7/10 males and 9/10 females at 30000 ppm; grey/blue contents of the jejunum were noted in 2/10 females at this dosage. No histopathological examinations were performed.",null,"Change",10000,30000,"ppm",{"$f":"IF(Z1678<>0,VLOOKUP(Z1678,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study not suitable for NOAEL setting. Group achieved intakes of Glyphosate in Groups 2 to 4 respectively, recorded during Weeks 5 and 6, ranged from 368 - 390, 1291 - 1335 and 3918 - 4453 mg/kg/day for males and 355 - 402, 1191 - 1271 and 3961 - 4397 mg/kg/day for females.","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","In life observation","Mortality",{"$f":"IF(Z1679<>0,VLOOKUP(Z1679,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"In the F0 generation, no unscheduled mortality occurred in the control, low- or high-dose groups. In the mid-dose group, one female died on day 20 of lactation, during the first litter interval (F1a). A second mid-dose female died on day 7 during the lactation period of the second litter interval (F1b). None of the mid-dose males died during this interval of study.\nIn the F1 generation, no unscheduled mortality occurred in the control or low-dose groups. In the mid-dose group one female was killed in a moribund condition during the post-mating period for the second litters (F2b). This female had mated during the first mating interval but did not deliver a litter; this female had not mated during the second mating period. No other mortality occurred in the mid-dose group. In the high-dose group, one female died during the first week of the growth period; this animal was caught in the feeder jar and death was considered accidental. A second high-dose female died during the gestation period for the second (F2b) litters. This female died on Day 21 of gestation and the uterus contained 15 term fetuses. No other mortality  ccurred in the high-dose group.\nIn the F2 generation, no mortality occurred in the control or high-dose groups. In the low-dose group one female died during the F3a lactation period. This female delivered a litter containing only  dead pups (13 pups) and died the day after parturition. No other mortality occurred in the low-dose group. In the mid-dose group, one male was killed in a moribund condition during the period between mating of the first and second litters. This male had mated and impregnated both females during the first mating period. No other mortality occurred in the mid-dose group.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1679<>0,VLOOKUP(Z1679,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","In life observation","Clinical signs",{"$f":"IF(Z1680<>0,VLOOKUP(Z1680,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"In-life physical observation data were considered comparable between the control and treated groups for each generation interval throughout the study. No adverse treatment-related effects were reported for adult F0, F1, and F2 animals.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1680<>0,VLOOKUP(Z1680,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","In life observation","Body weight",{"$f":"IF(Z1681<>0,VLOOKUP(Z1681,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"F0, F1, and F2: Mean body weight data during the growth and rest periods were comparable between the control and treated groups for each generation, throughout the study. Likewise, mean weight gain during the growth periods were comparable between these same groups for both sexes throughout all generations. No treatment effect on body weight data during the growth and rest periods was evident.\nMean body weight data during the gestation and lactation intervals and mean weight change during these same periods were considered comparable between the control and treated group for each pregnancy interval from each generation throughout the study.\nNo treatment effect was indicated in gestation - lactation body weight data throughout the study.\nAlso mean terminal body weight data were comparable between the control and treated groups for both males and females throughout the study.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1681<>0,VLOOKUP(Z1681,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","In life observation","Food consumption",{"$f":"IF(Z1682<>0,VLOOKUP(Z1682,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"F0, F1, and F2: Mean food consumption data were considered comparable between the control and treated groups (both sexes) during the growth and rest periods for each generation, throughout the study. No adverse effect of treatment on food consumption data was evident throughout the study.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1682<>0,VLOOKUP(Z1682,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Reproductive","Fertility (mammals)",{"$f":"IF(Z1683<>0,VLOOKUP(Z1683,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"F0: Male and female mating indices and male fertility indices during both mating intervals of the F0 generation were considered comparable between the control and treated groups. During the second mating interval of the F0, pregnancy rates were lower than control in each of the treated groups; however, no indication of a dose-response relationship was evident as the lowest pregnancy rate was seen in the mid-dose group. This reduction in pregnancy rate for the mid-dose group was not statistically significant. In the absence of a dose-response relationship the reduction in pregnancy rate during this mating interval (F1b) in the treated groups was not considered treatment-related.\nF1: In the F1 generation, mating indices (males and females) for both litter intervals were comparable between the control and treated groups. It is note-worthy that for both mating intervals of this generation, mating indices for control and some treated groups were lower than normally encountered in multi-generation studies. The reason for the poorer mating performance in this generation is unclear but no treatment effect was indicated since mating indices were lowest in the control group. Pregnancy and male fertility indices for the first mating interval of the F1 were comparable between the control and treated groups. During the second litter interval, pregnancy rates were lower than those seen for the first interval in control and treated groups. The lowest pregnancy rate was seen, in the high-dose group; however, this difference from the control value was not statistically significant. Pregnancy rates for the low- and mid-dose groups, during the second mating interval, were considered comparable to control. Male fertility indices for this same mating interval were considered comparable between the control and treated groups.\nF2: In the F2 generation mating indices for the treated groups were lower than control for each mating interval. During the first mating interval of the F2 generation, the female mating indices were lower than control in each of the treated groups; however, only in the high-dose group was this difference from control statistically significant. The female mating index for the control group at this interval was 100%, which is higher than normally encountered. In general, the female mating indices observed for the control groups in this study have shown considerable variability ranging from 70.9 to 100%. The poor mating performance for the treated groups during the first mating interval is attributed to two males in each treatment group that did not mate either female in their mating unit (each mating unit is comprised of one male and two females). During the second mating interval of the F2 generation, male mating performance improved in the mid- and high-dose groups as both mid-dose males and one of two high-dose males that did not mate during the first mating interval, mated and impregnated at least one female. Male mating indices for the low-dose group remained unchanged as the same two males that did not mate during the first interval, failed to mate during the second interval.\nPregnancy and fertility indices for the treated groups were comparable to control for both litter intervals of the F2 generation.\nOver the entire study no consistent, dose-related effect was seen in mating, fertility or pregnancy indices to indicate an adverse effect of treatment.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1683<>0,VLOOKUP(Z1683,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","F",">30","Reproductive","Gestation length",{"$f":"IF(Z1684<>0,VLOOKUP(Z1684,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Mean gestation length was comparable between the control and treated groups for each pregnancy interval in each generation (F0, F1, and F2).",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1684<>0,VLOOKUP(Z1684,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","F",">30","Reproductive","Number of live births",{"$f":"IF(Z1685<>0,VLOOKUP(Z1685,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The mean numbers of live, dead and toal pups at birth for each pregnancy interval were comparable between the control and treated groups for each generation (F0, F1, and F2).",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1685<>0,VLOOKUP(Z1685,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","F",">30","Reproductive","Litter size",{"$f":"IF(Z1686<>0,VLOOKUP(Z1686,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"The mean numbers of live, dead and total pups at birth and pup viability at birth for each pregnancy interval were comparable between the control and treated groups for each generation (F0, F1, and F2). Likewise, mean litter size data on day 21 of lactation (weaning) was comparable between the control and treated groups for each litter interval throughout the study for each generation (F0, F1, and F2).",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1686<>0,VLOOKUP(Z1686,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Offspring (F1+F2)","M + F",">30","Reproductive","Litter viability",{"$f":"IF(Z1687<>0,VLOOKUP(Z1687,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Mean litter size data on day 21 of lactation (weaning) was comparable between the control and treated groups for each litter interval throughout the study for each generation (F0, F1, and F2).\nThe indices of litters weaned were comparable between the control and treated groups for each lactation interval in the F0, F1, and F2 generation.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1687<>0,VLOOKUP(Z1687,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Offspring (F1+F2)","M + F",">30","Reproductive","Pup survival index",{"$f":"IF(Z1688<>0,VLOOKUP(Z1688,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"In the F0 generation, postnatal survival indices for Days 0-4 and 4-21 were comparable between the control and treated groups for the first lactation interval (F1a). For the second litter interval of the F0 (F1b), postnatal survival indices for the Day 0-4 interval were comparable between the control and treated groups. During the day 4-21 interval, survival indices were significantlv lower than control in each treatment qroup. The increase in pup mortality during this interval (i.e. days 4-21) was attributed to high pup mortality within one or more litters at each treatment level. In the low-dose group the lower pup survival was attributed to one female that experienced complete litter mortality (litter contained 14 live pups at day 4). In the mid-dose group, one female died on Day 7 of lactation and all seven pups in her litter died during the Day 4-7 lactation interval. Additionally, three mid-dose litters lost five or more pups from their litters during the day 4-21 lactation interval. In the high-dose group, one female lost nine of 12 pups during the day 4-21 lactation interval.\nIn the F1, F2, and F3 generations postnatal survival indices for days 0-4 and 4-21 during both litter intervals were considered comparable between the control and treated groups. Some statistically significant differences in these indices were observed between the control and treated groups; however, no trend was evident through successive generations to indicate an adverse effect of treatment.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1688<>0,VLOOKUP(Z1688,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Offspring (F1+F2)","M + F",">30","Developmental","Litter/pup weight",{"$f":"IF(Z1689<>0,VLOOKUP(Z1689,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Mean pup body weight data during each litter interval for each generation (F1, F2, and F3) were considered comparable between the control and treated groups. No adverse effects of treatment on pup weight data was evident. Accordingly, no treatment-related effect was evident in terminal body weight data for the F3b offspring.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1689<>0,VLOOKUP(Z1689,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Offspring (F1+F2)","M + F",">30","Reproductive","Sex ratio",{"$f":"IF(Z1690<>0,VLOOKUP(Z1690,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Pup sex distributions ratios at day 0 were generally comparable between the control and treated groups for each litter interval for each generation (F1, F2, and F3). Pup sex distributions at day 21 (weaning) were similar to distributions noted at day 0 in both the control and treated groups for each generation (F1, F2, and F3). No adverse treatment effect on sex distribution data was evident.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1690<>0,VLOOKUP(Z1690,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ Weight","Brain weight",{"$f":"IF(Z1691<>0,VLOOKUP(Z1691,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1691<>0,VLOOKUP(Z1691,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ Weight","Pituitary weight",{"$f":"IF(Z1692<>0,VLOOKUP(Z1692,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1692<>0,VLOOKUP(Z1692,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ Weight","Adrenals weight",{"$f":"IF(Z1693<>0,VLOOKUP(Z1693,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1693<>0,VLOOKUP(Z1693,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M",">30","Organ Weight","Testis weight",{"$f":"IF(Z1694<>0,VLOOKUP(Z1694,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1694<>0,VLOOKUP(Z1694,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","F",">30","Organ Weight","Ovary weight",{"$f":"IF(Z1695<>0,VLOOKUP(Z1695,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1695<>0,VLOOKUP(Z1695,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ Weight","Spleen weight",{"$f":"IF(Z1696<>0,VLOOKUP(Z1696,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1696<>0,VLOOKUP(Z1696,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ Weight","Kidney weight",{"$f":"IF(Z1697<>0,VLOOKUP(Z1697,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1697<>0,VLOOKUP(Z1697,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ Weight","Heart weight",{"$f":"IF(Z1698<>0,VLOOKUP(Z1698,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1698<>0,VLOOKUP(Z1698,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ Weight","Liver weight",{"$f":"IF(Z1699<>0,VLOOKUP(Z1699,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1699<>0,VLOOKUP(Z1699,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ Weight","Brain weight",{"$f":"IF(Z1700<>0,VLOOKUP(Z1700,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Mean brain weight data were considered comparable between the control and treated groups for both males and females for each generation (F0, F1, and F2).",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1700<>0,VLOOKUP(Z1700,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ Weight","Pituitary weight",{"$f":"IF(Z1701<>0,VLOOKUP(Z1701,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Mean pituitary weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females for each generation (F0, F1, and F2).",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1701<>0,VLOOKUP(Z1701,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ Weight","Adrenals weight",{"$f":"IF(Z1702<>0,VLOOKUP(Z1702,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Mean adrenal weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females from each generation (F0, F1, and F2). For the F1 generation, some statistically significant differences were noted between control and mid-dose treatment group both in mean adrenal weight data and in the relative weight data; however, no trends were evident within dose levels or through the generations.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1702<>0,VLOOKUP(Z1702,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M",">30","Organ Weight","Testis weight",{"$f":"IF(Z1703<>0,VLOOKUP(Z1703,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Mean testis weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for males from the F0, F1, and F2 generations.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1703<>0,VLOOKUP(Z1703,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","F",">30","Organ Weight","Ovary weight",{"$f":"IF(Z1704<>0,VLOOKUP(Z1704,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Mean ovary weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for females of all generations (F0, F1, and F2).",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1704<>0,VLOOKUP(Z1704,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ Weight","Spleen weight",{"$f":"IF(Z1705<>0,VLOOKUP(Z1705,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"In general, mean spleen weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females from the F0, F1, and F2 generation. Some statistically significant differences were noted between control and treated groups (mid dose) both in mean organ weight data and in the relative weight data (spleen); however, no trends were evident within dose levels or through the generations.  In the F2 female group, mean spleen weights (absolute and relative to brain and body weights) were significantly higher than the control value in the F2 mid-dose female group; however, mean spleen weight data for the low- and high-dose F2 females were comparable to control values. In the absence of an effect on spleen weight in the high-dose F2 female group, the change seen in spleen weight data for the mid-dose females was considered spurious and not biologically relevant.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1705<>0,VLOOKUP(Z1705,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ Weight","Kidney weight",{"$f":"IF(Z1706<>0,VLOOKUP(Z1706,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Mean organ weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females from the F0, F1, and F2 generation.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1706<>0,VLOOKUP(Z1706,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ Weight","Heart weight",{"$f":"IF(Z1707<>0,VLOOKUP(Z1707,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Mean organ weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females from the F0, F1, and F2 generation.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1707<>0,VLOOKUP(Z1707,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ Weight","Liver weight",{"$f":"IF(Z1708<>0,VLOOKUP(Z1708,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Mean liver weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females from the F0, F1, and F2 generation. In the F2 female group, mean liver/body weight ratios were significantly lower than control in each of the treated groups; however, no clear dose-relationship was apparent. Mean liver/brain weight ratios for the treated F2 females were lower than control; however, these differences from control values were not statistically significant.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1708<>0,VLOOKUP(Z1708,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z1709<>0,VLOOKUP(Z1709,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Gross postmortem examinations of the F0, F1 and F2 adults at terminal sacrifice (males and females) did not indicate an adverse effect of treatment.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1709<>0,VLOOKUP(Z1709,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)","12 male; 24 female","M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Offspring (F1+F2)","M + F",">30","Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z1710<>0,VLOOKUP(Z1710,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Gross postmortem observations of offspring at weaning (F1a, F2a,F3a F3b) on post-weaning (F1b, F2b) did not reveal an adverse effect of treatment. Likewise, evaluation of dead pups recovered at birth and during the 21-day lactation period did not reveal a treatment-related effect.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1710<>0,VLOOKUP(Z1710,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Stomach histopathology",{"$f":"IF(Z1711<>0,VLOOKUP(Z1711,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1711<>0,VLOOKUP(Z1711,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z1712<>0,VLOOKUP(Z1712,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Duodenum, Ileum, Colon: No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1712<>0,VLOOKUP(Z1712,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1713<>0,VLOOKUP(Z1713,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1713<>0,VLOOKUP(Z1713,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1714<>0,VLOOKUP(Z1714,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Investigated tissues were: two longitudinal sections of the brain, optic nerves, and Pineal gland (Pineal gland only in F2). No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1714<>0,VLOOKUP(Z1714,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Spinal cord histopathology",{"$f":"IF(Z1715<>0,VLOOKUP(Z1715,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1715<>0,VLOOKUP(Z1715,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Eyes histopathology",{"$f":"IF(Z1716<>0,VLOOKUP(Z1716,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1716<>0,VLOOKUP(Z1716,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","[Not in list]",{"$f":"IF(Z1717<>0,VLOOKUP(Z1717,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Harderian gland: No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1717<>0,VLOOKUP(Z1717,Interpretation!$C:$E,3,FALSE),\"\")","v":0},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M",">30","Organ histopathology","Testis histopathology",{"$f":"IF(Z1718<>0,VLOOKUP(Z1718,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1718<>0,VLOOKUP(Z1718,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M",">30","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1719<>0,VLOOKUP(Z1719,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1719<>0,VLOOKUP(Z1719,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M",">30","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1720<>0,VLOOKUP(Z1720,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1720<>0,VLOOKUP(Z1720,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M",">30","Organ histopathology","Accessory sex organs histopathology",{"$f":"IF(Z1721<>0,VLOOKUP(Z1721,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Preputial gland: No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1721<>0,VLOOKUP(Z1721,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","F",">30","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1722<>0,VLOOKUP(Z1722,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Uterus (Cervix not explicitly mentioned): No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1722<>0,VLOOKUP(Z1722,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","F",">30","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1723<>0,VLOOKUP(Z1723,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1723<>0,VLOOKUP(Z1723,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0)","F",">30","Organ histopathology","Accessory sex organs histopathology",{"$f":"IF(Z1724<>0,VLOOKUP(Z1724,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Clitoral gland investigated for F0 only. No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for generation F0 were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1724<>0,VLOOKUP(Z1724,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1725<>0,VLOOKUP(Z1725,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1725<>0,VLOOKUP(Z1725,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1726<>0,VLOOKUP(Z1726,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1726<>0,VLOOKUP(Z1726,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Urinary bladder histopathology",{"$f":"IF(Z1727<>0,VLOOKUP(Z1727,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1727<>0,VLOOKUP(Z1727,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Liver histopathology",{"$f":"IF(Z1728<>0,VLOOKUP(Z1728,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1728<>0,VLOOKUP(Z1728,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1729<>0,VLOOKUP(Z1729,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1729<>0,VLOOKUP(Z1729,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Thymus histopathology",{"$f":"IF(Z1730<>0,VLOOKUP(Z1730,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1730<>0,VLOOKUP(Z1730,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1731<>0,VLOOKUP(Z1731,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1731<>0,VLOOKUP(Z1731,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Heart histopathology",{"$f":"IF(Z1732<>0,VLOOKUP(Z1732,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1732<>0,VLOOKUP(Z1732,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z1733<>0,VLOOKUP(Z1733,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Mesenteric, mandibular, and cervical lymph nodes: No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1733<>0,VLOOKUP(Z1733,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Lung histopathology",{"$f":"IF(Z1734<>0,VLOOKUP(Z1734,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1734<>0,VLOOKUP(Z1734,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Trachea histopathology",{"$f":"IF(Z1735<>0,VLOOKUP(Z1735,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1735<>0,VLOOKUP(Z1735,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Oesophagus histopathology",{"$f":"IF(Z1736<>0,VLOOKUP(Z1736,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1736<>0,VLOOKUP(Z1736,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1737<>0,VLOOKUP(Z1737,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"THYROID: No microscopic findings were considered compound related.\nPARATHYROID: No microscopic findings were considered compound related.\nThe overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1737<>0,VLOOKUP(Z1737,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z1738<>0,VLOOKUP(Z1738,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1738<>0,VLOOKUP(Z1738,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Bone marrow histopathology",{"$f":"IF(Z1739<>0,VLOOKUP(Z1739,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1739<>0,VLOOKUP(Z1739,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Skeletal muscle histopathology",{"$f":"IF(Z1740<>0,VLOOKUP(Z1740,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1740<>0,VLOOKUP(Z1740,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Peripheral nerve histopathology",{"$f":"IF(Z1741<>0,VLOOKUP(Z1741,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Sciatic nerve: No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1741<>0,VLOOKUP(Z1741,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Skin histopathology",{"$f":"IF(Z1742<>0,VLOOKUP(Z1742,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1742<>0,VLOOKUP(Z1742,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0+F1)","M + F",">30","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z1743<>0,VLOOKUP(Z1743,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2), for both sexes, were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1743<>0,VLOOKUP(Z1743,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","life-time, all three generations","Weeks","Adult (F0)","M + F",">30","Organ histopathology","Aorta histopathology",{"$f":"IF(Z1744<>0,VLOOKUP(Z1744,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1744<>0,VLOOKUP(Z1744,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Stomach histopathology",{"$f":"IF(Z1745<>0,VLOOKUP(Z1745,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1745<>0,VLOOKUP(Z1745,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Small and large intestines histopathology",{"$f":"IF(Z1746<>0,VLOOKUP(Z1746,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Duodenum, Ileum, Colon: No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1746<>0,VLOOKUP(Z1746,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1747<>0,VLOOKUP(Z1747,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1747<>0,VLOOKUP(Z1747,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1748<>0,VLOOKUP(Z1748,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Tissues investigated: two longitudinal sections of the brain and optic nerves. No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1748<>0,VLOOKUP(Z1748,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Spinal cord histopathology",{"$f":"IF(Z1749<>0,VLOOKUP(Z1749,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1749<>0,VLOOKUP(Z1749,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Eyes histopathology",{"$f":"IF(Z1750<>0,VLOOKUP(Z1750,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1750<>0,VLOOKUP(Z1750,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","[Not in list]",{"$f":"IF(Z1751<>0,VLOOKUP(Z1751,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Harderian gland: No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1751<>0,VLOOKUP(Z1751,Interpretation!$C:$E,3,FALSE),\"\")","v":0},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M",">30","Organ histopathology","Testis histopathology",{"$f":"IF(Z1752<>0,VLOOKUP(Z1752,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1752<>0,VLOOKUP(Z1752,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M",">30","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1753<>0,VLOOKUP(Z1753,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1753<>0,VLOOKUP(Z1753,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M",">30","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1754<>0,VLOOKUP(Z1754,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1754<>0,VLOOKUP(Z1754,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","F",">30","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1755<>0,VLOOKUP(Z1755,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Uterus (Cervix not explicitly mentioned): No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1755<>0,VLOOKUP(Z1755,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","F",">30","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1756<>0,VLOOKUP(Z1756,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1756<>0,VLOOKUP(Z1756,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1757<>0,VLOOKUP(Z1757,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1757<>0,VLOOKUP(Z1757,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1758<>0,VLOOKUP(Z1758,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1758<>0,VLOOKUP(Z1758,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Urinary bladder histopathology",{"$f":"IF(Z1759<>0,VLOOKUP(Z1759,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1759<>0,VLOOKUP(Z1759,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Liver histopathology",{"$f":"IF(Z1760<>0,VLOOKUP(Z1760,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1760<>0,VLOOKUP(Z1760,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1761<>0,VLOOKUP(Z1761,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1761<>0,VLOOKUP(Z1761,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Thymus histopathology",{"$f":"IF(Z1762<>0,VLOOKUP(Z1762,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1762<>0,VLOOKUP(Z1762,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1763<>0,VLOOKUP(Z1763,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1763<>0,VLOOKUP(Z1763,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Heart histopathology",{"$f":"IF(Z1764<>0,VLOOKUP(Z1764,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1764<>0,VLOOKUP(Z1764,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z1765<>0,VLOOKUP(Z1765,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Mesenteric and cervical lymph nodes: No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1765<>0,VLOOKUP(Z1765,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Lung histopathology",{"$f":"IF(Z1766<>0,VLOOKUP(Z1766,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1766<>0,VLOOKUP(Z1766,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Trachea histopathology",{"$f":"IF(Z1767<>0,VLOOKUP(Z1767,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1767<>0,VLOOKUP(Z1767,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Oesophagus histopathology",{"$f":"IF(Z1768<>0,VLOOKUP(Z1768,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1768<>0,VLOOKUP(Z1768,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1769<>0,VLOOKUP(Z1769,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"THYROID: No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.\nPARATHYROID: No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1769<>0,VLOOKUP(Z1769,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z1770<>0,VLOOKUP(Z1770,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1770<>0,VLOOKUP(Z1770,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Bone marrow histopathology",{"$f":"IF(Z1771<>0,VLOOKUP(Z1771,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1771<>0,VLOOKUP(Z1771,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Skeletal muscle histopathology",{"$f":"IF(Z1772<>0,VLOOKUP(Z1772,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1772<>0,VLOOKUP(Z1772,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Peripheral nerve histopathology",{"$f":"IF(Z1773<>0,VLOOKUP(Z1773,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Sciatic nerve: No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1773<>0,VLOOKUP(Z1773,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Skin histopathology",{"$f":"IF(Z1774<>0,VLOOKUP(Z1774,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1774<>0,VLOOKUP(Z1774,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",70,"77-2063","Three generation reproduction study","DAR",null,1981,"Rat","Crl:CD® (Sprague Dawley derived)",10,"M + F","Not provided","Oral","Feed","3; 10; 30",3,30,"mg/kg bw/day","21 (PND0-21, exposure through milk)","Days","Offspring (F3)","M + F",">30","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z1775<>0,VLOOKUP(Z1775,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.",null,"No effect",30,">30","mg/kg bw/day",{"$f":"IF(Z1775<>0,VLOOKUP(Z1775,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",71,null,"Range-finding study, similar to OECD 407","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",97.67,"Oral","Feed","30000; 40000; 50000",30000,50000,"ppm",28,"Days","Adult","M + F",">50000","In life observation","Mortality",{"$f":"IF(Z1776<>0,VLOOKUP(Z1776,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1776<>0,VLOOKUP(Z1776,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Dose-range finder","Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",71,null,"Range-finding study, similar to OECD 407","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",97.67,"Oral","Feed","30000; 40000; 50000",30000,50000,"ppm",28,"Days","Adult","M + F",">50000","In life observation","Body weight",{"$f":"IF(Z1777<>0,VLOOKUP(Z1777,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Cumulative body weight change treated vs. control: M 40000= -53%* (day 1 - 8); M 40000=-40%* (day 1-16); M 50000=-100%* (day 1-8); M 50000=-50%* (day 1-16); M 50000=-44%* (day 1-23); M50000=-44%* (day 1-28); F 50000=-64%* (day 1-8); F 50000=-46%* (day 1-16); F 50000=-47%* (day 1-23); F 50000=-46%* (day 1-28); F 30000= -38%* (day 1-23); F 50000=-33%* (day 1-28)\nBody weight reduction are considered secondary to gastrointestinal effects.",null,"Decrease","<30000",30000,"ppm",{"$f":"IF(Z1777<>0,VLOOKUP(Z1777,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Dose-range finder","Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",71,null,"Range-finding study, similar to OECD 407","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",97.67,"Oral","Feed","30000; 40000; 50000",30000,50000,"ppm",28,"Days","Adult","M + F",">50000","In life observation","Food consumption",{"$f":"IF(Z1778<>0,VLOOKUP(Z1778,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1778<>0,VLOOKUP(Z1778,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Dose-range finder","Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",71,null,"Range-finding study, similar to OECD 407","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",97.67,"Oral","Feed","30000; 40000; 50000",30000,50000,"ppm",28,"Days","Adult","M + F",30000,"In life observation","Clinical signs",{"$f":"IF(Z1779<>0,VLOOKUP(Z1779,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Significant incidences of soft stools and/or diarrhea were noted for both sexes at all three exposure levels with the highest dose group most affected (M/F 30000= Soft stool, diarrhea; M/F 40000= soft  stool/diarrhea; M/F 50000=marked diarrhea).",null,"Increase","<30000",30000,"ppm",{"$f":"IF(Z1779<>0,VLOOKUP(Z1779,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Dose-range finder","Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",71,null,"Range-finding study, similar to OECD 407","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",97.67,"Oral","Feed","30000; 40000; 50000",30000,50000,"ppm",28,"Days","Adult","M + F",">50000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1780<>0,VLOOKUP(Z1780,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1780<>0,VLOOKUP(Z1780,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Dose-range finder","Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",71,null,"Range-finding study, similar to OECD 407","DAR",null,1989,"Rat","Sprague-Dawley",5,"M + F",97.67,"Oral","Feed","30000; 40000; 50000",30000,50000,"ppm",28,"Days","Adult","M + F",">50000","Organ histopathology","Liver histopathology",{"$f":"IF(Z1781<>0,VLOOKUP(Z1781,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1781<>0,VLOOKUP(Z1781,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Dose-range finder","Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",72,"77-2110","Range-finding study, similar to OECD 407","DAR",null,1978,"Mouse","CD-1",5,"M + F",98.5,"Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",28,"Days","Adult","M + F",">1000","In life observation","Mortality",{"$f":"IF(Z1782<>0,VLOOKUP(Z1782,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",800,">800","mg/kg bw/day",{"$f":"IF(Z1782<>0,VLOOKUP(Z1782,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Dose-range finder","Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",72,"77-2110","Range-finding study, similar to OECD 408","DAR",null,1978,"Mouse","CD-1",5,"M + F",98.5,"Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",28,"Days","Adult","M + F",">1000","In life observation","Clinical signs",{"$f":"IF(Z1783<>0,VLOOKUP(Z1783,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",800,">800","mg/kg bw/day",{"$f":"IF(Z1783<>0,VLOOKUP(Z1783,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Dose-range finder","Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",72,"77-2110","Range-finding study, similar to OECD 409","DAR",null,1978,"Mouse","CD-1",5,"M + F",98.5,"Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",28,"Days","Adult","M + F",">1000","In life observation","Body weight",{"$f":"IF(Z1784<>0,VLOOKUP(Z1784,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Slightly lower mean body weights, compared to control, were noted for males receiving 300 and 1000 mg/kg/day through week two. However, these a differences were not considered treatment-related but attributed to slightly lower pretest body weights.",null,"No effect",800,">800","mg/kg bw/day",{"$f":"IF(Z1784<>0,VLOOKUP(Z1784,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Dose-range finder","Yes","Yes"]
["Mammals","Repeated dose 28-day oral toxicity study in rodents",72,"77-2110","Range-finding study, similar to OECD 410","DAR",null,1978,"Mouse","CD-1",5,"M + F",98.5,"Oral","Feed","100; 300; 1000",100,1000,"mg/kg bw/day",28,"Days","Adult","M + F",">1000","In life observation","Food consumption",{"$f":"IF(Z1785<>0,VLOOKUP(Z1785,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Incidences of changes in food consumption not treatment-related",null,"No effect",800,">800","mg/kg bw/day",{"$f":"IF(Z1785<>0,VLOOKUP(Z1785,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Dose-range finder","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 407","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","In life observation","Mortality",{"$f":"IF(Z1786<>0,VLOOKUP(Z1786,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No treatment-related deaths were observed (1 male (control) and 1 female (10000 ppm) died spontaneously).",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1786<>0,VLOOKUP(Z1786,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 408","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","In life observation","Clinical signs",{"$f":"IF(Z1787<>0,VLOOKUP(Z1787,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1787<>0,VLOOKUP(Z1787,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 409","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",50000,"In life observation","Body weight",{"$f":"IF(Z1788<>0,VLOOKUP(Z1788,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Statistically significant decrease of body weights in males and females at 50000 ppm throughout the study period leading to final body weight reduction of -11%* in M at 50000ppm and -8%* in F at 50000ppm (compared to control). Incidences of statistically significant lower body weights were observed in males at 10000 ppm and females at 5000 and 10000 ppm.",null,"Decrease",10000,50000,"ppm",{"$f":"IF(Z1788<>0,VLOOKUP(Z1788,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 410","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","In life observation","Food consumption",{"$f":"IF(Z1789<>0,VLOOKUP(Z1789,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Incidents of statistically significant increased food consumption in M at 5000; 10000; 50000 ppm and in F at 5000; 50000 ppm.",null,"Increase",50000,">50000","ppm",{"$f":"IF(Z1789<>0,VLOOKUP(Z1789,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 411","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ Weight","Brain weight",{"$f":"IF(Z1790<>0,VLOOKUP(Z1790,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Relative organ weight (relative to body weight) was increased (M 50000 ppm =+11%*) which was attributed to lower terminal body weight and thus not of toxicological relevance. No effects on absolute organ weight were observed.",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1790<>0,VLOOKUP(Z1790,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 412","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M",">50000","Organ Weight","Testis weight",{"$f":"IF(Z1791<>0,VLOOKUP(Z1791,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute and relative (to body and brain weight) organ weight was not affected.",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1791<>0,VLOOKUP(Z1791,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 412","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","F",">50000","Organ Weight","Ovary weight",{"$f":"IF(Z1792<>0,VLOOKUP(Z1792,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute and relative (to body and brain weight) organ weight was not affected.",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1792<>0,VLOOKUP(Z1792,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 413","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ Weight","Heart weight",{"$f":"IF(Z1793<>0,VLOOKUP(Z1793,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Relative organ weight (relative to body weight) was increased (M 50000 ppm=+16%*) which was attributed to lower terminal body weight and thus not of toxicological relevance. No effects on absolute as well as relative (to brain weight) organ weight were observed.\n",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1793<>0,VLOOKUP(Z1793,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 414","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ Weight","Spleen weight",{"$f":"IF(Z1794<>0,VLOOKUP(Z1794,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute and relative (to body and brain weight) organ weight was not affected.",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1794<>0,VLOOKUP(Z1794,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 415","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ Weight","Kidney weight",{"$f":"IF(Z1795<>0,VLOOKUP(Z1795,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Relative organ weight (relative to body weight) was increased (M 50000 ppm =+18.5%*) which was attributed to lower terminal body weight and thus not of toxicological relevance. No effects on absolute as well as relative (to brain weight) organ weight were observed.\n",null,"Increase",50000,">50000","ppm",{"$f":"IF(Z1795<>0,VLOOKUP(Z1795,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 416","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ Weight","Liver weight",{"$f":"IF(Z1796<>0,VLOOKUP(Z1796,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Relative organ weight (relative to body weight) was increased ( M 10000 ppm=+9%*; M 50000 ppm=+12%* ) which was attributed to lower terminal body weight and thus not of toxicological relevance. No effects on absolute as well as relative (to brain weight) organ weight were observed.",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1796<>0,VLOOKUP(Z1796,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 417","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Spinal cord histopathology",{"$f":"IF(Z1797<>0,VLOOKUP(Z1797,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1797<>0,VLOOKUP(Z1797,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 418","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1798<>0,VLOOKUP(Z1798,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1798<>0,VLOOKUP(Z1798,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 419","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1799<>0,VLOOKUP(Z1799,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1799<>0,VLOOKUP(Z1799,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 420","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Gall bladder histopathology",{"$f":"IF(Z1800<>0,VLOOKUP(Z1800,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1800<>0,VLOOKUP(Z1800,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 421","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Stomach histopathology",{"$f":"IF(Z1801<>0,VLOOKUP(Z1801,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effect on gastro-intestinal tract was observed.",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1801<>0,VLOOKUP(Z1801,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 422","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1802<>0,VLOOKUP(Z1802,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1802<>0,VLOOKUP(Z1802,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 428","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1803<>0,VLOOKUP(Z1803,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1803<>0,VLOOKUP(Z1803,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 428","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1804<>0,VLOOKUP(Z1804,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1804<>0,VLOOKUP(Z1804,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 423","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Testis histopathology",{"$f":"IF(Z1805<>0,VLOOKUP(Z1805,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1805<>0,VLOOKUP(Z1805,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 424","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M",">50000","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1806<>0,VLOOKUP(Z1806,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1806<>0,VLOOKUP(Z1806,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 425","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","F",">50000","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1807<>0,VLOOKUP(Z1807,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1807<>0,VLOOKUP(Z1807,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 426","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z1808<>0,VLOOKUP(Z1808,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effect on mesenteric lymph nodes was observed.",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1808<>0,VLOOKUP(Z1808,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 427","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Skeletal muscle histopathology",{"$f":"IF(Z1809<>0,VLOOKUP(Z1809,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1809<>0,VLOOKUP(Z1809,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 428","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1810<>0,VLOOKUP(Z1810,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1810<>0,VLOOKUP(Z1810,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 428","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Bone marrow histopathology",{"$f":"IF(Z1811<>0,VLOOKUP(Z1811,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effect on bone and bone marrow was observed.",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1811<>0,VLOOKUP(Z1811,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 429","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1812<>0,VLOOKUP(Z1812,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No treatment-related effect observed (cortical hyperplasia in 3/8 M (control), 5/10 F (control), 1/10 F (50000 ppm); vacuolation 4/10 F (control) and 3/10 F (50000 ppm)).",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1812<>0,VLOOKUP(Z1812,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 430","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Lung histopathology",{"$f":"IF(Z1813<>0,VLOOKUP(Z1813,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No treatment-related effect was observed (Pneumonitis 1/10 M (control), 2/10 M (50000ppm), 1/10 F (control), 2/10 F (50000ppm); peribronchial lymphoid hyperplasia 4/10 M (control), 5/10 M (50000ppm), 1/10 F (control), 2/10 F (50000ppm); perivascullar lymphoid hyperplasia 2/10 M (control), 2/10 F (control), 1/10 F (50000 ppm)).",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1813<>0,VLOOKUP(Z1813,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 430","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Urinary bladder histopathology",{"$f":"IF(Z1814<>0,VLOOKUP(Z1814,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1814<>0,VLOOKUP(Z1814,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 431","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1815<>0,VLOOKUP(Z1815,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No treatment-related effect was observed (minimal interstitial inflammation 3/10 M (control), 4/10 M (50000 ppm), 4/10 F (control), 2/10 (50000 ppm)).",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1815<>0,VLOOKUP(Z1815,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 432","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Liver histopathology",{"$f":"IF(Z1816<>0,VLOOKUP(Z1816,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No treatment-related effect was observed (small focal accumulations of inflammatory cells in control and treated animals at 50000 ppm).",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1816<>0,VLOOKUP(Z1816,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",73,"77-2111","No guideline mentioned, similar to OECD 433","DAR",null,1979,"Mouse","CD-1",15,"M + F",98.7,"Oral","Feed","5000; 10000; 50000",5000,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1817<>0,VLOOKUP(Z1817,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No treatment-related effect observed (extramedullary hematopoiesus 8/10 M (control), 9/10 M (50000 ppm), 10/10 F (control), 10/10 F (50000 ppm); pigment 7/10 M (control), 6/10 F (50000ppm), 10/10 F (control), 10/10 F (50000ppm))",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1817<>0,VLOOKUP(Z1817,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F0)","M + F",">300","In life observation","Clinical signs",{"$f":"IF(Z1818<>0,VLOOKUP(Z1818,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Signs of systemic toxicity were not observed in F0 generation.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1818<>0,VLOOKUP(Z1818,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only Study not acceptable","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","In life observation","Clinical signs",{"$f":"IF(Z1819<>0,VLOOKUP(Z1819,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Signs of systemic toxicity were not observed in F1 generation.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1819<>0,VLOOKUP(Z1819,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","In life observation","Clinical signs",{"$f":"IF(Z1820<>0,VLOOKUP(Z1820,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Signs of systemic toxicity were not observed in F0 generation.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1820<>0,VLOOKUP(Z1820,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F0)","M + F",">300","In life observation","Body weight",{"$f":"IF(Z1821<>0,VLOOKUP(Z1821,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Body weight was not affected in F0 adults.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1821<>0,VLOOKUP(Z1821,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","In life observation","Body weight",{"$f":"IF(Z1822<>0,VLOOKUP(Z1822,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Body weight was not affected in F1 adults.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1822<>0,VLOOKUP(Z1822,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","In life observation","Body weight",{"$f":"IF(Z1823<>0,VLOOKUP(Z1823,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Body weight was not affected in F2 adults.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1823<>0,VLOOKUP(Z1823,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F0)","M + F",">300","In life observation","Food consumption",{"$f":"IF(Z1824<>0,VLOOKUP(Z1824,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption of F0 adults was not affected.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1824<>0,VLOOKUP(Z1824,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","In life observation","Food consumption",{"$f":"IF(Z1825<>0,VLOOKUP(Z1825,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption of F1 adults was not affected.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1825<>0,VLOOKUP(Z1825,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","In life observation","Food consumption",{"$f":"IF(Z1826<>0,VLOOKUP(Z1826,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption of F2 adults was not affected.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1826<>0,VLOOKUP(Z1826,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Offspring (F1)","F",">300","Developmental","Litter/pup weight",{"$f":"IF(Z1827<>0,VLOOKUP(Z1827,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect observed in F1 offspring.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1827<>0,VLOOKUP(Z1827,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Offspring (F1)","F",">300","Developmental","Litter/pup weight",{"$f":"IF(Z1828<>0,VLOOKUP(Z1828,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect observed in F2 offspring.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1828<>0,VLOOKUP(Z1828,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Offspring (F1)","F",">300","Developmental","Litter/pup weight",{"$f":"IF(Z1829<>0,VLOOKUP(Z1829,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect observed in F3 offspring.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1829<>0,VLOOKUP(Z1829,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Offspring (F1)","F",">300","Reproductive","Litter size",{"$f":"IF(Z1830<>0,VLOOKUP(Z1830,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect observed in F1 offspring.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1830<>0,VLOOKUP(Z1830,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Offspring (F2)","F",">300","Reproductive","Litter size",{"$f":"IF(Z1831<>0,VLOOKUP(Z1831,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect observed in F2 offspring.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1831<>0,VLOOKUP(Z1831,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Offspring (F3)","F",">300","Reproductive","Litter size",{"$f":"IF(Z1832<>0,VLOOKUP(Z1832,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect observed in F3 offspring.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1832<>0,VLOOKUP(Z1832,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Offspring (F1)","F",">300","Reproductive","Litter viability",{"$f":"IF(Z1833<>0,VLOOKUP(Z1833,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect observed in F1 offspring.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1833<>0,VLOOKUP(Z1833,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Offspring (F2)","F",">300","Reproductive","Litter viability",{"$f":"IF(Z1834<>0,VLOOKUP(Z1834,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect observed in F2 offspring.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1834<>0,VLOOKUP(Z1834,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Offspring (F3)","F",">300","Reproductive","Litter viability",{"$f":"IF(Z1835<>0,VLOOKUP(Z1835,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect observed in F3 offspring.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1835<>0,VLOOKUP(Z1835,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F0)","M",">300","Organ histopathology","Testis histopathology",{"$f":"IF(Z1836<>0,VLOOKUP(Z1836,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effects in F0 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1836<>0,VLOOKUP(Z1836,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z1837<>0,VLOOKUP(Z1837,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1837<>0,VLOOKUP(Z1837,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Oesophagus histopathology",{"$f":"IF(Z1838<>0,VLOOKUP(Z1838,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1838<>0,VLOOKUP(Z1838,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Stomach histopathology",{"$f":"IF(Z1839<>0,VLOOKUP(Z1839,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"GI tract (stomach and intestines were exmined.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1839<>0,VLOOKUP(Z1839,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1840<>0,VLOOKUP(Z1840,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1840<>0,VLOOKUP(Z1840,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Liver histopathology",{"$f":"IF(Z1841<>0,VLOOKUP(Z1841,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1841<>0,VLOOKUP(Z1841,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Lung histopathology",{"$f":"IF(Z1842<>0,VLOOKUP(Z1842,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1842<>0,VLOOKUP(Z1842,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Heart histopathology",{"$f":"IF(Z1843<>0,VLOOKUP(Z1843,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1843<>0,VLOOKUP(Z1843,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Aorta histopathology",{"$f":"IF(Z1844<>0,VLOOKUP(Z1844,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1844<>0,VLOOKUP(Z1844,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1845<>0,VLOOKUP(Z1845,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1845<>0,VLOOKUP(Z1845,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1846<>0,VLOOKUP(Z1846,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1846<>0,VLOOKUP(Z1846,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Urinary bladder histopathology",{"$f":"IF(Z1847<>0,VLOOKUP(Z1847,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1847<>0,VLOOKUP(Z1847,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M",">300","Organ histopathology","Testis histopathology",{"$f":"IF(Z1848<>0,VLOOKUP(Z1848,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1848<>0,VLOOKUP(Z1848,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M",">300","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z1849<>0,VLOOKUP(Z1849,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1849<>0,VLOOKUP(Z1849,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1850<>0,VLOOKUP(Z1850,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1850<>0,VLOOKUP(Z1850,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1851<>0,VLOOKUP(Z1851,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1851<>0,VLOOKUP(Z1851,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1852<>0,VLOOKUP(Z1852,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1852<>0,VLOOKUP(Z1852,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1853<>0,VLOOKUP(Z1853,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1853<>0,VLOOKUP(Z1853,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","M + F",">300","Organ histopathology","Eyes histopathology",{"$f":"IF(Z1854<>0,VLOOKUP(Z1854,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1854<>0,VLOOKUP(Z1854,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","F",">300","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1855<>0,VLOOKUP(Z1855,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1855<>0,VLOOKUP(Z1855,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","F",">300","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1856<>0,VLOOKUP(Z1856,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effects in F1 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1856<>0,VLOOKUP(Z1856,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M",">300","Organ histopathology","Testis histopathology",{"$f":"IF(Z1857<>0,VLOOKUP(Z1857,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1857<>0,VLOOKUP(Z1857,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z1858<>0,VLOOKUP(Z1858,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1858<>0,VLOOKUP(Z1858,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Oesophagus histopathology",{"$f":"IF(Z1859<>0,VLOOKUP(Z1859,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1859<>0,VLOOKUP(Z1859,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Stomach histopathology",{"$f":"IF(Z1860<>0,VLOOKUP(Z1860,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"F2: GI tract (stomach and intestines were exmined.)",null,"No effect",300,">300","ppm",{"$f":"IF(Z1860<>0,VLOOKUP(Z1860,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1861<>0,VLOOKUP(Z1861,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1861<>0,VLOOKUP(Z1861,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Liver histopathology",{"$f":"IF(Z1862<>0,VLOOKUP(Z1862,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1862<>0,VLOOKUP(Z1862,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Lung histopathology",{"$f":"IF(Z1863<>0,VLOOKUP(Z1863,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1863<>0,VLOOKUP(Z1863,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Heart histopathology",{"$f":"IF(Z1864<>0,VLOOKUP(Z1864,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1864<>0,VLOOKUP(Z1864,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Aorta histopathology",{"$f":"IF(Z1865<>0,VLOOKUP(Z1865,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1865<>0,VLOOKUP(Z1865,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1866<>0,VLOOKUP(Z1866,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1866<>0,VLOOKUP(Z1866,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1867<>0,VLOOKUP(Z1867,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1867<>0,VLOOKUP(Z1867,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Urinary bladder histopathology",{"$f":"IF(Z1868<>0,VLOOKUP(Z1868,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1868<>0,VLOOKUP(Z1868,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M",">300","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z1869<>0,VLOOKUP(Z1869,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1869<>0,VLOOKUP(Z1869,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1870<>0,VLOOKUP(Z1870,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1870<>0,VLOOKUP(Z1870,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1871<>0,VLOOKUP(Z1871,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1871<>0,VLOOKUP(Z1871,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1872<>0,VLOOKUP(Z1872,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1872<>0,VLOOKUP(Z1872,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1873<>0,VLOOKUP(Z1873,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1873<>0,VLOOKUP(Z1873,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","M + F",">300","Organ histopathology","Eyes histopathology",{"$f":"IF(Z1874<>0,VLOOKUP(Z1874,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1874<>0,VLOOKUP(Z1874,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","F",">300","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1875<>0,VLOOKUP(Z1875,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1875<>0,VLOOKUP(Z1875,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","F",">300","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1876<>0,VLOOKUP(Z1876,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effects in F2 observed.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1876<>0,VLOOKUP(Z1876,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F0)","F",">300","Reproductive","Fertility (mammals)",{"$f":"IF(Z1877<>0,VLOOKUP(Z1877,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Pregnancy rate was not changed for F0 females.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1877<>0,VLOOKUP(Z1877,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","F",">300","Reproductive","Fertility (mammals)",{"$f":"IF(Z1878<>0,VLOOKUP(Z1878,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Pregnancy rate was not changed for F1 females.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1878<>0,VLOOKUP(Z1878,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Multigenerational reproductive toxicity",74,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","8 M; 16 F","M + F","Not provided","Oral","Feed","75; 150; 300",75,300,"ppm","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","F",">300","Reproductive","Fertility (mammals)",{"$f":"IF(Z1879<>0,VLOOKUP(Z1879,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Pregnancy rate was not changed for F2 females.",null,"No effect",300,">300","ppm",{"$f":"IF(Z1879<>0,VLOOKUP(Z1879,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",75,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","10 M; 30 F","M + F","Not provided","Oral","Gavage/Intubation","5; 10",5,10,"mg/kg bw/day","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Adult (F0)","M",">10","Organ histopathology","Testis histopathology",{"$f":"IF(Z1880<>0,VLOOKUP(Z1880,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",10,">10","mg/kg bw/day",{"$f":"IF(Z1880<>0,VLOOKUP(Z1880,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Supportive only Study not acceptable","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",75,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","10 M; 30 F","M + F","Not provided","Oral","Gavage/Intubation","5; 10",5,10,"mg/kg bw/day","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Adult (F0)","F",">10","In life observation","Body weight",{"$f":"IF(Z1881<>0,VLOOKUP(Z1881,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",10,">10","mg/kg bw/day",{"$f":"IF(Z1881<>0,VLOOKUP(Z1881,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",75,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","10 M; 30 F","M + F","Not provided","Oral","Gavage/Intubation","5; 10",5,10,"mg/kg bw/day","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Adult (F0)","F",">10","In life observation","Food consumption",{"$f":"IF(Z1882<>0,VLOOKUP(Z1882,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",10,">10","mg/kg bw/day",{"$f":"IF(Z1882<>0,VLOOKUP(Z1882,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Supportive only","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",75,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","10 M; 30 F","M + F","Not provided","Oral","Gavage/Intubation","5; 10",5,10,"mg/kg bw/day","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Adult (F0)","F",">10","Reproductive","Litter size",{"$f":"IF(Z1883<>0,VLOOKUP(Z1883,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10,">10","mg/kg bw/day",{"$f":"IF(Z1883<>0,VLOOKUP(Z1883,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",75,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","10 M; 30 F","M + F","Not provided","Oral","Gavage/Intubation","5; 10",5,10,"mg/kg bw/day","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Offspring (F1)","M + F",">10","Developmental","Fetal development",{"$f":"IF(Z1884<>0,VLOOKUP(Z1884,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Growths rate of pups was not affected.",null,"No effect",10,">10","mg/kg bw/day",{"$f":"IF(Z1884<>0,VLOOKUP(Z1884,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",75,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","10 M; 30 F","M + F","Not provided","Oral","Gavage/Intubation","5; 10",5,10,"mg/kg bw/day","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Offspring (F1)","M + F",">10","Reproductive","Pup survival index",{"$f":"IF(Z1885<>0,VLOOKUP(Z1885,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10,">10","mg/kg bw/day",{"$f":"IF(Z1885<>0,VLOOKUP(Z1885,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",75,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","10 M; 30 F","M + F","Not provided","Oral","Gavage/Intubation","5; 10",5,10,"mg/kg bw/day","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Adult (F0)","F",">10","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z1886<>0,VLOOKUP(Z1886,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Number of corpora lutea and total implants in females killed at GD 13 were not affected.",null,"No effect",10,">10","mg/kg bw/day",{"$f":"IF(Z1886<>0,VLOOKUP(Z1886,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",75,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","10 M; 30 F","M + F","Not provided","Oral","Gavage/Intubation","5; 10",5,10,"mg/kg bw/day","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Offspring (F1)","M + F",">10","Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z1887<>0,VLOOKUP(Z1887,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Number of early and late in utero deaths in females killed at GD 13 were not affected.",null,"No effect",10,">10","mg/kg bw/day",{"$f":"IF(Z1887<>0,VLOOKUP(Z1887,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",75,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","10 M; 30 F","M + F","Not provided","Oral","Gavage/Intubation","5; 10",5,10,"mg/kg bw/day","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Offspring (F1)","M + F",">10","Developmental","Litter/pup weight",{"$f":"IF(Z1888<>0,VLOOKUP(Z1888,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Group mean pup weight was not affected.",null,"No effect",10,">10","mg/kg bw/day",{"$f":"IF(Z1888<>0,VLOOKUP(Z1888,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","One-generation reproduction toxicity study",75,"Not provided","No guideline mentioned","DAR",null,1988,"Rat","Wistar","10 M; 30 F","M + F","Not provided","Oral","Gavage/Intubation","5; 10",5,10,"mg/kg bw/day","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Offspring (F1)","M + F",">10","Reproductive","Number of live births",{"$f":"IF(Z1889<>0,VLOOKUP(Z1889,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",10,">10","mg/kg bw/day",{"$f":"IF(Z1889<>0,VLOOKUP(Z1889,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Supportive only","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","In life observation","Mortality",{"$f":"IF(Z1890<>0,VLOOKUP(Z1890,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1890<>0,VLOOKUP(Z1890,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","In life observation","Clinical signs",{"$f":"IF(Z1891<>0,VLOOKUP(Z1891,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1891<>0,VLOOKUP(Z1891,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","In life observation","Body weight",{"$f":"IF(Z1892<>0,VLOOKUP(Z1892,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1892<>0,VLOOKUP(Z1892,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",7500,"In life observation","Food consumption",{"$f":"IF(Z1893<>0,VLOOKUP(Z1893,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Indication for slight decrease in males and females at 7500ppm",null,"Decrease",5000,7500,"ppm",{"$f":"IF(Z1893<>0,VLOOKUP(Z1893,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ Weight","Liver weight",{"$f":"IF(Z1894<>0,VLOOKUP(Z1894,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1894<>0,VLOOKUP(Z1894,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",2000,"Organ Weight","Kidney weight",{"$f":"IF(Z1895<>0,VLOOKUP(Z1895,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute: F 7500ppm=-8%*; F 5000ppm=-11%*; F 2000ppm=-13%*\nrelative: M 2000ppm=+12%* ; F 2000ppm=-9%* (not dose-dependent)",null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1895<>0,VLOOKUP(Z1895,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ Weight","Adrenals weight",{"$f":"IF(Z1896<>0,VLOOKUP(Z1896,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1896<>0,VLOOKUP(Z1896,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M",">7500","Organ Weight","Testis weight",{"$f":"IF(Z1897<>0,VLOOKUP(Z1897,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1897<>0,VLOOKUP(Z1897,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",2000,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1898<>0,VLOOKUP(Z1898,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Hematology: RBC in F 2000ppm=+13.6%* and M 7500ppm=-1.4%* (males within normal range of historical controls); HCT in F 2000ppm=+13.2%* and M 7500ppm=-1.4%*; All values were close to the historical controls. \nSlight change in monocytes in males and females at 2000ppm however not considered treatment-related\nClincal chemistry: Ca in M 5000ppm increase; Na in M changed ; Cl in M 7500ppm increase (none of the clinical chemistry parameters is considered treatment-related)",null,"Change",5000,7500,"ppm",{"$f":"IF(Z1898<>0,VLOOKUP(Z1898,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1899<>0,VLOOKUP(Z1899,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1899<>0,VLOOKUP(Z1899,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1900<>0,VLOOKUP(Z1900,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1900<>0,VLOOKUP(Z1900,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Liver histopathology",{"$f":"IF(Z1901<>0,VLOOKUP(Z1901,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1901<>0,VLOOKUP(Z1901,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z1902<>0,VLOOKUP(Z1902,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1902<>0,VLOOKUP(Z1902,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Lung histopathology",{"$f":"IF(Z1903<>0,VLOOKUP(Z1903,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1903<>0,VLOOKUP(Z1903,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z1904<>0,VLOOKUP(Z1904,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1904<>0,VLOOKUP(Z1904,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z1905<>0,VLOOKUP(Z1905,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1905<>0,VLOOKUP(Z1905,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Kidney histopathology",{"$f":"IF(Z1906<>0,VLOOKUP(Z1906,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Kidney and urinary bladder were examined.",null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1906<>0,VLOOKUP(Z1906,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","F",">7500","Organ histopathology","Ovary histopathology",{"$f":"IF(Z1907<>0,VLOOKUP(Z1907,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1907<>0,VLOOKUP(Z1907,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z1908<>0,VLOOKUP(Z1908,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1908<>0,VLOOKUP(Z1908,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z1909<>0,VLOOKUP(Z1909,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1909<>0,VLOOKUP(Z1909,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M",">7500","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z1910<>0,VLOOKUP(Z1910,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1910<>0,VLOOKUP(Z1910,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Cervix histopathology",{"$f":"IF(Z1911<>0,VLOOKUP(Z1911,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1911<>0,VLOOKUP(Z1911,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Spleen histopathology",{"$f":"IF(Z1912<>0,VLOOKUP(Z1912,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1912<>0,VLOOKUP(Z1912,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Stomach histopathology",{"$f":"IF(Z1913<>0,VLOOKUP(Z1913,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"The GI tract was examined (stomach and intestines).",null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1913<>0,VLOOKUP(Z1913,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M",">7500","Organ histopathology","Testis histopathology",{"$f":"IF(Z1914<>0,VLOOKUP(Z1914,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1914<>0,VLOOKUP(Z1914,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Thymus histopathology",{"$f":"IF(Z1915<>0,VLOOKUP(Z1915,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1915<>0,VLOOKUP(Z1915,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z1916<>0,VLOOKUP(Z1916,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1916<>0,VLOOKUP(Z1916,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","M + F",">7500","Organ histopathology","Trachea histopathology",{"$f":"IF(Z1917<>0,VLOOKUP(Z1917,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1917<>0,VLOOKUP(Z1917,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",76,null,"OECD 408 (1981)","DAR",null,1990,"Rat","CD",10,"M + F",98.1,"Oral","Feed","2000; 5000; 7500",2000,7500,"ppm","90-92","Days","Adult","F",">7500","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z1918<>0,VLOOKUP(Z1918,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z1918<>0,VLOOKUP(Z1918,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",77,null,"not applicable; pilot study for OECD 414","DAR",null,1979,"Rabbit","Dutch Belted",5,"F",100,"Oral","Gavage/Intubation","125; 250; 500; 1250; 2500",125,2500,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",500,"In life observation","Mortality",{"$f":"IF(Z1919<>0,VLOOKUP(Z1919,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"4/5 at 500 mg/kg bw died between GD 15 and 22; 5/5 at 1250 mg/kg bw died on GD 10 and 11; 5/5 at 2500 mg/kg bw die on GD 9 and 10",null,"Increase",125,500,"mg/kg bw/day",{"$f":"IF(Z1919<>0,VLOOKUP(Z1919,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Pilot study","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",77,null,"not applicable; pilot study for OECD 414","DAR",null,1979,"Rabbit","Dutch Belted",5,"F",100,"Oral","Gavage/Intubation","125; 250; 500; 1250; 2500",125,2500,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",">2500","In life observation","Clinical signs",{"$f":"IF(Z1920<>0,VLOOKUP(Z1920,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"The single surviving female of the 500 mg/kg bw group aborted on GD 26.",null,"No effect",2500,">2500","mg/kg bw/day",{"$f":"IF(Z1920<>0,VLOOKUP(Z1920,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Pilot study","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",77,null,"not applicable; pilot study for OECD 414","DAR",null,1979,"Rabbit","Dutch Belted",5,"F",100,"Oral","Gavage/Intubation","125; 250; 500; 1250; 2500",125,2500,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",">2500","Organ histopathology","Gall bladder histopathology",{"$f":"IF(Z1921<>0,VLOOKUP(Z1921,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Yellow foci: 1/5 at 500 mg/kg bw and 1/5 at 1250 mg/kg bw \nErosions: 1/5 at 1250 mg/kg bw",null,"No effect",2500,">2500","mg/kg bw/day",{"$f":"IF(Z1921<>0,VLOOKUP(Z1921,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Pilot study","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",77,null,"not applicable; pilot study for OECD 414","DAR",null,1979,"Rabbit","Dutch Belted",5,"F",100,"Oral","Gavage/Intubation","125; 250; 500; 1250; 2500",125,2500,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",">2500","Organ histopathology","Stomach histopathology",{"$f":"IF(Z1922<>0,VLOOKUP(Z1922,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",2500,">2500","mg/kg bw/day",{"$f":"IF(Z1922<>0,VLOOKUP(Z1922,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Pilot study","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",77,null,"not applicable; pilot study for OECD 414","DAR",null,1979,"Rabbit","Dutch Belted",5,"F",100,"Oral","Gavage/Intubation","125; 250; 500; 1250; 2500",125,2500,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",">2500","Organ histopathology","Oesophagus histopathology",{"$f":"IF(Z1923<>0,VLOOKUP(Z1923,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",2500,">2500","mg/kg bw/day",{"$f":"IF(Z1923<>0,VLOOKUP(Z1923,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Pilot study","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",77,null,"not applicable; pilot study for OECD 414","DAR",null,1979,"Rabbit","Dutch Belted",5,"F",100,"Oral","Gavage/Intubation","125; 250; 500; 1250; 2500",125,2500,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",500,"In life observation","Body weight",{"$f":"IF(Z1924<>0,VLOOKUP(Z1924,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Severe body weight loss at 500 mg/kg bw ( -9%* on GD 24 compared to GD 0) was observed.",null,"Decrease",250,500,"mg/kg bw/day",{"$f":"IF(Z1924<>0,VLOOKUP(Z1924,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Pilot study","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",77,null,"not applicable; pilot study for OECD 414","DAR",null,1979,"Rabbit","Dutch Belted",5,"F",100,"Oral","Gavage/Intubation","125; 250; 500; 1250; 2500",125,2500,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",250,"Reproductive","Post implantation loss",{"$f":"IF(Z1925<>0,VLOOKUP(Z1925,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"A slight increase in the mean number of early and late resorptions and post-implantation loss was obsereved in animals of the 250 mg/kg bw/d dose group. Higher doses cannot be evaluated due to excessive maternal toxicity.",null,"Increase",125,250,"mg/kg bw/day",{"$f":"IF(Z1925<>0,VLOOKUP(Z1925,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Pilot study","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",77,null,"not applicable; pilot study for OECD 414","DAR",null,1979,"Rabbit","Dutch Belted",5,"F",100,"Oral","Gavage/Intubation","125; 250; 500; 1250; 2500",125,2500,"mg/kg bw/day","22 (GD 6-27)","Days","Adult","F",">250","Reproductive","Number of implantations, corpora lutea",{"$f":"IF(Z1926<>0,VLOOKUP(Z1926,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No significant effect on number of implantations or corpora lutea was obsereved in animals up to 250 mg/kg bw/d. Higher doses cannot be evaluated due to excessive maternal toxicity.",null,"No effect",250,">250","mg/kg bw/day",{"$f":"IF(Z1926<>0,VLOOKUP(Z1926,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Pilot study","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",77,null,"not applicable; pilot study for OECD 414","DAR",null,1979,"Rabbit","Dutch Belted",5,"F",100,"Oral","Gavage/Intubation","125; 250; 500; 1250; 2500",125,2500,"mg/kg bw/day","22 (GD 6-27)","Days","Fetus","F",250,"Reproductive","Numbers of embryonic or foetal deaths and viable foetuses",{"$f":"IF(Z1927<>0,VLOOKUP(Z1927,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",125,250,"mg/kg bw/day",{"$f":"IF(Z1927<>0,VLOOKUP(Z1927,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Pilot study","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","In life observation","Mortality",{"$f":"IF(Z1928<>0,VLOOKUP(Z1928,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1928<>0,VLOOKUP(Z1928,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",50000,"In life observation","Clinical signs",{"$f":"IF(Z1929<>0,VLOOKUP(Z1929,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"F and M at 50000 ppm = diarrhea during first 50 days was observed (normal thereafter).",null,"Increase",25000,50000,"ppm",{"$f":"IF(Z1929<>0,VLOOKUP(Z1929,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",25000,"In life observation","Body weight",{"$f":"IF(Z1930<>0,VLOOKUP(Z1930,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Reduced weight gain in M at 25000 and 50000 ppm. Terminal body weight M 50000 ppm= -18% (in comparison to control)\nTerminal body weight F 50000 ppm= -5% (in comparison to control)",null,"Decrease",12500,25000,"ppm",{"$f":"IF(Z1930<>0,VLOOKUP(Z1930,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","In life observation","Food consumption",{"$f":"IF(Z1931<>0,VLOOKUP(Z1931,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1931<>0,VLOOKUP(Z1931,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",50000,"Organ Weight","Kidney weight",{"$f":"IF(Z1932<>0,VLOOKUP(Z1932,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Relative: M at 25000 ppm and 50000 ppm; F no treatment-related effects",null,"Increase",12500,25000,"ppm",{"$f":"IF(Z1932<>0,VLOOKUP(Z1932,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",50000,"Organ Weight","Testis weight",{"$f":"IF(Z1933<>0,VLOOKUP(Z1933,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"An increase in relative but not absolute organ weight was observed at 25000 ppm and 50000 ppm. The increase was considered secondary to decreased body weights. Histopathology was not performed within this study. ",null,"Increase",12500,25000,"ppm",{"$f":"IF(Z1933<>0,VLOOKUP(Z1933,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",50000,"Organ Weight","Thymus weight",{"$f":"IF(Z1934<>0,VLOOKUP(Z1934,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Relative: M 50000 ppm= -13%*; F no treatment-related effects",null,"Decrease",25000,50000,"ppm",{"$f":"IF(Z1934<>0,VLOOKUP(Z1934,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",50000,"Organ Weight","Liver weight",{"$f":"IF(Z1935<>0,VLOOKUP(Z1935,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Relative: M at 6250 ppm; 12500 ppm; 25000 ppm and 50000 ppm; F no treament-related effects; F no treatment-related effects",null,"Increase",3125,6250,"ppm",{"$f":"IF(Z1935<>0,VLOOKUP(Z1935,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ Weight","Heart weight",{"$f":"IF(Z1936<>0,VLOOKUP(Z1936,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No treatment-related effects",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1936<>0,VLOOKUP(Z1936,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ Weight","[Not in list]",{"$f":"IF(Z1937<>0,VLOOKUP(Z1937,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Lung",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1937<>0,VLOOKUP(Z1937,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",12500,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z1938<>0,VLOOKUP(Z1938,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Hematology: mild increase in hct and RBC in M at 12500 ppm; 25000 ppm; 50000 ppm; mild increase in hgb in M at 25000 ppm; 50000 ppm; mild increase in plts in M at 50000 ppm\nminimal but significant increase in lymphocyte and plts counts, WBC, MCH, MCV in F\nClinical chemistry: Changes in: ALP in M and F at all time points (except 90 days), total bile acids in M (days 23 and 90) and F (day 23), total protein in F at all time points; sporadic increases in urea nitrogen and albumin",null,"Change",6250,12500,"ppm",{"$f":"IF(Z1938<>0,VLOOKUP(Z1938,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",25000,"Reproductive","Sperm numbers",{"$f":"IF(Z1939<>0,VLOOKUP(Z1939,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"A decrease in sperm numbers was observed from 25000 ppm. At the same dose level a significant reduction of body weight gain was observed (terminal body weight M 50000 ppm= -18% compared to control). Histopathology of testes was not performed within this study but a decrease in testes weight was not observed. The decreased count of sperm number is not considered to be endocrine-related but rather secondary to systemic toxicity.",null,"Decrease",12500,25000,"ppm",{"$f":"IF(Z1939<>0,VLOOKUP(Z1939,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",">50000","Organ Weight","Epididymis weight",{"$f":"IF(Z1940<>0,VLOOKUP(Z1940,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1940<>0,VLOOKUP(Z1940,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",">50000","Reproductive","Sperm motility",{"$f":"IF(Z1941<>0,VLOOKUP(Z1941,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1941<>0,VLOOKUP(Z1941,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",">50000","Reproductive","Sperm morphology",{"$f":"IF(Z1942<>0,VLOOKUP(Z1942,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1942<>0,VLOOKUP(Z1942,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","F",50000,"Reproductive","Estrus cyclicity",{"$f":"IF(Z1943<>0,VLOOKUP(Z1943,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Increased estrous cycle length was observed at 50000 ppm.",null,"Increase",25000,50000,"ppm",{"$f":"IF(Z1943<>0,VLOOKUP(Z1943,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1944<>0,VLOOKUP(Z1944,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1944<>0,VLOOKUP(Z1944,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1945<>0,VLOOKUP(Z1945,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Three sections frontal cortex and basal ganglia, parietal cortex and thalamus, cerebellum and pons were examined.",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1945<>0,VLOOKUP(Z1945,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Bone histopathology",{"$f":"IF(Z1946<>0,VLOOKUP(Z1946,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1946<>0,VLOOKUP(Z1946,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Bone marrow histopathology",{"$f":"IF(Z1947<>0,VLOOKUP(Z1947,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1947<>0,VLOOKUP(Z1947,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Oesophagus histopathology",{"$f":"IF(Z1948<>0,VLOOKUP(Z1948,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1948<>0,VLOOKUP(Z1948,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Eyes histopathology",{"$f":"IF(Z1949<>0,VLOOKUP(Z1949,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1949<>0,VLOOKUP(Z1949,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",78,"92-3135","not mentioned, similar to OECD 408","DAR",null,1992,"Rat","F344/N","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",3125,"Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z1950<>0,VLOOKUP(Z1950,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Parotid and submandibular salivary glands in M and F: Cytoplasmic alterations (basophilic change and hypertrophy of acinar cells) in M and F at 3125 ppm; 6250 ppm; 12500 ppm; 25000 ppm; 50000 ppm",null,"Change",null,3125,"ppm",{"$f":"IF(Z1950<>0,VLOOKUP(Z1950,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","In life observation","Mortality",{"$f":"IF(Z1951<>0,VLOOKUP(Z1951,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1951<>0,VLOOKUP(Z1951,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",25000,"In life observation","Body weight",{"$f":"IF(Z1952<>0,VLOOKUP(Z1952,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased body weight gains in M and F at 25000 ppm and 50000 ppm",null,"Decrease",12500,25000,"ppm",{"$f":"IF(Z1952<>0,VLOOKUP(Z1952,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",6250,"Organ Weight","Liver weight",{"$f":"IF(Z1953<>0,VLOOKUP(Z1953,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Relative:M at 6250 ppm; 12500 ppm; 25000 ppm; 50000 ppm; F no treatment-related effects",null,"Increase",3125,6250,"ppm",{"$f":"IF(Z1953<>0,VLOOKUP(Z1953,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",12500,"Organ Weight","Heart weight",{"$f":"IF(Z1954<>0,VLOOKUP(Z1954,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Relative: M at 12500 ppm; 25000 ppm; 50000 ppm; F no treatment-related effects",null,"Increase",6250,12500,"ppm",{"$f":"IF(Z1954<>0,VLOOKUP(Z1954,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",25000,"Organ Weight","Testis weight",{"$f":"IF(Z1955<>0,VLOOKUP(Z1955,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"An increase in relative but not absolute organ weight was observed at 25000 ppm and 50000 ppm. The increase was considered secondary to decreased body weights. Histopathology was not performed within this study. ",null,"Increase",12500,25000,"ppm",{"$f":"IF(Z1955<>0,VLOOKUP(Z1955,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",50000,"Organ Weight","Thymus weight",{"$f":"IF(Z1956<>0,VLOOKUP(Z1956,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Relative: M at 50000 ppm; F no treatment-related effects",null,"Increase",25000,50000,"ppm",{"$f":"IF(Z1956<>0,VLOOKUP(Z1956,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",6250,"Organ Weight","Kidney weight",{"$f":"IF(Z1957<>0,VLOOKUP(Z1957,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Relative: M at 6250 ppm; 12500 ppm; 25000 ppm; 50000 ppm; F no treatment-related effects",null,"Increase",3125,6250,"ppm",{"$f":"IF(Z1957<>0,VLOOKUP(Z1957,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",6250,"Organ Weight","[Not in list]",{"$f":"IF(Z1958<>0,VLOOKUP(Z1958,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Lung relative weigt: M at 6250 ppm; 12500 ppm; 25000 ppm; 50000 ppm; F no treatment-related effects",null,"Increase",3125,6250,"ppm",{"$f":"IF(Z1958<>0,VLOOKUP(Z1958,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","In life observation","Food consumption",{"$f":"IF(Z1959<>0,VLOOKUP(Z1959,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1959<>0,VLOOKUP(Z1959,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",">50000","Reproductive","Sperm motility",{"$f":"IF(Z1960<>0,VLOOKUP(Z1960,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1960<>0,VLOOKUP(Z1960,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","F",">50000","Reproductive","Estrus cyclicity",{"$f":"IF(Z1961<>0,VLOOKUP(Z1961,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1961<>0,VLOOKUP(Z1961,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z1962<>0,VLOOKUP(Z1962,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1962<>0,VLOOKUP(Z1962,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z1963<>0,VLOOKUP(Z1963,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Three sections frontal cortex and basal ganglia, parietal cortex and thalamus, cerebellum and pons were examined.",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1963<>0,VLOOKUP(Z1963,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Bone histopathology",{"$f":"IF(Z1964<>0,VLOOKUP(Z1964,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Femur and epiphysis was examined",null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1964<>0,VLOOKUP(Z1964,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Bone marrow histopathology",{"$f":"IF(Z1965<>0,VLOOKUP(Z1965,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1965<>0,VLOOKUP(Z1965,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Oesophagus histopathology",{"$f":"IF(Z1966<>0,VLOOKUP(Z1966,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1966<>0,VLOOKUP(Z1966,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Eyes histopathology",{"$f":"IF(Z1967<>0,VLOOKUP(Z1967,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1967<>0,VLOOKUP(Z1967,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",">50000","Organ histopathology","Gall bladder histopathology",{"$f":"IF(Z1968<>0,VLOOKUP(Z1968,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1968<>0,VLOOKUP(Z1968,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M + F",6250,"Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z1969<>0,VLOOKUP(Z1969,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Parotid salivary gland: Increase of basophilia in acinar cells (Cytoplasmic alteration) in M and F at 6250 ppm; 12500 ppm; 25000 ppm; 50000 ppm",null,"Change",3125,6250,"ppm",{"$f":"IF(Z1969<>0,VLOOKUP(Z1969,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",">50000","Reproductive","Sperm morphology",{"$f":"IF(Z1970<>0,VLOOKUP(Z1970,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1970<>0,VLOOKUP(Z1970,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",79,"92-3135 (NIH publication)","not mentioned, similar to OECD 408","DAR",null,1992,"Mouse","B6C3F1","10 (+ additional 10/sex for haematologic and clinical pathology parameters)","M + F",99,"Oral","Feed","3125; 6250; 12500; 25000; 50000",3125,50000,"ppm",90,"Days","Adult","M",">50000","Reproductive","Sperm numbers",{"$f":"IF(Z1971<>0,VLOOKUP(Z1971,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",50000,">50000","ppm",{"$f":"IF(Z1971<>0,VLOOKUP(Z1971,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes"]
["Mammals","Subacute oral in rodent ",80,"Literature","None, study published in literature","Publication","Dai, P. et al., Effect of glyphosate on reproductive organs in male rat. Acta Histochemica 118 (2016) 519–526",2016,"Rat","SD",8,"M","90 (as isopropylamine salt)","Oral","Gavage/Intubation","5; 50; 500",5,500,"mg/kg bw/day",5,"Weeks","Adult","M",">500","In life observation","Food consumption",{"$f":"IF(Z1972<>0,VLOOKUP(Z1972,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Average daily feed intake was significantly decreased at 50 mg/kg bw but not at 500 mg/kg bw. It is therefore suggested that the decrease of average daily feed intake is independent of glyphosate treatment. ",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1972<>0,VLOOKUP(Z1972,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","N/A"]
["Mammals","Subacute oral in rodent ",80,"Literature","None, study published in literature","Publication","Dai, P. et al., Effect of glyphosate on reproductive organs in male rat. Acta Histochemica 118 (2016) 519–526",2016,"Rat","SD",8,"M","90 (as isopropylamine salt)","Oral","Gavage/Intubation","5; 50; 500",5,500,"mg/kg bw/day",5,"Weeks","Adult","M",50,"In life observation","Body weight",{"$f":"IF(Z1973<>0,VLOOKUP(Z1973,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Although not statistically significant there was a dose-dependent decrease in daily weight gain. Mean terminal body weight was not statistically significantly changed. However, there was a ~10% reduction of mean body weights at 50 and 500 mg/kg bw groups providing an indication that the MTD was reached or exceeded.",null,"Decrease",5,50,"mg/kg bw/day",{"$f":"IF(Z1973<>0,VLOOKUP(Z1973,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","N/A"]
["Mammals","Subacute oral in rodent ",80,"Literature","None, study published in literature","Publication","Dai, P. et al., Effect of glyphosate on reproductive organs in male rat. Acta Histochemica 118 (2016) 519–526",2016,"Rat","SD",8,"M","90 (as isopropylamine salt)","Oral","Gavage/Intubation","5; 50; 500",5,500,"mg/kg bw/day",5,"Weeks","Adult","M",500,"Organ Weight","Seminal vesicles weight",{"$f":"IF(Z1974<>0,VLOOKUP(Z1974,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"A significant decrease in absolute (but not relative) weight of the seminal vesicle gland (weighed together with coagulating gland) was observed, which may be attributed to the non statistically significant reduced final body weight.",null,"Decrease",50,500,"mg/kg bw/day",{"$f":"IF(Z1974<>0,VLOOKUP(Z1974,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","N/A"]
["Mammals","Subacute oral in rodent ",80,"Literature","None, study published in literature","Publication","Dai, P. et al., Effect of glyphosate on reproductive organs in male rat. Acta Histochemica 118 (2016) 519–526",2016,"Rat","SD",8,"M","90 (as isopropylamine salt)","Oral","Gavage/Intubation","5; 50; 500",5,500,"mg/kg bw/day",5,"Weeks","Adult","M",500,"Organ Weight","Coagulating gland weight",{"$f":"IF(Z1975<>0,VLOOKUP(Z1975,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"A significant decrease in absolute (but not relative) weight of the coagulating gland (weighed together with seminal vesicles) was observed, which may be attributed to the non statistically significant reduced final body weight.",null,"Decrease",50,500,"mg/kg bw/day",{"$f":"IF(Z1975<>0,VLOOKUP(Z1975,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","N/A"]
["Mammals","Subacute oral in rodent ",80,"Literature","None, study published in literature","Publication","Dai, P. et al., Effect of glyphosate on reproductive organs in male rat. Acta Histochemica 118 (2016) 519–526",2016,"Rat","SD",8,"M","90 (as isopropylamine salt)","Oral","Gavage/Intubation","5; 50; 500",5,500,"mg/kg bw/day",5,"Weeks","Adult","M",">500","Organ Weight","Epididymis weight",{"$f":"IF(Z1976<>0,VLOOKUP(Z1976,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1976<>0,VLOOKUP(Z1976,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","N/A"]
["Mammals","Subacute oral in rodent ",80,"Literature","None, study published in literature","Publication","Dai, P. et al., Effect of glyphosate on reproductive organs in male rat. Acta Histochemica 118 (2016) 519–526",2016,"Rat","SD",8,"M","90 (as isopropylamine salt)","Oral","Gavage/Intubation","5; 50; 500",5,500,"mg/kg bw/day",5,"Weeks","Adult","M",">500","Organ Weight","Testis weight",{"$f":"IF(Z1977<>0,VLOOKUP(Z1977,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1977<>0,VLOOKUP(Z1977,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","N/A"]
["Mammals","Subacute oral in rodent ",80,"Literature","None, study published in literature","Publication","Dai, P. et al., Effect of glyphosate on reproductive organs in male rat. Acta Histochemica 118 (2016) 519–526",2016,"Rat","SD",8,"M","90 (as isopropylamine salt)","Oral","Gavage/Intubation","5; 50; 500",5,500,"mg/kg bw/day",5,"Weeks","Adult","M",">500","Organ Weight","Prostate weight",{"$f":"IF(Z1978<>0,VLOOKUP(Z1978,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1978<>0,VLOOKUP(Z1978,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","N/A"]
["Mammals","Subacute oral in rodent ",80,"Literature","None, study published in literature","Publication","Dai, P. et al., Effect of glyphosate on reproductive organs in male rat. Acta Histochemica 118 (2016) 519–526",2016,"Rat","SD",8,"M","90 (as isopropylamine salt)","Oral","Gavage/Intubation","5; 50; 500",5,500,"mg/kg bw/day",5,"Weeks","Adult","M",500,"Reproductive","Sperm numbers",{"$f":"IF(Z1979<>0,VLOOKUP(Z1979,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Total sperm count was decreased (epididymal sperm).",null,"Decrease",50,500,"mg/kg bw/day",{"$f":"IF(Z1979<>0,VLOOKUP(Z1979,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","N/A"]
["Mammals","Subacute oral in rodent ",80,"Literature","None, study published in literature","Publication","Dai, P. et al., Effect of glyphosate on reproductive organs in male rat. Acta Histochemica 118 (2016) 519–526",2016,"Rat","SD",8,"M","90 (as isopropylamine salt)","Oral","Gavage/Intubation","5; 50; 500",5,500,"mg/kg bw/day",5,"Weeks","Adult","M",">500","Clinical chemistry/hormones","Testosterone level",{"$f":"IF(Z1980<>0,VLOOKUP(Z1980,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"Although there was a trend towards decreased serum concentrations with dose, no statistically significant changes were noted.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1980<>0,VLOOKUP(Z1980,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","N/A"]
["Mammals","Subacute oral in rodent ",80,"Literature","None, study published in literature","Publication","Dai, P. et al., Effect of glyphosate on reproductive organs in male rat. Acta Histochemica 118 (2016) 519–526",2016,"Rat","SD",8,"M","90 (as isopropylamine salt)","Oral","Gavage/Intubation","5; 50; 500",5,500,"mg/kg bw/day",5,"Weeks","Adult","M",">500","Clinical chemistry/hormones","Estradiol level",{"$f":"IF(Z1981<>0,VLOOKUP(Z1981,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"Although there was a trend towards decreased serum (not dose-dependent), no statistically significant changes were noted.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1981<>0,VLOOKUP(Z1981,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","N/A"]
["Mammals","Subacute oral in rodent ",80,"Literature","None, study published in literature","Publication","Dai, P. et al., Effect of glyphosate on reproductive organs in male rat. Acta Histochemica 118 (2016) 519–526",2016,"Rat","SD",8,"M","90 (as isopropylamine salt)","Oral","Gavage/Intubation","5; 50; 500",5,500,"mg/kg bw/day",5,"Weeks","Adult","M",">500","Clinical chemistry/hormones","Progesterone",{"$f":"IF(Z1982<>0,VLOOKUP(Z1982,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"Although there was a trend towards decreased serum concentrations (not dose-dependent), no statistically significant changes were noted.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1982<>0,VLOOKUP(Z1982,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","N/A"]
["Mammals","Subacute oral in rodent ",80,"Literature","None, study published in literature","Publication","Dai, P. et al., Effect of glyphosate on reproductive organs in male rat. Acta Histochemica 118 (2016) 519–526",2016,"Rat","SD",8,"M","90 (as isopropylamine salt)","Oral","Gavage/Intubation","5; 50; 500",5,500,"mg/kg bw/day",5,"Weeks","Adult","M",">500","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z1983<>0,VLOOKUP(Z1983,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No statistically significant changes were observed.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1983<>0,VLOOKUP(Z1983,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","N/A"]
["Mammals","Subacute oral in rodent ",80,"Literature","None, study published in literature","Publication","Dai, P. et al., Effect of glyphosate on reproductive organs in male rat. Acta Histochemica 118 (2016) 519–526",2016,"Rat","SD",8,"M","90 (as isopropylamine salt)","Oral","Gavage/Intubation","5; 50; 500",5,500,"mg/kg bw/day",5,"Weeks","Adult","M",">500","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z1984<>0,VLOOKUP(Z1984,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No statistically significant changes were observed.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1984<>0,VLOOKUP(Z1984,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","N/A"]
["Mammals","Subacute oral in rodent ",80,"Literature","None, study published in literature","Publication","Dai, P. et al., Effect of glyphosate on reproductive organs in male rat. Acta Histochemica 118 (2016) 519–526",2016,"Rat","SD",8,"M","90 (as isopropylamine salt)","Oral","Gavage/Intubation","5; 50; 500",5,500,"mg/kg bw/day",5,"Weeks","Adult","M",">500","Organ histopathology","Testis histopathology",{"$f":"IF(Z1985<>0,VLOOKUP(Z1985,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No statistically significant changes were observed. In addition, no statistically significant changes were observed in androgen receptor (AR) immunoreactivity localized in the nuclei of cells, including Sertoli cells, peritubular myoid cells and Leydig cells. Moreover, the levels of catalase (CAT, U/mg protein), superoxide dismutase (SOD, U/mg protein) and malondialdehyde (MDA, µmol/g protein) were determined in testes and no statistically significant changes were observed.",null,"No effect",500,">500","mg/kg bw/day",{"$f":"IF(Z1985<>0,VLOOKUP(Z1985,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","N/A"]
["InVitroSteroidogenesis","Other Steroidogenesis in vitro assay",81,"Literature","None, study published in literature","Publication","Forgacs, A. et al., BLTK1 murine Leydig cells: a novel steroidogenic model for evaluating the effects of reproductive and developmental toxicants. Toxicological Sciences 127(2), 391–402 (2012)",2012,"Mouse","BLTK1 murine Leydig cells",null,null,"Not provided","Uptake from the medium (in vitro)",null,300,300,300,"µM",4,"Hours",null,null,">600","Hormones measurments","Testosterone synthesis",{"$f":"IF(Z1986<>0,VLOOKUP(Z1986,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Forgacs et al. (2012) evaluated the effect of 4 h exposures of glyphosate on testosterone production in BLTK1 murine Leydig cells in the presence and absence of an inducing dose of recombinant human chorionic gonadotropin (rhCG). Glyphosate at the maximum concentration of 300 μM did not alter rhCG induced testosterone concentrations in BLTK1 murine Leydig cells. Moreover, basal testosterone levels were not altered at a maximum concentration of 600 µM.",null,"No effect",null,null,"µM",{"$f":"IF(Z1986<>0,VLOOKUP(Z1986,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","N/A"]
["InVitroSteroidogenesis","Other Steroidogenesis in vitro assay",82,"Literature","None, study published in literature","Publication","Gigante, P. et al., Glyphosate affects swine ovarian and adipose stromal cell functions. Animal reproduction science, (2018 Aug) Vol. 195, pp. 185-196. Electronic Publication Date: 24 May 2018 Journal code: 7807205. E-ISSN: 1873-2232. L-ISSN: 0378-4320.",2018,"Swine","Granulosa cells",null,null,"Not provided","Uptake from the medium (in vitro)",null,"0.2; 4; 16",0.2,16,"µM",48,"Hours",null,null,0.2,"Hormones measurments","Estradiol level (in vitro)",{"$f":"IF(Z1987<>0,VLOOKUP(Z1987,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"17-ß-estradiol (E2) secretion was statistically signiﬁcantly inhibited (p < 0.05) at all tested concentrations but without a concentration-response relationship. ",null,"Decrease",null,null,"µM",{"$f":"IF(Z1987<>0,VLOOKUP(Z1987,Interpretation!$C:$E,3,FALSE),\"\")","v":"E"},null,"Yes","N/A"]
["InVitroSteroidogenesis","Other Steroidogenesis in vitro assay",82,"Literature","None, study published in literature","Publication","Gigante, P. et al., Glyphosate affects swine ovarian and adipose stromal cell functions. Animal reproduction science, (2018 Aug) Vol. 195, pp. 185-196. Electronic Publication Date: 24 May 2018 Journal code: 7807205. E-ISSN: 1873-2232. L-ISSN: 0378-4320.",2018,"Swine","Granulosa cells",null,null,"Not provided","Uptake from the medium (in vitro)",null,"0.2; 4; 16",0.2,16,"µM",48,"Hours",null,null,0.2,"Hormones measurments","Progesterone (in vitro)",{"$f":"IF(Z1988<>0,VLOOKUP(Z1988,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Progesteron (P4) secretion was statistically significantly increased (p < 0.05) at all tested concentrations but without a concentration-response relationship. ",null,"Increase",null,null,"µM",{"$f":"IF(Z1988<>0,VLOOKUP(Z1988,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","N/A"]
["InVitroSteroidogenesis","Other Steroidogenesis in vitro assay",82,"Literature","None, study published in literature","Publication","Gigante, P. et al., Glyphosate affects swine ovarian and adipose stromal cell functions. Animal reproduction science, (2018 Aug) Vol. 195, pp. 185-196. Electronic Publication Date: 24 May 2018 Journal code: 7807205. E-ISSN: 1873-2232. L-ISSN: 0378-4320.",2018,"Swine","Granulosa cells",null,null,"Not provided","Uptake from the medium (in vitro)",null,"0.2; 4; 16",0.2,16,"µM",48,"Hours",null,null,0.2,"Proliferation","Cellular proliferation",{"$f":"IF(Z1989<>0,VLOOKUP(Z1989,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Glyphosate statistically signiﬁcantly decreased cell proliferation (p < 0.001) as evaluated by BrdU incorporation and cell viability (p < 0.05) as measured by ATP production without a concentration-response relationship. ",null,"Decrease",null,null,"µM",{"$f":"IF(Z1989<>0,VLOOKUP(Z1989,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, T, S"},null,"Yes","N/A"]
["InVitroGeneral","In vitro method (general)",83,"Literature","None, study published in literature","Publication","Gorga, A. et al., In vitro effects of glyphosate and Roundup on Sertoli cell physiology. Toxicology in vitro : an international journal published in association with BIBRA, (2020 Feb) Vol. 62, pp. 104682.  Electronic Publication Date: 15 Oct 2019 Journal code: 8712158. E-ISSN: 1879-3177. L-ISSN: 0887-2333.",2020,"Rat","Sertoli cells",null,null,"Not provided","Uptake from the medium (in vitro)",null,"10; 100",10,100,"ppm","Multiple exposure times","Hours",null,null,null,"[Not in list]","No relevant effect observed",{"$f":"IF(Z1990<>0,VLOOKUP(Z1990,Interpretation!$C:$E,2,FALSE),\"\")","v":"No relevant effect observed"},"In vitro exposure of Sertolli cells to glyphosate was reported to alter Sertoli cell junction barrier permeability and to decrease testosterone-stimulated TER. Further, a redistribution of claudin11 was observed.\nGlyphosate did not modify the expression of the androgen receptor or intercellular junction proteins (claudin11, occludin and ZO-1). Further, intracellular signalling via P-p38-MAPK and P-ERK1/2 pathways were not affected. Lactate production, glucose uptake, GLUT1, FA oxidation, or FAT/CD36 and CPT1 expression was unaffected by glyphosate. Thus, the conducted molecular and cell biological investigations indicate that glyphosate does not influence testicular function due to disturbances of nutritional function or metabolism in Sertolli cells. In vitro exposure to glyphosate at non-cytotoxic concentrations (10 - 100 ppm) altered Sertoli cell junction barrier permeability and decreased testosterone-stimulated TER. Further, redistribution of claudin11 at the zone of contact between cells was detected after glyphosate stimulation. If the effects observed on Sertolli cell junction barrier permeability may contribute to a postulated effect on male reproductive function cannot be finally assessed. In general, an evaluation of such highly specific cell biological endpoints for hazard assessment is rather difficult as they cannot be transferred easily to intact organisms. As the biological in vivo relevance of such “isolated” in vitro/ex vivo findings is not validated for intact organisms, an interpretation of the obtained results on the redistribution of one special protein and cell junction barrier permeability is difficlut and not considered sufficiently conclusive. ",null,"Change",null,null,"ppm",{"$f":"IF(Z1990<>0,VLOOKUP(Z1990,Interpretation!$C:$E,3,FALSE),\"\")","v":0},null,"Yes","N/A"]
["InVitroEstrogen","ER Binding Assay",84,"Literature","None, study published in literature","Publication","Mesnage, R. et al., Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents. Food and Chemical Toxicology 108 (2017) 30-42",2017,"Human","MCF-7, MDA-MB-231 and T47D cell lines",null,null,"≥98","Uptake from the medium (in vitro)",null,"10000 - 1000000",10000,1000000,"µg ai/L","Multiple exposure times","Hours",null,null,">2500","Proliferation","Estrogen receptor",{"$f":"IF(Z1991<>0,VLOOKUP(Z1991,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Increased cell proliferation was observed in MCF-7 and T47D cells at 10,000 µg/L to 1,000,000 µg/L (but not in hormone-independent MDA-MB-231 cells) . Glyphosate stimulated ERE-mediated transcription of the luciferase reporter gene starting at a concentration of 1,000 µg/L. The analysis of gene ontology confirms that genes having their expression altered by treatment of MCF-7 cells with glyphosate were involved in cell cycle regulation, stimulation by steroid hormones and cell death through apoptosis. ONIOM binding energy assessment implies that binding of glyphosate to the ER is weak and unstable, suggesting that glyphosate is unlikely to bind to ERα. This study has demonstrated that glyphosate activates ERα through a ligand-independent pathway only at high concentrations that are not encountered at typical exposure levels. Glyphosate was reported to induce ERTA only at high concentrations (10,000 and 20,000 μg/L or 59 and 118 μM) and induction was concluded to result from an unknown ligand-independent ER mechanism. However, this result is inconsistent with the EDSP Tier 1 ERTA assay tested up to 1000 μM glyphosate.\n",null,"No effect",null,null,"µg ai/L",{"$f":"IF(Z1991<>0,VLOOKUP(Z1991,Interpretation!$C:$E,3,FALSE),\"\")","v":"E"},null,"Yes","N/A"]
["InVitroEstrogen","Other ER in vitro assay",85,"Literature","None, study published in literature","Publication","Thongprakaisang, S. et al., Glyphosate induces human breast cancer cells growth via estrogen receptors. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, (2013 Sep) Vol. 59, pp. 129-36.  Electronic Publication Date: 10 Jun 2013 Journal code: 8207483. E-ISSN: 1873-6351. L-ISSN: 0278-6915.",2013,"Human","T47D (hormone-dependent breast cancer cells); MDA-MB231 (hormone-independent breast cancer cells)",null,null,"> 98","Uptake from the medium (in vitro)",null,"10^-6 - 1",9.9999999999999995E-7,1,"µM",24,"Hours",null,null,9.9999999999999995E-7,"Proliferation","Estrogen receptor",{"$f":"IF(Z1992<>0,VLOOKUP(Z1992,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"The endpoints explored were the cell proliferation of hormone-dependent and hormone-independent cell lines with and without an ER antagonist, ERE-transcription activity with and without an ER antagonist, and expression of ERs. Glyphosate was found to produce cell proliferation in a hormone-dependent cancer cell line but not in a hormone-independent cancer cell line in the absence of E2. In the presence of a potent ER antagonist the cell proliferation caused by glyphosate in a hormone-dependent cancer cell line was reduced. The interaction of glyphosate with the ER was confirmed by ERE activation with and without an ER antagonist. When cells were co-incubated with glyphosate and E2, glyphosate suppressed the E2-induced ERE activation suggesting that glyphosate behaves as an antagonist in the presence of an endogenous agonist. It was demonstrated that glyphosate alters the expression of both ERα and ERβ in human breast cancer cells. However, Thongprakaisang et al., (2013) reported induction of 5 to 13-fold relative to controls for ER-driven transcriptional activity in T47D cells at the levels by glyphosate ranging from 1 10E-6 to 1 10E-12 M. Induction was blocked by the addition of 10 nM of the ER antagonist ICI 182780. In addition, proliferation in T47D cells after 5 d of exposure was reported to be 40% as measured by the MTT assay as an indirect assessment of cell number. Cell number in proliferations assays is best assessed by directly measuring cell number with flow cytometry. The increase in ER-driven transcriptional activity is highly inconsistent with the EDSP results and published studies using functionally equivalent test systems. Thongprakaisang et al., (2013) reported that glyphosate has greater estrogenic effect than a maximally inducing dose of 17β-estradiol, which is a highly questionable result based on what is known about structure and activity information for glyphosate. This finding led Mesnage et al. (2017) to conclude that the results of Thongprakaisang et al., (2013) are not biologically plausible and speculate that this result reflected an estrogenic contaminant in the assay.",null,"Change",null,null,"µM",{"$f":"IF(Z1992<>0,VLOOKUP(Z1992,Interpretation!$C:$E,3,FALSE),\"\")","v":"E"},null,"Yes","N/A"]
["InVitroGeneral","In vitro method (general)",86,"Literature","None, study published in literature","Publication","Vanlaeys, A. et al., Formulants of glyphosate-based herbicides have more deleterious impact than glyphosate on TM4 Sertoli cells. Toxicology in vitro : an international journal published in association with BIBRA, (2018 Oct) Vol. 52, pp. 14-22.  Electronic Publication Date: 5 Jun 2018 Journal code: 8712158. E-ISSN: 1879-3177. L-ISSN: 0887-2333.",2018,"Mouse","TM4 (immature Sertoli cell line)",null,null,"Not provided","Uptake from the medium (in vitro)",null,"10 - 10000",10,10000,"ppm",24,"Hours",null,null,">10000","Proliferation","Cellular proliferation",{"$f":"IF(Z1993<>0,VLOOKUP(Z1993,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"In this study the effect of glyphosate on murine TM4 Sertoli cells was investigated in vitro. The endpoints were cytotoxicity, glutathione transferase activity and lipid accumulation. Glyphosate was found to have no impact on cell viability after 24 hours of exposure at concentrations ranging from 10 ppm to 10,000 ppm. Glyphosate reduced succinate dehydrogenase to some extent over the entire concentration range from 10 (approx. 85 % of control) to 10,000 ppm (approx.75 % of control) with no dose-effect relationship and was found to have no impact on glutathione transferase activity. Exposure of TM4 cells to glyphosate for 24 hours at 2,500 or 5,000 ppm induces an increase in cytoplasmic lipid droplets. These concentrations are far beyond what is physiologically feasible in vivo. ",null,"No effect",null,null,"ppm",{"$f":"IF(Z1993<>0,VLOOKUP(Z1993,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, T, S"},"No specific ED-related parameters were addressed. This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate used is not sufficiently characterized and no positive controls were used in any of the assays conducted. ","Yes","N/A"]
["InVitroGeneral","In vitro method (general)",87,"Literature","None, study published in literature","Publication","Zhang, J.-W. et al., The toxic effects and possible mechanisms of glyphosate on mouse oocytes. Chemosphere, (2019 Dec) Vol. 237, pp. 124435.  Electronic Publication Date: 23 Jul 2019 Journal code: 0320657. E-ISSN: 1879-1298. L-ISSN: 0045-6535.",2019,"Mouse","Kunming mice oocytes",null,null,"Not provided","Uptake from the medium (in vitro)",null,"50; 100; 200; 500",50,500,"µM",14,"Hours",null,null,200,"Proliferation","[Not in list]",{"$f":"IF(Z1994<>0,VLOOKUP(Z1994,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"200 µM glyphosate treatment negatively affected development of mouse oocytes as indicated by reduced rates of germinal vesicle breakdown (GVBD) and first polar body extrusion. Further, molecular analysis indicated increased reactive oxygen species and an influence of glyphosate on DNA stability and intracellular signaling pathways relevant for apoptosis. As only one concentration was applied in this study, no distinction between spontaneous or treatment-related causes is possible and hence, biological significance of these observations is rather difficult to evaluate.\nIn vitro intracellular changes in Kunming mice oocytes were evaluated after being cultured in medium supplemented with 500 μM glyphosate. Findings included: decreased germinal vesicle breakdown, decreased first polar body extrusion, increased mRNA expression of anti-oxidant enzyme-related genes, abnormal spindle morphology, increased DNA double strand breaks, aggregated mitochondria, decreased mitochondrial membrane potential, increased protein expression of apoptosis factors, increased mRNA expression of apoptosis related genes and decreased autophagy-related genes. \n\nNo dose-response could be determined as only one concentration was tested, far in excess of that considered biologically relevant. Whilst some evaluations were conducted on oocytes harvested from a wider data set of 24 mice (protein expression levels of apoptosis factors by Western blot analysis), a number of the assessments were conducted on oocytes from just 12 mice (mRNA expression of oxidative stress-related, apoptosis-related and autophagy-related genes) or 6 mice (mitochondrial staining, measurement of mitochondrial membrane potential). This narrow source of oocytes limits the robustness of certain conclusions. Furthermore, there are insufficient details reported in the methods to establish whether mice were of the same age before oocyte harvesting or the purity of the glyphosate tested.  ",null,"Change",null,null,"µM",{"$f":"IF(Z1994<>0,VLOOKUP(Z1994,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"No specific ED-related parameters were addressed. This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because of the poor characterization of the glyphosate tested, no cytotoxicity testing,  the lack of a positive control and insufficient dose-response characterization at biologically relevant doses.","Yes","N/A"]
["InVitroSteroidogenesis","Other Steroidogenesis in vitro assay",88,"Literature","None, study published in literature","Publication","Perego, M.C. et al., Evidence for direct effects of glyphosate on ovarian function: glyphosate influences steroidogenesis and proliferation of bovine granulosa but not theca cells in vitro. Journal of applied toxicology : JAT, (20170600) Vol. 37, No. 6, pp. 692-698.  Electronic Publication Date: 5 Dec 2016 Journal code: 8109495. E-ISSN: 1099-1263. L-ISSN: 0260-437X.",2017,"Cow","Bovine granulosa and theca cells",null,null,"> 99.5","Uptake from the medium (in vitro)",null,"0.01; 0.3; 0.5; 1.7; 5",0.01,5,"mg/L","24 - 48","Hours",null,null,0.5,"Steroidogenesis","Cellular proliferation",{"$f":"IF(Z1995<>0,VLOOKUP(Z1995,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Statistically significant effects have been observed at 0.5 and 5 µg/mL on cell proliferation in FSH/IGF1 stimulated granulosa cells. (In the presence of FSH only, glyphosate had no effect on granulosa cell (GC) viability. In the presence of FSH and IGF1, glyphosate reduced GC proliferation without a dose-response at 0.5 and 5 μg/mL but not at lower test concentrations (0.01 and 0.3 μg/mL). Without FSH or IGF1, 1.7 μg/mL of glyphosate slightly increased GC proliferation in response to serum (≤11 %).) However, no effect on theca cell proliferation was observed.\n",null,"Change",null,null,"mg/L",{"$f":"IF(Z1995<>0,VLOOKUP(Z1995,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, T, S"},"This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate tested was not sufficiently characterized, no positive controls were used and the tests were conducted with only one or 2 test concentrations of glyphosate.","Yes","N/A"]
["InVitroSteroidogenesis","Other Steroidogenesis in vitro assay",88,"Literature","None, study published in literature","Publication","Perego, M.C. et al., Evidence for direct effects of glyphosate on ovarian function: glyphosate influences steroidogenesis and proliferation of bovine granulosa but not theca cells in vitro. Journal of applied toxicology : JAT, (20170600) Vol. 37, No. 6, pp. 692-698.  Electronic Publication Date: 5 Dec 2016 Journal code: 8109495. E-ISSN: 1099-1263. L-ISSN: 0260-437X.",2017,"Cow","Bovine granulosa and theca cells",null,null,"> 99.5","Uptake from the medium (in vitro)",null,"0.01; 0.3; 0.5; 1.7; 5",0.01,5,"mg/L","24 - 48","Hours",null,null,5,"Steroidogenesis","Estradiol level (in vitro)",{"$f":"IF(Z1996<>0,VLOOKUP(Z1996,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"In the presence of FSH only, glyphosate had no effect on estradiol production. In the presence of FSH and IGF1, estradiol production was reduced at 5 μg/mL only, but not at any other dose in granulosa cells.\n",null,"Decrease",null,null,"mg/L",{"$f":"IF(Z1996<>0,VLOOKUP(Z1996,Interpretation!$C:$E,3,FALSE),\"\")","v":"E"},"This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate tested was not sufficiently characterized, no positive controls were used and the tests were conducted with only one or 2 test concentrations of glyphosate.","Yes","N/A"]
["InVitroSteroidogenesis","Other Steroidogenesis in vitro assay",88,"Literature","None, study published in literature","Publication","Perego, M.C. et al., Evidence for direct effects of glyphosate on ovarian function: glyphosate influences steroidogenesis and proliferation of bovine granulosa but not theca cells in vitro. Journal of applied toxicology : JAT, (20170600) Vol. 37, No. 6, pp. 692-698.  Electronic Publication Date: 5 Dec 2016 Journal code: 8109495. E-ISSN: 1099-1263. L-ISSN: 0260-437X.",2017,"Cow","Bovine granulosa and theca cells",null,null,"> 99.5","Uptake from the medium (in vitro)",null,"0.01; 0.3; 0.5; 1.7; 5",0.01,5,"mg/L","24 - 48","Hours",null,null,">5","Steroidogenesis","Progesterone (in vitro)",{"$f":"IF(Z1997<>0,VLOOKUP(Z1997,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Progesterone production was neither affected in granulosa nor in theca cells.",null,"No effect",null,null,"mg/L",{"$f":"IF(Z1997<>0,VLOOKUP(Z1997,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate tested was not sufficiently characterized, no positive controls were used and the tests were conducted with only one or 2 test concentrations of glyphosate.","Yes","N/A"]
["InVitroSteroidogenesis","Other Steroidogenesis in vitro assay",88,"Literature","None, study published in literature","Publication","Perego, M.C. et al., Evidence for direct effects of glyphosate on ovarian function: glyphosate influences steroidogenesis and proliferation of bovine granulosa but not theca cells in vitro. Journal of applied toxicology : JAT, (20170600) Vol. 37, No. 6, pp. 692-698.  Electronic Publication Date: 5 Dec 2016 Journal code: 8109495. E-ISSN: 1099-1263. L-ISSN: 0260-437X.",2017,"Cow","Bovine granulosa and theca cells",null,null,"> 99.5","Uptake from the medium (in vitro)",null,"0.01; 0.3; 0.5; 1.7; 5",0.01,5,"mg/L","24 - 48","Hours",null,null,">5","Steroidogenesis","CYP19",{"$f":"IF(Z1998<>0,VLOOKUP(Z1998,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"The combined IGF1 plus FSH treatment increased (P<0.05) CYP19A1 and CYP11A1 mRNA abundance by threefold and twofold, respectively, above untreated control GC. Glyphosate (5μg/mL) had no significant effect on CYP19A1 or CYP11A1 mRNA in GC co-treated with FSH and IGF1.",null,"No effect",null,null,"mg/L",{"$f":"IF(Z1998<>0,VLOOKUP(Z1998,Interpretation!$C:$E,3,FALSE),\"\")","v":"S"},"This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate tested was not sufficiently characterized, no positive controls were used and the tests were conducted with only one or 2 test concentrations of glyphosate.","Yes","N/A"]
["InVitroSteroidogenesis","Other Steroidogenesis in vitro assay",88,"Literature","None, study published in literature","Publication","Perego, M.C. et al., Evidence for direct effects of glyphosate on ovarian function: glyphosate influences steroidogenesis and proliferation of bovine granulosa but not theca cells in vitro. Journal of applied toxicology : JAT, (20170600) Vol. 37, No. 6, pp. 692-698.  Electronic Publication Date: 5 Dec 2016 Journal code: 8109495. E-ISSN: 1099-1263. L-ISSN: 0260-437X.",2017,"Cow","Bovine granulosa and theca cells",null,null,"> 99.5","Uptake from the medium (in vitro)",null,"0.01; 0.3; 0.5; 1.7; 5",0.01,5,"mg/L","24 - 48","Hours",null,null,">5","Steroidogenesis","Androstenedione (in vitro)",{"$f":"IF(Z1999<>0,VLOOKUP(Z1999,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Glyphosate at 5 μg/mL had no effect on the theca cell (TC)  production of androstenedione. ",null,"No effect",null,null,"mg/L",{"$f":"IF(Z1999<>0,VLOOKUP(Z1999,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate tested was not sufficiently characterized, no positive controls were used and the tests were conducted with only one or 2 test concentrations of glyphosate.","Yes","N/A"]
["InVitroEstrogen","BG1Luc Estrogen Receptor Transactivation Assay",89,"Literature","None, study published in literature","Publication","Brennan, J.C. et al., Development of a recombinant human ovarian (BG1) cell line containing estrogen receptor alpha and beta for improved detection of estrogenic/antiestrogenic chemicals. Environ Toxicol Chem. (2016) 35:91-100\nCorrigendum, 2017",2016,"Human","Human ovarian cell line (variant of MCF 7: VM7Luc4E2 and VM7ERβc9)",null,null,"Not provided","Uptake from the medium (in vitro)",null,10,10,10,"µM",24,"Hours",null,null,">10","Receptor (trans)activation","Estrogen receptor",{"$f":"IF(Z2000<>0,VLOOKUP(Z2000,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Glyphosate did not show any estrogenic activity at a concentration of 10 μM in two cell lines or via the two human estrogen receptor (hER) subtypes, hERα and hERβ. Based on the OECD 455 guideline for the BG1 assay, relative activity for the test substance that is <20% of the response of a maximally inducing concentration of E2 is considered to be negative. Therefore, glyphosate is conlcluded to have no ERα, ERβ agonistic activities, in vitro.\nIt needs to be noted that according to the published Corrigendum, the cell lines used were a variant of human breast cancer cell line MCF7. Thus, the recombinant cell lines are VM7Luc4E2 and VM7ERβc9.",null,"No effect",null,null,"µM",{"$f":"IF(Z2000<>0,VLOOKUP(Z2000,Interpretation!$C:$E,3,FALSE),\"\")","v":"E"},null,"Yes","N/A"]
["InVitroSteroidogenesis","Aromatase Assay",90,"Literature","None, study published in literature","Publication","Defarge, M. et al., Coformulants in glyphosate-based herbicides disrupt aromatase activity in human cells below toxic levels. Int J Environ Res Public Health. 2016 Feb 26;13(3).",2016,"Human","Human placental choriocarcinoma cells (JEG3)",null,null,"Not provided (Isopropyl ammonium salt of glyphosate was tested)","Uptake from the medium (in vitro)",null,"up to 10000",null,10000,"ppm",24,"Hours",null,null,">2000","Steroidogenesis","CYP19",{"$f":"IF(Z2001<>0,VLOOKUP(Z2001,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Glyphosate did not significantly inhibit aromatase activity at non-cytotoxic concentrations (up to approximately 2000 ppm [mg/L]).",null,"No effect",null,null,"ppm",{"$f":"IF(Z2001<>0,VLOOKUP(Z2001,Interpretation!$C:$E,3,FALSE),\"\")","v":"S"},"3000 ppm (maximum concentration tested) is equivalent to a concentration of 17,741 μM which is way above the highest concentration to be tested under EPA Guideline (1000 µM).","Yes","N/A"]
["Mammals","Subacute oral in rodent ",91,"Literature","None, study published in literature","Publication","Johansson, H. et al., Exposure to a glyphosate-based herbicide formulation, but not glyphosate alone, has only minor effects on adult rat testis. Reproductive toxicology (Elmsford, N.Y.), (20181200) Vol. 82, pp. 25-31. Electronic Publication Date: 27 Sep 2018 Journal code: 8803591. E-ISSN: 1873-1708. L-ISSN: 0890-6238.",2018,"Rat","SD",10,"M","≥96","Oral","Gavage/Intubation","2.5; 25",2.5,25,"mg/kg bw/day",14,"Days","Adult","M",">25","Organ histopathology","Testis histopathology",{"$f":"IF(Z2002<>0,VLOOKUP(Z2002,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No adverse histopathology in any of the glyphosate exposed groups was observed when compared with controls. The seminiferous tubules were intact and displayed active spermatogenesis with comparable spermatogenic cycling between examined specimens (qualitative assessment). Neither were there any differences between exposed and control animals with regard to missing germ cell layers or multinucleated germ cells. The interstitial space was comparable between glyphosate treated groups and controls. Moreover, the number of apoptotic cells was comparable between control testes and all glyphosate treated groups.",null,"No effect",25,">25","mg/kg bw/day",{"$f":"IF(Z2002<>0,VLOOKUP(Z2002,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Reliable with restrictions: non-standard study design with a 14-day exposure by having two dose groups established for glyphosate and one for the formulation.","Yes","N/A"]
["Mammals","Subacute oral in rodent ",91,"Literature","None, study published in literature","Publication","Johansson, H. et al., Exposure to a glyphosate-based herbicide formulation, but not glyphosate alone, has only minor effects on adult rat testis. Reproductive toxicology (Elmsford, N.Y.), (20181200) Vol. 82, pp. 25-31. Electronic Publication Date: 27 Sep 2018 Journal code: 8803591. E-ISSN: 1873-1708. L-ISSN: 0890-6238.",2018,"Rat","SD",10,"M","≥96","Oral","Gavage/Intubation","2.5; 25",2.5,25,"mg/kg bw/day",14,"Days","Adult","M",">25","Clinical chemistry/hormones","Testosterone level",{"$f":"IF(Z2003<>0,VLOOKUP(Z2003,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"Intra-testicular testosterone level was investigated.",null,"No effect",25,">25","mg/kg bw/day",{"$f":"IF(Z2003<>0,VLOOKUP(Z2003,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Reliable with restrictions: non-standard study design with a 14-day exposure by having two dose groups  established for glyphosate and one for the formulation.","Yes","N/A"]
["Mammals","Subacute oral in rodent ",91,"Literature","None, study published in literature","Publication","Johansson, H. et al., Exposure to a glyphosate-based herbicide formulation, but not glyphosate alone, has only minor effects on adult rat testis. Reproductive toxicology (Elmsford, N.Y.), (20181200) Vol. 82, pp. 25-31. Electronic Publication Date: 27 Sep 2018 Journal code: 8803591. E-ISSN: 1873-1708. L-ISSN: 0890-6238.",2018,"Rat","SD",10,"M","≥96","Oral","Gavage/Intubation","2.5; 25",2.5,25,"mg/kg bw/day",14,"Days","Adult","M",">25","Clinical chemistry/hormones","Steroidogenesis (genes/enzyme changes)",{"$f":"IF(Z2004<>0,VLOOKUP(Z2004,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"The Leydig cell-specific steroidogenesis factors CYP11A1 and STAR were both expressed at comparative levels between the glyphosate treated animals and the controls. Also no difference in expression and distribution was noted between glyphosate treated groups and controls for the steroidogenic enzyme HSD3B1 and the germ cell-specific factor DDX4. ",null,"No effect",25,">25","mg/kg bw/day",{"$f":"IF(Z2004<>0,VLOOKUP(Z2004,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Reliable with restrictions: non-standard study design with a 14-day exposure by having two dose groups  established for glyphosate and one for the formulation.","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",92,"Literature","None, study published in literature","Publication","Panzacchi, S. et al.,The Ramazzini Institute 13-week study on glyphosate-based herbicides at human-equivalent dose in Sprague Dawley rats: study design and first in-life endpoints evaluation, Environmental Health Std Num: 1476069X, Volume: 17, Issue: 1, Pages: 52, Pub Date: 5/29/2018",2018,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0+F1)","M + F",">1.75","In life observation","Mortality",{"$f":"IF(Z2005<>0,VLOOKUP(Z2005,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"All 24 dams and 108 rats from the 6-week and 13-week cohorts survived until sacrifice.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2005<>0,VLOOKUP(Z2005,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"The results are to be interpreted together with Study ID 93 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate and AMPA in urine and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",92,"Literature","None, study published in literature","Publication","Panzacchi, S. et al.,The Ramazzini Institute 13-week study on glyphosate-based herbicides at human-equivalent dose in Sprague Dawley rats: study design and first in-life endpoints evaluation, Environmental Health Std Num: 1476069X, Volume: 17, Issue: 1, Pages: 52, Pub Date: 5/29/2018",2018,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0)","F",">1.75","In life observation","Body weight",{"$f":"IF(Z2006<>0,VLOOKUP(Z2006,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Body weight and body weight gain of the dams during gestation and lactation were not statistically different among groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2006<>0,VLOOKUP(Z2006,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"The results are to be interpreted together with Study ID 93 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate and AMPA in urine and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",92,"Literature","None, study published in literature","Publication","Panzacchi, S. et al.,The Ramazzini Institute 13-week study on glyphosate-based herbicides at human-equivalent dose in Sprague Dawley rats: study design and first in-life endpoints evaluation, Environmental Health Std Num: 1476069X, Volume: 17, Issue: 1, Pages: 52, Pub Date: 5/29/2018",2018,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Offspring (F1)","M + F",">1.75","In life observation","Body weight",{"$f":"IF(Z2007<>0,VLOOKUP(Z2007,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Post-weaning body weight of female and male offspring was homogeneous and no statistically significant differences in body weight gain were observed among groups. ",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2007<>0,VLOOKUP(Z2007,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"The results are to be interpreted together with Study ID 93 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate and AMPA in urine and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",92,"Literature","None, study published in literature","Publication","Panzacchi, S. et al.,The Ramazzini Institute 13-week study on glyphosate-based herbicides at human-equivalent dose in Sprague Dawley rats: study design and first in-life endpoints evaluation, Environmental Health Std Num: 1476069X, Volume: 17, Issue: 1, Pages: 52, Pub Date: 5/29/2018",2018,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0)","F",">1.75","In life observation","Food consumption",{"$f":"IF(Z2008<>0,VLOOKUP(Z2008,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Water and feed consumption during gestation and lactation were not different across groups (dams).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2008<>0,VLOOKUP(Z2008,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"The results are to be interpreted together with Study ID 93 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate and AMPA in urine and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",92,"Literature","None, study published in literature","Publication","Panzacchi, S. et al.,The Ramazzini Institute 13-week study on glyphosate-based herbicides at human-equivalent dose in Sprague Dawley rats: study design and first in-life endpoints evaluation, Environmental Health Std Num: 1476069X, Volume: 17, Issue: 1, Pages: 52, Pub Date: 5/29/2018",2018,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Offspring (F1)","M + F",">1.75","In life observation","Food consumption",{"$f":"IF(Z2009<>0,VLOOKUP(Z2009,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Post weaning water and feed consumption were not affected by treatment (pups).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2009<>0,VLOOKUP(Z2009,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"The results are to be interpreted together with Study ID 93 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate and AMPA in urine and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",92,"Literature","None, study published in literature","Publication","Panzacchi, S. et al.,The Ramazzini Institute 13-week study on glyphosate-based herbicides at human-equivalent dose in Sprague Dawley rats: study design and first in-life endpoints evaluation, Environmental Health Std Num: 1476069X, Volume: 17, Issue: 1, Pages: 52, Pub Date: 5/29/2018",2018,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0+F1)","M + F",">1.75","In life observation","Clinical signs",{"$f":"IF(Z2010<>0,VLOOKUP(Z2010,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"There was no clinical evidence of alterations in activity or behavior, reflexes, eyes or skin, respiratory, gastrointestinal, genito-urinary and cardiovascular systems.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2010<>0,VLOOKUP(Z2010,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"The results are to be interpreted together with Study ID 93 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate and AMPA in urine and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0)","F",">1.75","Reproductive","Gestation length",{"$f":"IF(Z2011<>0,VLOOKUP(Z2011,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Gestational length did not differ significantly between groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2011<>0,VLOOKUP(Z2011,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Offspring (F1)","M + F",">1.75","Reproductive","Litter size",{"$f":"IF(Z2012<>0,VLOOKUP(Z2012,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Mean litter size (incuding dead and alive pups determined on PND 0, 1, 4, 7, 10, 13, 16, 19, 21, 25) did not differ significantly between groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2012<>0,VLOOKUP(Z2012,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Offspring (F1)","M + F",">1.75","Reproductive","Sex ratio",{"$f":"IF(Z2013<>0,VLOOKUP(Z2013,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Sex ratio was determined on PND 1 and did not differ significantly between groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2013<>0,VLOOKUP(Z2013,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","One-generation reproduction toxicity study",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Offspring (F1)","M + F",">1.75","Abnormalities","Ano-Genital distance",{"$f":"IF(Z2014<>0,VLOOKUP(Z2014,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"AGD was measured on PND 4 (including bw determination). AGD was statistically significantly increased in males only (absolute values: 4.26 mm vs 4.02 mm in control) and the author also reports this for the AGD adjusted for body weight. However, the numbers for the AGD index are not provided. Moreover, when taking into account the provided box plots and dot plots regarding AGD and AGD index, a significant increase in AGD index is not obvious.",null,"Increase",1.75,1.75,"mg/kg bw/day",{"$f":"IF(Z2014<>0,VLOOKUP(Z2014,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Offspring (F1)","M + F",1.75,"Reproductive","Litter viability",{"$f":"IF(Z2015<>0,VLOOKUP(Z2015,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Live birth index was calculated on PND 0. The mean live birth index was comparable between groups, although the number of dams with stillbirths was higher in the glyphosate (4/8) group compared to control (2/8).",null,"No effect","<1.75",">1.75","mg/kg bw/day",{"$f":"IF(Z2015<>0,VLOOKUP(Z2015,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Offspring (F1)","M + F",">1.75","Reproductive","Pup survival index",{"$f":"IF(Z2016<>0,VLOOKUP(Z2016,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Survival index was calculated on PND 1, 4, 7, 10, 13, 16, 19, 21, 25.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2016<>0,VLOOKUP(Z2016,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Offspring (F1)","M",">1.75","Reproductive","Age at balanopreputial separation",{"$f":"IF(Z2017<>0,VLOOKUP(Z2017,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Age and body weight at PPS was not affected.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2017<>0,VLOOKUP(Z2017,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Offspring (F1)","F",">1.75","Reproductive","Age at Vaginal opening",{"$f":"IF(Z2018<>0,VLOOKUP(Z2018,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Age and body weight at VO was not affected.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2018<>0,VLOOKUP(Z2018,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Offspring (F1)","F",">1.75","Reproductive","Age at first estrus",{"$f":"IF(Z2019<>0,VLOOKUP(Z2019,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Female offspring in the control- and glyphosate-treated groups presented the FE within 6 days from the VO. (The female rats belonging to the developmental cohort (8F/group) were also monitored for the time to first estrous (FE), defined as the first day on which only cornified epithelial cells were observed on a vaginal smear, determined by vaginal cytology for 14 consecutive days, starting 3 days after vaginal opening was observed.)",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2019<>0,VLOOKUP(Z2019,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","F",">1.75","Reproductive","Estrus cyclicity",{"$f":"IF(Z2020<>0,VLOOKUP(Z2020,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Starting on approximately PND 95 and for the duration of 3 weeks, daily vaginal lavage was performed on female rats belonging to the 13-week cohort (10 F/group).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2020<>0,VLOOKUP(Z2020,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0)","F",">1.75","Organ Weight","Adrenals weight",{"$f":"IF(Z2021<>0,VLOOKUP(Z2021,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"F0: Absolute and relative weight was unaffected.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2021<>0,VLOOKUP(Z2021,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0)","F",">1.75","Organ Weight","Ovary weight",{"$f":"IF(Z2022<>0,VLOOKUP(Z2022,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"F0: Absolute and relative weight was unaffected.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2022<>0,VLOOKUP(Z2022,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0)","F",">1.75","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z2023<>0,VLOOKUP(Z2023,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"F0: Absolute and relative weight was unaffected.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2023<>0,VLOOKUP(Z2023,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0)","F",">1.75","Clinical chemistry/hormones","Testosterone level",{"$f":"IF(Z2024<>0,VLOOKUP(Z2024,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"Total testosterone levels in dams were not affected.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2024<>0,VLOOKUP(Z2024,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0)","F",">1.75","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z2025<>0,VLOOKUP(Z2025,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"F0",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2025<>0,VLOOKUP(Z2025,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M + F",">1.75","Organ histopathology","Mammary gland histopathology (male)",{"$f":"IF(Z2026<>0,VLOOKUP(Z2026,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Assessed for both F1 exposure groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2026<>0,VLOOKUP(Z2026,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0)","F",">1.75","Organ histopathology","Ovary histopathology",{"$f":"IF(Z2027<>0,VLOOKUP(Z2027,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"F0",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2027<>0,VLOOKUP(Z2027,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0)","F",">1.75","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z2028<>0,VLOOKUP(Z2028,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"F0",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2028<>0,VLOOKUP(Z2028,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0)","F",">1.75","Organ histopathology","Vagina histopathology",{"$f":"IF(Z2029<>0,VLOOKUP(Z2029,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"F0",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2029<>0,VLOOKUP(Z2029,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M + F",">1.75","Organ Weight","Adrenals weight",{"$f":"IF(Z2030<>0,VLOOKUP(Z2030,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"F1: No effect was obsereved on absolute and relative organ weight of both exposure groups (6 and 13 weeks).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2030<>0,VLOOKUP(Z2030,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M",">1.75","Organ Weight","Prostate weight",{"$f":"IF(Z2031<>0,VLOOKUP(Z2031,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect was observed on absolute and relative organ weight of both exposure groups (6 and 13 weeks; weighed together with bladder).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2031<>0,VLOOKUP(Z2031,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M",">1.75","Organ Weight","Seminal vesicles weight",{"$f":"IF(Z2032<>0,VLOOKUP(Z2032,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"}," No effect was obsereved on absolute and relative organ weight (seminal vesicles and coagulating gland) of both exposure groups (6 and 13 weeks).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2032<>0,VLOOKUP(Z2032,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M",">1.75","Organ Weight","Epididymis weight",{"$f":"IF(Z2033<>0,VLOOKUP(Z2033,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect was obsereved on absolute and relative organ weight of both exposure groups (6 and 13 weeks).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2033<>0,VLOOKUP(Z2033,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M",">1.75","Organ Weight","Testis weight",{"$f":"IF(Z2034<>0,VLOOKUP(Z2034,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect was obsereved on absolute and relative organ weight of both exposure groups (6 and 13 weeks).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2034<>0,VLOOKUP(Z2034,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","F",">1.75","Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z2035<>0,VLOOKUP(Z2035,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"F1: No effect was observed on absolute and relative organ weight (including cervix) of both exposure groups (6 and 13 weeks).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2035<>0,VLOOKUP(Z2035,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","F",">1.75","Organ Weight","Ovary weight",{"$f":"IF(Z2036<>0,VLOOKUP(Z2036,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"F1: No effect was obsereved on absolute and relative organ weight of both exposure groups (6 and 13 weeks).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2036<>0,VLOOKUP(Z2036,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0)","F",">1.75","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z2037<>0,VLOOKUP(Z2037,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"F0",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2037<>0,VLOOKUP(Z2037,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","F",">1.75","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z2038<>0,VLOOKUP(Z2038,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Assessed for both F1 exposure groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2038<>0,VLOOKUP(Z2038,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M + F",">1.75","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z2039<>0,VLOOKUP(Z2039,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Including parathyroid (assessed for both F1 exposure groups).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2039<>0,VLOOKUP(Z2039,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M + F",">1.75","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z2040<>0,VLOOKUP(Z2040,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Assessed for both F1 exposure groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2040<>0,VLOOKUP(Z2040,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M + F",">1.75","Organ histopathology","Urinary bladder histopathology",{"$f":"IF(Z2041<>0,VLOOKUP(Z2041,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Bladder histopathology and weight was examined (assessed for both F1 exposure groups).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2041<>0,VLOOKUP(Z2041,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M",">1.75","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z2042<>0,VLOOKUP(Z2042,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Assessed for both F1 exposure groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2042<>0,VLOOKUP(Z2042,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M",">1.75","Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z2043<>0,VLOOKUP(Z2043,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Seminal vesicles and coagulating gland (assessed for both F1 exposure groups).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2043<>0,VLOOKUP(Z2043,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M",">1.75","Organ histopathology","Testis histopathology",{"$f":"IF(Z2044<>0,VLOOKUP(Z2044,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Assessed for both F1 exposure groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2044<>0,VLOOKUP(Z2044,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M",">1.75","Organ histopathology","Epididymis histopathology",{"$f":"IF(Z2045<>0,VLOOKUP(Z2045,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Assessed for both F1 exposure groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2045<>0,VLOOKUP(Z2045,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","F",">1.75","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z2046<>0,VLOOKUP(Z2046,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Assessed for both F1 exposure groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2046<>0,VLOOKUP(Z2046,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","F",">1.75","Organ histopathology","Ovary histopathology",{"$f":"IF(Z2047<>0,VLOOKUP(Z2047,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Assessed for both F1 exposure groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2047<>0,VLOOKUP(Z2047,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","F",">1.75","Organ histopathology","Vagina histopathology",{"$f":"IF(Z2048<>0,VLOOKUP(Z2048,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Assessed for both F1 exposure groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2048<>0,VLOOKUP(Z2048,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M",">1.75","Reproductive","Sperm morphology",{"$f":"IF(Z2049<>0,VLOOKUP(Z2049,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Assessed for both F1 exposure groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2049<>0,VLOOKUP(Z2049,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M",">1.75","Reproductive","Sperm numbers",{"$f":"IF(Z2050<>0,VLOOKUP(Z2050,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Assessed for both F1 exposure groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2050<>0,VLOOKUP(Z2050,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M",">1.75","Reproductive","Sperm motility",{"$f":"IF(Z2051<>0,VLOOKUP(Z2051,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Sperm transit time was calculated (assessed for both F1 exposure groups).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2051<>0,VLOOKUP(Z2051,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M + F",">1.75","Clinical chemistry/hormones","Testosterone level",{"$f":"IF(Z2052<>0,VLOOKUP(Z2052,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"F1: Serum concentration of free (fT) and total testosterone (TT), 5α-dihydrotestosterone (DHT) were analysed in both cohorts (6 and 13 weeks).\nNo statistically significant differences in serum TT, fT and DHT concentrations were observed in males or females belonging to both cohorts. A non-statistically significant increase in TT was observed in females of both cohorts only and fT was decreased after 6 weeks but not 13 weeks of exposure.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2052<>0,VLOOKUP(Z2052,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M + F",">1.75","Clinical chemistry/hormones","Estradiol level",{"$f":"IF(Z2053<>0,VLOOKUP(Z2053,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"F1: 17β-estradiol (E2). No statistically relevant effect observed in males (effect in females not possible to evaluate statistically due to insufficinet sample size considering the different stages of estrous cycle).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2053<>0,VLOOKUP(Z2053,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M + F",">1.75","Clinical chemistry/hormones","Follicle Stimulating Hormone (FSH) level",{"$f":"IF(Z2054<>0,VLOOKUP(Z2054,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"Using plasma samples from 40 pups (20 females and 20 males) randomly selected from the 6-week cohort (N = 48 total). FSH and LH were also assessed in 40 pups (20 females and 20 males) randomly selected from the 13-week cohort (N = 60 total).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2054<>0,VLOOKUP(Z2054,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M + F",">1.75","Clinical chemistry/hormones","Luteinizing Hormone (LH) level",{"$f":"IF(Z2055<>0,VLOOKUP(Z2055,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"Using plasma samples from 40 pups (20 females and 20 males) randomly selected from the 6-week cohort (N = 48 total). FSH and LH were also assessed in 40 pups (20 females and 20 males) randomly selected from the 13-week cohort (N = 60 total).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2055<>0,VLOOKUP(Z2055,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M + F",1.75,"Clinical chemistry/hormones","Thyroid-stimulating hormone level (TSH)",{"$f":"IF(Z2056<>0,VLOOKUP(Z2056,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"A statistically significant increase was observed in males of the 6 weeks exposure group only. No effect was observed after 13 weeks of exposure in males or in females. (Using plasma samples from 40 pups (20 females and 20 males) randomly selected from the 6-week cohort (N = 48 total).)",null,"Increase","<1.75",1.75,"mg/kg bw/day",{"$f":"IF(Z2056<>0,VLOOKUP(Z2056,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M + F",">1.75","Clinical chemistry/hormones","Prolactin",{"$f":"IF(Z2057<>0,VLOOKUP(Z2057,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"Using plasma samples from 40 pups (20 females and 20 males) randomly selected from the 6-week cohort (N = 48 total).",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2057<>0,VLOOKUP(Z2057,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, T, S"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",93,"Literature","None, study published in literature","Publication","Manservisi F. et al., The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system, Environmental Health (2019) Std Num: 1476069X, Volume: 18, Issue: 1, Pages: 15\n",2019,"Rat","SD","8 dams; 18 pups (8 for 6 week cohort + 10 for 13 week cohort)","M + F",">99.5","Oral","Water",1.75,1.75,1.75,"mg/kg bw/day","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","M + F",">1.75","Clinical chemistry/hormones","Other hormones",{"$f":"IF(Z2058<>0,VLOOKUP(Z2058,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"Further hormones: sex hormone binding globuline (SHBG), growth hormone (GH), adrenocorticotropic hormone (ACTH), brain-derived neurotrophic factor (BDNF) levels were not affected in both F1 exposure groups.",null,"No effect",1.75,">1.75","mg/kg bw/day",{"$f":"IF(Z2058<>0,VLOOKUP(Z2058,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",94,"Literature","None, study published in literature","Publication","Pham T.H. et al., Perinatal Exposure to Glyphosate and a Glyphosate-Based Herbicide Affect Spermatogenesis in Mice. Toxicological sciences (2019) Vol. 169, No. 1, pp. 260-271. Journal code: 9805461. E-ISSN: 1096-0929. L-ISSN: 1096-0929.\n",2019,"Mouse","Swiss","At least 5 animals derived from at least 3 to 4 different litters in each group.","F","≥99.2","Oral","Water","0.5; 5; 50",0.5,50,"mg/kg bw/day","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Offspring (F1)","M",">50","In life observation","Body weight",{"$f":"IF(Z2059<>0,VLOOKUP(Z2059,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Body weight was not affected in 5 and 35 day old males at any dose. An increase in 20 day old males was observed but is not considered biologically relevant since only the low dose was affected (no information on statistical significance provided).",null,"No effect",50,">50","mg/kg bw/day",{"$f":"IF(Z2059<>0,VLOOKUP(Z2059,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the test conditions were not clearly described and the number of animals tested per dose level is too limited.   ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",94,"Literature","None, study published in literature","Publication","Pham T.H. et al., Perinatal Exposure to Glyphosate and a Glyphosate-Based Herbicide Affect Spermatogenesis in Mice. Toxicological sciences (2019) Vol. 169, No. 1, pp. 260-271. Journal code: 9805461. E-ISSN: 1096-0929. L-ISSN: 1096-0929.\n",2019,"Mouse","Swiss","At least 5 animals derived from at least 3 to 4 different litters in each group.","F","≥99.2","Oral","Water","0.5; 5; 50",0.5,50,"mg/kg bw/day","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Offspring (F1)","M",0.5,"Clinical chemistry/hormones","Testosterone level",{"$f":"IF(Z2060<>0,VLOOKUP(Z2060,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"Serum testosterone level was statistically significantly decreased in the low and high dose group in 35 day old males. However, no dose-response was observed. No significant effect was observed in 8 months old rats.",null,"Decrease","<0.5",0.5,"mg/kg bw/day",{"$f":"IF(Z2060<>0,VLOOKUP(Z2060,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the test conditions were not clearly described and the number of animals tested per dose level is too limited.   ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",94,"Literature","None, study published in literature","Publication","Pham T.H. et al., Perinatal Exposure to Glyphosate and a Glyphosate-Based Herbicide Affect Spermatogenesis in Mice. Toxicological sciences (2019) Vol. 169, No. 1, pp. 260-271. Journal code: 9805461. E-ISSN: 1096-0929. L-ISSN: 1096-0929.\n",2019,"Mouse","Swiss","At least 5 animals derived from at least 3 to 4 different litters in each group.","F","≥99.2","Oral","Water","0.5; 5; 50",0.5,50,"mg/kg bw/day","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Offspring (F1)","M",">50","Organ Weight","Epididymis weight",{"$f":"IF(Z2061<>0,VLOOKUP(Z2061,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Epididymides weights were determined in 35 day and 8 months old males and no statistically significant effect was observed.",null,"No effect",50,">50","mg/kg bw/day",{"$f":"IF(Z2061<>0,VLOOKUP(Z2061,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the test conditions were not clearly described and the number of animals tested per dose level is too limited.   ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",94,"Literature","None, study published in literature","Publication","Pham T.H. et al., Perinatal Exposure to Glyphosate and a Glyphosate-Based Herbicide Affect Spermatogenesis in Mice. Toxicological sciences (2019) Vol. 169, No. 1, pp. 260-271. Journal code: 9805461. E-ISSN: 1096-0929. L-ISSN: 1096-0929.\n",2019,"Mouse","Swiss","At least 5 animals derived from at least 3 to 4 different litters in each group.","F","≥99.2","Oral","Water","0.5; 5; 50",0.5,50,"mg/kg bw/day","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Offspring (F1)","M",0.5,"Organ Weight","Testis weight",{"$f":"IF(Z2062<>0,VLOOKUP(Z2062,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Relative testes weight was not affected in 20 day old males. A decrease in relative weight was observed in the low and mid dose group aged 35 days reaching statistical significance for the low dose only. In 8 months old rats a decrease in relative testes weight was observed for the low and the high dose group achieving statistical significance for the low dose only. Since no dose-response was observed and the absolute testes weight is not provided, the effects on testes weight are considered isolated findings. ",null,"Decrease","<0.5",0.5,"mg/kg bw/day",{"$f":"IF(Z2062<>0,VLOOKUP(Z2062,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the test conditions were not clearly described and the number of animals tested per dose level is too limited.   ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",94,"Literature","None, study published in literature","Publication","Pham T.H. et al., Perinatal Exposure to Glyphosate and a Glyphosate-Based Herbicide Affect Spermatogenesis in Mice. Toxicological sciences (2019) Vol. 169, No. 1, pp. 260-271. Journal code: 9805461. E-ISSN: 1096-0929. L-ISSN: 1096-0929.\n",2019,"Mouse","Swiss","At least 5 animals derived from at least 3 to 4 different litters in each group.","F","≥99.2","Oral","Water","0.5; 5; 50",0.5,50,"mg/kg bw/day","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Offspring (F1)","M",">50","Organ Weight","Seminal vesicles weight",{"$f":"IF(Z2063<>0,VLOOKUP(Z2063,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Seminal vesicles weights were determined in 35 day and 8 months old males and no statistically significant effect was observed.",null,"No effect",50,">50","mg/kg bw/day",{"$f":"IF(Z2063<>0,VLOOKUP(Z2063,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the test conditions were not clearly described and the number of animals tested per dose level is too limited.   ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",94,"Literature","None, study published in literature","Publication","Pham T.H. et al., Perinatal Exposure to Glyphosate and a Glyphosate-Based Herbicide Affect Spermatogenesis in Mice. Toxicological sciences (2019) Vol. 169, No. 1, pp. 260-271. Journal code: 9805461. E-ISSN: 1096-0929. L-ISSN: 1096-0929.\n",2019,"Mouse","Swiss","At least 5 animals derived from at least 3 to 4 different litters in each group.","F","≥99.2","Oral","Water","0.5; 5; 50",0.5,50,"mg/kg bw/day","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Offspring (F1)","M",">50","Organ histopathology","Testis histopathology",{"$f":"IF(Z2064<>0,VLOOKUP(Z2064,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Number of germ and Sertoli cells as well as undifferentiated spermatogonia were determined via immunostaining. No effect was observed in the number of Sertoli cells. A decrease in spermatogonia was observed in the mid dose group (no information on statistical significance, tested in 35 day old rats). Since no dose-relationship was observed, the effect is considered biologically not relevant.\nAn increase in vacuoles in the seminiferous epithelium of the testis and empty tubules were observed in glyphosate groups compared with control. However, this was only observed in 20 day old animals and not in animals aged 35 days. Therefore, this is considered a reversible finding and not adverse.",null,"No effect",50,">50","mg/kg bw/day",{"$f":"IF(Z2064<>0,VLOOKUP(Z2064,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the test conditions were not clearly described and the number of animals tested per dose level is too limited.   ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",94,"Literature","None, study published in literature","Publication","Pham T.H. et al., Perinatal Exposure to Glyphosate and a Glyphosate-Based Herbicide Affect Spermatogenesis in Mice. Toxicological sciences (2019) Vol. 169, No. 1, pp. 260-271. Journal code: 9805461. E-ISSN: 1096-0929. L-ISSN: 1096-0929.\n",2019,"Mouse","Swiss","At least 5 animals derived from at least 3 to 4 different litters in each group.","F","≥99.2","Oral","Water","0.5; 5; 50",0.5,50,"mg/kg bw/day","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Offspring (F1)","M",">50","Reproductive","Sperm numbers",{"$f":"IF(Z2065<>0,VLOOKUP(Z2065,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Spermatozoa number was not statistically significantly affected.",null,"No effect",50,">50","mg/kg bw/day",{"$f":"IF(Z2065<>0,VLOOKUP(Z2065,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the test conditions were not clearly described and the number of animals tested per dose level is too limited.   ","Yes","N/A"]
["Mammals","Subchronic oral toxicity in rodents",94,"Literature","None, study published in literature","Publication","Pham T.H. et al., Perinatal Exposure to Glyphosate and a Glyphosate-Based Herbicide Affect Spermatogenesis in Mice. Toxicological sciences (2019) Vol. 169, No. 1, pp. 260-271. Journal code: 9805461. E-ISSN: 1096-0929. L-ISSN: 1096-0929.\n",2019,"Mouse","Swiss","At least 5 animals derived from at least 3 to 4 different litters in each group.","F","≥99.2","Oral","Water","0.5; 5; 50",0.5,50,"mg/kg bw/day","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Offspring (F1)","M",">50","Clinical chemistry/hormones","Steroidogenesis (genes/enzyme changes)",{"$f":"IF(Z2066<>0,VLOOKUP(Z2066,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"Aromatase and Cyp11A1 mRNA levels were not affected.",null,"No effect",50,">50","mg/kg bw/day",{"$f":"IF(Z2066<>0,VLOOKUP(Z2066,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the test conditions were not clearly described and the number of animals tested per dose level is too limited.   ","Yes","N/A"]
["Mammals","Subacute oral in rodent ",95,"Literature","None, study published in literature","Publication","Ren X. et al., Effects of chronic glyphosate exposure to pregnant mice on hepatic lipid metabolism in offspring. Environmental pollution (2019) Vol. 254, No. Pt A, pp. 112906.  Electronic Publication Date: 20 Jul 2019 Journal code: 8804476. E-ISSN: 1873-6424. L-ISSN: 0269-7491.\n",2019,"Mouse","ICR","10 dams (5 sacrificed on GD 19); 2 offsprings/sex per mother per timepoint","F","Not provided","Oral","Water",5000,5000,5000,"mg/L water","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Offspring (F1)","M + F",">5000","Developmental","Litter/pup weight",{"$f":"IF(Z2067<>0,VLOOKUP(Z2067,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Group mean body weight of pups by sex showed no statistical differences from control. There was no effect on average birth weight of pups, the slight difference observed in the glyphosate-treated group should be attributed to the slightly larger mean litter size observed (14.4 pups compared to 10.8 in the control group).",null,"No effect",5000,">5000","mg/L water",{"$f":"IF(Z2067<>0,VLOOKUP(Z2067,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Given the small group size, the large inter animal variability observed, the lack of consistency between the same parameter across the sexes, timepoints or sampling matrices, and the deficiencies listed above, it not possible to clearly attribute any of the observed differences to glyphosate exposure. Therefore, the current study provides no evidence that glyphosate exposure causes lipid metabolism disruption in offspring following prenatal (in utero) exposure.  \nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate used is not sufficiently characterized, only one dose level was tested, there was large inter animal variability observed and too few animals per dose level were analysed. Moreover, the dose is not provided in mg/kg bw/d.","Yes","N/A"]
["Mammals","Subacute oral in rodent ",95,"Literature","None, study published in literature","Publication","Ren X. et al., Effects of chronic glyphosate exposure to pregnant mice on hepatic lipid metabolism in offspring. Environmental pollution (2019) Vol. 254, No. Pt A, pp. 112906.  Electronic Publication Date: 20 Jul 2019 Journal code: 8804476. E-ISSN: 1873-6424. L-ISSN: 0269-7491.\n",2019,"Mouse","ICR","10 dams (5 sacrificed on GD 19); 2 offsprings/sex per mother per timepoint","F","Not provided","Oral","Water",5000,5000,5000,"mg/L water","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Adult","F",5000,"In life observation","Food consumption",{"$f":"IF(Z2068<>0,VLOOKUP(Z2068,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Water consumption of dams was statistically significantly reduced. Feed intake was reduced (not statistically significant).",null,"Decrease","<5000",5000,"mg/L water",{"$f":"IF(Z2068<>0,VLOOKUP(Z2068,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Given the small group size, the large inter animal variability observed, the lack of consistency between the same parameter across the sexes, timepoints or sampling matrices, and the deficiencies listed above, it not possible to clearly attribute any of the observed differences to glyphosate exposure. Therefore, the current study provides no evidence that glyphosate exposure causes lipid metabolism disruption in offspring following prenatal (in utero) exposure.  \nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate used is not sufficiently characterized, only one dose level was tested, there was large inter animal variability observed and too few animals per dose level were analysed. Moreover, the dose is not provided in mg/kg bw/d.","Yes","N/A"]
["Mammals","Subacute oral in rodent ",95,"Literature","None, study published in literature","Publication","Ren X. et al., Effects of chronic glyphosate exposure to pregnant mice on hepatic lipid metabolism in offspring. Environmental pollution (2019) Vol. 254, No. Pt A, pp. 112906.  Electronic Publication Date: 20 Jul 2019 Journal code: 8804476. E-ISSN: 1873-6424. L-ISSN: 0269-7491.\n",2019,"Mouse","ICR","10 dams (5 sacrificed on GD 19); 2 offsprings/sex per mother per timepoint","F","Not provided","Oral","Water",5000,5000,5000,"mg/L water","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Adult","F",">5000","In life observation","Body weight",{"$f":"IF(Z2069<>0,VLOOKUP(Z2069,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Body weight gain of pregnant mice was not statistically significantly affected.",null,"No effect",5000,">5000","mg/L water",{"$f":"IF(Z2069<>0,VLOOKUP(Z2069,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Given the small group size, the large inter animal variability observed, the lack of consistency between the same parameter across the sexes, timepoints or sampling matrices, and the deficiencies listed above, it not possible to clearly attribute any of the observed differences to glyphosate exposure. Therefore, the current study provides no evidence that glyphosate exposure causes lipid metabolism disruption in offspring following prenatal (in utero) exposure.  \nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate used is not sufficiently characterized, only one dose level was tested, there was large inter animal variability observed and too few animals per dose level were analysed. Moreover, the dose is not provided in mg/kg bw/d."]
["Mammals","Subacute oral in rodent ",95,"Literature","None, study published in literature","Publication","Ren X. et al., Effects of chronic glyphosate exposure to pregnant mice on hepatic lipid metabolism in offspring. Environmental pollution (2019) Vol. 254, No. Pt A, pp. 112906.  Electronic Publication Date: 20 Jul 2019 Journal code: 8804476. E-ISSN: 1873-6424. L-ISSN: 0269-7491.\n",2019,"Mouse","ICR","10 dams (5 sacrificed on GD 19); 2 offsprings/sex per mother per timepoint","F","Not provided","Oral","Water",5000,5000,5000,"mg/L water","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Adult","F",">5000","Reproductive","Litter size",{"$f":"IF(Z2070<>0,VLOOKUP(Z2070,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Number of fetuses was not statistically significantly affected.",null,"No effect"]
["Mammals","Subacute oral in rodent ",95,"Literature","None, study published in literature","Publication","Ren X. et al., Effects of chronic glyphosate exposure to pregnant mice on hepatic lipid metabolism in offspring. Environmental pollution (2019) Vol. 254, No. Pt A, pp. 112906.  Electronic Publication Date: 20 Jul 2019 Journal code: 8804476. E-ISSN: 1873-6424. L-ISSN: 0269-7491.\n",2019,"Mouse","ICR","10 dams (5 sacrificed on GD 19); 2 offsprings/sex per mother per timepoint","F","Not provided","Oral","Water",5000,5000,5000,"mg/L water","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Offspring (F1)","M + F",5000,"Organ histopathology","Liver histopathology",{"$f":"IF(Z2071<>0,VLOOKUP(Z2071,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Hepatic steatosis with excessive lipid droplet formation was observed.",null,"Change","<5000",5000,"mg/L water",{"$f":"IF(Z2071<>0,VLOOKUP(Z2071,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Given the small group size, the large inter animal variability observed, the lack of consistency between the same parameter across the sexes, timepoints or sampling matrices, and the deficiencies listed above, it not possible to clearly attribute any of the observed differences to glyphosate exposure. Therefore, the current study provides no evidence that glyphosate exposure causes lipid metabolism disruption in offspring following prenatal (in utero) exposure.  \nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate used is not sufficiently characterized, only one dose level was tested, there was large inter animal variability observed and too few animals per dose level were analysed. Moreover, the dose is not provided in mg/kg bw/d.","Yes","N/A"]
["Mammals","Subacute oral in rodent ",95,"Literature","None, study published in literature","Publication","Ren X. et al., Effects of chronic glyphosate exposure to pregnant mice on hepatic lipid metabolism in offspring. Environmental pollution (2019) Vol. 254, No. Pt A, pp. 112906.  Electronic Publication Date: 20 Jul 2019 Journal code: 8804476. E-ISSN: 1873-6424. L-ISSN: 0269-7491.\n",2019,"Mouse","ICR","10 dams (5 sacrificed on GD 19); 2 offsprings/sex per mother per timepoint","F","Not provided","Oral","Water",5000,5000,5000,"mg/L water","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Offspring (F1)","M + F",5000,"Clinical chemistry/hormones","PPAR nuclear receptor (in vivo)",{"$f":"IF(Z2072<>0,VLOOKUP(Z2072,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"There were significant differences in the expression levels of the genes SREBP1C, SREBP2, Fasn, Hmgcr, Hmgcs and PPARa.\nThe relative expression levels of the genes SREBP1C, SREBP2, Fasn, Acc, Scd, Hmgcr, Hmgcs1 and Hmgcs2 showed a significant increase in GD19 fetuses and PND7 and PND21 offspring. These genes are closely related\nto hepatic lipid production, so their elevation contributes to increased fat storage. However, this kind of increase does not match well to the trend in serum lipid content alteration. The levels of PPARa in PND7 males and PND21 females increased remarkably, which is likely due to the growing demand for lipid catabolism caused by the increased lipid content.\n(The expression levels of the genes SREBP1C (Sterol Regulatory Element Binding Protein 1C), SREBP2 (Sterol Regulatory Element Binding Protein 2), Fasn (Fatty acid synthase, which catalyzes fatty acid synthesis), Scd (Stearoyl-CoA Desaturase 1), Acc (Acetyl-CoACarboxylase), Hmgcr (3-hydroxy-3-methyl-glutaryl-CoA reductase), Hmgcs1 (3-hydroxy-3-methylglutaryl-CoA synthase 1), Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthase 2) and PPARa (Peroxisome proliferator-activated receptor alpha) were determined. The relative expression levels of the above genes were normalized to b-actin expression.)",null,"Change","<5000",5000,"mg/L water",{"$f":"IF(Z2072<>0,VLOOKUP(Z2072,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, T, S"},"Given the small group size, the large inter animal variability observed, the lack of consistency between the same parameter across the sexes, timepoints or sampling matrices, and the deficiencies listed above, it not possible to clearly attribute any of the observed differences to glyphosate exposure. Therefore, the current study provides no evidence that glyphosate exposure causes lipid metabolism disruption in offspring following prenatal (in utero) exposure.  \nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate used is not sufficiently characterized, only one dose level was tested, there was large inter animal variability observed and too few animals per dose level were analysed. Moreover, the dose is not provided in mg/kg bw/d.","Yes","N/A"]
["Mammals","Subacute oral in rodent ",95,"Literature","None, study published in literature","Publication","Ren X. et al., Effects of chronic glyphosate exposure to pregnant mice on hepatic lipid metabolism in offspring. Environmental pollution (2019) Vol. 254, No. Pt A, pp. 112906.  Electronic Publication Date: 20 Jul 2019 Journal code: 8804476. E-ISSN: 1873-6424. L-ISSN: 0269-7491.\n",2019,"Mouse","ICR","10 dams (5 sacrificed on GD 19); 2 offsprings/sex per mother per timepoint","F","Not provided","Oral","Water",5000,5000,5000,"mg/L water","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Offspring (F1)","M + F",5000,"Clinical chemistry/hormones","HDL/LDL ratio (considered T-mediated only in combination with other thyroid endpoints)",{"$f":"IF(Z2073<>0,VLOOKUP(Z2073,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"The concentrations of lipids such as triglycerides (TGs), total cholesterol (T-CHO), and low-density lipoprotein cholesterols (LDL-C) increased to a significant extent in both the serum and livers. \n(The following serum biochemical indexes were determined: aspartate transaminase (AST), alanine transaminase (ALT), TG, T-CHO, low- and high-density lipoprotein cholesterol (LDL-C and HDL-C). Additionally,  TG, T-CHO, LDL-C and HDL-C content was measured in liver homogenate.)",null,"Increase","<5000",5000,"mg/L water",{"$f":"IF(Z2073<>0,VLOOKUP(Z2073,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Given the small group size, the large inter animal variability observed, the lack of consistency between the same parameter across the sexes, timepoints or sampling matrices, and the deficiencies listed above, it not possible to clearly attribute any of the observed differences to glyphosate exposure. Therefore, the current study provides no evidence that glyphosate exposure causes lipid metabolism disruption in offspring following prenatal (in utero) exposure.  \nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate used is not sufficiently characterized, only one dose level was tested, there was large inter animal variability observed and too few animals per dose level were analysed. Moreover, the dose is not provided in mg/kg bw/d.","Yes","N/A"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","In life observation","Mortality",{"$f":"IF(Z2074<>0,VLOOKUP(Z2074,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2074<>0,VLOOKUP(Z2074,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","In life observation","Clinical signs",{"$f":"IF(Z2075<>0,VLOOKUP(Z2075,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2075<>0,VLOOKUP(Z2075,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","In life observation","Body weight",{"$f":"IF(Z2076<>0,VLOOKUP(Z2076,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2076<>0,VLOOKUP(Z2076,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","In life observation","Food consumption",{"$f":"IF(Z2077<>0,VLOOKUP(Z2077,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2077<>0,VLOOKUP(Z2077,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ Weight","Liver weight",{"$f":"IF(Z2078<>0,VLOOKUP(Z2078,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2078<>0,VLOOKUP(Z2078,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ Weight","Kidney weight",{"$f":"IF(Z2079<>0,VLOOKUP(Z2079,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2079<>0,VLOOKUP(Z2079,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ Weight","Adrenals weight",{"$f":"IF(Z2080<>0,VLOOKUP(Z2080,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2080<>0,VLOOKUP(Z2080,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ Weight","Testis weight",{"$f":"IF(Z2081<>0,VLOOKUP(Z2081,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2081<>0,VLOOKUP(Z2081,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","In life observation","Clinical chemistry and haematology",{"$f":"IF(Z2082<>0,VLOOKUP(Z2082,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2082<>0,VLOOKUP(Z2082,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Adrenals histopathology",{"$f":"IF(Z2083<>0,VLOOKUP(Z2083,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2083<>0,VLOOKUP(Z2083,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Brain histopathology examination",{"$f":"IF(Z2084<>0,VLOOKUP(Z2084,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2084<>0,VLOOKUP(Z2084,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Liver histopathology",{"$f":"IF(Z2085<>0,VLOOKUP(Z2085,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2085<>0,VLOOKUP(Z2085,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Salivary glands histopathology",{"$f":"IF(Z2086<>0,VLOOKUP(Z2086,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2086<>0,VLOOKUP(Z2086,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Lung histopathology",{"$f":"IF(Z2087<>0,VLOOKUP(Z2087,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2087<>0,VLOOKUP(Z2087,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Lymph nodes histopathology",{"$f":"IF(Z2088<>0,VLOOKUP(Z2088,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2088<>0,VLOOKUP(Z2088,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Mammary gland histopathology (female)",{"$f":"IF(Z2089<>0,VLOOKUP(Z2089,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2089<>0,VLOOKUP(Z2089,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Kidney histopathology",{"$f":"IF(Z2090<>0,VLOOKUP(Z2090,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2090<>0,VLOOKUP(Z2090,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Ovary histopathology",{"$f":"IF(Z2091<>0,VLOOKUP(Z2091,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2091<>0,VLOOKUP(Z2091,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Pancreas histopathology",{"$f":"IF(Z2092<>0,VLOOKUP(Z2092,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2092<>0,VLOOKUP(Z2092,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Pituitary histopathology",{"$f":"IF(Z2093<>0,VLOOKUP(Z2093,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2093<>0,VLOOKUP(Z2093,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z2094<>0,VLOOKUP(Z2094,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2094<>0,VLOOKUP(Z2094,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Cervix histopathology",{"$f":"IF(Z2095<>0,VLOOKUP(Z2095,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2095<>0,VLOOKUP(Z2095,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Spleen histopathology",{"$f":"IF(Z2096<>0,VLOOKUP(Z2096,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2096<>0,VLOOKUP(Z2096,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Stomach histopathology",{"$f":"IF(Z2097<>0,VLOOKUP(Z2097,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2097<>0,VLOOKUP(Z2097,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Testis histopathology",{"$f":"IF(Z2098<>0,VLOOKUP(Z2098,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2098<>0,VLOOKUP(Z2098,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Thymus histopathology",{"$f":"IF(Z2099<>0,VLOOKUP(Z2099,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2099<>0,VLOOKUP(Z2099,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Thyroid histopathology",{"$f":"IF(Z2100<>0,VLOOKUP(Z2100,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2100<>0,VLOOKUP(Z2100,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Trachea histopathology",{"$f":"IF(Z2101<>0,VLOOKUP(Z2101,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2101<>0,VLOOKUP(Z2101,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",96,null,"OECD 408 (1981)","DAR",null,1989,"Rat","CD",10,"M + F",97.1,"Oral","Feed","2000; 3000; 5000; 7500",2000,7500,"ppm",90,"Days","Adult","M + F",">7500","Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z2102<>0,VLOOKUP(Z2102,[4]Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},null,null,"No effect",7500,">7500","ppm",{"$f":"IF(Z2102<>0,VLOOKUP(Z2102,[4]Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"100, 150, 250 or 375 mg/kg bw/day for males and females","Yes","Yes"]

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[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"In vitro mechanistic","In vitro mechanistic","In vitro mechanistic","In vitro mechanistic","In vitro mechanistic","In vitro mechanistic","In vitro mechanistic","In vitro mechanistic","In vitro mechanistic","In vivo mechanistic","In vivo mechanistic","In vivo mechanistic","In vivo mechanistic","In vivo mechanistic","In vivo mechanistic","In vivo mechanistic","In vivo mechanistic","In vivo mechanistic","In vivo mechanistic","In vivo mechanistic","In vivo mechanistic","In vivo mechanistic","In vivo mechanistic","In vivo mechanistic","In vivo mechanistic","In vivo mechanistic","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","EATS-mediated","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Sensitive to, but not diagnostic of, EATS","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Target organ toxicity","Systemic toxicity","Systemic toxicity","Systemic toxicity","Systemic toxicity","Systemic toxicity","[Not in list]","No relevant effect observed"]
["Study ID Matrix","Source","Year","Type of toxicity","Study Principle","Species","Doses tested","Dose unit","Route of administration","Exposure","Exposure unit","Generation/Life stage","Additional remarks","Relevance","Reliability","Androgen receptor","Androstenedione (in vitro)","Cellular proliferation","CYP19","Estradiol level (in vitro)","Estrogen receptor","Progesterone (in vitro)","Steroidogenesis (genes/enzyme changes) (in vitro)","Testosterone synthesis","Cowpers glands weight (Hershberger)","Estradiol level","Follicle Stimulating Hormone (FSH) level","Glans penis weight  (Hershberger)","LABC weight (Hershberger)","Luteinizing Hormone (LH) level","Other hormones","PPAR nuclear receptor (in vivo)","Progesterone","Prolactin","Prostate weight (Hershberger)","Seminal vesicles weight (Hershberger)","Steroidogenesis (genes/enzyme changes)","T3 and T4 level","Testosterone level","Thyroid-stimulating hormone level (TSH)","Uterus weight (UT assay)","Accessory sex organs histopathology","Age at balanopreputial separation","Age at first estrus","Age at Vaginal opening","Ano-Genital distance","Cervix histopathology","Coagulating gland histopathology","Coagulating gland weight","Epididymis histopathology","Epididymis weight","Estrus cyclicity","Genital abnormalities","HDL/LDL ratio (considered T-mediated only in combination with other thyroid endpoints)","LABC weight","Mammary gland histopathology (female)","Mammary gland histopathology (male)","Ovary histopathology","Ovary weight","Prostate histopathology (with seminal vesicles and coagulating glands)","Prostate weight","Seminal vesicles histopathology","Seminal vesicles weight","Sperm morphology","Sperm motility","Sperm numbers","Testis histopathology","Testis weight","Thyroid histopathology","Thyroid weight","Uterus histopathology (with cervix)","Uterus weight (with cervix)","Vagina histopathology","Vaginal smears","Adrenals histopathology","Adrenals weight","Brain histopathology examination","Brain weight","Dystocia","Fertility (mammals)","Fetal development","Functional observation battery","Gestation length","Litter size","Litter viability","Litter/pup weight","Number of implantations, corpora lutea","Number of live births","Number of ovarian follicles","Numbers of embryonic or foetal deaths and viable foetuses","Pituitary histopathology","Pituitary weight","Post implantation loss","Pre implantation loss","Presence of anomalies (external, visceral, skeletal","Pup development","Pup survival index","Reproduction","Sex ratio","Time to mating","Aorta histopathology","Bone histopathology","Bone marrow histopathology","Eyes histopathology","Gall bladder histopathology","Heart histopathology","Heart weight","Kidney histopathology","Kidney weight","Liver histopathology","Liver weight","Lung histopathology","Lymph nodes histopathology","Oesophagus histopathology","Pancreas histopathology","Peripheral nerve histopathology","Salivary glands histopathology","Skeletal muscle histopathology","Skin histopathology","Small and large intestines histopathology","Spinal cord histopathology","Spleen histopathology","Spleen weight","Stomach histopathology","Thymus histopathology","Thymus weight","Trachea histopathology","Urinary bladder histopathology","Body weight","Clinical chemistry and haematology","Clinical signs","Food consumption","Mortality","[Not in list]","No relevant effect observed"]
[5,"DAR",2007,"Mammals","Repeated dose 90-day oral toxicity study in non-rodents","Dog","30; 300; 1000","mg/kg bw/day","Oral",90,"Days","Adult","Animals of the high dose group were treated for 11 weeks only due to clinical signs","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ",null,null,"No effect >1000 ","No effect >1000 ",null,null,null,null,"No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 ","Change 1000 (Prostate atrophy was observed in 2/3 animals at 1000 mg/kg bw/day. )","Decrease 1000 (Absolute and relative organ weights were decreased at 1000 mg/kg bw/day (-68 and -56%; statistical significance only for absolute weight).)",null,null,null,null,null,"No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 ","Change 1000 (Decreased uterus size at macroscopical examination at 1000 mg/kg bw/day, uterine atrophy in 2/3 females at 1000 mg/kg bw/day, treatment-related)","No effect >1000 ",null,null,"No effect >1000 ","Increase 300 (Absolute and relative organ weights were increased in males at  300 mg/kg bw/day (+18 and +25%) and 1000 mg/kg bw/day (+21 and +70%), statistical significance only for rel. weight at 1000 mg/kg bw, no histopathological findings, toxicological significance doubtful)",null,"No effect >1000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ","No effect >1000 ",null,null,null,null,null,null,null,null,null,"Change 1000 (Sternum: increased number of adipocytes in 2/3 males and 3/3 females at 1000 mg/kg bw/day, treatment-related)",null,null,null,null,null,"No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 ",null,null,null,null,null,null,null,null,null,null,null,"No effect 30 (Absolute and relative organ weights were decreased in males at 30 mg/kg bw/day (-16 and -7%), at 300 mg/kg bw/day (-25 and -19%) and at 1000 mg/kg bw/day (-35 and -10%), findings not statistically significant, no histopathological findings and no effects in females, thus toxicological significance doubtful)",null,null,null,null,null,"Decrease 1000 (Reduced mean body weight (-28%) and lower weight gain in males (+4% vs +31% in controls) and body weight loss in females (-7% vs. +14% in controls) at 1000 mg/kg bw/day (males: study week 4-11, females: study week 1-11), treatment-related)","Change 1000 (Haematology: no treatment-related findings (ocassional changes in Hb, Ht in females at 1000 mg/kg bw/day, reduced RBC in males at 30 and 300 mg/kg bw/day and reduced leucocytes in females at 30 mg/kg bw/day were without dose relation)\nClinical chemistry: ALT ↑ in 2/3 males and 1/3 females at 1000 mg/kg bw, ALP↓ in 3/3 females at 1000 mg/kg bw/day, T.Prot and Alb ↓ in 3/3 females at 1000 mg/kg bw/day, treatment-related (not treatment-related findings: ocassionally Na↓, Creat↓ and urea ↓ in males at 1000 mg/kg bw, P↑ in females at 30 mg/kg bw/day, Gluc↓ in both sexes at 1000 mg/kg bw/day, findings not consistent throughout the study or not dose-related)\nUrinalysis: ↓ mean specific gravity in 1/3 males and 3/3 females at 1000 mg/kg bw/day, ↑ mean urinary volume and less marked colour in 3/3 females at 1000 mg/kg bw/day, treatment-related)","Increase 1000 (At 1000 mg/kg bw/day: liquid/soft feces in 3/3 males and 3/3 females, vomiting in 2/3 females, thin appearance in 1/3 males and 3/3 females, dehydration in 1/3 males and 2/3 females, pallor of ears and mouth in 1/3 females, treatment-related)","Decrease 1000 (Food consumption: reduced food consumption, varying from 25-75% of the amount given, was observed on many occasions in both sexes at 1000 mg/kg bw (males: study week 4-11, females: study week 1-11), treatment-related)","Change 1000 (Each 1/4 males and 1/4 females were sacrificed for human reasons on Days 61 and 72, associated with clinical signs and histopathological findings, treatment-related)"]
[6,"DAR",1999,"Mammals","Repeated dose 90-day oral toxicity study in non-rodents","Dog","200; 2000; 10000","ppm","Oral",90,"Days","Adult","Achieved test substance intake: 5.2, 54.2 and 252.4 mg/kg bw/day (males) and 5.4, 52.8 and 252.7 mg/kg bw/day (females)","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 ",null,null,null,null,null,null,null,null,"No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ",null,null,null,"No effect >10000 ","No effect >10000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 (Minimal to mild mineralisation and mild cytoplasmic vacuolisation of the tubular epithelium, not treatment-related)","No effect >10000 ","No effect >10000 (Minimal to mild leucocyte infiltration in 3/4 and 3/4 males and in 4/4 and 4/4 females at 0 and 10000 ppm, not treatment-related)","No effect >10000 ",null,null,"No effect >10000 (Minimal to mild lymphocytic infiltration, not treatment-related )",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 ","Change >10000 (Haematology: after 45 days of treatment: dose-related increase in clotting time in both sexes at all dose , treatment-related but fully reversible (non-treatment-related findings: MCH  ↑ in females at 10000 ppm, but within normal range); after 90 days of treatment: Neutrophils↓ in males at 2000 ppm, WBC↑ in females at 200 ppm, and Hct, MCV and MCH↑in females at 10000 ppm, within HCD); all effects were considered non-adverse\nClinical chemistry:  after 45 days of treatment: ALP↑ and GGT ↑ in males at 10000 ppm, GGT ↑ in females at 10000 ppm (non-treatment-related findings: T.Bilirubin ↑ in females at ≥ 2000 ppm and Ca ↑ in females at 10000 ppm, but within normal range); after 90 days of treatment: T.Bilirubin ↑ in both sexes at 10000 ppm, treatment- and dose-related; all effects were considered non-adverse\nUrinalysis: no adverse effects observed)","No effect >10000 ","Decrease 10000 (Food consumption: decreased in both sexes at 10000 ppm during study week 2, fully reversible\nfood efficiency: no adverse effects observed)","No effect >10000 "]
[7,"DAR",1996,"Mammals","Repeated dose 90-day oral toxicity study in non-rodents","Dog","1600; 8000; 40000","ppm","Oral",90,"Days","Adult","Achieved test substance intake: 39.7, 198 and 1015 mg/kg bw/day (males) and 39.8, 201 and 1014 mg/kg bw/day (females)","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >40000 ",null,null,null,null,null,"No effect >40000 ","No effect >40000 ","No effect >40000 ","No effect >40000 ","No effect >40000 ","No effect >40000 ",null,null,null,null,null,"No effect >40000 ","No effect >40000 ","No effect >40000 ","No effect >40000 ","No effect >40000 ",null,null,null,"No effect >40000 ","No effect >40000 ",null,"No effect >40000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >40000 ","No effect >40000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >40000 ","No effect >40000 ","No effect >40000 ","No effect >40000 ",null,null,null,null,null,null,null,"No effect >40000 (Cutaneous histiocytoma in 1/4 females at 40000, not treatment-related)",null,null,null,null,null,null,null,null,null,"No effect >40000 ","No effect >40000 (Haematology: no treatment-related findings (statistically significant changes: RBC ↑ in males at 1600 and 8000 ppm, MCV ↓in males at 1600 ppm, MCHC ↓ in females at 40000 ppm, considered incidental as no other findings were observed)\nClinical chemistry: no treatment-related findings (statistically significant changes: Cl ↑ in males at 2000 and 40000 ppm (minimal magnitude, no dose-relation), Alb ↑ in females at 2000 ppm, no dose relation)\nUrinalysis: decreased pH in 3/4 females at 40000 ppm, statistically not significant, attributed to the acidic nature of the test item)","No effect >40000 ","No effect >40000 ","No effect >40000 "]
[8,"DAR",1996,"Mammals","Repeated dose 90-day oral toxicity study in non-rodents","Dog","2000; 10000; 50000","ppm","Oral",90,"Days","Adult","Achieved test substance intake: 68, 323 and 1680 mg/kg bw/day (males) and 68, 334 and 1750 mg/kg bw/day (females), 1/4 dogs at 10000 ppm received no test item on 2 days on week 5","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ",null,null,"No effect >50000 ","No effect >50000 ",null,null,null,null,"No effect >50000 ",null,"No effect >50000 ","No effect >50000 ","No effect >50000 (Imperfect spermatogenesis and minimal secretory activity in 1/4, 1/4, 1/4 and 2/4 males at 0, 2000, 10000 and 50000 ppm, not treatment-related)",null,null,null,null,null,null,"No effect >50000 ","No effect >50000 ","No effect >50000 ","Decrease 2000 (Rel weight reduced in females at 2000 and 10000 ppm, no dose-relation, considered to be without toxicological significance)","No effect >50000 ",null,null,null,"No effect >50000 ","No effect >50000 ",null,"No effect >50000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ","Increase 10000 (Abs+rel weight increased in males at ≥ 10000 ppm, treatment-related but considered toxicologically not relevant due to the absence of histopathological findings)","No effect >50000 ","Increase 10000 (Abs+rel weight increased in males at ≥ 10000 ppm, treatment-related but considered toxicologically not relevant due to the absence of histopathological findings)","No effect >50000 (Minor granulomatous/inflammatory lesions were occasionally observed, no dose-relation, incidental, not treatment-related)","No effect >50000 (Minor granulomatous/inflammatory lesions were occasionally observed, no dose-relation, incidental, not treatment-related)",null,null,null,null,null,null,"No effect >50000 ",null,null,null,null,null,null,null,null,"Decrease 50000 (Depressed in males (not statistically significant) and females (occasionally statistically significant) at 50000 ppm, treatment-related)","Change 50000 (Haematology: no treatment-related findings\nClinical chemistry: at 50000 ppm Alb ↓, Ca ↓and T.Protein ↓ in males , treatment-related, and ALP ↑ in females\nUrinalysis: no treatment-related findings)","No effect >50000 (Findings of minor nature were not related to treatment)","No effect >50000 ","No effect >50000 "]
[9,"DAR",2007,"Mammals","Chronic toxicity","Dog","30; 125; 500","mg/kg bw/day","Oral",1,"Year","Adult",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >500 ","No effect >500 ",null,null,null,null,"No effect >500 ","No effect >500 ","No effect >500 ","No effect >500 ","No effect >500 ","No effect >500 ",null,null,null,null,null,"No effect >500 ","No effect >500 ","No effect >500 ","No effect >500 ","No effect >500 ","No effect >500 ","No effect >500 ",null,"No effect >500 ","No effect >500 ",null,"No effect >500 (Abs. weight stat. significantly reduced in males at 125 mg/kg bw/day, no dose-relation, no macroscopic/microscopic findings, not toxicologically relevant)",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >500 ","No effect >500 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >500 ","No effect >500 ","No effect >500 ","No effect >500 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >500 (Decreased body weight in males at 500 mg/kg bw/day, within historical control data, sporadic body weight changes in single dogs among all dose groups, not treatment-related)","No effect >500 (Haematology: no treatment-related findings (not treatment-related findings: APTT↓, MCHC↓, Eosinophils↓, all slight and/or not dose-related)\nClinical chemistry: no treatment-related findings (not treatment-related findings: Pi↓, Ca↓, T.Protein↓, Gluc↑, A/G ratio↑, ALP↑, all slight and/or not dose-related or within historical controls)\nUrinalysis: no treatment-related findings)","No effect >500 (Vomiting, soft feces, thin appearance, hyperactivity, ptyalism, cutaneous signs and nodules on the ears were occasionally observed among all dose groups, not treatment-related)","No effect >500 (Occasional fluctuations (25-75% of amount given) in control and treated animals, not test item-related)","No effect >500 "]
[10,"DAR",1997,"Mammals","Chronic toxicity","Dog","1600; 8000; 50000","ppm","Oral",1,"Year","Adult","Achieved test substance intake: 34.1, 182 and 1203 mg/kg bw/day (males) and 37.1, 184 and 1259 mg/kg bw/day (females)","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ",null,null,null,null,null,"No effect >50000 ","No effect >50000 ","No effect >50000 ","No effect >50000 ","No effect >50000 ","No effect >50000 ",null,null,null,null,null,"No effect >50000 ","No effect >50000 ","No effect >50000 ","No effect >50000 ","No effect >50000 ",null,null,null,"No effect >50000 ","No effect >50000 ",null,"No effect >50000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ","No effect >50000 (Abs+rel weight decreased in males at 1600 ppm, no dose-relation, not treatment-related)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ","No effect >50000 ","No effect >50000 ","No effect >50000 ","No effect >50000 (Slight focal pneumonia / focal granulumatous pneumonia in1/4, 1/4, 1/4 and 4/4 females at 0, 1600, 8000 and 50000 ppm, common finding in untreated rats, statistically not significant, not related to treatment)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 50000 (Retarded body weight gain in both sexes at 50000 ppm (terminated bw were -6% in males, -11% in females when compared to controls, not statistically significant), treatment-related)","Change 50000 (Haematology: Ht↓, Hb↓and RBC↓ in females at 50000 ppm, anemic condition may be caused by malnutrition, treatment-related (no abnormalities in males)\nClinical chemistry: Cl↑ (week 26), Alb↓ and Pi↓ (both week 52) in females at 50000 ppm, treatment-related (not treatment-related: Ca↓ in females at 1600 and 50000 ppm at week 52, CPK↓ in males at 8000 ppm in week 52, no dose-relation)\nUrinalysis: reduced pH in both sexes at 50000 ppm, attributed to the acidic nature of the test item)","Increase 50000 (Loose stool in 3/4 males and 4/4 females at 50000 ppm, treatment-related)","No effect >50000 ","No effect >50000 "]
[11,"DAR",1996,"Mammals","Chronic toxicity","Dog","3000; 15000; 30000","ppm","Oral",1,"Year","Adult","Achieved test substance intake: 90.9, 440.3 and 906.5 mg/kg bw/day (males) and 92.1, 447.8 and 926.2 mg/kg bw/day (females)","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 ",null,null,"No effect >30000 ","No effect >30000 ",null,null,null,null,"No effect >30000 ",null,"No effect >30000 ",null,"No effect >30000 ",null,null,null,null,null,null,"No effect >30000 ","No effect >30000 ","No effect >30000 ","No effect >30000 ","No effect >30000 ",null,null,null,"No effect >30000 ","No effect >30000 (Abs+rel weight slightly increased in males at 3000 ppm, exaggerated by a low value for one male in the control group, not treatment-related)",null,"No effect >30000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 ","No effect >30000 ","No effect >30000 ","No effect >30000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 (Red areas or diffuse reddening in 1/4, 2/4 and 2/4 females at 3000, 15000 and 30000 ppm, no dose-relation, in the absence of a similar effect in males the findings were considered not treatment-related)","Decrease 30000 (Reduced body weight (-11%) in females at 30000 ppm during the second half of the study, reflects a palatability effect)","No effect >30000 (Haematology: no treatment-related findings \nClinical chemistry: no toxicologically relevant findings (not treatment-related findings:  T.Chol.↑ was increased in both sexes at 3000 and 30000 ppm in weeks 26+52, no dose-relation; P↓ in males in week 52, due to higher control levels; Na↓, in males at 30000 ppm due to one male of this group; ALT, AST, Creat. kinase occasionally increaased, no dose-relation)\nUrinalysis: no treatment-related findings )","No effect >30000 (Salivation in both sexes among all doses with increased incidences in 2/4 males and 1/4 females the high dose group, attributed to anticipation of feeding, not related to treatment; low incidence of scrotal skin redddening in 2/4 males at 15000 ppm and in 1/4 males at 30000 ppm, not treatment-related; incidences of fluid feces, vomiting, blood or mucus in feces were noted but not related to treatment\nophthalmology: low incidence of corneal or lentiocular opacities among treatment and control animals, not treatment-related)","No effect >30000 ","No effect >30000 "]
[51,"DAR",1989,"Mammals","Subacute oral in non-rodent ","Dog","100; 300; 1000 *see remarks","mg/kg bw/day","Oral","Study part A: 21\nStudy Part B: 14","Days","Adult","* The study was separated in parts A and B. For each part each one male and one female dog were used.\nStudy part A: the male and the female dog were treated at all dose levels: 100 mg/kg bw/day in study Days 1-7, 300 mg/kg bw/day in study Days 8-14 and 1000 mg/kg bw/day in study Days 15-21\nStudy part B: both dogs were treated at 1000 mg/kg bw/day for 14 days","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (Relative and absolute organ weight were not affected.)",null,"No effect >1000 (Relative and absolute organ weight were not affected.)",null,"No effect >1000 ",null,null,null,null,null,null,null,null,null,null,null,"Decrease 100 (Study part A (21 days of treatment): Absolute and relative spleen weight were considered reduced in the female animal.\nStudy part B (14 days of treatment): no abnormalities observed)",null,null,null,null,null,"No effect >1000 ","Change 1000 (Haematology: \nStudy part A (21 days treatment): the male dog showed a reduced Hb and a mild increase in reticulocytes on Day 22 (treatment period 1000 mg/kg bw/day), not treatment-related, attributed to repeated blood sampling\nStudy part B (14 days treatment): no treatment-related findings\nClinical chemistry: \nStudy part A (21 days treatment): mild increase in ALT in the male dog and reduced cholesterol in the male and the female dog over the whole treatment period, considered to be not treatment-related\nStudy part B (14 days treatment): mild increase in ALT in the male dog, considered to be not treatment-related\nUrinalysis (available for study part B only, 14 days treatment): no adverse effects observed\nFaecal occult blood: no adverse effects observed)","No effect >1000 (Study part A (21 days of treatment): No abnormal findings were observed.\nStudy part B (14 days of treatment): the female dog showed loose faeces during the course of the treatment period, findings were not attributed to treatment)","No effect >1000 ","No effect >1000 "]
[57,"DAR",1983,"Mammals","Mammals Not il list","Dog","10; 60; 300","mg/kg bw/day","Oral",6,"Months","Adult","Study was performed for 6 month instead of 3 months (90 days)","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >300 (Examined together with testes.)",null,null,null,null,null,"No effect >300 ","No effect >300 ","No effect >300 ","No effect >300 (No effect on relative and absolute organ weight was observed.)","No effect >300 ",null,null,null,null,null,null,"No effect >300 ","No effect >300 (Non-statistically significant increase in absolute organ weight at 300 mg/kg bw/day which was attributed to one animal. No histopathological changes were observed and thus, the increase is considered not treatment-related.)","No effect >300 ","No effect >300 (Absolute weight was statistically significantly decreased in males at 60 mg/kg bw/day, relative weight was increased in females at 10 mg/kg bw/day (statistically not significant). No dose-response and no effect in thyroid histopathology were observed.)","No effect >300 ",null,null,null,"No effect >300 ","No effect >300 (No effect on relative and absolute organ weight was observed.)","No effect >300 ","No effect >300 (No effect on relative and absolute organ weight was observed.)",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >300 ","No effect >300 (No effect on relative and absolute organ weight was observed.)",null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >300 (Heart and aorta were subject to histopathology.)","No effect >300 (Rel. weight increased in females at 60 mg/kg bw/day (statist. not signif.), no dose-relation, not treatment-related)","No effect >300 (Urinary bladder was examined as well.)","No effect >300 (No effect on relative and absolute organ weight was observed.)","No effect >300 ","No effect >300 (No effect on relative and absolute organ weight was observed.)","No effect >300 ","No effect >300 ",null,"No effect >300 ","No effect >300 (The sciatic nerve was examined.)","No effect >300 (Mandibular salivary glands were investigated.)",null,null,"No effect >300 ",null,"No effect >300 ",null,"No effect >300 (Stomach and esophagus were histopathologically examined.)","No effect >300 ",null,null,null,"No effect >300 (Beginning midway through the study, the body weights (also final body weights) of males in the high-dose group were slightly decreased (-4-6%) beginning from the mid of the study (not statistically significant). Body weight of females was not affected.)","Change 300 (Haematology: Statistically significantly increased MCHC in both sexes at different sampling time points, no dose-relation, within normal range, not related to treatment\nClinical chemistry: A dose-related increase in alkaline phosphatase activity was observed in males and females at all doses (statistically significant in high-dose males (month 5) only) and total lactic dehydrogenase levels statist. signif. decreased in males at 60 and 300 mg/kg bw/day after 4 months of treatment until study termination. As no gross or microscopic liver lesions were observed, biological relevance equivocal and parameter not considered T-related\nUrinalysis: No treatment-related effects observed.)","No effect >300 ","No effect >300 ","No effect >300 "]
[58,"DAR",1985,"Mammals","Chronic toxicity","Dog","20; 100; 500","mg/kg bw/day","Oral",1,"Year","Adult",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >500 (Cervix examined together with uterus. )",null,null,"No effect >500 ","No effect >500 (Epididymides were weighed together with testes. Absolute and relative organ weights were not affected.)",null,null,null,null,"No effect >500 ","No effect >500 ","No effect >500 ","No effect >500 (Absolute and relative organ weights were not affected.)","No effect >500 ",null,null,null,null,null,null,"No effect >500 ","No effect >500 (Absolute and relative organ weights were not affected.)","No effect >500 ","No effect >500 (Absolute and relative organ weights were not affected.)","No effect >500 ",null,null,null,"No effect >500 ","No effect >500 (Absolute and relative organ weights were not affected.)",null,"No effect >500 (Abs. weight statist. signif. decreased in males at 100 mg/kg bw/day, not dose-related and therefore not attributed to treatment. Moreover, no microscopic changes observed.)",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >500 ","Decrease 100 (Abs. + rel. weight statist. signif. decreased in males only at 100 and 500 mg/kg bw/day, treatment-related but no microscopical abnormalities observed.)",null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >500 (Histopathology was performed for heart and aorta.)","No effect >500 (Absolute and relative organ weights were not affected.)","No effect >500 (Kidney, ureter and urinary bladder were examined.)","No effect >500 (Absolute and relative organ weights were not affected.)","No effect >500 ","No effect >500 (Absolute and relative organ weights were not affected.)","No effect >500 (Lung and trachea were examined.)","No effect >500 (Mesenteric lymph nodes were examined.)",null,"No effect >500 ","No effect >500 (The sciatic nerve was examined.)","No effect >500 (The mandibular salivary glands were examined.)",null,null,"No effect >500 ","No effect >500 (The cervical, midthoracic and lumbar sections were examined.)","No effect >500 ",null,"No effect >500 ","No effect >500 ",null,null,null,"No effect >500 ","No effect >500 (Haematology: No treatment related findings (mild elevations in RBC, HGB and HCT in females at 20 mg/kg bw/day, not dose-related and within normal range; mild changes in MCHC in males at 100 mg/kg bw/day after 12 months and in females at 10 and 100 mg/kg bw/day after 3 and 12 month, not dose-related).\nClinical chemistry: No treatment-related findings (statistically significant decrease in P and changes in SGPT, Na, K, Ca, Gluc and Alb were transient and within normal ranges and therefore not related to treatment).\nUrinalysis: No adverse effects observed.)","Increase 20 (Increased incidences of abnormal excrement (bloody stool, yellow mucoid stool, diarrhea, emesis) were observed in a few females at 20 and 500 mg/kg bw/day; most observations were attributed to 1 female of each group (1/6), no findings at 100 mg/kg bw/day females or in males (all dose groups), considered to be not dose-related and of questionable biological significance; skin redness with slight alopecia in 1/6 females at 100 and in 1/6 females at 500 mg/kg bw/day, treatment-related \nOphthalmoscopy: no treatment-related findings)","No effect >500 ","No effect >500 "]
[59,"DAR",1990,"Mammals","Chronic toxicity","Dog","30; 300; 1000","mg/kg bw/day","Oral",1,"Year","Adult",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ","No effect >1000 (Epididymides were weighed with testes. Absolute and relative organ weights were not affected.)",null,null,null,null,"No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 (Absolute and relative organ weights were not affected.)","No effect >1000 ","No effect >1000 (Absolute and relative organ weights were not affected.)",null,null,null,null,null,"No effect >1000 ","No effect >1000 (Absolute and relative organ weights were not affected.)","No effect >1000 ","No effect >1000 (Absolute and relative organ weights were not affected.)","No effect >1000 ","No effect >1000 (Absolute and relative organ weights were not affected.)",null,null,"No effect >1000 ","No effect >1000 (Absolute and relative organ weights were not affected.)","No effect >1000 (The brain was sectioned at 3 levels (cerebral cortex, mid-brain and cerebellum with medulla) for histopathological examination.)","No effect >1000 (Absolute and relative organ weights were not affected.)",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ","No effect >1000 (Absolute and relative organ weights were not affected.)",null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (Heart and aorta were examined.)","No effect >1000 (Absolute and relative organ weights were not affected.)","No effect >1000 ","No effect >1000 (Absolute and relative organ weights were not affected.)","No effect >1000 (Prominent lobulation and pale patches at necropsy in animals of all groups, not treatment-related)","No effect >1000 (Liver and drained gall bladder were weighed. Absolute and relative organ weights were not affected.)","No effect >1000 (Gross necropsy: Pale or dark patches were commonly observed among all groups, not treatment-related\nHistopathology: Performed for trachea and lung. Localised inflammatory lesions including small granulomas correlating with macroscopical findings in lung in 1/4, 3/4, 1/4 and 3/4 males and in 1/4, 1/4, 0/4 and 0/4 females at 0, 30, 300 and 1000 mg/kg bw/day, not treatment-related)","No effect >1000 (Submandibular and mesenteric lymph nodes were examined.)","No effect >1000 ","No effect >1000 ","No effect >1000 (Sciatic nerve was examined.)","No effect >1000 (Submaxillary, sublingual, parotid salivary glands were examined.)",null,null,"No effect >1000 ",null,"No effect >1000 ","No effect >1000 (Absolute and relative organ weights were not affected.)","No effect >1000 ","No effect >1000 ","No effect >1000 (Absolute and relative organ weights were not affected.)",null,"No effect >1000 (Thickened wall in 1/4 males at 1000 mg/kg bw/day and in 1/4 females at 30 mg/kg bw/day, microscopically verified as muscular hypertrophy and in 2/4 females at 30 mg/kg bw/day, microscopically verified as lymphocyte infiltration, not treatment-related)","Decrease 30 (Reduced mean body weight gain in males at 30 (-17%), 300 (-25%) and 1000 mg/kg bw/day (-25%) and in females at 1000 mg/kg bw/day (-19%), statistically not significant, treatment-relation not clear)","No effect >1000 (Haematology: No treatment-related findings\nClinical chemistry: No treatment-related findings\nUrinalysis: No treatment-related findings\nFaeces: Occult blood determinations performed in faecal samples were negative for all animals throughout the study.\nBrain cholinesterase: No effect was observed.)","Increase 1000 (Increased incidences of changes in faecal consistency (soft, loose, liquid) were recorded more frequently at 1000 mg/kg bw/day, treatment-related (not treatment-related observations: vomiting, salivation, minor wound bites and conjunctivitis were infrequently observed, no dose or treatment relation)\nOphthalmoscopy: no treatment-related findings)","No effect >1000 ","No effect >1000 ","No effect >1000 (Relative and absolute pancreas weight was not affected.)"]
["59a","DAR",1990,"Mammals","Chronic toxicity","Dog","30; 300; 1000","mg/kg bw/day","Oral",1,"Year","Adult",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (Absolute and relative lung weight was not affected.)"]
[4,"DAR",1995,"Mammals","Repeated dose 90-day oral toxicity study in rodents","Mouse","5000; 10000; 50000","ppm","Oral",90,"Days","Adult","Achieved test substance intake: 600.2, 1221 and 6295 mg/kg bw/day (males) and 765.0, 1486 and 7435 mg/kg bw/day (females)","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ","No effect >50000 ",null,"No effect >50000 ",null,null,null,null,null,"No effect >50000 ",null,"No effect >50000 ",null,"No effect >50000 ",null,"No effect >50000 ",null,null,null,null,"No effect >50000 ","No effect >50000 ","No effect >50000 ",null,"No effect >50000 ",null,"No effect >50000 ",null,"No effect >50000 ","No effect >50000 ",null,"No effect >50000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ","No effect >50000 ","No effect >50000 ","No effect >50000 ",null,null,null,null,null,null,null,null,"Change 50000 (Macroscopic finding: caecum distention in 12/12 males and 10/12 females at 50000 ppm and in 1/12 females at 10000 ppm at necropsy, no histopathological findings)",null,null,null,null,null,null,null,"Change 50000 (Cystitis of the urinary bladder in 4/12 males at 50000 ppm (0/12 in the control group), treatment-related; no effects in females)","Decrease 50000 (Decreased body weight (-9% at week 13) in males at 50000 ppm, occasionally statistically significant, treatment-related)","Change 50000 (Haematology: ↓ Ht, ↓ Hb and ↓ RBC and anemia in females at 50000 ppm, treatment-related; no changes in males\nClinical chemistry:  ↑ALP in both sexes at 50000 ppm, ↑ P in females at 50000 ppm, treatment-related (not treatment-related findings: ↓GPT in females at 50000 ppm, ↑ Creat.phosphokinase in females at 5000 and 50000 ppm, ↑BUN in females at 10000 ppm)\nUrinalysis: reduced pH in males of all treatment-groups, attributed to the acidic nature of the test substance)","No effect >50000 ","Decrease 50000 (Food consumption: decreased (-6%) in males at 50000 ppm during the treatment period, treatment-related \nfood efficiency: decreased (m:-21%; f: -12%  ) in both sexes at 50000 ppm during the treatment period, treatment-related )","No effect >50000 ","Increase 10000 (Caecum: abs+rel weight increased (m: +15%/+11%; f: +22%/+17%) in both sexes at ≥ 10000 ppm (stat.significant at 50000 ppm), treatment-related)"]
[19,"DAR",2001,"Mammals","Carcinogenicity","Mouse","100; 1000; 10000","ppm","Oral",18,"Months","Adult","Achieved test substance intake: 14.5, 149.7 and 1453.8  mg/kg bw/day (males) and 15.0, 151.2 and 1466.8 mg/kg bw/day (females); haematology only differential leukocytes examined, no clinical chemistry, no urinalysis performed","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 ","No effect >10000 ",null,"No effect >10000 (Histopathology, non-neoplastic findings dead/moribund animals: lymphocyte infiltration in 4/22, 1/20, 0/22 and 3/27 males and cell debris in tubules in 0/22, 1/20, 4/22 and 0/27 males at 0, 100, 1000 and 10000 ppm, no dose response, not treatment-related)",null,null,null,null,null,"No effect >10000 ",null,"No effect >10000 (Gross pathology, terminal kill animals: bursal cysts in 13/34, 11/34, 11/30 and 13/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related)","No effect >10000 ","No effect >10000 ",null,"No effect >10000 (Histopathology, non-neoplastic findings dead/moribund animals: atrophy in 3/22, 3/20, 5/22 and 5/27 males at 0, 100, 1000 and 10000 ppm, not treatment-related)",null,null,null,null,"No effect >10000 (Histopathology, non-neoplastic findings dead/moribund animals: atrophy/ degenerative changes in 9/22, 4/20, 11/22 and 9/27 males at 0, 100, 1000 and 10000 ppm, not treatment-related)","No effect >10000 ","No effect >10000 (Histopathology, non-neoplastic findings dead/moribund animals: amyloidosis in 4/22, 3/20, 5/22 and 5/27 males and 3/16, 1/16, 1/20 and 2/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related)",null,"No effect >10000 (Histopathology, non-neoplastic findings dead/moribund animals: cystic glands in 5/16, 3/16, 2/20 and 7/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nhistopathology, non-neoplastic findings terminal kill animals: cystic endometrial hyperplasia in 17/34, 5/34, 4/30 and 8/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nhistopathology, neoplastic findings: 10 tumours observed, mostly endometrial stromal sarcomas. No dose- or treatment-relation identified.)",null,null,null,"No effect >10000 (Histopathology, non-neoplastic findings dead/moribund animals: subcapsular cell hyperplasia in 3/22, 8/20, 7/22 and 10/27 males and 12/16, 11/16, 13/20 and 15/20 females at 0, 100, 1000 and 10000 ppm; amyloidosis in 7/22, 9/20, 10/22 and 11/27 males and 3/16, 0/16, 1/20 and 3/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nhistopathology, non-neoplastic findings terminal kill animals: subcapsular cell hyperplasia in 15/28 and 13/23 males and 27/34 and 22/30 females at 0 and 10000 ppm and amyloidosis in 7/28 and 8/23 males and 1/27 and 3/30 females at 0 and 10000 ppm, not treatment-related)","No effect >10000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 ",null,null,null,null,null,null,null,null,null,null,"No effect >10000 (Histopathology, non-neoplastic findings dead/moribund animals: increased granulopoesis in femur in 5/22, 3/20, 2/22 and 2/27 males and 1/16, 3/16, 0/20 and 4/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related; increased hematopoesis in femur in 1/22, 1/20, 8/22 and 5/27 males and 0/16, 1/16, 2/20 and 3/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related; increased hematopoesis in sternum with marrow in 2/22, 1/20, 5/22 and 6/27 males and 0/16, 1/16, 3/20 and 3/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nhistopathology, non-neoplastic findings terminal kill animals: increased hematopoesis in sternum with marrow in 5/28 and 2/23 males and 6/34 and 8/30 females at 0 and 10000 ppm, not treatment-related\nhistopathology, neoplastic findings: 11 tumors observed, osteomas, no treatment relation)",null,null,null,"No effect >10000 (Histopathology, non-neoplastic findings dead/moribund animals: degenerative changes in 11/22, 14/20, 13/22 and 16/27 males and 4/16, 2/16, 4/20 and 1/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related)",null,"No effect >10000 (Gross pathology, terminal kill animals: rough/ uneven surface in 1/28, 2/30, 2/28 and 5/23 males at 0, 100, 1000 and 10000 ppm, considered incidental as histopathological findings were absent\nHistopathology, non-neoplastic findings dead/moribund animals: nephropathy in 9/22, 7/20, 10/22 and 12/27 males and 5/16, 1/16, 5/20 and 3/20 females at 0, 100, 1000 and 10000 ppm; amyloidosis in 6/22, 4/20, 10/22 and 9/27 males and 3/16, 2/16, 2/20 and 4/20 females at 0, 100, 1000 and 10000 ppm\nhistopathology, non-neoplastic findings terminal kill animals: nephropathy in 7/28, 4/30, 3/28 and 6/23 males and 5/34, 2/34, 0/30 and 2/30 females at 0, 100, 1000 and 10000 ppm and amyloidosis in 7/28, 2/30, 2/28 and 8/23 males and 0/34, 1/34, 0/30 and 3/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related)","No effect >10000 ","No effect >10000 (Gross pathology, dead/moribund animals: enlarged in 3/22, 1/20, 3/22 and 1/27 males and 3/16, 4/16, 2/20 and 2/20 females at 0, 100, 1000 and 10000 ppm, no dose depedency but associated with histopathological findings\ngross pathology, terminal kill animals: masses in 4/28, 4/30, 2/28 and 2/23 males and 1/34, 1/34, 2/30 and 2/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nHistopathology, non-neoplastic findings dead/moribund animals: amyloidosis in 10/22, 9/20, 10/22 and 11/27 males and 5/16, 1/16, 4/20 and 5/20 females at 0, 100, 1000 and 10000 ppm, no dose dependency, not treatment-related\nhistopathology, non-neoplastic findings terminal kill animals: necrobiotic foci in 2/28, 0/30, 0/28 and 1/23 males and 4/34, 1/34, 0/30 and 7/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related; extramedullary hematopoesis in 5/28, 0/30, 2/28 and 5/23 males and 2/34, 2/34, 0/30 and 6/30 females at 0, 100, 1000 and 10000 ppm; amyloidosis in 9/28, 1/30, 3/28 and 8/23 males and 2/34, 2/34, 0/30 and 5/30 females at 0, 100, 1000 and 10000 ppm\nhistopathology, neoplastic findings: 26 tumors observed, mostly hepatocellular adenomas, no treatment relation)","No effect >10000 ","No effect >10000 (Histopathology, neoplastic findings: 11 tumors observed, mostly bronchioalveolar adenomas, no treatment relation)","No effect >10000 (Gross pathology, dead/moribund animals: enlarged superficial lymph nodes in 7/22, 5/20, 5/22 and 6/27 males and 2/16, 6/16, 9/20 and 4/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related; enlarged mandibular lymph nodes in 3/22, 6/20, 3/22 and 3/27 males and 1/16, 2/16, 3/20 and 3/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related; enlarged mesenteric lymphnodes in 8/22, 9/20, 8/22 and 11/27 males and 8/16, 9/16, 10/20 and 7/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related\ngross pathology, terminal kill animals: enlarged axillary lymph nodes in 5/28, 3/30, 5/28 and 0/23 males and 3/34, 6/34, 1/30 and 4/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related; enlarged superficial ing. lymph nodes in 3/28, 1/30, 2/28 and 2/23 males and 0/34, 3/34, 1/30 and 2/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related; enlarged mandibular lymph nodes in 12/28, 19/30, 19/28 and 14/23 males and 15/34, 15/34, 12/30 and 13/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related; discolourated mesenteric lymph nodes in 7/28, 9/30, 7/28 and 6/23 males and 2/34, 3/34, 2/30 and 12/30 females at 0, 100, 1000 and 10000 ppm, no dose relation, not treatment-related; enlarged mesenteric lymph nodes in 13/28, 14/30, 15/28 and 10/23 males and 10/34, 12/34, 9/30 and 19/30 females at 0, 100, 1000 and 10000 ppm, no dose relation, not treatment-related, associated with neoplasia of the hemolymphoreticular system and lymphoid hyperplasia\nHistopathology, non-neoplastic findings dead/moribund animals: mandibular lymph node hyperplasia in 6/22, 5/20, 3/22 and 7/27 males and 3/16, 3/16, 2/20 and 6/20 females at 0, 100, 1000 and 10000 ppm; extramedullary hematopoesis in 3/22, 2/20, 5/22 and 3/27 males and 1/16, 1/16, 1/20 and 2/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nhistopathology, non-neoplastic findings terminal kill animals: mesenteric lymph nodes hyperplasia in 12/28, 12/30, 17/28 and 9/23 males and 13/34, 20/34, 16/30 and 11/30 females at 0, 100, 1000 and 10000 ppm; meseneteric extramedullary hematopoesis in 8/28, 10/30, 9/28 and 6/23 males and 6/34, 9/34, 4/30 and 8/30 females at 0, 100, 1000 and 10000 ppm; mandibular lymph node hyperplasia in 13/28, 24/30, 24/28 and 14/23 males and 21/34, 24/34, 23/30 and 11/30 females at 0, 100, 1000 and 10000 ppm; mandibular extramedullary hematopoesis in 5/28, 7/30, 9/28 and 9/23 males and 3/34, 9/34, 7/30 and 4/30 females at 0, 100, 1000 and 10000 ppm, considered to be incidental; hyperplasia in superficial ing lymph nodes in 3/28, 0/30, 0/28 and 6/23 males and 6/34, 2/34, 0/30 and 6/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nhistopathology, neoplastic findings: mesenteric lymph nodes: 9 tumours observed among all groups (1/16 and 2/20 dead/moribund females at 0 and 10000 ppm, 1/16 dead/moribund males at 100 ppm and 1/28, 1/27 and 1/23 terminal kill males at 0, 1000 and 10000 ppm and in 2/30 terminal kill females at 10000 ppm), mostly hemangiomas (7/9), no treatment relation)",null,"No effect >10000 (Histopathology, non-neoplastic findings dead/moribund animals: amyloidosis in 1/22, 6/20, 4/22 and 4/27 males at 0, 100, 1000 and 10000 ppm and in 1/16 control females, not treatment-related)",null,null,null,"No effect >10000 (Gross pathology, dead/moribund animals: alopecia/patchy alopecia in 2/22, 1/20, 0/22 and 3/27 males and 1/16, 0/16, 2/20 and 0/20 females at 0, 100, 1000 and 10000 ppm, not dose- or treatment-related\nHistopathology, non-neoplastic findings dead/moribund animals: epidermal hyperplasia in 10/22, 13/20, 7/22 and 10/27 males and 6/16, 5/16, 6/20 and 6/20 females at 0, 100, 1000 and 10000 ppm; suppurative necrotising dermatitis/healing in 5/22, 6/20, 2/22 and 5/27 males and 3/16, 1/16, 4/20 and 1/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related)","No effect >10000 (Rectum: histopathology, non-neoplastic findings terminal kill animals: lymphoid hyperplasia in 2/28 and 0/23 males at 0 and 10000 ppm and in 0/34, 1/34, 1/30 and 4/30 females at 0, 100, 1000 and 10000 ppm, lower than histoircal control data, considered to be incidental)",null,"No effect >10000 (Gross pathology, dead/moribund animals: enlarged in 8/22, 8/20, 11/22 and 13/27 males and 10/16, 11/16, 12/20 and 7/20 females at 0, 100, 1000 and 10000 ppm, no dose depedency but associated with histopathological findings\ngross pathology, terminal kill animals: enlarged in 8/28, 11/30, 11/28 and 10/23 males and 9/34, 15/34, 6/30 and 14/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related, associated with neoplasia of the hemolymphoreticular system, amyloidosis and increased extramedullary hematopoesis\nHistopathology, non-neoplastic findings dead/moribund animals: increased extramedullary hematopoesis in 3/22, 7/20, 1/22 and 3/27 males and 5/16, 5/16, 3/20 and 6/20 females at 0, 100, 1000 and 10000 ppm; amyloidosis in 12/22, 8/20, 10/22 and 12/27 males and 5/16, 1/16, 4/20 and 4/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nhistopathology, non-neoplastic findings terminal kill animals: increased extramedullary hematopoesis in 10/28, 13/30, 11/28 and 5/23 males and 9/34, 18/34, 10/30 and 10/30 females at 0, 100, 1000 and 10000 ppm; amyloidosis in 10/28, 9/30, 9/28 and 8/23 males and 2/34, 5/34, 3/30 and 5/30 females at 0, 100, 1000 and 10000 ppm, no dose relation, considered to be incidental)",null,"No effect >10000 (Histopathology, non-neoplastic findings dead/moribund animals: cystic glands in 8/22, 8/20, 9/22 and 16/27 males and 1/16, 4/16, 5/20 and 6/20 females at 0, 100, 1000 and 10000 ppm, within historical control range, considered to be incidental\nhistopathology, non-neoplastic findings terminal kill animals: cystic glands in 9/28, 19/30, 22/28 and 17/23 males and 22/34, -/34, -/30 and 19/30 females at 0, 100, 1000 and 10000 ppm, no dose-dependent increase in severity)","No effect >10000 (Gross pathology, dead/moribund animals: enlarged in 0/22, 1/20, 0/22 and 3/27 males and 0/16, 3/16, 1/20 and 2/20 females at 0, 100, 1000 and 10000 ppm, associated with neoplasms of the hemolymphoreticular system, no dose relation\nhistopathology, non-neoplastic findings terminal kill animals: involution in 13/28 and 6/23 males and in 6/34 and 7/30 females at 0 and 10000 ppm, no involution in 9/28 and 9/23 males and in 20/34 and 14/30 females at 0 and 10000 ppm, not treatment-related)",null,null,null,"No effect >10000 (Occasional fluctuations of body weight in males at 100 and 1000 ppm, no dose response, not treatment-related)","No effect >10000 (Haematology: only differential leukocyte count was analysed, data appeared to be within the range of biological variation\nClinical chemistry: not performed\nUrinalysis: not performed)","No effect >10000 (Clinical signs: no treatment-related findings (incidences of alopecia and skin injuries among all test groups, common finding in this species)\nOpthalmology: no treatment-related findings (cataract in 1/50 females at 100 ppm, corneal opacity in 1/50, 1/50 and 2/50 at 0, 100 and 1000 ppm. considered incidental))","No effect >10000 (Food consumption: occasionally altered in both sexes among all groups throughout the study, no dose relation, of minor degree and/or not consistent, considered to be incidental\nFood efficiency: no treatment-related findings)","Increase 10000 (Increased mortality at 10000 ppm (survival was 56, 60, 56 and 46% in males and 62, 64, 58 and 53% in females at 0, 100, 1000 and 10000 ppm); mortality rates at study termination were 44, 40, 44 and 54% at 0, 100, 1000 and 10000 ppm, life expectancy was not affected in any treated group)"]
[20,"DAR",2009,"Mammals","Carcinogenicity","Mouse","500; 1500; 5000","ppm","Oral",18,"Months","Adult","Achieved test substance intake: 71.4, 234.2 and 810 mg/kg bw/day (males) and 97.9, 299.5 and 1081.2 mg/kg bw/day (females); no haematology, clinical chemistry and unrinalysis performed, blood smear taken from tail vein, differential white cell counts were determined for animals killed in extremis or for humane reasons, and for all high dose and control animals","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >5000 (Preputial gland: no treatment-related findings (inflammatory and atrophic lesions, age-related; abscess formation occasionally observed, one instance of keratin cyst formation))",null,null,null,null,null,"No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (focal epithelial hyperplastic and atrophic changes frequently observed, age-related; mononuclear cell foci, mixed inflammatory cell infiltrates, interstitial fibrosis and abscess formation occasionally ore rarely observed)\nhistopathology, neoplastic findings: no neoplastic lesions observed)",null,"No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (reduced spermatozoal content, spermatocoel and spermatocoel granuloma formation, eosinophilic contents, interstitial mononuclear cells and fibrosis, distention of ducts observed with low incidences, age-related)\nhistopathology, neoplastic findings: no neoplastic changes)","No effect >5000 ",null,null,null,null,"No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (secretory distention of ducts frequently observed, age-related; glandular hyperplasia occasionally observed, age-related; instances of subcutaneous cyst formation)\nhistopathology, neoplastic findings: no treatment-related findings (adenocarcinomas or adenosquamous carcinomas in 2/51, 3/51 and 1/51 females at 500, 1500 and 5000 ppm))","No effect >5000 ((only two animals examined))","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (follicular and non-follicular cysts frequently observed, age-related; cystic and haemorrhagic follicles or corpora lutea in several control and high dose animals; interstitial cell hyperplasia, vasculitis, rete cyst formation, cystic distention of the oviducts, haemorrhagic cyst formation, necrosis and interstitial haemorrhage occasionally observed)\nhistopathology, neoplastic findings: no treatment-related findings (tumours in 1/51 control and 5/51 females at 5000 ppm (9 treated females in total affected), diversity of tumor type did not suggest a treatment relation))","No effect >5000 ","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (focal epithelial hyperplastic and atrophic changes frequently observed, age-related; mononuclear cell foci, mixed inflammatory cell infiltrates, interstitial fibrosis and abscess formation occasionally ore rarely observed)\nhistopathology, neoplastic findings: no neoplastic lesions observed)",null,"No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (variations in secretory content, instances of cystic distention, focal hyperplasia of the epithelial lining of the vesicles, mononuclear cell foci, mixed inflammatory cell infiltrates, fibrous thickening, atrophy and abscess formation; hyperplasia of the coagulating gland in 1/51 males at 5000 ppm)\nhistopathology, neoplastic findings: no treatment-related findings (adenoma of the vesicular epithelium in 2/51 control males and leiomyosarcoma in 1/51 high dose males))",null,null,null,null,"No effect >5000 (histopathology, non-neoplastic findings: bilateral testicular atrophy, statistically significant in males at 5000 ppm, considered not toxicologically significant; interstitial (Leydig) cell hyperplasia in most animals, age-related; incidental findings included spermatocoel formation, focal mineralisation of tubules, focal hyperplasia of the rete tubular epithelium, cyst formation)\nhistopathology, neoplastic findings: no treatment-related findings (benign interstitial (Leydig) cell tumours in 2/51 control males))","No effect >5000 ","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (distention and coalescence of follicles, focal follicular cell hyperplasia, focal C-cell hyperplasia, vasculitis, focal inflammation, follicular cell hypertrophy and mononuclear cell foci occasionally observed)\nhistopathology, neoplastic findings: no tumours observed)",null,"No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (cystic endometrial hyperplasia in most mice and uterine atrophy, age-related; instances of vasculitis, lymphoid foci, haemorrhagic cyst formation and angiectasis)\nhistopathology, neoplastic findings: no treatment-related findings (tumours observed in 20 mice, but group distribution was unrelated to treatment, 6 different tumour types; most frequently observed tumour was endometrial stromal polyp; histiocytic sarcomas in 5 animals))",null,"No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (epithelial keratinisation as normal cyclical change; one case of peripheral lymphocyte infiltration)\nhistopathology, neoplastic findings: no neoplastic changes)",null,"No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (focal hyperplasia of subcapsular cortical cells and focal hyperplasia of medullary cells in both sexes among all groups and focal cortical hypertrophy in males, age-related findings; focal hyperplasia of cortical cells and cortical atrophy were rarely observed)\nhistopathology, neoplastic findings: no treatment-related findings (cortical adenoma in 3/51 and 3/51 males at 0 and 5000 ppm, cortical carcinoma in 1/51 control males))","No effect >5000 ","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (isolated instances of dilatation of the lateral ventricles, crystalline clefts/ granuloma formation, focal mineralisation, vacuolation of the cerebral cortex and mononuclear cell foci; extensive abscess formation with areas of necrosis in 1/51 control males)\nhistopathology, neoplastic findings: no treatment-related findings (meningeal sarcoma in 1/51 males at 5000 ppm, oligodenroglioma in 1/51 and 1/51 control male and control female mice))","No effect >5000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (isolated instances of focal hyperplasia, developmental cysts or mononuclear cell foci, no toxicological significance)\nhistopathology, neoplastic findings: no treatment-related findings (three adenomas in females, no dose relation))",null,null,null,null,null,null,null,null,null,"No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (few observations without toxicological significance)\nhistopathology, neoplastic findings: no neoplastic lesions observed)","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (hyperostosis in 1/51 control females)\nhistopathology, neoplastic findings: no treatment-related findings (benign osteoma of the sternum in 1/51 control females))","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (adipose infiltration observed in most animals of both sexes, no dose relation on frequency and severity; myeloid hyperplasia in a few mice of either sex, no treatment-related group distribution; fibroplasia, angiectasis and foci/areas of necrosis occasionally observed)\nhistopathology, neoplastic findings: no treatment-related findings (myeloid leukaemia in 1/51 males at 500 ppm and in 1/51 females at 1500 ppm, lipoma in the marrow cavity of the sternum in 1/51 females at 5000 ppm))","No effect >5000 (Eyes: Histopathology, non-neoplastic findings: no treatment-related findings (spontaneous lesions such as retinal atrophy, retinal disruption, corneal ulceration, focal mineralisation of cornea/iris, keratitis, thickening of the iris and inflammation of the anterior chamber; lenticular degeneration more frenquently observed, considered as common background change)\nhistopathology, neoplastic findings: no neoplastic changes observed\nHarderian gland: histopathology, non-neoplastic findings: mononuclear cell foci and foci areas of atrophy, age related; instances of epithelial hyperplasia and generalised distention of the glands, not treatment-related\nhistopathology, neoplastic findings: Harderian gland adenomas in 4/51 males and 4/51 females at 0 and 5000 ppm each; carcinoma in 2/51 control females, not treatment-related\nLacrimal gland: histopathology, non-neoplastic findings: mononuclear cell foci and isolated instances of periductal/interstitial fibrosis, not treatment-related\n)","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (focal epithelial cell hyperplasia, amorphous bodies in the lumen, vasculitis, cystic distention, focal necrosis, thickening of the wall and epithelial ulceration occasionally observed)\nhistopathology, neoplastic findings: no neoplasms observed)","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (myocarditis/fibrosis and vacuolisation of myocardial fibres commonly observed in males of all groups, no dose-related incidence or serverity; atrial thrombus formation, distention/thinning of the ventricular wall, vasculitis, focal ossification, focal mineralisation, atrial inflammation or fibrosis, atrial distention, pericardial inflammatory or fibrous thickening, focal necrosis/haemorrhage, mononuclear cell foci occasionally observed)\nhistopathology, neoplastic findings: no primary neoplastic lesions observed)",null,"No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (groups of basophilic tubules, mononuclear cell foci, distention of isolated tubules or glomerula spaces frequently observed in both sexes among all groups; chronic nephropathy occasionally observed, tubular vacuolation or dilatation, focal mineralisation, vasculitis, cortical scarring, hydronephrosis, papillary necrosis, focal haemorrhage or necrosis, hyperplasia of the papillary/pelvic epithelium, amyloid deposition and pigment accumulation, no dose relation regarding incidence or severity)\nhistopathology, neoplastic findings: no treatment-related findings (haemangiosarcoma in 1/51 females at 1500 ppm))","No effect >5000 ","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (centrilobular hepatocyte vacuolation, periportal hepatocyte vacuolation, focal or centrilobular hepatocyte necrosis, areas or nodules of necrosis, lobular necrosis, thrombus formation, non-neoplastic cyst formation, granulocytic or myelopoietic foci, scattered lipid vacuolation of hepatocytes, higher grades of severity of pigment accumulation, focal hepatocyte hypertrophy, and proliferation of sinusoid lining cells occasionally observed; foci of altered hepatocytes in 4/51, 2/51, 2/51 and 1/51 males at 0, 500, 1500 and 5000 ppm and in 1/51 females at 5000 ppm)\nhistopathology, neoplastic findings: no treatment-related findings (total hepatocellular tumours in 7/51, 12/51, 11/51 and 6/51 males at 0, 500, 1500 and 5000 ppm and in 1/51 females at 500 ppm; adenoma in 2/12 interim dead males at 1500 ppm, carcinoma in 1/16 interim dead males at 5000 ppm; adenoma in 1/39, 1/41, 2/39 and 2/35 terminal kill males at 0, 500, 1500 and 5000 ppm, carcinoma in 6/39, 11/41, 7/39 and 3/35 terminal kill males at 0, 500, 1500 and 5000 ppm and in 1/38 terminal kill females at 500 ppm))","No effect >5000 ","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (accumulation of perivascular/peribronchiolar lymphocytes, accumulation of alveolar macrophages, associated with pulmonary neoplasia, focal pneumonitis, focal fibrosis, hyperplasia of the bronchioloar epithelium, focal pleural thickening, foci/area of haemorrhage, granulomatous foci, thrombus formation, perivascular acute inflammatory cells occasionally observed; cuboidal cell metaplasia of the alveolar in few animals, pre-neoplastic change)\nhistopathology, neoplastic findings: no treatment-related findings (adenoma in 2/12 interim dead males at 1500 ppm, in 9/39, 7/41, 7/39 and 4/35 terminal kill males  and 2/37, 4/38, 2/38 and 2/40 terminal kill females at 0, 500, 1500 and 5000 ppm; adenocarcinoma in 2/12, 1/10, 2/12 and 2/16 interim dead males and in 3/39, 4/41, 5/39 and 9/35 terminal kill males and in 5/37, 2/38, 2/38 and 3/40 terminal kill females at 0, 500, 1500 and 5000 ppm))","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (myelopoiesis, lymphoid hyperplasia, histiocytosis and angiectasis occasionally observed, age-related)\nhistopathology, neoplastic findings: no treatment-related findings (malignant lymphoma in 0/51, 1/51, 2/51 and 5/51 males and 11/51, 8/51, 10/51 and 11/51 females at 0, 500, 1500 and 5000 ppm; histiocystic sarcoma in a few females observed))","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (background inflammatory lesions in a few animals))","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (exocrine atrophy, exocrine cell hyperplasia, areas of necrosis, interstitial fibrosis, prominent lymphoid foci occasionally seen; islet cell hyperplasia in a few mice)\nhistopathology, neoplastic findings: no treatment-related findings (islet cell adenocarcinoma in 1/51 control females))","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (fibre degeneration in several control and treated females; isolated instances of focal mineralisation and neuritis)\nhistopathology, neoplastic findings: no neoplasms observed)","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (secretory depletion of the submandibular gland was frequently observed and more prevalent in females, no treatment related distribution; isolated instances if lymphocyte infiltration, distention of ducts, atropy, abscess formation, hypertrophy of mucous acini and peripheral inflammation)\nhistopathology, neoplastic findings: no neoplastic lesions)","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (isolated instances of mononuclear cell foci, vasculitis and focal mineralisation, spontaneous changes)\nhistopathology, neoplastic findings: no neoplastic changes)","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (several spontaneous lesions: epidermal ulceration, scab formation, inflammatory lesions, abscess formation, focal acanthosis, focal mineralisation, focal dermal thickening, focal necrosis occasionally observed; few instances of ectasia, atrophy or inflammation of unidentified subcutaneous glandular tissue)\nhistopathology, neoplastic findings: no treatment-related findings (dermal/subcutaneous fibrosarcoma in 6 males among all treatment-groups; haemangiosarcoma in 1/51 females at 500 ppm)\nTail: no treaetment-related findings (subcutaneous keratin cyst in a few mice of either sex; isolated instances of focal hyperostosis of bone, focal acanthosis and hyperkeratosis, focal inflammation))","No effect >5000 (Intestinal tract: histopathology, non-neoplastic findings: no treatment-related findings (isolated instances of mucosal hypertrophy, mucosal hyperplasia, focal mucosal ulceration, submucosal oedema and inflammatory cell infiltration at various levels)\n histopathology, neoplastic findings: no treatment-related findings (benign adenoma in 1/51 control females))",null,"No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (higher grades of severity of extramedullary haematopoesis frequently observed in mice of either sex; lymphoid hyperplsaia, atrophy of lymphoid tissue and of the red pulp, background changes)\nhistopathology, neoplastic findings: no treatment-related findings (haemangioma in 1/51 control males, haemangiosarcoma in 1/51 and 1/51 females at 0 and 5000 ppm))",null,"No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (mucosal hyperplasia commonly observed, age-related; acanthosis and hypokeratosis of the forestomach frequently observed in both sexes, no toxicological significance, subepithelial and mucosal inflammation, epithelial ulceration, mineralisation of the muscularis, diverticulum formation and focal mucosal necrosis occasionally observed)\nhistopathology, neoplastic findings: no gastric neoplasia observed)","No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (lymphoid hyperplasia, atrophy and peripheral inflammatory cells occasionally observed upon all groups, more prevalent in females, age-related ;one incidence of histiocytic sarcoma in 1/7 examined females at 1500 ppm at terminal kill))",null,null,"No effect >5000 (Histopathology, non-neoplastic findings: no treatment-related findings (epithelial/subepithelial or peripheral inflammatory cell infiltrates, epithelial ulceration, subepithelial haemorrhage, acute inflammatory cells in the lumen and amorphous contents occasionally observed)\nhistopathology, neoplastic findings: no neoplasms observed)","No effect >5000 ","No effect >5000 (Haematology (differential white blood cell count performed only ): no treatment-related findings\nClinical chemistry: not performed\nUrinalysis: not performed)","No effect >5000 (No treatment-related findings. Wounds, scab formation, loss of whiskers, fur loss and limb swelling occasionally observed, consequence of intra-cage aggression)","No effect >5000 (Food consumption: no treatment-related findings\nFood efficiency: reduced in females of all dose levels in weeks 1 and 2, reduced in males at 5000 ppm in week 4 to 5, considered as an isolated event and not treatment-related)","No effect >5000 (No treatment-related findings, mortality rate was highest in males at 5000 ppm and lowest in females at 5000 ppm (survival up to terminal kill: 39/51, 41/51, 39/51 and 35/51 males and 37/51, 38/51, 38/51 and 40/51 females at 0, 500, 1500 and 5000 ppm))","No effect >5000 (Nasal cavities: no treatment-related findings (focal epithelial hyperplasia in both sexes frequently observed, epithelial inflammation, exudate overlaying the epithelium, dilatation of subepithelial glands, focal epithelial ulceration, prominent fibroplasia and resorption of bone occasionally observed; dental dysplasia and dental erosion/abscess formation in a few control and treated males)\nPharynx: no treatment-related findings (mononuclear cell infiltrates, exudate overlaying the epithelium, focal epithelial hyperplasia in a few animals, extensive inflammation and abscess formation in the supra-pharyngeal tissues in one control mouse)\nLarynx: no treatment-related findings (dilatation of subepithelial glands and epithelial/subepithelial inflammatory cell infiltrates, incidental)\nTrachea: no treatment-related findings (dilatation of subepithelial glands frequently observed in both sexes, isolated instances of inflammation)\nTongue: no treatment-related findings (focal inflammation, fibrosis, ulceration, vasculitis and abscess formation occasionally observed))"]
[21,"DAR",1997,"Mammals","Carcinogenicity","Mouse","1600; 8000; 40000","ppm","Oral",18,"Months","Adult","Achieved test substance intake: 165.0, 838.1 and 4348 mg/kg bw/day (males) and 153.2, 786.8 and 4116 mg/kg bw/day (females); no detailed haematology and clinical chemistry, but differential white blood cell count was determined; urinalysis only from males conducted in week 21","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >40000 ","No effect >40000 ",null,"No effect >40000 ",null,null,null,null,null,"No effect >40000 ",null,"No effect >40000 ",null,"No effect >40000 ",null,"No effect >40000 ",null,null,null,null,"No effect >40000 (Gross pathology: reduced incidence of atrophy at 40000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings\nHistopathology, neoplastic findings: no treatment-related findings)","No effect >40000 ","No effect >40000 (Histopathology, non-neoplastic findings: no treatment-related findings (reduced incidences of amyloid deposition in thyroid and parathyroid at 1600 and 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups)\nHistopathology, neoplastic findings: no treatment-related findings)",null,"No effect >40000 (Gross pathology: reduced incidence of cysts in females (found dead/killed in extremis and at terminal kill) at 40000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings (reduced incidences of amyloid deposition at 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups)\nHistopathology, neoplastic findings: no treatment-related findings)",null,"No effect >40000 ",null,"No effect >40000 ","No effect >40000 ",null,"No effect >40000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >40000 ",null,null,null,null,null,null,null,null,null,null,null,"No effect >40000 (Histopathology, non-neoplastic findings: femur: decreased incidences of haematopoesis in females at ≥ 1600 ppm, not treatment-related; sternum and vertebra:  decreased incidences of haematopoesis in females at ≥ 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups\nHistopathology, neoplastic findings: haematopoetic and lymphatic system, malignant lymphoma in 2/29 terminal kill males at 40000 ppm and in 4/32, 0/36, 5/40 and 3/35 terminal kill females at 0, 1600, 8000 and 40000 ppm, considered to be incidental)","No effect >40000 (Gross pathology: reduced incidence of opacity in females at 8000 and 40000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings\nHistopathology, neoplastic findings: no treatment-related findings)",null,null,null,"No effect >40000 (Gross pathology: reduced incidence of pale color and corse surface in females at 8000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings (reduced incidences of cortical cysts in both sexes at 40000 ppm; reduced incidences of glomerula amyoidosis in females at 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups)\nHistopathology, neoplastic findings: no treatment-related findings)","Increase 40000 (Rel weight stat. sign. increased in females at 40000 ppm, no treatment-relation as histopathology revealed no abnormalities)","No effect >40000 (Histopathology, non-neoplastic findings: no treatment-related findings (decreased incidences of microgranuloma in females of groups found dead/killed in extremis and at terminal kill at 40000 ppm and decreased incidences of amyloid deposition in males at 40000 ppm and in females at ≥ 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups)\nHistopathology, neoplastic findings: no treatment-related findings)","No effect >40000 ","No effect >40000 (Gross pathology: masses in 9/50, 14/50, 17/50 and 15/50 males and in 10/50, 8/50, 20/50 and 11/50 females at 0, 1600, 8000 and 40000 ppm, findings predominantly observed at terminal kill, no dose relation\nHistopathology, non-neoplastic findings: no treatment-related findings (increased alveolar epithelial cell hyperplasia in males at 1600 ppm, no dose-response relationship)\nHistopathology, neoplastic findings: no treatment-related findings)","No effect >40000 (Gross pathology: swelling of cervical lymph nodes, reduced incidence in females at 8000 ppm, increased incidence swelling of mesenteric lymph nodes in males at  40000ppm (0/50 in control, 6/50 at 40000 ppm with 5/6 in animals found dead/killed in extrmis), increased incidence of swollen lymph nodes in females found dead/killed in extremis at ≥ 8000 ppm\nHistopathology, non-neoplastic findings: no treatment-related findings (decreased incidence of plasma cell hyperplasia in females at ≥ 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups; decreased incidences of myeloid cell aggregation in males at 1600 ppm)\nHistopathology, neoplastic findings: haematopoetic and lymphatic system, malignant lymphoma in 2/29 terminal kill males at 40000 ppm and in 4/32, 0/36, 5/40 and 3/35 terminal kill females at 0, 1600, 8000 and 40000 ppm, considered to be incidental)",null,null,null,null,null,"No effect >40000 (Gross pathology: no treatment-related findings (loss of hair increased in males at 8000 ppm and decreased in females at 40000 ppm, reduced incidences of wounds in males at 40000 ppm and reduced incidences of ulcer/erosion in females at ≥ 8000 ppm, reduced incidences of swelling in males at 1600 and 40000 ppm, no dose relation)\nHistopathology, non-neoplastic findings: no treatment-related findings\nHistopathology, neoplastic findings: no treatment-related findings)","Change 40000 (Gross pathology: Caecum distention in males (28%) and females (36%) at 40000 ppm (14/50 males and 18/50 females at 40000 ppm, findings predominantly observed in terminal kill animals (11/29 males, 16/35 females), no animals of other groups, treatment-related); anal prolaps in the anus of 5/50 males at 40000 ppm, no findings in any other group, related to findings of loose stool; reduced incidence of amyloid deposition in the small intestine of females at 1600 and 8000 ppm, not treatment-related; small intestine: reduced incidence of amyloid deposition in females at 1600 and 8000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings\nHistopathology, neoplastic findings: no treatment-related findings)",null,"No effect >40000 (Gross pathology: reduced incidence in swelling of spleen in males at 1600 ppm and in females at 1600 and 8000 ppm, no dose relation\nHistopathology, non-neoplastic findings: no treatment-related findings (decreased incidences of extramedullary haematopoesis in  both sexes at 8000 ppm; amyloid deposition in females at ≥ 1600 ppm, attributed to decreased occurence of skin lesions in the treated groups)\nHistopathology, neoplastic findings: no treatment-related findings)",null,null,null,null,null,null,"Decrease 8000 (Occasional decreases among groups at 8000 and 40000 ppm throughout the treatment in both sexes, reduction in females at 8000 during weeks 6, 9 and 24 were considered to be treatment-related, body weight gain was comparable to those of controls at study termination)","Change 8000 (Haematology (differential white blood cell count only): no treatment-related findings, increased lymphocytes in males and decreased neutrophils in males killed in extremis at 40000 ppm and increased lymphocytes in females at week 78, findings were attributed to skin lesions of high grade in moribund animals of the control group, which had high values of leukocytes and reduced values of lymphocytes, considered to be of sporadic nature\nClinical Chemistry: not performed\nUrinalysis: decreased pH in males at ≥ 8000 ppm, treatment-related but considered to be without toxicological significance as no histopathological findings were seen)","No effect >40000 (No treatment-related findings (increased loss of tactile hair loss in males at 40000 ppm and in females at 1600 ppm, masses in the anus (associated with neoplastic changes) and pale coloured skin in males at 40000 ppm, hairloss in males at 8000 ppm, loose stool in both sexes from week 20/21 onwards at 40000 ppm))","Decrease 8000 (Food consumption: statistically significantly depressed (-6% overall) in males at 40000 ppm at weeks 1 and 68 and in females (-7% overall) at 40000 ppm at weeks 1, 4, 8, 12, 20, 28, 40, 48 and 68, treatment-related\nFood efficiency: decreased in both sexes at 40000 ppm (-9% and -24% in males and femeles, respectively) and in females at 8000 ppm  throughout the study period (-16% overall), treatment-related)","No effect >40000 (No significant differences between groups. Cumulative mortality was 24/50, 16/50, 23/50 and 21/50 in males and 18/50, 14/50, 10/50 and 15/50 in females at 0, 1600, 8000 and 40000 ppm)","Increase 40000 (Caecum: abs+rel weight stat. signif. increased in both sexes at 40000 ppm, treatment-related, no macroscopic lesions at histopathology but occurence of anal prolapse as a change related to loose stool)"]
[36,"DAR",2012,"Mammals","Repeated dose 28-day oral toxicity study in rodents","Mouse","500; 1500; 5000","ppm","Oral",28,"Days","Adult","Doses are equivalent to 150.1, 449.1, 1447.5 mg/kg bw/day","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 5000 (absolute/relaitve)",null,null,"No effect > 5000 (absolute/relaitve)",null,null,"No effect > 5000 ",null,"No effect > 5000 ","No effect > 5000 ","No effect > 5000 "]
[56,"DAR",1991,"Mammals","Repeated dose 90-day oral toxicity study in rodents","Mouse","200; 1000; 4500","mg/kg bw/day","Oral",90,"Days","Adult",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >4500 ",null,null,"No effect >4500 ","No effect >4500 (Epididymides weight was examined together with testes.)",null,null,null,null,"No effect >4500 ","No effect >4500 ","No effect >4500 ","No effect >4500 ","No effect >4500 ","No effect >4500 (Increased abs. weight (statistically not significant) and statist. signif. increased rel. weight at 1000 mg/kg bw/day, were considered incidental since no effect was observed in the high dose group. Moreover, no histopathological changes were observed.)","No effect >4500 ",null,null,null,null,"No effect >4500 ","No effect >4500 (Statistically signif. increased abs + rel weight at 200 and 1000 mg/kg bw/day, no dose-relation, considered to be by chance)","No effect >4500 ",null,"No effect >4500 ","No effect >4500 ",null,null,"No effect >4500 ","No effect >4500 ",null,"No effect >4500 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >4500 ","No effect >4500 (Statistically signif. increased abs. weight in females only at 4500 mg/kg bw/day, considered incidental due to the lack of a dose-response relationship and the variability seen in the other dose groups. Moreover, no histopathological changes were observed.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >4500 ","No effect >4500 (Increased incidence of cortical tubular epithelial hypertrophy in 1/10, 2/10 and 5/10 females and in 2/10, 0/10 and 2/10 males at 0, 200 and 1000 mg/kg bw/day, no findings in the high dose group. Due to lacking dose-response, the effect is not considered treatment-related (probably early stage in the development of nephropathy).)","No effect >4500 ","No effect >4500 ","No effect >4500 (Liver was weighed together with gall bladder.)","No effect >4500 ",null,null,null,null,null,null,null,null,null,null,"No effect >4500 ",null,"No effect >4500 ","No effect >4500 (Statistically signif. increased abs.+rel. weight in males only at the mid dose group (1000 mg/kg bw/day) was considered to be incidental, since no dose-response was observed.)",null,null,"No effect >4500 ","No effect >4500 (Haematology: No toxicologically relevant finding was observed. (Prothrombin time statist. signif. increased in females at 200 mg/kg bw/day, no dose-relation, considered to be incidental)\nClinical chemistry:  No toxicologically relevant finding was observed. (Dose-related increase in glucose levels in males over all test item treated groups, statistically not signifant; increase in  plasma cholinesterase and AP and decrease of K in males over all dose groups, not dose-related, toxicological significance of this finding is unclear; slightly increased glucose and AP levels in females in all test item treated groups, statistically not significant, no dose-response relationship)\nUrinalysis: Not performed)","No effect >4500 ","No effect >4500 (Neither food nor water consumtion were affected.)","No effect >4500 ","No effect >4500 (Lung weight was not affected.)"]
[67,"DAR",1989,"Mammals","Carcinogenicity","Mouse","100; 300; 1000","mg/kg bw/day","Oral",2,"Years","Adult",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Epididymides were weighed together with testes. Absolute organ weight was not affected.)",null,null,null,null,"No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Absolute organ weight was not affected.)","No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Absolute organ weight was not affected.)",null,null,null,null,null,"No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Testes were weighed with epididymides. Absolute organ weight was not affected.)","No effect > 1000 (Histopathological examination was performed for control and high dose group. No effects were observed in thyroid and parathyroid.)",null,"No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Absolute organ weight was not affected.)",null,null,"No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Absolute organ weight was not affected.)","No effect 1000 (Histopathological examination was performed for control and high dose group. The incidence of increased mineral deposits in the brain was higher in the high dose group (13/50, P<0.05) compared to control (4/49) in males only and is a common finding of mice of this strain and age. No effect was observed in females. Therefore, the effect is not considered toxicologically relevant.)","No effect > 1000 (Absolute organ weight was not affected.)",null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Absolute organ weight was not affected.)",null,null,null,null,null,null,null,null,null,"No effect > 1000 (Histopathological examination was performed for control and high dose group.)",null,null,"No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Heart and aorta were investigated. Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Absolute organ weight was not affected.)","No effect > 1000 ","No effect > 1000 (Absolute organ weight was not affected.)","No effect > 1000 ","No effect > 1000 (Liver with gall bladder was weighed. Absolute organ weight was not affected.)","No effect > 1000 ","No effect > 1000 (Mesentric lymph nodes were investigated. Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Sciatic nerve was investigated in control and high dose group.)","No effect > 1000 (Parotid, sublingual and submaxilliar salivary glands were investigated. Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Thigh was investigated. Histopathological examination was performed for control and high dose group.)",null,"No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Cervical, thoracic and lumbar parts of spinal cord were investigated of control and high dose group.)","No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Absolute organ weight was not affected.)","No effect > 1000 (Histopathological examination was performed for control and high dose group of the glandular and non-glandular stomach.)","No effect > 1000 (Histopathological examination was performed for control and high dose group.)","Increase 300 (Males: Absolute thymus weight was increased in the intermediate and high dose groups (P<0.01 and P<0.05 respectively) compared to control. Thymus weight was also increased in the intermediate and high dose groups after covariance analysis. The increase in high dose males was due to one animal which had an enlarged thymus infiltrated with lymphoma cells. Moreover, since no effect was observed at necropsy or histopathological examination, the increased thymus weight is considered not toxicologically relevant. \nFemales: No effect on organ weight was observed.)","No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Histopathological examination was performed for control and high dose group.)","No effect > 1000 (Treatment groups showed a comparable weight gain compared to controls.\nA slight decrease in absolute body weight at Week 40 was evident in all groups of both sexes except control and intermediate dose females. This transient effect is not considered to be attributable to the test substance.)","No effect > 1000 (Haematology: No effect on differential blood count was observed (weeks 52, 77, 102).)","No effect > 1000 (There were no notable intergroup differences in either sex. There were no notable intergroup differences in the incidences of externally palpable masses.)","No effect > 1000 (No effect on food and water (visual assessment) consumption was observed.)","No effect > 1000 (There were 208 pre-terminal deaths throughout the study. There was no evidence to suggest that any of these deaths were treatment-related. )","No effect > 1000 (Neoplastic findings:  \nThere were no statistically significant increases in incidence of any tumour. The number of animals with tumours, both benign and malignant, was similar between the control and high dose groups (m+f).\nAnimals with multiple tumour types was slightly increased in the high dose group of both sexes (males: 16/50 and females: 11/50) compared to control (males: 11/50 and females: 6/50) causing a slight increase in the total number of tumours in the high dose group of both sexes (males: 60 and females: 43) compared to control (males: 49 and females: 36). \nHaemangiosarcoma was evident in 4/50 high dose males, 2/50 low dose females and 1/50 high dose females (not significant) compared to the respective controls (m+f: 0/50).\nHistiocytic sarcoma in the lymphoreticular/haemopoietic tissue was evident in 2 low and 2/50 high dose males and 3 low, 3 intermediate and 1/50 high dose females (not significant) compared to the respective controls (m+f: 0/50).\nThe incidences of haemangiosarcoma and histiocytic sarcoma were higher in all groups of both sexes exposed to the test substance. Similar incidences of haemangiosarcoma and histiocytic sarcoma have been seen in other studies using mice of a similar age and strain (historic control data). Due to the lack of a dose relationship, statistical significance and the incidences in this study falling within the historic control ranges, these changes are not considered to be due to test substance treatment.\n)"]
[68,"DAR",1983,"Mammals","Chronic toxicity","Mouse","1000; 5000; 30000","ppm","Oral",2,"Years","Adult","equivalent to 180.4, 891.8 and 5342.4 mg/kg bw/day for males and 208.4, 1005.6 and 7045.5 mg/kg bw/day for females","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 30000 ",null,null,null,null,null,"No effect > 30000 ","No effect > 30000 ","No effect > 30000 ","No effect > 30000 (The mean absolute and relative (to body and brain weight) ovarian weights for the high-dose females were markedly elevated, although differences from control were not statistically significant. These differences were due to a single animal, whose ovarian weight was approximately six times the mean ovarian weight for the group when this value was excluded. Differences from control excluding this animal were not apparent.)","No effect > 30000 ",null,null,null,null,null,null,"No effect > 30000 ","Increase 30000 (At terminal sacrifice, the mean absolute and relative weights (to brain and body weight) of the testes were elevated for the high-dose group. (Epididymis was not weighed.) No histopathological effects were observed.)","No effect > 30000 ",null,"No effect > 30000 (Uterus histopathology was performed including uterine horns and cervix.)",null,null,null,"No effect > 30000 ","No effect > 30000 (The mean absolute and relative (to body and brain weight) adrenals weight were not affected.)","No effect > 30000 ","No effect > 30000 (The mean absolute and relative (to body and brain weight) brain weight were not affected.)",null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 30000 ",null,null,null,null,null,null,null,null,null,"No effect > 30000 ","No effect > 30000 ","No effect > 30000 (Bone marrow histopathology was performed of the costochondral juction).)","No effect > 30000 (Eyes were examined includong the optic nerve and contiguous Harderian glands.)","No effect > 30000 ","No effect > 30000 ","No effect > 30000 (The mean absolute and relative (to body and brain weight) heart weight were not affected.)","No effect > 30000 ","No effect > 30000 (The mean absolute and relative (to body and brain weight) kidneys weight were not affected.)","Change > 30000 (Centrilobular hepatocyte hypertrophy: 6%, 10%, 18% and 34% in control to high dose groups, respectively (no further neoplasms). This change may represent an adaptation to hepatocellular metabolism.)","No effect > 30000 (The mean absolute and relative (to body and brain weight) liver weight were not affected.)","No effect > 30000 ","No effect > 30000 (Mediastinal, mesenteric and regional lymph nodes were examined.)","No effect > 30000 ","No effect > 30000 ","No effect > 30000 (The sciatic nerve was examined.)","No effect > 30000 (mandibular )","No effect > 30000 (The biceps femoris was examined.)",null,"No effect > 30000 ","No effect > 30000 ","No effect > 30000 ","No effect > 30000 (The mean absolute and relative (to body and brain weight) spleen weight were not affected.)","No effect > 30000 ","No effect > 30000 ",null,"No effect > 30000 ","No effect > 30000 (A slight-to-mild epithelial hyperplasia of the urinary bladder in males. The incidence was 6%, 6%, 20% and 16% controls through high-dose, respectively. Even though the increase at the mid- and high-dose was present, no test substance relationship was derived based on the missing dose-relationship.)","Decrease 30000 (Mean body weights for the high-dose males were generally lower than control (-11% at Week 102) and were (mostly) statistically significant. Mean body weights for the high-dose females and the males and females at the low- and mid-dose levels were not affected. Mean fasted body weight at termination of the study was statistically significantly reduced for male high dose animals. Moreover, no effect on body weight gain was observed for all dose groups.)","No effect > 30000 (Haematology (12, 18, 24 months): Differences observed (after 12 month) were not attributed to treatment. Moreover, morphologic evaluation of leukocytes and erytrocytes showed no effect.)","No effect > 30000 (No treatment-related clinical signs were observed.)","No effect > 30000 (No consistent effect on feed and water consumption was observed.)","No effect > 30000 (The incidence of mortality was considered to demonstrate no dose- or test substance-related adverse effect.)","No effect > 30000 (Neoplastic findings were those commonly encountered in mice: Bronchiolaralveolar tumors of the lungs, hepatocellular neoplasms, and tumors of the lymphoreticular system accounted for the majority encountered. There were no suspected test substance-associated trends in the incidence of these tumors or in any of the other spontaneously occurring neoplasms. Lymphoreticular tumors tended to be more frequent in treated animals, particularly the females. The numbers were relatively small and differences from the control failed to provide supportive evidence that the neoplasms had a test substance\nrelationship.\nThe other neoplasms that occurred with any frequency in treated mice only were renal tubule adenomas (males: 3 present at the high-dose; 1 at the mid-dose level). However, the distribution of this benign tumor was considered spurious and unrelated to treatment.\n\n\nRenal tubule adenomas (males only; 3 in high-dose and 1 in the mid-dose) -> spurious and unrelated to treatment due to the absence of other renal lesions.)"]
[72,"DAR",1978,"Mammals","Repeated dose 28-day oral toxicity study in rodents","Mouse","100; 300; 1000","mg/kg bw/day","Oral",28,"Days","Adult","Dose-range finder","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (Slightly lower mean body weights, compared to control, were noted for males receiving 300 and 1000 mg/kg/day through week two. However, these a differences were not considered treatment-related but attributed to slightly lower pretest body weights.)",null,"No effect >1000 ","No effect >1000 (Incidences of changes in food consumption not treatment-related)","No effect >1000 "]
[73,"DAR",1979,"Mammals","Repeated dose 90-day oral toxicity study in rodents","Mouse","5000; 10000; 50000","ppm","Oral",90,"Days","Adult","Mean substance intake: M 5000 ppm=945 mg/kg bw/day; M 10000 ppm=1867 mg/kg bw/day; M 50000 ppm= 9707 mg/kg bw/day; F 5000 ppm=1528 mg/kg bw/day; F 10000 ppm= 2735 mg/kg bw/day; F 50000 ppm=14858 mg/kg bw/day ","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ",null,null,null,null,null,null,null,"No effect >50000 ","No effect >50000 (Absolute and relative (to body and brain weight) organ weight was not affected.)","No effect >50000 ",null,null,null,null,null,null,"No effect >50000 ","No effect >50000 (Absolute and relative (to body and brain weight) organ weight was not affected.)","No effect >50000 ",null,"No effect >50000 ",null,null,null,"No effect >50000 (No treatment-related effect observed (cortical hyperplasia in 3/8 M (control), 5/10 F (control), 1/10 F (50000 ppm); vacuolation 4/10 F (control) and 3/10 F (50000 ppm)).)",null,"No effect >50000 ","No effect >50000 (Relative organ weight (relative to body weight) was increased (M 50000 ppm =+11%*) which was attributed to lower terminal body weight and thus not of toxicological relevance. No effects on absolute organ weight were observed.)",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ",null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 (No effect on bone and bone marrow was observed.)",null,"No effect >50000 ",null,"No effect >50000 (Relative organ weight (relative to body weight) was increased (M 50000 ppm=+16%*) which was attributed to lower terminal body weight and thus not of toxicological relevance. No effects on absolute as well as relative (to brain weight) organ weight were observed.\n)","No effect >50000 (No treatment-related effect was observed (minimal interstitial inflammation 3/10 M (control), 4/10 M (50000 ppm), 4/10 F (control), 2/10 (50000 ppm)).)","Increase >50000 (Relative organ weight (relative to body weight) was increased (M 50000 ppm =+18.5%*) which was attributed to lower terminal body weight and thus not of toxicological relevance. No effects on absolute as well as relative (to brain weight) organ weight were observed.\n)","No effect >50000 (No treatment-related effect was observed (small focal accumulations of inflammatory cells in control and treated animals at 50000 ppm).)","No effect >50000 (Relative organ weight (relative to body weight) was increased ( M 10000 ppm=+9%*; M 50000 ppm=+12%* ) which was attributed to lower terminal body weight and thus not of toxicological relevance. No effects on absolute as well as relative (to brain weight) organ weight were observed.)","No effect >50000 (No treatment-related effect was observed (Pneumonitis 1/10 M (control), 2/10 M (50000ppm), 1/10 F (control), 2/10 F (50000ppm); peribronchial lymphoid hyperplasia 4/10 M (control), 5/10 M (50000ppm), 1/10 F (control), 2/10 F (50000ppm); perivascullar lymphoid hyperplasia 2/10 M (control), 2/10 F (control), 1/10 F (50000 ppm)).)","No effect >50000 (No effect on mesenteric lymph nodes was observed.)",null,"No effect >50000 ",null,null,"No effect >50000 ",null,null,"No effect >50000 ","No effect >50000 (No treatment-related effect observed (extramedullary hematopoiesus 8/10 M (control), 9/10 M (50000 ppm), 10/10 F (control), 10/10 F (50000 ppm); pigment 7/10 M (control), 6/10 F (50000ppm), 10/10 F (control), 10/10 F (50000ppm)))","No effect >50000 (Absolute and relative (to body and brain weight) organ weight was not affected.)","No effect >50000 (No effect on gastro-intestinal tract was observed.)",null,null,null,"No effect >50000 ","Decrease 50000 (Statistically significant decrease of body weights in males and females at 50000 ppm throughout the study period leading to final body weight reduction of -11%* in M at 50000ppm and -8%* in F at 50000ppm (compared to control). Incidences of statistically significant lower body weights were observed in males at 10000 ppm and females at 5000 and 10000 ppm.)",null,"No effect >50000 ","Increase >50000 (Incidents of statistically significant increased food consumption in M at 5000; 10000; 50000 ppm and in F at 5000; 50000 ppm.)","No effect >50000 (No treatment-related deaths were observed (1 male (control) and 1 female (10000 ppm) died spontaneously).)"]
[79,"DAR",1992,"Mammals","Repeated dose 90-day oral toxicity study in rodents","Mouse","3125; 6250; 12500; 25000; 50000","ppm","Oral",90,"Days","Adult","Average substance intake over study period: M 3125 ppm= 507 mg/kg bw/day; M 6250 ppm= 1065 mg/kg bw/day; M 12500 ppm= 2273 mg/kg bw/day; M 25000 ppm= 4776 mg/kg bw/day; M 50000ppm= 10780 mg/kg bw/day; F 3125 ppm= 753 mg/kg bw/day; F 6250 ppm= 1411 mg/kg bw/day; F 12500 ppm= 2707 mg/kg bw/day; F 25000 ppm= 5846 mg/kg bw/day; F 50000 ppm= 11977 mg/kg bw/day","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ",null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ","No effect >50000 ","No effect >50000 ",null,"Increase 25000 (An increase in relative but not absolute organ weight was observed at 25000 ppm and 50000 ppm. The increase was considered secondary to decreased body weights. Histopathology was not performed within this study. )",null,null,null,null,null,null,"No effect >50000 ",null,"No effect >50000 (Three sections frontal cortex and basal ganglia, parietal cortex and thalamus, cerebellum and pons were examined.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 (Femur and epiphysis was examined)","No effect >50000 ","No effect >50000 ","No effect >50000 ",null,"Increase 12500 (Relative: M at 12500 ppm; 25000 ppm; 50000 ppm; F no treatment-related effects)",null,"Increase 6250 (Relative: M at 6250 ppm; 12500 ppm; 25000 ppm; 50000 ppm; F no treatment-related effects)",null,"Increase 6250 (Relative:M at 6250 ppm; 12500 ppm; 25000 ppm; 50000 ppm; F no treatment-related effects)",null,null,"No effect >50000 ",null,null,"Change 6250 (Parotid salivary gland: Increase of basophilia in acinar cells (Cytoplasmic alteration) in M and F at 6250 ppm; 12500 ppm; 25000 ppm; 50000 ppm)",null,null,null,null,null,null,null,null,"Increase 50000 (Relative: M at 50000 ppm; F no treatment-related effects)",null,null,"Decrease 25000 (Decreased body weight gains in M and F at 25000 ppm and 50000 ppm)",null,null,"No effect >50000 ","No effect >50000 ","Increase 6250 (Lung relative weigt: M at 6250 ppm; 12500 ppm; 25000 ppm; 50000 ppm; F no treatment-related effects)"]
[94,"Publication",2019,"Mammals","Subchronic oral toxicity in rodents","Mouse","0.5; 5; 50","mg/kg bw/day","Oral","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Offspring (F1)","This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the test conditions were not clearly described and the number of animals tested per dose level is too limited.   ","Yes","N/A",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50 (Aromatase and Cyp11A1 mRNA levels were not affected.)",null,"Decrease 0,5 (Serum testosterone level was statistically significantly decreased in the low and high dose group in 35 day old males. However, no dose-response was observed. No significant effect was observed in 8 months old rats.)",null,null,null,null,null,null,null,null,null,null,null,"No effect >50 (Epididymides weights were determined in 35 day and 8 months old males and no statistically significant effect was observed.)",null,null,null,null,null,null,null,null,null,null,null,"No effect >50 (Seminal vesicles weights were determined in 35 day and 8 months old males and no statistically significant effect was observed.)",null,null,"No effect >50 (Spermatozoa number was not statistically significantly affected.)","No effect >50 (Number of germ and Sertoli cells as well as undifferentiated spermatogonia were determined via immunostaining. No effect was observed in the number of Sertoli cells. A decrease in spermatogonia was observed in the mid dose group (no information on statistical significance, tested in 35 day old rats). Since no dose-relationship was observed, the effect is considered biologically not relevant.\nAn increase in vacuoles in the seminiferous epithelium of the testis and empty tubules were observed in glyphosate groups compared with control. However, this was only observed in 20 day old animals and not in animals aged 35 days. Therefore, this is considered a reversible finding and not adverse.)","Decrease 0,5 (Relative testes weight was not affected in 20 day old males. A decrease in relative weight was observed in the low and mid dose group aged 35 days reaching statistical significance for the low dose only. In 8 months old rats a decrease in relative testes weight was observed for the low and the high dose group achieving statistical significance for the low dose only. Since no dose-response was observed and the absolute testes weight is not provided, the effects on testes weight are considered isolated findings. )",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50 (Body weight was not affected in 5 and 35 day old males at any dose. An increase in 20 day old males was observed but is not considered biologically relevant since only the low dose was affected (no information on statistical significance provided).)"]
[95,"Publication",2019,"Mammals","Subacute oral in rodent ","Mouse",5000,"mg/L water","Oral","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Offspring (F1)","Given the small group size, the large inter animal variability observed, the lack of consistency between the same parameter across the sexes, timepoints or sampling matrices, and the deficiencies listed above, it not possible to clearly attribute any of the observed differences to glyphosate exposure. Therefore, the current study provides no evidence that glyphosate exposure causes lipid metabolism disruption in offspring following prenatal (in utero) exposure.  \nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate used is not sufficiently characterized, only one dose level was tested, there was large inter animal variability observed and too few animals per dose level were analysed. Moreover, the dose is not provided in mg/kg bw/d.","Yes","N/A",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Change 5000 (There were significant differences in the expression levels of the genes SREBP1C, SREBP2, Fasn, Hmgcr, Hmgcs and PPARa.\nThe relative expression levels of the genes SREBP1C, SREBP2, Fasn, Acc, Scd, Hmgcr, Hmgcs1 and Hmgcs2 showed a significant increase in GD19 fetuses and PND7 and PND21 offspring. These genes are closely related\nto hepatic lipid production, so their elevation contributes to increased fat storage. However, this kind of increase does not match well to the trend in serum lipid content alteration. The levels of PPARa in PND7 males and PND21 females increased remarkably, which is likely due to the growing demand for lipid catabolism caused by the increased lipid content.\n(The expression levels of the genes SREBP1C (Sterol Regulatory Element Binding Protein 1C), SREBP2 (Sterol Regulatory Element Binding Protein 2), Fasn (Fatty acid synthase, which catalyzes fatty acid synthesis), Scd (Stearoyl-CoA Desaturase 1), Acc (Acetyl-CoACarboxylase), Hmgcr (3-hydroxy-3-methyl-glutaryl-CoA reductase), Hmgcs1 (3-hydroxy-3-methylglutaryl-CoA synthase 1), Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthase 2) and PPARa (Peroxisome proliferator-activated receptor alpha) were determined. The relative expression levels of the above genes were normalized to b-actin expression.))",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Increase 5000 (The concentrations of lipids such as triglycerides (TGs), total cholesterol (T-CHO), and low-density lipoprotein cholesterols (LDL-C) increased to a significant extent in both the serum and livers. \n(The following serum biochemical indexes were determined: aspartate transaminase (AST), alanine transaminase (ALT), TG, T-CHO, low- and high-density lipoprotein cholesterol (LDL-C and HDL-C). Additionally,  TG, T-CHO, LDL-C and HDL-C content was measured in liver homogenate.))",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >5000 (Group mean body weight of pups by sex showed no statistical differences from control. There was no effect on average birth weight of pups, the slight difference observed in the glyphosate-treated group should be attributed to the slightly larger mean litter size observed (14.4 pups compared to 10.8 in the control group).)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Change 5000 (Hepatic steatosis with excessive lipid droplet formation was observed.)"]
[95,"Publication",2019,"Mammals","Subacute oral in rodent ","Mouse",5000,"mg/L water","Oral","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Adult","Given the small group size, the large inter animal variability observed, the lack of consistency between the same parameter across the sexes, timepoints or sampling matrices, and the deficiencies listed above, it not possible to clearly attribute any of the observed differences to glyphosate exposure. Therefore, the current study provides no evidence that glyphosate exposure causes lipid metabolism disruption in offspring following prenatal (in utero) exposure.  \nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate used is not sufficiently characterized, only one dose level was tested, there was large inter animal variability observed and too few animals per dose level were analysed. Moreover, the dose is not provided in mg/kg bw/d.","Yes","N/A",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >5000 (Number of fetuses was not statistically significantly affected.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >5000 (Body weight gain of pregnant mice was not statistically significantly affected.)",null,null,"Decrease 5000 (Water consumption of dams was statistically significantly reduced. Feed intake was reduced (not statistically significant).)"]
[30,"DAR",1995,"Mammals","Prenatal developmental toxicity study","Rabbit","10; 100; 300","mg/kg bw/day","Oral","13 (GD 6-18)","Days","Adult","Treatment on gestation days 6-18, caesarian section on gestation day 27","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >300 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >300 (Gravid uterus weight was not affected.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >300 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 300 (Decreased bw at 300 mg/kg bw/day on gestation days 16-24, not statistically significant; decreased bw gain at 300 mg/kg bw/day during gestation days 0-16 and 0-24)",null,"Increase 300 (Loose stool in 4/17 females during the dosing period at 300 mg/kg bw/day  and soiled fur in the perianal region in 2 of them, loose stool remained in 2/4 affected females of this group after dosing, one of the affected does aborted on gestation day 26 and the other one prematurely delivered on gestation day 27, treatment-related (not treatment-related findings: hair loss in 1/17 and 1/16 females at 10 and 100 mg/kg bw/day during dosing and in  1/17 and 1/16 females at 10 and 100 mg/kg bw/day post-dosing, loose stool and red material on the tray in 2/18 control females after dosing, loose stool in 1/17 females at 10 mg/kg bw/day post-dosing))","No effect >300 ","Increase 300 (1/18 females died at 300 mg/kg bw/day, histopathology revealed pale color in the liver and ascites in the abdomnial cavity, treatment relation could not be entirely denied (not treatment-related findings: 1/18 females at 10 mg/kg bw/day died, necropsy revealed no abnormalities))"]
[30,"DAR",1995,"Mammals","Prenatal developmental toxicity study","Rabbit","10; 100; 300","mg/kg bw/day","Oral","13 (GD 6-18)","Days","Fetus","Treatment on gestation days 6-18, caesarian section on gestation day 27","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >300 ",null,null,null,null,"No effect >300 ",null,null,null,"No effect >300 ",null,null,null,null,"No effect >300 (High incidence of maternal rabbits with fetuses with any malformation at 300 mg/kg bw/day, malformations were of inconsistent type and comprised external, visceral and skeletal malformations in single animals, considered to be sporadic)",null,null,null,"No effect >300 "]
[31,"DAR",1996,"Mammals","Prenatal developmental toxicity study","Rabbit","50; 200; 400","mg/kg bw/day","Oral","13 (GD 7-19)","Days","Adult","Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect 400 (Gross necropsy: blood and dead fetuses in 1/2 dead females at 400 mg/kg bw/day, treatment-related (there were no histopathological findings))",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 400 ",null,null,null,null,null,"No effect 400 (Increased at 400 mg/kg bw/day due to 1/18 females with nine late deaths (69.2%), not treatment-related; increased at 200 mg/kg bw/day due to early fetal deaths, no dose relation, considered to be not treatment-related)","No effect > 400 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Change 400 (Macroscopic findings in 2/4 females at 400 mg/kg bw/day that died/were killed in extremis, treatment-related (fluid-filled large intestines, haemorrhage, ulceration and sloughing of the stomach, duodenum, congestion and colon, rectum and appendix gas distended; the animal killed in extremis had blood and dead fetuses in the uterus))",null,null,null,null,"Decrease 200 (Reduced bw gain at ≥ 200 mg/kg bw/day from days 9-29 of gestation, treatment-related. Statistical significance was observed for body weight gain in the high dose group only from Days 13-29 post coitum.)",null,"Increase 400 (Scours (16/18 does), reduced faecal output (6/18 does) and diarrhoea (10/18 does) at 400 mg/kg bw/day, treatment-related (lethargy, ptosis, hunched posture, hypothermia and blood on tray in 1/18 females at 400 mg/kg bw/day killed in extremis) (not treatment-related: vaginal bleeding in 1/18 females at 200 mg/kg bw/day, no dose-relation, not evaluated as toxicological effect, scours in 5/18, 10/18 and 7/18 females at 0, 50 and 200 mg/kg bw/day))","Decrease 400 (Food consumption: Reduced at 400 mg/kg bw/day during the dosing period, treatment-related)","Increase 400 (Intercurrent deaths in 2/18 females at 400 mg/kg bw/day (one died on gestation day 19, one was sacrificed in extremis on day 20, histopathological findings of the stomach and intestine in the animal found dead, treatment-related (further mortalities, not treatment-related: each 1/18 females at 0 and 200 mg/kg bw/day, mal-dosing))"]
[31,"DAR",1996,"Mammals","Prenatal developmental toxicity study","Rabbit","50; 200; 400","mg/kg bw/day","Oral","13 (GD 7-19)","Days","Fetus","Treatment on gestation days 7-19, caesarian section on gestation day 37","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 400 ",null,null,"No effect >400 ",null,"No effect > 400 ",null,null,null,"Increase 200 (Dead fetuses in 1/2 dead females at 400 mg/kg bw/day, treatment-related. Slight increase in late fetal death at 400 mg/kg bw/day leading to an increase of total fetal deaths, attributed to one animal with nine late deaths resulting a post-implatation loss of 69.2%, not treatment-related; increased early fetal death leading to an increase in total fetal death at 200 mg/kg bw/day, no dose relation, considered to be unrelated to treatment)",null,null,null,null,"No effect > 400 (No treatment-related findings. Incidences of external and visceral malformations observed in single animals, no dose relation. Incidences of skeletal malformations of different types were higher but comparable between treatment and control animals and therefore not attributed to treatment.)",null,null,null,"No effect > 400 "]
[32,"DAR",1996,"Mammals","Prenatal developmental toxicity study","Rabbit","100; 175; 300","mg/kg bw/day","Oral","13 (GD 8-20)","Days","Adult","Treatment on gestation days 8-20, caesarian section on gestation day 30","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 300 (Absolute gravid uterine weight)",null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 300 (Mean fetal weight was reduced, which was attributed to 2 litters with particularly low fetal weight.)","No effect > 300 ",null,null,"No effect > 300 (viable foetuses; number of intra-uterine deaths early+late, )",null,null,"No effect > 300 ","No effect > 300 ",null,null,null,null,"No effect > 300 (The proportion of male fetuses was increased in the 175 mg/kg bw/day group. This was not considered treatment-related since no dose-response was observed.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 175 (Body weight; statiscially significant; all animals except one showed recovery in the post dosing period)",null,"Increase 175 (Sings of diarrhoea; reduction in faecal output; staining in the genital area (300 mg/kg bw/day group); not significant for all groups)","Decrease 175 (Statistically significant)","No effect > 300 (1/20; 2/20; 2/20; 2/20 in the control, 100, 175 and 300 mg/kg bw/day group, respectively. The mortality was not considered to be treatment-related.)"]
[32,"DAR",1996,"Mammals","Prenatal developmental toxicity study","Rabbit","100; 175; 300","mg/kg bw/day","Oral","13 (GD 8-20)","Days","Fetus","Treatment on gestation days 8-20, caesarian section on gestation day 30","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 300 (Only very minor changes in ossification were observed in the 300 mg/kg bw/day group but not considered treatment-related but due to lower bodyweight of the foetuses)"]
[33,"DAR",1980,"Mammals","Prenatal developmental toxicity study","Rabbit","75; 175; 350","mg/kg bw/day","Oral","22 (GD 6-27)","Days","Adult","Treatment on gestation days 6-27, caesarian section on gestation day 28","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 350 (A slight decrease in mean fetal body weight was observed in all treatment groups which was comparable to historical control data.)","No effect > 350 ",null,null,"No effect > 350 (An increase in the mean number of viable foetuses in the 75 mg/kg bw/day was considered as not toxicologically relevant.)",null,null,"No effect > 350 ",null,null,null,null,null,"No effect > 350 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 350 (Mean maternal body weight gain was not affected.)",null,"Increase 175 (Increase in soft stool and diarrhea (from 175 mg/kg bw/d); nasal discharge (350 mg/kg bw/day group only))",null,"Increase 350 (11/16 animals died in the high dose group; 2/16, 1/16 and 3/16 animals died in the control, 75 and 175 mg/kg bw/day group, respectively. Reasons for mortality were: pneumonia, gastroenteritis, enteritis, respiratory disease, gastroenteritis and caecal ulcerations)"]
[33,"DAR",1980,"Mammals","Prenatal developmental toxicity study","Rabbit","75; 175; 350","mg/kg bw/day","Oral","22 (GD 6-27)","Days","Fetus","Treatment on gestation days 6-27, caesarian section on gestation day 28","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 350 (Malformations were noted only in treatment groups but not considered to be treatment-related due to a lack of a dose-related pattern and because the frequency did not exceed the historical control data; not increased due to control)"]
[34,"DAR",1993,"Mammals","Prenatal developmental toxicity study","Rabbit","20; 100; 500","mg/kg bw/day","Oral","13 (GD 6-18)","Days","Adult","Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 500 (absolute)",null,null,null,null,null,null,null,null,null,null,null,"No effect > 500 ",null,"Increase 20 (Litter weight was statistically significant higher in the low and mid dose group, but not in the high dose group)","No effect > 500 ",null,null,"No effect > 500 ",null,null,"No effect > 500 ","No effect > 500 ",null,null,null,null,"No effect > 500 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 500 (Lower body weight was observed at differnet stages of the study, but due to lower initial body weight the effect is not considered treatment-related; body weight gain is unaffected)",null,"Increase 500 (toxic syntoms of the respiratory and the gastrointestinal tract (rales, dyspnoea, diaahoea/soft stool and weakness))","No effect > 500 (Feed intake was only decreased in the pre-dosing period)","Increase 500 (4/16 and 8/15 animals died in the 100 and 500 mg/kg bw/day group, respectively.)"]
[34,"DAR",1993,"Mammals","Prenatal developmental toxicity study","Rabbit","20; 100; 500","mg/kg bw/day","Oral","13 (GD 6-18)","Days","Fetus","Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 28","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Increase 20 (A significant increase in dilated heart was observed in all treatment groups while other incidences of visceral malformations were not considered treatment-related; no treatment and dose-related significant major skeletal malformations; no significant or dose-relationship of the incidences of external malformations)"]
[35,"DAR",1989,"Mammals","Prenatal developmental toxicity study","Rabbit","125; 250; 500","mg/kg bw/day","Oral","13 (GD 6-18)","Days","Adult","Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 29","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 500 (absolute)",null,null,null,null,null,null,null,null,null,null,null,"No effect > 500 ",null,null,"No effect > 500 (No effect on corpora lutea was observed. Low number of viable implants and increase in non-viable implants in high dose group (not statistically significant). )",null,null,"Decrease 500 (Two animals of the high dose group aborted which is considered secondary to maternal toxicity. )",null,null,"No effect > 500 ","No effect > 500 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 500 (Reduced body weight was observed in the high dose group.)",null,"No effect > 500 ","Decrease 500 "]
[35,"DAR",1989,"Mammals","Prenatal developmental toxicity study","Rabbit","125; 250; 500","mg/kg bw/day","Oral","13 (GD 6-18)","Days","Fetus","Supplementary study: Treatment on gestation days 6-18, caesarian section on gestation day 29","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 500 (Fetal body weight per litter was not affected.)",null,null,null,null,null,null,null,null,"Decrease 500 (External: Tail abnormal, low-set ears; Visceral: ventricular septal defect, postvacal lung lobe absent, kidneys absent; skeletal: Rudimentary rib on lumbar arch)"]
[46,"DAR",1991,"Mammals","Prenatal developmental toxicity study","Rabbit","50; 150; 450","mg/kg bw/day","Oral","13 (GD 7-19)","Days","Adult","Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 450 (No effect on corpora lutea or implantation rate were observed (established parameters prior to treatment). )",null,null,"No effect > 450 (No effect on abortions was observed. Number of embryonic deaths was in treated groups was increased compared to concurrent control. However, this effect is not considered treatment-related since the concurrent control values were atypically low and observed incidences in treatment groups were within the  range of historic control data. Consequently viable fetuses at GD 29 and weight were reduced in treated groups. (A total of 18, 12, 15 and 13 pregnant females (and 163, 104, 112 and 95 foetuses) in control, 50, 150, 450 mg/kg bw/d group, respectively have been included in assessment.))",null,null,"No effect > 450 (An increase compared to concurrent control group was observed based on the increase of embryonic deaths. However, this effect was considered not treatment-related since the concurrent control group values were very low, no dose-related effect was observed, and incidence was only slightly above the historic control.)","No effect > 450 (No effect on pre-implantation loss was observed. However, treatment was started after implantation.)",null,null,null,null,"No effect > 450 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 150 (Body weight gain was slightly reduced from 150 mg/kg bw (GD11-19))",null,"Increase 50 (Light increase in females with gastro-intestinal disturbances (from 50 mg/kg bw/day), dose-related increase in the incidence of females showing soft/liquid faeces; sings of inappetence (150 mg/kg bw/day group and higher dose groups))","Decrease 150 (Food consumption was decreased throughout the treatment period.)","Increase 450 (1/20 animals of the high dose group died after abortion: gastro-intestinal disturbances; heart and kidneys pale; a few haemorrhagic depressions in the stomach (concurrent severe reduction in food intake; body weight loss))"]
[46,"DAR",1991,"Mammals","Prenatal developmental toxicity study","Rabbit","50; 150; 450","mg/kg bw/day","Oral","13 (GD 7-19)","Days","Fetus","Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 450 (Litter weight was similarly reduced at all dose-levels, reflecting the differences in the litter size. However, no change on mean fetal weight was observed.)",null,null,null,null,null,null,null,null,"No effect > 450 (Increases in fetuses with heart malformations (from 150 mg/kg bw/d) were not considered treatment-related when compared to historic control data of 13 studies performed the same year. Group mean incidences of anomalies and malformations showed no significant differences compared to the control group.)"]
[47,"DAR",1991,"Mammals","Prenatal developmental toxicity study","Rabbit","100; 250; 625","mg/kg bw/day","Oral","13 (GD 7-19)","Days","Adult","Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 625 ",null,null,"No effect > 625 (There were no treatment-related effects on corpora lutea count, implantation rate (all established prior to treatment).)",null,null,"No effect > 625 (No effect on embryonic deaths was observed.)",null,null,"No effect > 625 ","No effect > 625 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 100 (Transient body weight gain reductions were observed in the low and mid dose group and throughout the treatment period for the high dose group. )",null,"Increase 100 (Signs of gastro-intestinal disturbances and inappetence were observed in all dose groups.)","Decrease 100 (A marked reduction was observed in the high dose group and slight or transient reductions in the low and mid-dose group.)","Increase 625 (2/6 animals died in the high dose group (following marked body weight loss, inappetence, complete litter loss).)"]
[47,"DAR",1991,"Mammals","Prenatal developmental toxicity study","Rabbit","100; 250; 625","mg/kg bw/day","Oral","13 (GD 7-19)","Days","Fetus","Treatment on gestation days 7-19, caesarian section on gestation day 29","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 625 ",null,null,null,null,null,null,null,null,"No effect > 625 ",null,null,null,"No effect > 625 "]
[48,"DAR",1991,"Mammals","Prenatal developmental toxicity study","Rabbit","500; 750; 1000","mg/kg bw/day","Oral"," 7 (high dose) -13 (mid and low dose)","Days","Adult",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 750 (Marked weight loss was observed from 750 mg/kg bw/day (not significant).)",null,"Increase 500 (Soft feces (from 500 mg/kg bw/day); gastro-intestinal disturbances (from 750 mg/kg bw/day); haemorrhagic depressions of the stomach and damp/stained fur of the tail (1000 mg/kg bw/day).)","Decrease 1000 "]
[62,"DAR",1982,"Mammals","Repeated dose dermal toxicity","Rabbit","100; 1000; 5000","mg/kg bw/day","Dermal",21,"Days","Adult","Treatment of intact and abraded skin, treatment area 1-2% (100 mg/kg bw/day), 5-10% (1000 mg/kg bw/day) and 15-20% (5000 mg/kg bw/day), treatment on 5 days/week for 6 h/day under occlusive conditions","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >5000 ",null,null,null,null,null,null,null,"No effect >5000 ","No effect >5000 ","No effect >5000 ",null,"No effect >5000 ",null,null,null,null,"No effect >5000 (Traces of mild degeneration of seminiferous tubules were observed in control and treartment groups which were attributed to non-specific stress caused by treatment procedures.\n)","No effect >5000 ",null,"No effect >5000 ","No effect >5000 ",null,null,null,null,"No effect >5000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >5000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >5000 ","Increase >5000 (A significant increase in mean relative organ weight was observed in females of the 5000 mg/kg bw/d group which was not considered toxicologically relevant since no histopathological effects were observed.)","No effect >5000 ","No effect >5000 ",null,null,null,null,null,null,null,"No effect >5000 (No treatment-related findings. Findings of inflammation evident as mild dermal inflammatory cell infiltrate was comparable for treated and untreated skin among all groups in both sexes. (inflammation of treated skin in 3/5, 4/5, 3/5 and 3/5 males and of untreated skin in 5/5, 4/5, 4/5 and 3/5 males; inflammation of treated skin in 4/5, 4/5, 5/5 and 5/5 females and of untreated skin in 4/5, 5/5, 4/5 and 5/5 females))",null,null,null,null,null,null,null,null,null,"No effect >5000 ","No effect >5000 (Haematology: No treatment-related findings (statist. signif. increase in Hb and Hct in males at 100 mg/kg bw/day, no dose-relation)\nClinical chemistry: No treatment-related findings (statist. siginif. increase in Na in males at 5000 mg/kg bw/day, statist. signif. increase in glucose in females at 100 and 5000 mg/kg bw/day, statist. signif. decreased LDH in females at 5000 mg/kg bw/day were considered to be without biological significance)\nUrinalysis: not performed)","No effect >5000 (Clinical signs of systemic toxicity: soft stool, diarrhea and mucoid diarrhea and ocular and nasal discharge were observed in a few animals of both sexes among all groups, not treatment-related\nLocal skin reactions: doubtful or barely perceptible to very slight erythema at 5000 mg/kg bw/day in 3/5 males and 3/5 females with abraded skin and in 3/5 males and 2/5 females with intact skin, doubtful to barely perceptable edema at 5000 mg/kg bw/day in 2/5 males and 2/5 females with abraded skin and in 2/5 males and 2/5 females with intact skin, not considered biologically significant)","No effect >5000 ","No effect >5000 "]
[63,"DAR",1994,"Mammals","Repeated dose dermal toxicity","Rabbit","500; 1000; 2000","mg/kg bw/day","Dermal",28,"Days","Adult","Treatment: 10% coverage body surface area, 5 days/week for 6h/day under occlusive conditions","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >2000 ",null,null,null,null,null,null,null,null,"No effect >2000 ","No effect >2000 (Absolute and organ weight relative to brain weight was assessed.)","No effect >2000 ",null,null,null,null,null,"No effect >2000 (Atrophy, congestion and focal fatty degeneration in 1/5 and 1/5 males of control and high dose group, not treatment-related)","No effect >2000 (Absolute and organ weight relative to brain weight was assessed.)","No effect >2000 ","No effect >2000 (Fresh brain weight was recorded.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >2000 ","No effect >2000 (Absolute and organ weight relative to brain weight was assessed.)","No effect >2000 ","No effect >2000 (Absolute and organ weight relative to brain weight was assessed.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >2000 ","No effect >2000 (Haematology: no treatment-related findings. Mean corpuscular volume of platelets and variation of platelet volume were statist. signif. decreased in females at 1000 and 2000 mg/kg bw/day were within normal limits and therefore not attributed to treatment.\nClinical chemistry: no treatment-related findings. Statist. signif. increased urea values in males at 2000 mg/kg bw/day were within normal limits and therefore not attributed to treatment.\nUrinalysis: not performed)","No effect >2000 (Clinical signs of systemic toxicity: no adverse effects observed\nLocal skin reactions: very slight erythema in males at 2000 mg/kg bw/day through Days 7-20 and in females at 500 mg/kg bw/day lasting for 5 days were not attributed to treatment. No edema was observed.)","No effect >2000 ","No effect >2000 "]
[66,"DAR",1980,"Mammals","Prenatal developmental toxicity study","Rabbit","75; 175; 350","mg/kg bw/day","Oral","22 (GD 6-27)","Days","Adult","Vehicle: 0.5% aqueous Methocel","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >350 (There were no biologically meaningful or statistically significant differences in the mean numbers of total implantations or corpora lutea in any of the treatment groups when compared to the control group.)",null,null,"No effect >350 (Non-viable fetuses were not present in any group and there were no biologically relevant or statistically significant differences in the mean numbers of early or late resorptions in any of the treatment groups when compared to the control group. A statistically significant, though not biologically relevant increase was noted in the mean number of viable fetuses in the 75 mg/kg/day dosage group which was considered incidental. There were no biologically relevant or statistically significant differences in the mean numbers of total implantations or corpora lutea in any of the treatment groups when compared to the control group.\nABORTIONS: Two rabbits in the control group aborted and were sacrificed, both on gestation day 22. In the 175 mg/kg/day dosage group, one rabbit aborted and was sacrificed on gestation day 27. One rabbit in the 350 mg/kg/day dosage group aborted and was sacrificed on gestation day 23. Therefore, no treatment-related increase in the incidence of abortions was noted.)",null,null,"No effect >350 (There were no biologically relevant or statistically significant differences in the mean numbers of early or late resorptions in any of the treatment groups when compared to the control group.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >350 (There were no relevant differences in mean maternal body weight gain in any of the treatment groups when compared to the control group throughout the entire gestation period.)",null,"Change 175 (Soft stool and diarrhea were noted in all groups during the treatment period. A slight increase was noted, however, in the 175 mg/kg/day dosage group when compared to the control group and either soft stool, diarrhea or both were noted in each animal at least once during the treatment period in the 350 mg/kg/day dosage group. A definite increase in nasal discharge was also noted in the 350 mg/kg/day dosage group when compared to the control group.)",null,"Increase 350 (Two rabbits in the control group aborted and were sacrificed (GD 22). One rabbit in the 75 mg/kg/day dosage group died on gestation day 26. In the 175 mg/kg/day dosage group, one rabbit aborted and was sacrificed on gestation day 27 and two rabbits died, one each on gestation days 22 and 25. One rabbit in the 350 mg/kg/day dosage group aborted and was sacrificed on gestation day 23 and 10 died by gestation day 21. One rabbit in this group died on gestation day 3. On the same day, a replacement female was selected and artificially inseminated.)"]
[66,"DAR",1980,"Mammals","Prenatal developmental toxicity study","Rabbit","75; 175; 350","mg/kg bw/day","Oral","22 (GD 6-27)","Days","Fetus","Vehicle: 0.5% aqueous Methocel","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >350 (Each fetus was first examined for external malformations and variations and subsequently dissected, internally sexed, and examined for visceral malformations and variations. No genital abnormalities were reported.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >350 (There were no biologically relevant or statistically significant differences in mean fetal body weight in any of the treatment groups when compared to the control group. A slight decrease was noted in mean fetal body weight in all treated groups when compared to the control group, however, the parameter was comparable to the historical control.)",null,null,null,null,null,null,null,null,"No effect >350 (All fetuses were individually weighed and examined for external malformations and variations, including the palate and eyes. Each fetus was dissected, internally sexed and examined for visceral malformations and variations, including the brain by a mid-coronal slice. There were no statistically significant or biologically meaningful differences in the number of litters with malformations in any of the treatment groups when compared to the control group. Malformations were noted only in the treatment groups, however, this was not considered to be treatment-related as they did not occur in a dose-related pattern, were not similar in nature and the frequency did not exceed that of the historical control.)",null,null,null,"No effect >350 (There were no biologically meaningful or statistically significant differences in the mean numbers of fetal sex distribution in any of the treatment groups when compared to the control group.)"]
[77,"DAR",1979,"Mammals","Prenatal developmental toxicity study","Rabbit","125; 250; 500; 1250; 2500","mg/kg bw/day","Oral","22 (GD 6-27)","Days","Adult","Pilot study","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >250 (No significant effect on number of implantations or corpora lutea was obsereved in animals up to 250 mg/kg bw/d. Higher doses cannot be evaluated due to excessive maternal toxicity.)",null,null,null,null,null,"Increase 250 (A slight increase in the mean number of early and late resorptions and post-implantation loss was obsereved in animals of the 250 mg/kg bw/d dose group. Higher doses cannot be evaluated due to excessive maternal toxicity.)",null,null,null,null,null,null,null,null,null,null,null,"No effect >2500 (Yellow foci: 1/5 at 500 mg/kg bw and 1/5 at 1250 mg/kg bw \nErosions: 1/5 at 1250 mg/kg bw)",null,null,null,null,null,null,null,null,"No effect >2500 ",null,null,null,null,null,null,null,null,null,"No effect >2500 ",null,null,null,null,"Decrease 500 (Severe body weight loss at 500 mg/kg bw ( -9%* on GD 24 compared to GD 0) was observed.)",null,"No effect >2500 (The single surviving female of the 500 mg/kg bw group aborted on GD 26.)",null,"Increase 500 (4/5 at 500 mg/kg bw died between GD 15 and 22; 5/5 at 1250 mg/kg bw died on GD 10 and 11; 5/5 at 2500 mg/kg bw die on GD 9 and 10)"]
[77,"DAR",1979,"Mammals","Prenatal developmental toxicity study","Rabbit","125; 250; 500; 1250; 2500","mg/kg bw/day","Oral","22 (GD 6-27)","Days","Fetus","Pilot study","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect 250 "]
[1,"DAR",1996,"Mammals","Repeated dose 90-day oral toxicity study in rodents","Rat","1000; 5000; 20000","ppm","Oral",90,"Days","Adult","Achieved test substance intake: 81.33, 413.5 and 1612 mg/kg bw/day (males) and 90.42, 446.9 and 1821 mg/kg bw/day (females)","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,null,"No effect >20000 ",null,null,null,null,null,null,null,"No effect >20000 ",null,null,null,null,null,null,null,null,"No effect >20000 ","No effect >20000 (Reduced weight in all treatment groups (high value of single male in control group), not statistically significant, not treatment-related)","No effect >20000 ",null,"No effect >20000 ",null,null,null,"No effect >20000 ","No effect >20000 ",null,"No effect >20000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 20000 (Abs. weight in males reduced at 20000 ppm, attributed to reduced body weight)","No effect >20000 ","No effect 20000 (Rel. weight increased in males at 20000 ppm, not considered treatment related (no histopathological findings))","No effect >20000 ","Decrease 10000 (Abs. weight in males reduced at 1000 and 20000 ppm, no consistent trend, changes at 20000 ppm attributed to reduced body weight)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 20000 (Decreased in males at 20000 ppm over the whole study period, -8% in final bw (no effect in females), treatment-related)","Change 20000 (Haematology: reduced platelet count in both sexes at ≥ 5000 ppm, marginal increase in prothrombin time in males at all doses, both considered to be not tox. relevant\nClinical chemistry: ALT↑ and ALP ↑in both sexes at 20000 ppm throughout the study, treatment-related (non-treatment related findings: AST ↑ in females at 20000 ppm at week 4, ALT in males+females ocassionally increased at 5000 ppm, ALP in males at 1000 and 5000 ppm marginally increased, ALP↑ in each one females at control group and 1000 ppm in week 13, no dose-response relationship; ↓plasma urea (both sexes), plasma glucose (males) and triglyceride levels (males) at 20000 ppm)\nUrinalysis: lower pH in both sexes at 20000 ppm and higher values at 1000 and 5000 ppm for females, marginal changes within historical control data)","No effect >20000 (Low incidence of diarrhoea and pale faeces in both sexes at 20000 ppm in week 2, reversible, not unequivocally related to treatment\nophthalmoscopy: incidences of abnormal findings occasionally observed in control and 20000 ppm rats, not treatment-related)","Decrease 20000 (Food consumption: reduced in males at 20000 ppm from week 5, not significant, treatment-related\nfood efficiency: reduced in males at 20000 ppm throughout the study, treatment-related)","No effect >20000 "]
[2,"DAR",1996,"Mammals","Repeated dose 90-day oral toxicity study in rodents","Rat","1000; 10000; 50000","ppm","Oral",90,"Days","Adult","Achieved test substance intake: 90, 844 and 4188 mg/kg bw/day (males) and 79, 730 and 3706 mg/kg bw/day (females); histopathology: Ctrl + 50000 ppm examined only","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ",null,null,null,null,null,null,null,null,"No effect >50000 ","No effect >50000 ","No effect >50000 ","No effect >50000 ","No effect >50000 ",null,"No effect >50000 ","No effect >50000 ",null,null,null,"No effect >50000 ","Increase 50000 (Relative weight increased in all treatment groups, no histopathological correlate, effect at 50000 ppm attributed to reduced body weight and considered to be without toxicological relevance, in other dose groups attributable to slighly lower control group means)","No effect >50000 ",null,"No effect >50000 ",null,"No effect >50000 ",null,"No effect >50000 ","Increase 50000 (Relative weight increased in males at 50000 ppm, minimal effect, considered incidental in the absence of histopathological findings)",null,"Increase 10000 (Relative weight increased in males at ≥ 10000 ppm, effect at 10000 ppm considered incidental, effect at 50000 ppm attributed to reduced body weight and considered to be without toxicological relevance)",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ","Decrease 50000 (Absolute weight decreased in males at 50000 ppm, attributed to the reduced bw, toxicologically not significant; abs. weight decreased in females at ≥ 10000 ppm, not treatment-related, effect attributed to one control  group female with abnormally high value)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Change 50000 (Absolute weight reduced in both sexes and rel. weight increased in males at 50000 ppm, attributed to reduced body weight, considered to be without toxicological significance)","No effect >50000 (Hydronephrosis in one or both kidneys in 2/10, 1/10 and 1/10 males at 1000, 10000 and 50000 ppm and in 3/10 females at 1000 ppm, not treatment-related )","Increase 50000 (Relative weight increased in both sexes at 50000 ppm. However, no relevant treatment-related histopathological changes were observed.)","No effect >50000 ","Increase 50000 (Rel. weight increased in both sexes at 50000 ppm, treatment-related)",null,null,null,null,null,null,null,null,"Change 1000 (Caecum: macroscopical findings: enlarged and fluid-filled in 10/10 males and 10/10 females at 50000 ppm; microscopical findings: atrophy in 5/10 males and 5/10 females at 50000 ppm and for 1/10 males and 2/10 females at 10000 ppm, probably attributed to caecal distention )",null,"No effect >50000 ","Decrease 50000 (Absolute weight reduced in both sexes at 50000 ppm, attributed to reduced body weight, without toxicological significance)",null,null,null,null,null,"Decrease 50000 (Reduced body weight gain in males and females at 50000 ppm during the fist 4 weeks, effects partially reversible in males and fully reversible in females, treatment-related)","Change 10000 (Haematology: MCHC ↑ in females at 50000 ppm within historical control data, Neutrophils ↑ in males at 1000 and 50000 ppm, no dose-relation, findings incidental\nClinical chemistry: Ca ↓ and ALP ↑ in both sexes at ≥ 10000 ppm, P↑ and Creat↓ in both sexes at 50000 ppm, total plama protein and albumin ↓ in females at 50000 ppm, treatment-related (non-treatment-related findings: plasma urea↓ and Na ↓ in both sexes at 50000, within historical control data) \nUrinalysis: haemoglobin in urine ↑ in both sexes at 50000 ppm, particulate matter in sediment in males at 50000 ppm, findings may be attributed to faecal contamination)","Increase 50000 (Soft faeces and diarrhoea in 10/10 males and 10/10 females at 50000 ppm from Day 4 until termination, treatment-related )","Decrease 50000 (Food consumption/efficiency: reduced in males and females at 50000 ppm during the first 4 weeks, effects partially reversible in males and fully reversible in females, effects in line with reduced bw development, treatment-related)","No effect >50000 "]
[3,"DAR",1995,"Mammals","Repeated dose 90-day oral toxicity study in rodents","Rat","3000; 10000; 30000","ppm","Oral",90,"Days","Adult","Achieved test substance intake: 168.4, 569 and 1735 mg/kg bw/day (males) and 195.2, 637 and 1892 mg/kg bw/day (females)","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 ","No effect >30000 ",null,"No effect >30000 ",null,null,null,null,null,"No effect >30000 ","No effect >30000 ","No effect >30000 ",null,"No effect >30000 ",null,"No effect >30000 ",null,null,null,null,"No effect >30000 ","No effect >30000 ","No effect >30000 ",null,"No effect >30000 ",null,"No effect >30000 ",null,"No effect >30000 ","No effect >30000 ","No effect >30000 ","Increase 30000 (Rel. weight increased in females at 30000 ppm, considered to be the secondary change attributed to decreased body weight (no change in males))",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 (Polycystic kidney in 1/12 males at 10000 ppm and in 1/12 females at 30000 ppm, not treatment-related)","No effect 30000 ","No effect >30000 (Bile duct proliferation and cholangiectatis in 1/12 males at 10000 ppm and in 1/12 females at 30000 ppm, not treatment-related)","No effect >30000 (Rel. weight increased in females at 30000 ppm, not treatment-related, effect attributable to the genetic disorder of one animal)",null,null,null,null,null,null,null,null,"Change 10000 (Caecum: distention in 9/12 males and 7/12 females at 30000 ppm and in 3/12 males and 0/12 females at 10000 ppm, macroscopical finding, treatment-related)",null,null,null,null,null,null,null,null,"Decrease 30000 (Decreased bw (5--10% ) in both sexes at 30000 ppm, treatment-related)","Change 30000 (Haematology: no abnormalities observed\nClinical chemistry:  ALP ↑ in females at 30000 ppm, treatment-related (findings without toxicological relevance: Alb ↓ in females at 30000 ppm)\nUrinalysis: lower pH in males at ≥ 10000 ppm and in females at 30000 ppm, attributed to the acidic nature of the test substance (findings without toxicological significante: decreased urine protein in males at ≥ 10000 ppm and in females at 30000 ppm, not treatment-related findings: increased urine volume in females at 30000 ppm))","No effect >30000 (Poor general condition in 1/12 females (emaciation, decreased spontaneous motor activity), not treatment-related)","Decrease 30000 (Food consumption: statistically significantly decreased in both sexes at 30000 ppm during the first week, in line with reduced body weight, treatment-related (not treatment-related findings: decreased  food consumption in both sexes at 3000 ppm)\nfood efficiency: statistically significantly decreased (-5-6 %) in both sexes at 30000 ppm during the first week, in line with reduced body weight, treatment-related )","No effect >30000 ","Increase 30000 (Caecum: abs. + rel. weight statistically significantly increased in both sexes,  in line with pathological findings, treatment related)"]
[12,"DAR",1996,"Mammals","Chronic toxicity","Rat","2000; 8000; 20000","ppm","Oral",1,"Year","Adult","Achieved test substance intake: 141, 560 and 1409 mg/kg bw/day (males) and 167, 671 and 1664 mg/kg bw/day (females)","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,null,"No effect >20000 ","No effect >20000 (Abs + rel weights reduced in males at 2000 ppm, not dose-related, not treatment-related)",null,null,null,null,"No effect >20000 ",null,"No effect >20000 ",null,"No effect >20000 ",null,"No effect >20000 ",null,null,null,null,"No effect >20000 ","No effect >20000 ","No effect >20000 ",null,"No effect >20000 ",null,null,null,"No effect >20000 ","No effect >20000 ",null,"No effect >20000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 (Chronic progressive glomerulonenephropathy in 23/24 and 22/24 males at 0 and 20000 ppm, intratubular microlithiasis in 22/24 and 18/24 females at 0 and 20000 ppm, no treatment-related)","No effect >20000 (Abs. weight reduced in females at 8000 ppm, not dose-related, not treatment-related)","No effect >20000 (Minor degree of proliferative cholangitis in 12/24 and 11/24 males and 10/24 and 19/24 females at 0 and 20000 ppm, in line with historical control data, not treatment-related )","No effect >20000 (Abs. weight reduced in females at 8000 ppm, not dose-related, not treatment-related)",null,null,null,null,null,"Change 8000 (Mild focal basophilia of the acinar cells of the parotid salivary glands in both sexes at ≥ 8000 ppm, treatment-related but not toxicologically significant (2/24, 0/24, 3/24 and 13/24 males and 2/24, 0/24, 6/24 and 15/24 females at 0, 2000, 8000 and 20000 ppm))",null,null,null,null,null,null,null,null,null,null,null,"Decrease 8000 (Reduced body weight at ≥ 8000 ppm in both sexes, treatment-related)","Change 2000 (Haematology: no treatment-related findings (changes on several parameters were found but there was no dose-relation and differences were small + inconsistent)\nClinical chemistry: ALP↑ in females at ≥ 2000 and in males at ≥ 8000 ppm, treatment-related but toxicologically not significant as no pathological change was found; Creat↓ in males at ≥ 2000 ppm, no dose-relation; T.Chol↓ and TG↓ in males at ≥ 8000 ppm at weeks 14+27; ALT↑ in both sexes at ≥8000 ppm; Creat. Kinase↑ in both sexes at 20000 ppm, treatment-related (further parameters were occasionally changed in both sexes but there was no dose-relation, differences were small and inconsistent)\nUrinalysis: reduced volume in males at ≥ 8000 ppm in week 13+26 and in 2000 ppm at week 26, treatment-related)","Increase 20000 (Slight increase in urinary staining (wet and dry) at 20000 ppm in both sexes )","Decrease 8000 (Food consumption: reduced in both sexes at ≥ 8000 ppm, treatment-related (20000 ppm: reduced during the first 12 weeks of the study, 8000 ppm: occasionally reduced at the end of the study)\nfood efficiency: reduced in both sexes at 20000 ppm, treatment-related  (reduced during the first 4 weeks of the study))","No effect >20000 "]
[13,"DAR",1996,"Mammals","Combined chronic toxicity/carcinogenicity studies","Rat","100; 1000; 10000","ppm","Oral",2,"Years","Adult","Achieved test substance intake: 6.3, 59.4 and 595.2 mg/kg bw/day (males) and 8.6, 88.5 and 886.0 mg/kg bw/day (females)","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 ",null,"No effect >10000 (Neoplastic findings, dead/moribund animals: no treatment-related findings (undifferentiated sarcoma in 1/32 males at 1000 ppm))",null,null,null,null,null,"No effect >10000 (Interim kill: no abnormal findings \nterminal kill: ductectasia and acinectasia in 4/26, 1/24, 4/17 and 6/29 dead and moribund rats and 4/24, 2/26, 10/32 and 1/21 surviving rats of the 0, 100, 1000 and 10000 ppm group, statistically not significant, no dose-relation, age-related (not treatment-related: altered massed (adenoma/adenocarcinoma) at gross necropsy)\nNeoplastic findings, dead/moribund animals: no treatment-related findings (adenoma in 1/23, 1/22, 3/16 and 3/28 females at 0, 100, 1000 and 10000 ppm)\nNeoplastic findings, surviving animals: not treatment-related findings (adenoma in 1/17, 2/8, 5/17 and 2/20 females at 0, 100, 1000 and 10000 ppm; adenocarcinoma in 1/17 females at 0 ppm))",null,"No effect >10000 (Interim kill: cysts in 5/10 and 8/20 females of control and 10000 ppm at gross necropsy, not treatment-related\nterminal kill: cysts in 8/26, 3/24, 0/17 and 3/29 dead and moribund rats and 1/24, 4/26, 5/32 and 1/21 surviving rats of the 0, 100, 1000 and 10000 ppm group, age-related)","No effect >10000 ","No effect >10000 (Cysts in 16/30, 13/30, 18/32 and 12/21 dead or moribund males and 16/20, 0/20, 0/18 and 22/29 surviving males in the 0, 100, 1000 and 10000 ppm group)",null,"No effect >10000 ",null,null,null,null,"No effect >10000 (Interim kill: no abnormal findings \nterminal kill: small in size in 6/20, 4/20, 2/18 and 8/29 males and flabby in 6/20, 5/20, 0/18 and 8/29 males at gross necropsy and lower incidences of atrophy in 7/30, 10/30, 6/32 and 4/21 dead or moribund males and 8/20, 7/20, 1/18 and 11/29 surviving males in the 0, 100, 1000 and 10000 ppm group, not dose-related\nNeoplastic findings, dead/moribund animals: no treatment-related findings (Leydig cell tumor in 2/31 males at 1000 ppm; seminoma in 1/31 males at 1000 ppm)\nNeoplastic findings, surviving rats: no treatment-related findings (Leydig cell tumor in 2/20 and 3/29 males at 0 and 10000 ppm))","No effect >10000 ","No effect >10000 (Neoplastic findings, dead/moribund animals: no treatment-related effect (C-cell adenoma in each 1/29 males and 1/17 females at 1000 ppm)\nNeoplastic findings, surviving animals: no treatment-related findings (C-cell adenoma in 2/19 and 1/29 males and 2/24 and 1/20 females at 0 and 10000 ppm))",null,"No effect >10000 (Interim kill: small masses or polyps in 3/10 and 3/20 females at 0 and 10000 ppm at gross necropsy, not treatment-related\nterminal kill: focal irregular thickening in 7/24, 3/26, 12/33 and 6/21 females at gross necropsy, treatment-related but without dose-relation (not treatment-related: inflammatory changes at histopathology in 3/24, 2/26, 9/32 and 4/21 females at 0, 100, 1000 and 10000, not significant, no dose-relation)\nNeoplastic findings, dead/moribund animals: no treatment-related findings (adenocarcinoma in 1/17 females at 1000 ppm; anaplastic carcinoma in 1/24 females at 100 ppm; leiomyosarcoma in 1/29 females at 10000 ppm)\nNeoplastic findings, surviving animals: no treatment-related findings (adenoma in 1/21 females at 10000 ppm; adenocarcinoma in 2/22 females at 1000 ppm; adenomal papillary in 1/10 females at 100 ppm; hemangioma in 1/22 females at 1000 ppm))",null,null,null,"No effect >10000 (Interim kill: no abnormal findings \nterminal kill: vacuolar degeneration in dead/moribund and surviving rats among all treatment and control groups, blood filled cystic spaces in dead/moribund rats and medullary cell hyperplasia in surviving rats at similar incidences, not treatment-related\nNeoplastic findings, dead/moribund animals: no treatment-related findings (cortical cell adenoma in 2/30 males at 0 ppm and in 1/17 females at 1000 ppm; pheochromocytoma in 7/30, 3/30, 4/32 and 4/21 males at 0, 100, 1000 and 10000 ppm and in 2/29 females at 10000 ppm)\nNeoplastic findings, surviving rats: no treatment-related findings (cortical cell adenoma in 1/20 and 1/4 males at 0 and 1000 ppm and in 2/7 and 1/21 females at 1000 and 10000 ppm; pheochromocytoma in 6/20, 2/3, 2/4 and 12/29 males and 1/24, 0/4, 4/7 and 2/21 females at 0, 100, 1000 and 10000 ppm; malignant pheochromocytoma in 1/4 and 1/29 males at 1000 and 10000 ppm))","No effect >10000 ","No effect >10000 (Neoplastic findings, dead/moribund animals: not treatment-related findings (metastatic squamous cell carcinoma in 1/21 males at 10000 ppm)\nNeoplastic findings in surviving rats: no treatment-related findings (metastatic pituitary adenocarcinoma in 1/24 females at 0 ppm))","No effect >10000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 (Interim kill: no abnormal findings \nterminal kill: incidences of enlargement in 5/44, 12/46, 7/51 and 3/50 rats at gross necropsy, treatment-related but without dose-relation\nNeoplastic findings, dead/moribund animals: no treatment-related findings (adenocarcinoma in 1/27 males at 100 ppm; adenoma in 2/29, 2/27, 3/30 and 1/20 males and in 5/25, 8/22, 3/16 and 5/29 females at 0, 100, 1000 and 10000 ppm)\nNeoplastic findings, surviving rats: no treatment-related findings (adenocarcinoma in 1/24 females at 0 ppm; adenoma in 1/20, 2/3, 0/1 and 4/29 males and 2/24, 5/11, 4/7 and 1/21 females at 0, 100, 1000 and 10000 ppm))",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 (Interim kill: no abnormal findings \nterminal kill: cateract in 4/44, 4/46, 6/51 and 10/50 and corneal opacity in 4/44, 2/46, 5/51 and 3/50 rats at 0, 100, 1000 and 10000 ppm, not treatment-related)",null,"No effect >10000 (Neoplastic findings, dead/moribund animals: no treatment-related findings (metastatic histiocytic sarcoma in 1/30, 1/32 and 1/21 males at 0, 1000 and 10000 ppm; round cell sarcoma of pericardium in 1/17 females at 1000 ppm)\nNeoplastic findings, surviving animals: no treatment-related findings (metastatic histiocytic sarcoma in 1 of 1/26 and 1 of 1/26 examined female tissues at 100 and 1000 ppm))",null,"No effect >10000 (Interim kill: lymphocytic infiltration, not treatment-related\nterminal kill: nephritis-tubulo/tubulo-interstitial/interstitial in 18/56, 14/54, 15/49 and 12/50 dead and moribund rats and 20/44, 2/46, 2/50 and 19/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, attributed to subclinical infections and/or age\nNeoplastic findings, dead/moribund animals: no treatment-related findings (metastatic cholangio carcinoma in 1/30 males at 100 ppm; metastatic histiosarcoma in 1/32 males at 1000 ppm)\nNeoplastic findings, surviving animals: no treatment-related findings (lymphosarcoma in 1 of 1/26 examined female tissues at 1000 ppm))","No effect >10000 ","No effect >10000 (Interim kill: focal discolouration in 0/10 and 13/20 male and 1/10 and 4/20 females, haemorrhages in 0/10 and 3/20 males and 1/10 and 6/20 females, small cysts in 0/10 and 4/20 males and 0/10 and 1/20 females of the 0 and 10000 ppm group at gross necropsy, treatment-related (not treatment-related: clear cell foci and areas at histopathology)\nterminal kill: decrease in masses in 34/44, 36/46, 31/51 and 30/50 rats at gross necropsy in the 0, 100, 1000 and 10000 ppm group, treatment-related, clear cell foci and area in  26/56, 38/54, 38/49 and 27/50 dead and moribund rats and 61, 80, 66 and 70 incidences in 44, 46, 50 and 50 surviving rats of the 0, 100, 1000 and 10000 ppm group, pre-neoplastic changes, no dose-relation (not treatment-related: foci of discoloration and cysts, frequently observed adenoma/carcinoma in all groups)\nNeoplastic findings, dead/moribund rats: no treatment-related findings (cholangiocarcinoma in 0/30, 2/30, 2/32 and 2/21 males at 0, 100, 1000 and 10000 ppm and 1/26 females at 0 ppm; hepatocellular adenoma in 9/30, 9/30, 6/32 and 6/21 males and 2/26, 8/23, 3/17 and 5/29 females at 0, 100, 1000 and 10000 ppm; hepatocellular carcinoma in 12/30, 12/30, 9/32 and 5/21 males and 4/26, 4/23, 2/17 and 5/29 females at 0, 100, 1000 and 10000 ppm; intrahepatic bile duct adenoma in 1/30 and 1/30 males at 0 and 100 ppm; histiocytic sarcoma in 2/30, 2/32 and 1/21 males at 0, 1000 and 10000 ppm and in 1/26 females at 0 ppm; tumour emboli in 1/32 and 1/21 males at 1000 and 10000 ppm; fibrosarcoma in 1/30 males at 100 ppm)\nNeoplastic findings, surviving rats: no treatment-related findings (cholangiocarcinoma in 1/20, 1/20 and 1/29 males at 0, 100 and 10000 ppm; hepatocellular adenoma in 15/20, 13/20, 4/16 and 15/29 males and 16/24, 10/25, 16/32 and 8/21 females at 0, 100, 1000 and 10000 ppm; hepatocellular carcinoma in in 9/20, 16/20, 9/16 and 19/29 males and 6/24, 11/25, 12/32 and 4/21 females at 0, 100, 1000 and 10000 ppm; intrahepatic bile duct adenoma in 1/20 males at 0 ppm and in 1/25 females at 100 ppm; histiocytic sarcoma in 1/20 and 1/16 males at 100 and 1000 ppm and in 3/32 females at 1000 ppm; tumour emboli in 1/20 and 1/16 males at 0 and 1000 ppm; lymphosarcoma in 1/20 males at 0 ppm; benign mixes intrahepatic bile duct adenoma in 1/16 males at 1000 ppm))","No effect >10000 (Interim kill: no change\nterminal kill: weighing not performed as too many tumors were present)","No effect >10000 (Interim kill: no treatment-related findings (not treatment-related findings: petechiae/ecchymoses, collapse, consolidation, emphysema at gross necropsy, congestion, atelectatis, perivascular lymphocytic aggregations at histopathology, findings were explained by subclinical infections or age-related)\nterminal kill: no treatment related findings (suppurative pneumonia/ bronchopneumonia in 26/56, 21/54, 20/49 and 21/50 dead and moribund rats and chronic inflammation in 7/44, 6/46, 5/50 and 8/50 surviving rats of the 0, 100, 1000 and 10000 ppm group at histopathology; consolidation/ focal consolidation in 19/56, 13/54, 12/49 and 18/50 rats at gross necropsy in the 0, 100, 1000 and 10000 ppm group)\nNeoplastic findings, dead/moribund rats: no treatment-related findings (adenoma in 1/24 females at 100 ppm; metastatic histiocytic sarcoma in 1/30, 1/31 and 1/21 males at 0, 1000 and 10000 ppm and in 1/26 females at 0 ppm; metaastatic cholangiosarcoma in 1/30 males at 100 ppm; metastatic hepatocellular carcinoma in 1/30 and 1/21 males at 100 and 10000 ppm; bronchio alveolar adenoma in 1/17 females at 1000 ppm; metastatic squamous cell carcinoma in 1/30 males at 0 ppm; giant cell tumor in 1/21 males at 10000 ppm; fibroma in 1/24 females at 100 ppm; metastatic round cell sarcoma in 1/17 females at 1000 ppm)\nNeoplastic findings, surviving rats: no treatment-related findings (bronchio-alveolar adenocarcinoma in 1/3 males at 1000 ppm; metastatic hepatocellular carcinoma in 1/3 males at 1000 ppm; bronchio-alveolar adenoma in 1/24 females at 0 ppm; histiocytic sarcoma in 1/5 females at 1000 ppm))","No effect >10000 (Interim kill: no abnormal findings \nterminal kill: lymphoid hyperplasia of the mandibular lymph node in 11/56, 30/54, 15/49 and 23/50 dead and moribund rats and 24/44, 14/46, 10/50 and 35/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, no dose-relation (not treatment-related: lymphoid hyperplasia of the mediastinal lymph nodes at 100 ppm in dead/moribund rats)\nNeoplastic findings, dead/moribund rats: no treatment-related findings in mediastinal lymph nodes (metastatic histiocytic sarcoma in 1/28 and 1/30 males at 0 and 1000 ppm and in 1/26 females at 0 ppm; metastatic cholangiocarcinoma in 1/28 males at 100 ppm and in 1/26 females at 0 ppm; metastatic hepatocellular carcinoma in 1/28 males at 100 ppm; giant cell tumor and histiocytic sarcoma in 1/20 males at 10000 ppm)\nNeoplastic findings, surviving rats: no treatment-related findings (histiocytic sarcoma of mesenteric lymph nodes in 1/20 males at 0 ppm; histiocytic sarcoma of mediastinal lymph nodes in 1 of 1/26 examined female tissues at 100 ppm; lymphoma of mandibular lymph nodes in 2/29 males at 10000 ppm))",null,"No effect >10000 (Neoplastic findings, dead/moribund animals: no treatment-related findings (islet adenoma in 1/28 males of the 0 ppm group; metastatic cholangio-carcinoma in 1/30 males at 100 ppm and 1/26 females at 0 ppm; undifferentiated metastatic sarcoma in 1/32 males at 1000 ppm and metastatic histiocytic sarcoma in 1/26 females at 0 ppm, considered to be incidental)\nNeoplastic findings, surviving animals: no treatment-related findings (islet cell adenoma in 1/20 and 1/29 males at 0 and 10000 ppm and in 1/21 females at 10000 ppm; metastatic lymphosarcoma in 1/20 males at 0 ppm))",null,null,null,null,"No effect >10000 (Colon: no treatment-related findings (not treatment-related: colon lymphoid hyperplasia at histopathology in 4/56, 3/54, 8/49 and 3/50 dead and moribund rats and 8/44, 0/46, 0/50 and 12/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, considered age-related)\nCaecum: Neoplastic findings, surviving animals: no treatment-related findings (histiocytic sarcoma in 1 of 1/20 examined male tissues at 100 ppm))",null,"No effect >10000 (Lymphoid hyperplasia in 2/56, 8/54, 2/49 and 4/50 dead and moribund rats and 7/44, 0/46, 3/50 and 2/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, not treatment-related\nNeoplastic findings, dead/moribund animals: no treatment-related findings (metastatic cholangiocarcinoma in 1/30 males at 100 ppm))",null,null,"No effect >10000 (Involution in 25/56, 35/54, 40/49 and 32/50 dead and moribund rats and 25/44, 0/46, 0/50 and 34/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, age-related\nNeoplastic findings, surviving animals: no treatment-related findings (thyoma in 1/24 females at 0 ppm))",null,"No effect >10000 (Suppurative inflammation in 4/56, 10/54, 1/49 and 6/50 dead and moribund rats and chronic inflammation in 6/44, 0/46, 0/50 and 8/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, not treatment-related\nNeoplastic findings, surviving animals: no treatment-related findings (metastatic histiocytic sarcoma in 1/1 females at 100 ppm)\n)","No effect >10000 (Neoplastic findings, dead/moribund animals: no treatment-related findings (transitional cell carcinoma in 1/28 females at 10000 ppm))","No effect >10000 (No treatment-related effect (reduced body weight in males during the first 4 weeks in all treatment groups, statistically not significant; significant increase in females at 1000 ppm at 12 month was considered incidental))","Change 10000 (Haematology: no treatment-related findings (not treatment-related findings: surviving rats: occasional fluctuations of several parameters were all witihn historical control data, no dose-relation; Ht↑ (after 6 months) and Eosinophils↑ (after 18 months) in females at 10000 ppm were slightly outside historical control data, not consistent/ moribund rats: lymphocyte count↓ and neutrophil count↑ in both sexes among all treatment and control groups)\nClinical chemistry: Alb↓  and ALP↑ in females at 10000 after 6 months, treatment-related, GGT↓ in males at 10000 ppm after 12 months, treatment-related (not treatment-related findings, occasional fluctuations were all within historical control range, not consistent or without dose relation)\nUrinalysis: Protein↑ in females at 10000 ppm, treatment-related (non treatment-related findings: occasional fluctuations  of other parameters were not consistent throughout the study and/or not dose-related))","No effect >10000 (No treatment-related findings (weakness, loss of body weight, nasal discharge and snuffling were common toxic signs among both sexes of all treatment and control groups, soft stool/diarrhoea and alopecia were found in males of all groups, no dose-relation))","No effect >10000 (Food consumption: no treatment-related findings (occasional fluctuations in males of all groups; reduced in females in all treatment groups during months 8-13 and 18-22, statistically not significant)\nfood efficiency: no treatment-related findings)","No effect >10000 (No treatment-related findings (no mortality before interim kill, after 24 month pre-terminal deaths were 23/50, 21/50, 23/50 and 16/50 in males and 16/50, 11/50, 10/50 and 18/50 in females; higher survival in pre-terminally dead females at 10000 ppm was considered incidental))"]
[14,"DAR",1997,"Mammals","Combined chronic toxicity/carcinogenicity studies","Rat","3000; 10000; 30000","ppm","Oral",2,"Years","Adult","Achieved test substance intake: 104.0, 354 and 1127 mg/kg bw/day (males) and 114.7, 393 and 1247 mg/kg bw/day (females)","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 ",null,"No effect >30000 ",null,null,null,null,null,"No effect >30000 ","No effect >30000 ","No effect >30000 ",null,"No effect >30000 (Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: decreased incidences of inflammation at 30000 ppm: 6/18, 5/20, 2/18 and 2/29 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n)",null,"No effect >30000 ",null,null,null,null,"No effect >30000 (Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nanimals at terminal kill: increased incidence of arteritis at 3000 ppm: 1/18, 7/20, 3/18 and 2/29 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n)","Increase 30000 (Increased rel. weight in males at 30000 ppm in week 26, considered secondary to body weight changes or sporadic)","No effect >30000 (Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nanimals found dead/killed in extremis: decreased incidences of C-cell hyperplasia in females at 30000 ppm: 8/35, 6/31, 3/34 and 2/36 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n)",null,"No effect >30000 ",null,"No effect >30000 ",null,"No effect >30000 (Gross necropsy: \nall animals: decrease in masses in females at 30000 ppm (5/78, 3/79, 6/78 and 0/78 females at 0, 3000, 10000 and 30000 ppm)\nanimals found dead/killed in extremis: enlarged organ in 8/35, 3/31, 1/34 and 2/36 females at 0, 3000, 10000 and 30000 ppm\nHistopathology, non-neoplastic: \nanimals found dead/killed in extremis: decreased incidence of peliosis adrenalis in females at 3000 ppm: 18/35, 8/31, 13/34 and 10/36 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings (pheochromocytoma in 8/18, 4/20, 3/18 and 4/29 terminally killed males and in 14/76, 9/75, 5/80 and 10/78 in all males at 0, 3000, 10000 and 30000 ppm)\n)","No effect >30000 ","No effect >30000 ","No effect >30000 (Increased rel. weight in males at 30000 ppm in week 26, considered secondary to body weight changes or sporadic)",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 (Gross necropsy: reduced masses in males found dead/killed in extremis at 10000 ppm\nHistopathology, non-neoplastic: no treatment-related findings\nHistopathology, neoplastic: no treatment-related findings (lower incidences of anterior adenoma in males at 10000 ppm (22/32, 21/30, 14/32 and 18/21 decedent males and 34/35, 29/31, 28/33 and 31/36 decedent females at 0, 3000, 10000 and 30000 ppm, no toxicological significance)\n)",null,null,null,null,null,null,null,null,null,null,"No effect >30000 (Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nanimals at terminal kill: bone marrow femur: decreased incidences of hematopoesis in males at 3000 ppm: 9/18, 8/20, 10/18 and 6/29 at 0, 3000, 10000 and 30000 ppm; bone marrow sternum: decreased incidences of hematopoesis in males at 3000 ppm: 10/18, 8/20, 10/18 and 6/29 at 0, 3000, 10000 and 30000 ppm; bone marrow vertebra: decreased incidences of hematopoesis in males at 3000 ppm: 9/18, 8/20, 10/18 and 6/29 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n)",null,null,null,"No effect >30000 (Gross necropsy: no abnormal findings observed\nHistopathology, non-neoplastic: \nall animals: decreased incidences of myocardial atrophy/fibrosis in females: 22/78, 19/79, 20/78 and 8/78 females at 0, 3000, 10000 and 30000 ppm\ninterim kill animals week 78: increasede incidences of myocardial atrophy/fibrosis in males: 2/6, 5/5, 5/10 and 1/8 at 0, 3000, 10000 and 30000 ppm\nanimals found dead/killed in extremis: decreased incidences of myocardial atrophy/fibrosis in females: 9/35, 7/31, 6/34 and 3/36 females at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n)",null,"No effect >30000 (Gross necropsy: coarse surface in males found dead/killed in extremis at 30000 ppm, attributed to chronic nephropathy\nHistopathology, non-neoplastic: \niniterim kill animals week 52: decreased incidendes of chronic nephropathy in males at 10000 ppm: 9/10, 9/10, 4/10 and 9/10 at 0, 3000, 10000 and 30000 ppm\nanimals found dead/killed in extremis: decreased incidence of mineralization in pelvic epithelium in females at 30000 ppm: 6/35, 3/31, 3/34 and 0/36 at 0, 3000, 10000 and 30000 ppm; decreased incidences of pyelitis/pyelonephritis in females at 30000 ppm: 7/35, 3/31, 3/34 and 1/36 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: increased incidence of adenomas in males found dead/killed in extremis at 30000 ppm (3/23 males), not significant\n)","No effect >30000 (Increased in females at 30000 ppm in week 26, considered secondary to body weight changes or sporadic)","No effect >30000 (Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: reduced incidence of focal hepatocellular fatty change in females of the interim kill at week 26: 4/10, 0/10, 2/10 and 0/10 at 0, 3000, 10000 and 30000 ppm, reduced incidence of micro granuloma in females of the interim kill at week 78: 5/8, 0/9, 3/8 and 1/8 at 0, 3000, 10000 and 30000 ppm and in females of the terminal kill: 4/15, 0/19, 3/16 and 0/14 at 0, 3000, 10000 and 30000 ppm, reduced incidences of spongiosis hepatitis in males of the terminal kill: 7/18, 6/20, 2/18 and 3/29 at 0, 3000, 10000 and 30000 ppm, peliosis hepatis in 6/30 males at 3000 ppm found dead/killed in extremis when compared to control (1/32)\nHistopathology, neoplastic: no treatment-related findings\n)","No effect >30000 (Increased rel. weight in males at 30000 ppm in week 26, considered secondary to body weight changes or sporadic)","No effect >30000 (Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nanimals at terminal kill: decreased incidences of foam cell aggregation in males at 30000 ppm: 6/18, 6/20, 2/18 and 2/29 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n)","No effect >30000 (Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nanimals found dead/killed in extremis: decreased incidences of plasma cell hyperplasia in females at 30000 ppm: 5/35, 2/31, 2/34 and 0/36 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n)",null,"No effect >30000 (Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nanimals at terminal kill: acinar cell atrophy in males at 3000 ppm: 3/18, 10/20, 7/18 and 10/29 and arteritis in males at 3000 ppm: 0/18, 5/20, 1/18, 3/29 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n)","No effect >30000 (Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nterminal kill animals: decreased incidences of sciatic nerve fibre degerenation in females at 3000 ppm: 5/15, 1/19, 3/16 and 1/14 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings\n)",null,null,"Change 10000 (Gross necropsy: \nall animals: hair loss in females at 30000 ppm (treatment relation unclear), thickened areas in males at 30000 ppm and in females at ≥ 10000 ppm, callosities in paw in females at 10000 ppm\nanimals found dead/killed in extremis: hair loss in females at 30000 ppm, thickened areas in both sexes at 30000 ppm, callosities in paw in females at 30000 ppm\nanimals terminal kill: callosities in paw reduced in males at 30000 ppm, increased in females at 10000 ppm\nHistopathology, non-neoplastic: \nterminal kill animals: decreased incidences of plantar granuloma in males at 30000 ppm (12/18, 11/20, 11/18 and 8/29) and increased incidences in females at 10000 ppm (6/15, 8/19, 13/16 and 7/14) at 0, 3000, 10000 and 30000 ppm\nanimals found dead/killed in extremis: follicular hyperkeratosis in males at 30000 ppm (3/32, 2/30, 1/32 and 10/21) and plantar granuloma in females at 30000 ppm (3/35, 6/31, 7/34 and 10/36) at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings)","Change 30000 (Caecum: significantly increased incidence of distention  (m: 32/78; f: 18/78)  in both sexes at 30000 ppm (macroscopical finding) , treatment-related but without histopathological abnomalities\n)",null,"No effect >30000 (Gross necropsy: no abnormalities observed\nHistopathology, non-neoplastic: \nall animals: increased extramedullary hematopoesis in males at 10000 ppm (11/76, 18/75, 23/80 and 18/78 in males and 22/78, 28/79, 23/78 and 26/78 in females at 0, 3000, 10000 and 30000 ppm)\nterminal kill animals: increased extramedullary hematopoesis in males at 10000 ppm (1/18, 5/20, 8/18 and 6/29 in males and 10/15, 10/19, 11/16 and 9/14 females at 0, 3000, 10000 and 30000 ppm)\nHistopathology, neoplastic: no treatment-related findings\n)",null,null,null,null,null,null,"Decrease 10000 (Decreased body weight gain in males at ≥ 10000 ppm and in females at 30000 ppm (terminal bw: 93-95% of control) during the treatment period, treatment-related, in line with reduced food consumption and low food efficiency )","Change 10000 (Haematology: Ht↑ and PT↓ in males at 30000 ppm in week 104, attributed to altered values of the control animals which had callosities in the hind paw and anemia due to haemorrhage from the ulcered surfaces of the callosities\nClinical chemistry: Gluc↓ and Glob↓ in females at 30000 ppm, considered secondary to the decreased body weight gain , Creat↓ (week 26) in females at ≥ 10000 ppm, GPT↓ in males (week 52) at 30000 ppm, treatment-related but considered not to be of toxicological significance, ALP↑(week 52) in females at 30000 ppm, treatment-relation unclear  (not treatment-related findings: ALP↑ in males at 3000 ppm in week 78, Alb↓ in females at 3000 ppm in week 26, A/G↓ in females at 3000 ppm in week 26 and in males at 30000 ppm in week 104, attributed to the presence of callosities in control animals, T.Bil↓ in females at 3000 ppm in week 26, Cl↓ in males at 3000 and 10000 ppm in week 104, no dose-relation) \nUrinalysis: low pH in both sexes at ≥ 10000 ppm throughout the treatment period, attributed to the metabolic features of the test item; reduced protein in males at 30000 ppm at study week 26, treatment-related but toxicologically not significant as no blood chemistry or histopathological findings were noted (not treatment-related findings: dark coloured urine in females at ≥ 3000 ppm at study week 104, increased volume in males at 3000 ppm at week 104, no dose-relation))","Increase 30000 (Loose stool and soiled and/or wetted fur in perianal/genital region in both sexes at 30000 ppm, bradypnea and integument mass (tail) in males at 30000 ppm,  treatment-related (non treatment-related findings: decreased spontaneous motor activity and bradypnea in males at 3000 ppm, ptosis in females at 3000 ppm, reduced tactile hairloss in males at ≥ 3000 ppm and in females at 3000 and 10000 ppm, reduced integument wounds and hairloss in males at 30000 ppm))","Decrease 30000 (Food consumption: decreased in males at 30000 ppm during the first weeks of treatment, treatment-related (not treatment-related findings: increased in females at 3000 ppm during study week 48)\nfood efficiency: decreased in both sexes at 30000 ppm during the first 13 weeks of treatment (not treatment-related findings: reduced in males at 10000 ppm during the first 6 weeks))","No effect >30000 (Decreased in males at 30000 ppm (42%) when compared to control (64%) during the last study year, not treatment-related (temporal findings: increased in males at 10000 ppm during the first study year, decreased in males at 3000 ppm during the last study year, final mortality rate comparable to those of controls), no effect in females)","Increase 10000 (Caecum: abs+rel weight increased (>20%) in both sexes at 10000 ppm (occasional stat. significance), at 30000 ppm stat. significant over the entire study period , treatment-related and in line with pathological findings (not treatment-related: increased abs+rel weight in females at 3000 ppm in week 104)\n)"]
[15,"DAR",2001,"Mammals","Combined chronic toxicity/carcinogenicity studies","Rat","2000; 6000; 20000","ppm","Oral",2,"Years","Adult","Achieved test substance intake: 121, 361 and 1214 mg/kg bw/day (males) and 145, 437 and 1498 mg/kg bw/day (females); final termination data was a few days different for males and females (male groups were terminated in week 104 because survival in the control, low and mid dose groups was approaching 25%, females survived to scheduled termination after week 104)","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,null,"No effect >20000 ","No effect >20000 ",null,null,null,null,"No effect >20000 ",null,"No effect >20000 ","No effect >20000 ","Change 20000 (Gross necropsy: increased (3/64) firmness at 20000 ppm, treatment-related\nHistopathology, non-neoplastic findings: prostatitis at 20000 ppm, increased incidences in all treated group within historical control range, but as the control value in this study was low the treatment-relationship cannot be dismissed entirely\nHistopathology, neoplastic findings: no treatment-related findings)",null,"No effect >20000 ",null,null,null,null,"No effect >20000 (Histopathology, non-neoplastic findings: decreased incidence of tubular degeneration at 20000 ppm, treatment-related, considered to be without adverse consequence\nHistopathology, neoplastic findings: no treatment-related findings)","No effect >20000 (Abs+rel weight reduced in all treated groups at terminal kill, considered as not treatment-related as no effect was seen at the interim kill in week 53 and a dose-response was lacking, however, histopathological changes were evident)","No effect >20000 ",null,"No effect >20000 ","No effect >20000 ",null,null,"No effect >20000 ","Decrease 6000 (Abs+rel weight decreased in females at ≥ 6000 ppm, partly significant but mainly within historical control data, not considered toxicologically relevant due to the absence of effects in males and histopathological findings)","No effect >20000 (Gross necropsy: compression of the base in females at 20000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings\nHistopathology, neoplastic findings: no treatment-related findings)","No effect >20000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Change 6000 (Gross necropsy: enlarged in males at 6000 ppm and 20000 ppm, treatment-related\nHistopathology, non-neoplastic findings: papillary necrosis with varying degrees of mineralisation of the papilla and/or transitional cell hyperplasia in both sexes but particularly in males at 20000 ppm, papillary haemorrhage in 2 males and 2 females at 20000 ppm, treatment-related (papillary haemorrhage in one male at 2000 ppm considered to be incidental, hydronephrosis in males at ≥ 6000 ppm, within historical control data)\nHistopathology, neoplastic findings: no treatment-related findings)","No effect >20000 (Abs+rel weight increased (+10%) in males at 6000 ppm, not treatment-related since no dose-response)","Change 6000 (Gross necropsy: increased masses in males at 20000 and/or 6000 ppm, treatment-related\nHistopathology, non-neoplastic findings: proliferative cholangitis and hepatitis in males at 20000 ppm at interim and terminal kill, treatment-related (not treatment-related: fatty vacuolisation in males at ≥ 6000 ppm, below historical control levels)\nHistopathology, neoplastic findings: no treatment-related findings (hepatocellular adenoma in males at 20000 ppm, not statistically significant with Fisher'S Exact test but with Peto test, as no preneoplastic foci or adenocarcinomas were found and a dose-response was absent, findings were considered to be unrelated to treatment))","Decrease 20000 (Abs+rel. weight decreased (-7%) in interim killed males at 20000 ppm, in line with histopathological findings, treatment-related)","No effect >20000 (Gross necropsy: increased incidences of mottled lungs in males at 20000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings\nHistopathology, neoplastic findings: no treatment-related findings)","No effect >20000 (Gross necropsy: increased incidences of cystic changes at cervical lymph node in males at 20000 ppm, enlarged redded thymic lymph nodes in females at ≥ 6000 ppm, not treatment-related\nHistopathology, non-neoplastic findings: no treatment-related findings\nHistopathology, neoplastic findings: no treatment-related findings)",null,"No effect >20000 (Slight exocrine hyperplasia in males at 20000 ppm, within historical control data, not treatment-related)",null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 20000 (Decreased in males (-5%) and females (-8%) at 20000 ppm throughout the study, treatment-related)","Change 20000 (Haematology: no treatment-related findings (Hb↑ and PT↓ in all females at the interim kill, no dose-relation)\nClinical chemistry: ALP↑ (weeks 1-79) in both sexes at 20000 ppm, ALT↑ in males (weeks 1-79) and occasionally in females at 20000 ppm, T.Bil↑ (throughout the study) and AST↑ (at interim kill) in males at 20000 ppm, findings in males in line with increased liver weight, hepatitis and proliferative cholangitis, treatment-related (not treatment-related/ no tox. relevance: occasionally reduced TG and Chol. in males at 20000 ppm, ALP↑ during the first study year and variations in ALT at 6000 ppm, considered to be without toxicological significance as no histopathological abnormalities were found, Creat↓ in females at 6000 ppm in week 27 and at 20000 ppm in week 14 )\nUrinalysis: pH↓ in males at 20000 ppm, attributed to the acidic nature of the test material; blood/RBC↑  in both sexes at 20000 ppm, treatment-related)","Increase 20000 (Clinical signs: red-brown staining of tray papers, particularly in males at 20000 ppm, treatment-related (not treatment-related findings: red/brown colored urine in 3/52 males and 1/52 females at 20000 ppm)\nFunctional observational battery: decreased landing foot splay in females at 20000 ppm, not treatment-related)","Decrease 20000 (Food consumption: statistically significantly reduced in males (-6%) and females (-5-6%) at 20000 ppm during the first study year, treatment-related\nfood efficiency: statistically significantly reduced in both sexes at 20000 ppm during study weeks 1-4, reduced in males at 20000 ppm in weeks 1-12, treatment-related (not treatment-related: slightly increased in females at 20000 ppm during weels 9-12))","Increase 20000 (Statistically increased in males at 20000 ppm, attributed to the overall decreased severity of glomerula nephropathy occuring as a consequence of lower food consumption and body weight gain in this group; no effect in females)"]
[16,"DAR",1993,"Mammals","Combined chronic toxicity/carcinogenicity studies","Rat","10; 100; 300; 1000","mg/kg bw/day","Oral",2,"Years","Adult","Achieved test substance intake: 10-14, 85-113, 282-344 and 912-1137 mg/kg bw/day (males) and 9-12, 90-113, 261-375 and 833-1146 mg/kg bw/day (females)","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ",null,null,null,null,null,"No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 ",null,null,null,null,null,"No effect >1000 ","No effect >1000 ","No effect >1000 ",null,"No effect >1000 ","No effect >1000 ",null,null,"No effect >1000 ","No effect >1000 (Abs weight decreased in interim kill males at ≥ 300 mg/kg bw/day, not treatment-related as changes were not seen after body weight correction (examined in 10/70 animals each sex and all interim killed animals ))",null,"No effect >1000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ","No effect >1000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (Abs weight increased in terminal kill females at 300 mg/kg bw/day, no dose-relation)","No effect >1000 (Decreased incidence of nephropathy in interim kill males at ≥ 100 mg/kg bw/day and reduced severity of nephropathy in terminal kill males at 1000 mg/kg bw/day, toxicologically not relevant (findings of unknown toxicological significance: decreased incidence of urothelial hyperplasia in terminal kill females at ≥ 300 mg/kg bw/day))","Decrease 100 (Absolute and relative weight decreased in terminal kill males at 100 and 1000 mg/kg bw/day, which was reported as not relevant.)","No effect >1000 ","Decrease 100 (Rel weight reduced in interim kill females at ≥ 100 mg/kg bw/day, treatment-related but without histopathological findings (not treatment-related findings: abs weight decreased in interim kill males at ≥ 300 mg/kg bw/day, not treatment-related as changes were not seen after body weight correction;  abs weight reduced in interim kill females at 100 and 1000 mg/kg bw/day))",null,null,null,null,null,"Change 100 (Interim kill: mild cellular alterations of submaxillary salivary glands at ≥ 300 mg/kg bw/day in males and at 1000 mg/kg bw/day in females, treatment-related; mild to severe cellular alterations of the parotid salivary gland in males at ≥ 100 mg/kg bw/day  and in females at ≥ 300 mg/kg bw/day, treatment-related\nterminal kill:  cellular alterations of submaxillary salivary glands at ≥ 100 mg/kg bw/day in males and at 1000 mg/kg bw/day in females, treatment-related; cellular alterations of the parotid salivary gland in both sexes at ≥ 100 mg/kg bw/day, treatment-related)",null,null,null,null,null,null,null,null,null,null,null,"Decrease 1000 (Reduced body weight gain in both sexes at 1000 mg/kg bw/day in week 52 and 104 (m: -14-32%; f: -11-17%) and, treatment-related (not treatment-related findings: reduced at interim kill at 100 and 300 mg/kg bw/day, not reproduced at terminal kill, occasional fluctuations among all groups, no dose-relation))","Change 100 (Haematology: Ht and MCH were occasionally increased at 100 and 1000 mg/kg bw/day in males, Hb occasionally increased in males at ≥ 100 mg/kg bw/day and in females at 1000 mg/kg bw/day, MCH occasionally increased in females at 1000 mg/kg bw/day, not treatment-related as changes were of small magnitude and inconsistent during the study, Eosinophils↓, Lymphocytes↓ and WBC↓ in females, effect not dose-related and not consistent throughout the study, high degree of individual variation, not reproducible\nClinical chemistry: ALP↑ in males at 1000 mg/kg bw/day and in females at 100 mg/kg bw/day, treatment-related but without histopathological abnormalities (not treatment-related findings: T.Bil↑ in females, effect not consistent, high degree of individual variation, not reproducible, T.Chol↓ in males at 100 and 1000 mg/kg bw/day, no dose relationship, reproducibility questionable, occasional variations in BUN, Glc and Ca, ALT and AST, Alb, T.Chol in males, no dose-relation, incidental, occasional variations of Creat and P in females, no dose-relation and/or inconsistent effect)\nUrinalysis: pH↓ in males at 1000 mg/kg bw/day, toxicological significance unknown)","Increase 300 (Pale faeces in males and females at ≥ 300 mg/kg bw/day from weeks 16-104, treatment-related, considered to be not toxicologically significant)","No effect >1000 ","No effect >1000 ","Increase 100 (Paratoid salivary glands: abs+rel weight increased in interim kill males at ≥ 100 mg/kg bw/day, treatment-related\nSublingual and submaxillary salivary glands: abs+rel weight increased in interim kill animals of both sexes at 1000 mg/kg bw/day, increased abs+rel weight in terminal kill females at 300 mg/kg bw/day, treatment-related (not treatment-related: rel weight increased in interim kill females at 10 mg/kg bw/day))"]
[17,"DAR",1990,"Mammals","Combined chronic toxicity/carcinogenicity studies","Rat","2000; 8000; 20000","ppm","Oral",2,"Years","Adult","Achieved test substance intake: 89, 362 and 940 mg/kg bw/day (males) and 113, 457 and 1183 mg/kg bw/day (females)","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,null,"No effect >20000 ",null,null,null,null,null,"No effect >20000 ","No effect >20000 ","No effect >20000 ",null,"No effect >20000 ",null,"No effect >20000 ",null,null,null,null,"No effect >20000 ","No effect >20000 ","No effect >20000 ",null,"No effect >20000 ",null,"No effect >20000 ",null,"No effect >20000 ",null,null,"No effect >20000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ","No effect 20000 ","No effect >20000 ","Increase 20000 (Bw rel weight increased at interim kill and abs+brain rel weight increased at terminal kill in males at 20000 ppm, treatment-related)",null,null,null,"No effect >20000 (Pancreas islet cell adenomas in males at 2000 ppm, not dose-related (2/58, 8/57, 5/60 and 7/59 males and 5/60, 1/60, 4/60 and 0/59 females at 0, 2000, 8000 and 20000 ppm), not attributed to treatment (no further corresponding effects of hyperplasia or carcinoma))",null,null,null,null,null,null,null,null,"No effect >20000 (Histopathology: inflammation of gastric squamous mucosa in females at 8000 ppm (0/59, 3/60, 9/60 and 6/59 at 0, 2000, 8000 and 20000 ppm), findings predominantly observed in decedent animals, inflammation in surviving animals restricted to each one surviving male and female at 20000 ppm, no dose relation, considered not treatment-related)",null,null,null,null,"Decrease 20000 (Statistically significantly decreased in females at 20000 ppm from study Day 51 until month 20 (bw 86% of control after 20 month, -23% bw gain after 20 month), treatment-related, no effects in males)","No effect >20000 (Haematology: occasional fluctuations without toxicological significance (data within historical control range, of small magnitude and/or not dose-related)\nClinical chemistry: occasional fluctuations without toxicological significance (data within historical control range, of small magnitude and/or not dose-related; ALP↑ in females at 20000 ppm was attributed to a single animal)\nUrinalysis: increased specific gravity (month 6) and decreased pH (months 6, 18 and 24) in males at 20000 ppm, treatment-related, considered toxicologically not significant as histopathological findings were absent)","Increase 20000 (No signs of clinical toxicity\nOphthalmology (examined by 3 independent experts): increased incidences of degenerative lens changes in males at 20000 ppm, within historical control range, treatment-related as histopathological abnormalities were exacerbated by treatment)","No effect >20000 (Food consumption: occasionally increased in males at 2000 and 20000 ppm, considered toxicologically not significant\nFood efficiency: no abnormalities observed)","No effect >20000 "]
[18,"DAR",2009,"Mammals","Combined chronic toxicity/carcinogenicity studies","Rat","1500; 5000; 15000","ppm","Oral",2,"Years","Adult","Mean achieved test substance intake: 85.5, 285.2 and 1077.4 mg/kg bw/day in males and 104.5, 348.6 and 1381.9 mg/kg bw/day in females, interim kill animals are termed \"satellite\" animals in report","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >15000 (Histopathology, non-neoplastic: rare instances of keratinisation of the cervix, not treatment-related)",null,null,"No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (reduced spermatozoal count, spermatocoel granuloma formation, abscess formation and sclerotic nodule observed with low incidences, considered age-related)\nhistopathology, neoplastic: no treatment-related findings (mesothelioma in 1/51 control and 2/51 males at 1500 ppm))","No effect >15000 ",null,null,null,null,"No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (secretory glandular hyperplasia in the majority of females examined with lower incidence in high dose females; secretory distention of ducts and galactocoel formation occasionally seen, common findings in aging rats, isolated findings of keratin cyst formation and acute inflammatory cell infiltrates)\nhistopathology, neoplastic: no treatment-related findings (fibroadenoma, adenoma, adenocarcinoma in 9/51, 12/51, 8/51 and 13/51 females at 0, 1500, 5000 and 15000 ppm, attributed to aging))","No effect >15000 (Histopathology, non-neoplastic: no significant changes\nhistopathology, neoplastic: no significant changes)","No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (atrophy and absence of recent corpora lutea, follicular and non-follicular cysts, interstitial cell hyperplasia occasionally observed in all groups, age-related; isolated instances of abscess formation, peripheral inflammatory cells and thrombus formation, considered to be spontaneous)\nhistopathology, neoplastic: no treatment-related findings (granulosa cell tumors, granulosa-theca cell tumors, anaplasstic sacroma in 5/51, 3/51, 1/51 and 0/51 females at 0, 1500, 5000 and 15000 ppm))","No effect >15000 ","No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (atrophic changes commonly observed in control and treated groups, age-related; focal epithelial hyperplasia, inflammatory cell infiltrates, interstitial fibrosis, interstitial haemorrhage and prostatis occasionally observed, considered as spontaneous changes)\nhistopathology, neoplastic: no neoplastic lesions found)",null,"No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (reduced secretory content of one or both vesicles occasionally observed among all groups, increased incidences of bilateral secretory reduction in high dose males, not considered treatment-related; isolated instances of secretory distention, generalised atrophy of vesicles and atrophy or degeneration of the secretory content, age-related; peripheral and luminal inflammatory cells and abscess formation rarely observed in all groups)\nhistopathology, neoplastic: no neoplastic lesions observed)",null,null,null,null,"No effect >15000 (No treatmen-related effects observed)","No effect >15000 ","No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (C-cell hyperplasia among all rats of all groups, age-related; focal hyperplasia in the parathoid glands of a few male rats)\nhistopathology, neoplastic: no treatment-related findings (follicular adenoma in 5/51, 1/51, 0/51 and 6/51 males and in 3/51, 0/51, 0/51 and 2/51 females at 0, 1500, 5000 and 15000 ppm; follicular adenocarcinoma in in 1/51 males at 5000 ppm and in 0/51 and 1/51 females at 0and 1500 ppm; parafollicular adenoma in in 9/51, 1/51, 0/51 and 3/51 males and in 6/51, 1/51, 1/51 and 0/51 females at 0, 1500, 5000 and 15000 ppm; parafollicular adenocarcinoma in in 2/51and 1/51 males at 0 and 1500 ppm and in 1/51 female 1500 ppm and hibernoma in 1/51 males at 15000 ppm))",null,"No effect >15000 (No treatment-related histopathological changes were observed. (Histopathology, non-neoplastic: no treatment-related findings: cystic endometrial hyperplasia in control and treatment-groups, age-related; uterine dilatation statistically significantly increased in high dose females, considered to be without toxicological significance; rare instances of keratinisation of the cervix, haemorrhage, pyometra, keratin cyst formation, abscess formation and squamous cell carcinoma; Neoplastic: no treatment-related findings (52 uterine tumours in 46 rats, 7/46 rats had more than 1 tumour type, 24/52 incidences of endometrial stromal polyps, 21/52 incidences of adenocarcinomas and 7/52 incidences of leiomyoma, stromal sarcoma or angiosarcoma in females over all groups (16/51, 12/51, 9/51 and 15/51 females at 0, 1500, 5000 and 15000 ppm)))","No effect >15000 ","No effect >15000 (No histopathological abnormalities observed)",null,"No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings, foci of altered cortical cells (hypertrophic or vacuolated) were frequently observed in both sexes among all groups, haemocysts in females of all groups, no dose-relation, attributed to aging; mononuclear cell foci, focal hyperplasia of medullary and cortical cells, focal extramedullary hematopoesis, focal necrosis, complete atrophy and congestion were occasionally observed\nhistopathology, neoplastic: no treatment-related findings (tumors of adrenal gland (cortical tumors, phaeochromocytomas, ganglioneuroma) in 4/51, 1/51, 3/51 and 2/51 males and  1/51, 1/51, 0/51 and 1/51 females at 0, 1500, 5000 and 15000 ppm))","No effect >15000 ","No effect >15000 (Histopathology, non-neoplastic: isolated necrotic, degenerative or inflammatory lesions occasionally observed, no toxicological significance; occasional instances of distortion of the brain and dilatation of the lateral ventricles, consequence of expansive pituitary neoplasia in either sex\nhistopathology, neoplastic: no treatment-related findings (astrocytoma, meningeal granular cell tumor, oligodendroglioma or ependymoma in 1/51, 1/51, 0/51 and 2/51 males and 2/51, 1/51, 0/51 and 0/51 females at 0, 1500, 5000 and 15000 ppm))","No effect >15000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >15000 (Histopathology, non-neoplastic: focal hyperplasia, focal haemorrhage and cyst formation occasionally observed without toxicological significance\nhistopathology, neoplastic: no treatment-related findings (age related adenoma and adenocarcinoma observed in both sex, not treatment related))",null,null,null,null,null,null,null,null,null,null,"No effect >15000 (Histopathology, non-neoplastic: no significant lesions\nhistopathology, neoplastic: benign osteoma of the cranium in 1/51 males at 15000 ppm)","Change 15000 (Histopathology, non-neoplastic: increased incidence of severe adipose infiltration in males at 15000 ppm at terminal kill, treatment-related, attributed to myeloid hyperplasia, no abnormalities in high dose females (not treatment-related: increased incidence of severe adipose infiltration in premature dead animals at 1500 and 5000 ppm)\nhistopathology, neoplastic: myeloid hyperplasia was noted in a few rats of either sex, no dose relation, no treatment relation, no primary neoplastic lesions were seen)","No effect >15000 (Histopathology, non-neoplastic: eyes: no treatment-related effects (retinal atrophy and lenticular degeneration were occasionally observed in rats of either sex, within historical control range; keratitis, corneal vacuolation, focal mineralisation of the cornea, posterior adhesions occasionally observed, spontaneous lesions)/ harderian gland: mononuclear ell foci and/or focal atrophy occasionally observed in both sexes, age-related, glandular epithelial hyperplasia/hypertrophy was frequently observed, spontaneous change, no treatment relation\nhistopathology, neoplastic: no treatment-related findings: no abnormalities observed)",null,"No effect >15000 (Histopathology, non-neoplastic: focal myocarditis/fibrosis commonly observed in both sexes bit mainly in males, no dose relation, not treatment-related; focal mineralisation and Schwann cell hyperplasia observed rarely as spontaneous lesion, not treatment-related\nhistopathology, neoplastic: no treatment-related findings (malignant Schwannoma in 1/51 males at 1500 ppm and in 2/51 control females))",null,"Change 15000 (Histopathology, non-neoplastic findings: renal mineralisation, reduced pelvic mineralisation and increased corticomedullary mineralisation in premature death and terminal kill females at 15000 ppm, reduced incidences of hyperplasia in the renal pelvic/papillary epithelium in females at 15000 ppm, reduced pelvic mineralisation in males at 15000 ppm, treatment-related (not treatment-related findings: progressive glomerulonephropathy in rats of both sexes with greater prevalence in males, age-related, pyelitis in males at 5000 ppm, tubular necrosis in premature dead control females, renal tubular hyperplasia in 1/51 females at 1500 ppm and in 1/51 males and 1/51 females at 15000 ppm, occasional findings without dose relation included papillary necrosis, pyeliti, hydronephrosis, cortical cyst formation, tubular dilatation, generalised tubular basophilia, tubular mineralisation, cortical scarring, hypertrophy of the collecting duct epithelium, congestion)\nhistopathology, neoplastic findings: no treatment-related findings (renal tumors (lipoma, tubular carcinoma, clear cell carcinoma) in 1/51 and 1/51 males at 0 and 15000 ppm and in 1/51 females at 5000 ppm))","No effect >15000 ","No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (mononuclear cell foci frequently observed in both sexes but with a higher incidence in males at 1500 and 5000 ppm, highly variable finding in aging rats; lipid vacuolation, focal, diffuse or zonal distribution was frequently observed in either sex, no treatment relation/dose relation, statistically significant excess pigment in high dose females at terminal kill, considered not treatment-related due to low incidence and secondary nature of the condition; occasionally observed hepatic necrosis, focal/centrilobular distribution, subcaspular congestion/telangiecatsis, focal haemorrhage, cyst formation, congestion, bile duct proliferation, hyperplasia, dilatation or thickening, focal myelopoesis, malformation, thrombus formation, inflammatory cell infiltration, dilatation of sinusoids, basophilia or enlargement, periportal fibrosis, not treatment-related, foci/areas of altered hepatocytes as precursors of hepatic neoplasia in 0/51, 2/51, 6/51 and 2/51 males and in 32/51, 37/51, 33/51 and 36/51 females at 0, 1500, 5000 and 15000 ppm)\nhistopathology, neoplastic: no treatment-related findings (hepatocellular adenoma/carcinoma, cholangiocarcinoma in 1/51, 2/51, 1/51 and 1/51 males and 2/51, 0/51, 2/51 and 1/51 females at 0, 1500, 5000 and 15000 ppm))","No effect >15000 ","No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (accumulations of perivascular/peribroncheolar lymphocytes among all groups, statistically significantly increased in females at 15000 ppm, considered to be without toxicological significance as the difference was numerically small; lower incidence and severity of accumulations of alveolar macrophages in females at 15000 ppm, non-adverse; focal pneumonitis, cuboidal cell metaplasia, thickening of alveolar walls, thrombus formation, granulomas reaction, diffuse mononuclear cell infiltrates, abscess formation and pleural thickening occasionally observed among all groups, not treatment-related)\nhistopathology, neoplastic: no pulmonary neoplastic findings)","No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (cysts, cystic distentiion of sinusoids, lymphoid atrophy, accumulations histiocytes, focal endothelial hyperplasia and haemorrhage were occasionally observed, common findings in aging rats)\nhistopathology, neoplastic: no treatment-related findings (angioma, angiosarcoma in 11/51, 4/51, 3/51 and 6/51 males and in 3/51, 1/51, 0/51 and 1/51 females at 0, 1500, 5000 and 15000 ppm))",null,"No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (islet cell hyperplasia frequently noted in males and occasionally in females, no dose relation; lower incidence of exocrine atrophy in males at 15000 ppm; occasional observations of exocrine hypertrophy, inflammatory lesions, cystic distention, dilatation or epithelial hyperplasia of ducts, peripheral abscess formation)\nhistopathology, neoplastic: no treatment-related findings (islet cell adenoma/carcinoma in 4/51, 1/51, 2/51 and 1/51 males and in 0/51, 0/51, 1/51 and 0/51 females at 0, 1500, 5000 and 15000 ppm))","No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (fibre degeneration/necrosis in a few treated and control animals, isolated instances of mononuclear cell infiltration and nuclear pyknosis)\nhistopathology, neoplastic: no neoplasms observed)","No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (isolated instances of secretory depletion, focal hyperplasia and focal hypertrophy of the mucous acini in the submandibulary gland)\nhistopathology, neoplastic: no treatment-related findings (acinar adenoma in the paratoid gland of 1/51 males at 15000 ppm, considered to be spontaneous))","No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (isolated instances of mononuclear cell foci, fibre atrophy and fibre degeneration/necrosis among all groups, age-related)\nhistopathology, neoplastic: no neoplasms observed)","No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings but several spontaneous lesions observed (dilatation of hair folicles, subepithelial inflammatory cell infiltrates, abscess formation, epidermal ulceration, cystic cutaneous lymph node, nodule fat necrosis, cystic hair follicles, keratin cyst formation, focal acanthosis, subcutaneous fibrosis and dermal thickening occasionally observed among all groups; areas of necrosis/giant cell reaction to keratin in males with statistically increased significance at 15000 ppm, secondary lesion associated with development of keratoacanthoma)\nhistopathology, neoplastic: no treatment-related findings (8 types of cutaneous tumors with benign keratoacanthoma as most pervalent in male rats of all groups, 6 types of subcutaneous tumors among all groups, none of them with special prevalence; most of the tumor types diagnosed occured in males of all groups, 7 of them were fibrosarcoma))","No effect >15000 (Histopathology, non-neoplastic: isolated instances of mucosal ulceration and diverticulum formation, not treatment-related\nhistopathology, neoplastic: no treatment-related findings (leiomyoma in the rectum of 1/51 males at 5000 ppm and leiomyosarcoma in 1/51 females at 15000 ppm))","No effect >15000 (Histopathology, non-neoplastic: isolated necrotic, degenerative or inflammatory lesions occasionally observed, no toxicological significance\nhistopathology, neoplastic: no treatment-related findings (ependymoma in 1/51 females of the control group))","No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (extramedullary hematopoesis in the majority of rats among both sexes and all groups, within historical control data; atrophy of lymphoid tissue, atrophy of the red pulp, mononuclear cell proliferation, areas of necrosis and hyperaemia were occasionally observed)\nhistopathology, neoplastic: no treatment-related findings (angioma in 1/51 males at 15000 ppm and angiosarcoma in 1/51 control males))",null,"No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (acanthosis/hyperkeratosis in both sexes among all groups, no treatment relation; occasional observations included dilatation of gastric glands, subepithelial inflammatory cell infiltrates, acanthosis, hyperkeratosis, subepithelial oedema, ulceration of the forestomach or mucosa, mucosal erosion, focal mineralisation and mucosal atropy)\nhistopathology, neoplastic: no treatment-related findings (squamous papilloma in the forestomach of 1/51, 0/51, 2/51 and 1/51 males and 0/51, 1/51, 0/51 and 0/51 females at 0, 1500, 5000 and 15000 ppm))","No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (moderate to severe lymphoid atrophy in rats of both sexes among all groups, no effect on thymic atrophy)\nhistopathology, neoplastic: no treatment-related findings (lymphocytic thymoma, carcinoma in 0/51, 1/51, 1/51 and 2/51 males and 7/51, 2/51, 4/51 and 4/51 females at 0, 1500, 5000 and 15000 ppm))",null,"No effect >15000 (Histopathology, non-neoplastic: no treatment-related findings (dilatation of subepithelial glands noted in a few control and treated rats of either sex; isolated instances of inflammation and excess mineralisation of cartilage)\nhistopathology, neoplastic: no neoplasms observed)","No effect >15000 (Urinary bladder: histopathology, non-neoplastic: no treatment-related findings (epithelial/subepithelial or peripheral inflammatory cell infiltrates, epithelial erosion, subepithelial haemorrhage, epithelial hyperplasia and focal mineralisation were occasionally observed)\nhistopathology, neoplastic: no treatment-related findings (benign transitional cell papilloma in 1/51 males at 1500 ppm)\nUrether: distention in 1/51 females at 5000 ppm, not treatment-related)","No effect >15000 (Overall body weight gain was comparable for all treatment groups (91% for males and 97% for females at 15000 ppm when compared to controls))","Change 15000 (Haematology: no treatment-related findings (not treatment-related findings: APTT↑ in males at ≥ 1500 ppm at 6 months, APTT↑ and leucocytes↓ in females at ≥ 1500 ppm at 18 months, PT↑ in females at 15000 ppm after 6 months, neutrophils↑ in males at 15000 ppm and in females at 5000 ppm after 18 months, Hb↓ in females at ≥ 5000 ppm after 12 months, Hb↑ and Ht↑ in males at 1500 ppm after 6 months, lymphocytes↓ in females at 15000 ppm after 18 months, monocytes↑ in females at 1500 ppm after 24 months, MCHC↓ in males at ≥ 5000 ppm at 6 months)\nClinical chemistry:  ALP↑ in males at 15000 ppm 6, 12 and 18 months, marginal, considered to be a minor adaptive change to test substance intake; increase in plasma electrolytes in both sexes at 15000 ppm, treatment-related, considered minor and adaptive responses (further findings without toxicological relevance: changes in plasma electrocytes in all groups (Na↑ and Cl↑ in both sexes and K↑ in males at ≥ 1500 ppm and Ca↓ in females at 15000 ppm after 18 months, Na↓ in satellite females at 15000 ppm after 12 months, P↓ in both sexes at 1500 ppm after 18 months and P↑ in males at 15000 ppm after 24 months) no dose relation, toxicological significance unclear; TBil↑ in males at ≥ 1500 ppm after 18 months, A/G ratio↓ in females at ≥ 1500 ppm after 24 months, ALT↑ in satellite males at 150000 ppm after 6 months, in females after 12 months and in males after 18 months, TG↑ in females at 150000 ppm after 12 months, ALP↑ in satellite males at 5000 ppm after 12 months, urea↑ in females at 1500 ppm after 6 months, all findings without dose-relation and/or inconsistency throughout the study)\nUrinalysis: no treatment-related findings)","No effect >15000 (Clinical signs: No treatment-related findings\nFunctional observation: No treatment-related findings)","No effect >15000 (Food consumption: occasional fluctuations, not treatment-related\nFood efficiency: occasional fluctuations, not treatment-related)","No effect >15000 (No treatment-related mortality. There were no deaths within the satellite/interim kill groups.)","No effect >15000 (Nasal cavities: histopathology, non-neoplastic: no treatment-related findings (dilatation of subepithelial glands in rats of either sex, spontaneous change, statistically significantly decreased in males at 15000 ppm, incidental; chronic inflammatory lesions adjacent to the palate, associated with plant material/ hair fragments, reaction to foreign material impacted ti gland ducts; inflammatory/non-inflammatory exudate overlying the endothelium, focal epithelial ulceration, thrombus formation, fungal growth and dental hyperplasia occasionally observed)\nhistopathology, neoplastic: no treatment-related findings (polypoid adenoma in 2/51, 1/51, 0/51 and 0/51 males at 0, 1500, 5000 and 15000 ppm)\nPharynx: histopathology, non-neoplastic: no treatment-related findings (inflammatory cell lesions, inflammatory exudate and mucous cell hyperplasia/hypertrophy in a few animals)\nhistopathology, neoplastic: squamous cell papilloma in 1/51 females at 15000 ppm\nLarynx: histopathology, non-neoplastic: no treatment-related findings (distention of glands commonly observed among all control and treated rats of either sex; focal ulceration and debris in the ventral pouch, considered incidental)\nhistopathology, neoplastic: no neoplastic findings\nTongue: histopathology, neoplastic: no treatment-related findings (isolated instances of mononuclear cell infiltrates and mucous cysts in the epithelium in males, without toxicological significance)\nhistopathology, neoplastic: no treatment-related findings (benign granular cell tumor in 1/51 females at 15000 ppm))"]
[22,"DAR",2007,"Mammals","Two-generation reproduction toxicity test","Rat","1500; 5000; 15000","ppm","Oral",10,"Weeks","Adult (F0+F1)","Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >15000 ","No effect >15000 ","No effect >15000 ","No effect >15000 (Gross necropsy: no treatment-related findings (low incidence of small epididymides in terminal kill animals of F1 generation))","No effect >15000 ","No effect >15000 (Higher number of irregular cycles in F1 females at ≥ 5000 ppm, not reflected in pre-coital intervals, considered to be incidental and to be of no toxicological significance)","No effect >15000 ",null,null,null,null,"No effect >15000 ","No effect >15000 ","No effect >15000 (Histopathology: no treatment-related findings (interstitial chronic inflammatory cell infiltrates, common background finding))","No effect >15000 ","No effect >15000 ","No effect >15000 ","No effect >15000 ","No effect >15000 ","No effect >15000 ","No effect >15000 (Gross necropsy: no treatment-related findings (low incidence of small testes in terminal kill animals of the F0 and F1 generation))","No effect >15000 ",null,"No effect >15000 (Absolute thyroid weight was increased in F0 females at 5000 ppm. Relative thyroid weight was decreased in F0 males at 1500 and 5000 ppm. Both changes were not considered treatment-related and no dose-reponse-relationship was deduced.)","No effect >15000 (Gross necropsy: no treatment-related findings (red fluid filled in the dead F0 female at 15000 ppm containing under-developed and late death fetuses, dead fetuses in 1/28 F0 females at 5000 ppm killed in extremis and dead fetuses and placentae in 1/24 F1 females of the control group killed in extremis; discolouration of the horn in terminal kill F0 females)\nHistopathology: no treatment-related findings (focal haemorrhage, foam cell accumulations and haemosiderin pigment deposition in the peripheral uterine tissue of pregnant rats, commonly encountered consequences of pregnancy and parturition))","No effect >15000 ","No effect >15000 (Gross necropsy: no treatment-related findings (blood around the vagina in 1/28 F0 females at 5000 ppm killed in extremis))","No effect >15000 ","No effect >15000 (Histopathology: lower incidence of vacoulation in all F1 male treated rats, treatment relation cannot be excluded, non-adverse, abscence of a dose response suggests that the background range of the controls was high and caused the effect (not treatment-related findings: bilateral extensice necrosis of the renal cortex in the single dead F1 control female))","No effect >15000 ","No effect >15000 (Gross necropsy: no treatment-related findings (pallor in the dead F0 female at 15000 ppm, pallor of the medulla at low incidences in terminal kill animals of the F1 generation))","No effect >15000 (Abs. weight reduced in F1 males at 15000 ppm, considered to be incidental)",null,"No effect >15000 (No treatment-related findings (the following females failed to achieve pregnancy: 1/28 F0 control, 1/28 F0 1500 ppm, 1/24 and 1/24 F1 control and F1 at 1500 ppm, 1/24 F1 at 15000 ppm, no dose relation, normal variation))",null,null,"No effect >15000 ",null,null,null,"No effect >15000 ","No effect >15000 ","No effect >15000 ( increased number of large follicles in F1 females at 15000 ppm, in the absence of supporting data from uterine examination and any differences in the number of offspring the increase was indicative of normal biological variation, toxicologically not important)",null,"No effect >15000 ","No effect >15000 ","No effect >15000 ","No effect >15000 ",null,null,null,"No effect >15000 (From the F0 generation, 26/28, 27/28, 27/28 and 26/28 females and from the F1 generation 22/24, 23/24, 24/24 and 23/24 females successfully gave birth at 0, 1500, 5000 and 15000 ppm)",null,"No effect >15000 ",null,null,null,null,null,null,null,"No effect >15000 (Gross necropsy: no treatment-related findings (pallor in one F0 female found dead at 15000 ppm; dark kidneys in the interim dead control female of the F1 generation; mottled appearance, enlargement and increased renal pelvic cavitation in terminal kill animals of the F0 and F1 generation))","No effect >15000 (Abs.+rel. weight increased in F0 females at 15000 ppm, abs. weight increased in F1 females at 5000 ppm, no histopathological findings, considered to be adaptive in nature and non-adverse, no effect in males)","No effect >15000 (Gross necropsy: no treatment-related findings (pallor in the dead F0 female at 15000 ppm, mottled appearence in the interim dead F1 control female))","Increase 15000 (Absolute and relative weight increased in F0 and F1 females only at 15000 ppm without any histopathological findings. Therefore, increased organ weight is considered to be adaptive and non-adverse.)",null,null,null,"No effect >15000 (Gross necropsy: no treatment-related findings (enlarged and fluid-filled in the dead control female of the F1 generation))",null,null,null,null,null,null,"No effect >15000 (Gross necropsy: No treatment-related findings.)","No effect >15000 (Abs. weight reduced in F1 males at 15000 ppm, considered to be incidental)",null,"No effect >15000 (Gross necropsy: no treatment-related findings (low incidence of small thymus in terminal kill animals of the F0 generation))",null,null,null,"Decrease 15000 (No adverse effect of bodyweight change was evident for treated animals in comparison to controls throughout the treatment period for both the F0 and F1 generations except for post-partum females treated with 15000 ppm. During the final week of lactation, both the F0 and F1 generations showed statistically significant less bodyweight loss in comparison to controls.)",null,"No effect >15000 (No treatment-related findings (findings considered unrelated to treatment: incidences of red/brown staining of the external body surface, generalised fur loss, scab formation and red/brown staining on cage tray-liners in treated and control F0 + F1 animals, abrasion to the dorsal/cranial regions in males at 0 and 15000 ppm, physical injury to the tail apex in 1/28 females at 1500 ppm, red swollen ears in 1/28 and 1/28 females at 5000 and 15000 ppm; red stained urine, exophthalmia and piloerection each in one high dose group male or female, considered to be incidental; presence of mass in single animals, age-related; blood around the vagina in 1/28 females each at 0 and 5000 ppm; one control female showed lethargy, piloerection, hunched posture and staining around ano-genital region and was killed in extremis, incidence of protruding sternums in F1 females of control and treaetment groups, related to lactation phase))","No effect >15000 ","No effect >15000 (No treatment-related deaths; 1/28 P0 males at 1500 ppm was killed for humane reasons, 1/28 P0 females at 15000 ppm was found dead, 1/28 P0 females at 5000 ppm was killed in extremis; 1/24 control F1 females was killed for humane reasons)"]
[22,"DAR",2007,"Mammals","Two-generation reproduction toxicity test","Rat","1500; 5000; 15000","ppm","Oral",10,"Weeks","Offspring (F1+F2)","Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >15000 ","No effect >15000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >15000 ",null,null,null,null,null,"No effect >15000 ",null,null,null,"No effect >15000 (Surface righting reflex were unaffected and all offspring displayed normal auditory and visual responses. The mid-air righting for F2 litters in the low-, mid- and high dose group were significantly reduced compared to the control group in a non-dose responsive manner, and this finding does not have implication of substance related involvement.)",null,"No effect >15000 ","No effect >15000 ","No effect >15000 ",null,null,null,null,null,null,null,null,"No effect >15000 (Macroscopical abnormalities detected were considered to be normal low incidence findings in offspring of the age and strain)","No effect >15000 ",null,null,"No effect >15000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >15000 ",null,null,"No effect >15000 (Abs. weight reduced in F2 males at 15000 ppm, considered to be without toxicological significance)",null,null,null,null,"No effect >15000 "]
[22,"DAR",2007,"Mammals","Two-generation reproduction toxicity test","Rat","1500; 5000; 15000","ppm","Oral",10,"Weeks","Offspring (F1)","Mean achieved test substance intake: 104, 351 and 1063 mg/kg bw/day in males and 197, 641 and 1989 mg/kg bw/day in females","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Increase 15000 (Preputial separation (PPS) was statistically significantly delayed at 15000 ppm  (about 1000 mg/kg bw/d), which is similar to the limit dose of the test system. The age at PPS was increased to  45.9 ± 3.1 days versus 43.0 ± 2.3 days in control group with no further signs of developmental retardation, hence, a higher mean bodyweight was noted at attainment of PPS. The delay of PPS is of marginal magnitude and considered to be based on biological variation.)"]
[23,"DAR",2000,"Mammals","Two-generation reproduction toxicity test","Rat","1000; 3000; 10000","ppm","Oral","10 (pre-mating)","Weeks","Adult (F0+F1)","Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 (Higher number of cycles in F0 females at 10000 ppm, lower cycle length in F1 females at 10000 ppm, marginal and inconsistent finding, not treatment-related)",null,null,null,null,null,"No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ",null,null,"No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ",null,"No effect >10000 (Rel. weight increased in F0 males at ≥ 3000 ppm, abs. weight comparable to control group, considered to be incidental)",null,"No effect >10000 (There was no effect on pre-coital interval or the proportion of successful matings.)",null,null,"No effect >10000 ",null,null,null,"No effect >10000 ",null,"No effect >10000 ",null,"No effect >10000 ","No effect >10000 ","No effect >10000 ",null,null,null,null,null,null,"No effect >10000 ",null,null,null,null,null,null,null,"No effect >10000 ","No effect >10000 (Rel. weight increased in F0 males at 10000 ppm, abs. values comparable to control group,  considered to be incidental)","No effect >10000 ","No effect >10000 (Rel. weight increased in F0 males at 10000 ppm, abs. values comparable to control group,  considered to be incidental)",null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 ",null,null,null,null,null,"Decrease 10000 (Decreased body weight in F1 males at 10000 ppm during week 1, decreased body weight gain in F1 males at 10000 ppm from weeks 2 to 8, treatment-related (there were no effects in females during maturation, gestation and lactation))",null,"No effect >10000 (No treatment-related findings. Annular constrictions in tails of the F0 and F1 males and females during pre-mating, almost all males and half of the females affected in all groups, considered to be incidental)","Decrease 10000 (Food consumption: decreased in F1 males at 10000 ppm during pre-mating, treatment-related \nFood efficiency: increased in F1 males at 10000 ppm during weeks 5-8, treatment-related)","No effect >10000 (No treatment-related findings )"]
[23,"DAR",2000,"Mammals","Two-generation reproduction toxicity test","Rat","1000; 3000; 10000","ppm","Oral","10 (pre-mating)","Weeks","Offspring (F1+F2)","Mean achieved test substance intake in males: 108.0, 322.2 and 1072.9 mg/kg bw/day (99.4, 292.6 and 984.7 mg/kg bw/day in F0 males and 116.5, 351.8 and 1161.0 mg/kg bw/day in F1 males)\nMean achieved test substance intake in females: 113.9, 346.8 and 1136.2 mg/kg bw/day during maturation, 90.4, 277.9 and 910.9 mg/kg bw/day during gestation and 227.9, 752.4 and 2424.8 mg/kg bw/day during lactation","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 ",null,"No effect >10000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 ",null,null,null,null,null,"No effect >10000 ","No effect >10000 (Slightly increased in F1 and F2 pups of all treated groups (16/23, 15/22, 19/22 and 18/24 in F1 and 16/22, 17/23, 20/21 and 21/25 in F2 litters with all pups born at 0, 1000, 3000 and 10000 ppm), not treatment-related)","Decrease 10000 (Decreased in F1 pups of the 10000 ppm group from day 8 to day 29 in males and from day 5 to day 29 in females)",null,"No effect >10000 (Slightly higher in F1 and F2 pups in the test item treated groups, not treatment-related)",null,null,null,null,null,null,"No effect >10000 (Increased pelvis dilatation in F2A females at 10000 ppm (3/58, 1/59, 2/57 and 9/69 at 0, 1000, 3000 and 10000 ppm), common spontaneous change, considered to be incidental)",null,null,null,"No effect >10000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 ",null,null,"No effect >10000 ",null,null,null,null,"No effect >10000 "]
[24,"DAR",1997,"Mammals","Two-generation reproduction toxicity test","Rat","1200; 6000; 30000","ppm","Oral","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F0+F1)","Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 ","No effect >30000 ",null,"No effect >30000 ","No effect >30000 ","No effect >30000 ","No effect >30000 ",null,null,null,null,"No effect >30000 ","No effect >30000 (Rel. weight decreased in F1 females at 1200 ppm, not treatment-related, considered to be incidental)","No effect >30000 ",null,"No effect >30000 ","No effect >30000 ","No effect >30000 ","No effect >30000 ","No effect >30000 ","No effect >30000 ","No effect >30000 ",null,null,"No effect >30000 ","No effect >30000 ","No effect >30000 ","No effect >30000 ",null,"No effect >30000 ",null,"Increase 30000 (Rel. weight increased in F0 males at 30000 ppm, considered to be a change associated with low body weight in this group)","No effect >30000 ","No effect 30000 (Fertility indices in F1 animals were 95.8% (23/24), 95.8% (23/24), 87.5% (21/24) and 79.2% (23/24) at 0, 1200, 6000 and 30000 ppm. Slight reduction at 30000 ppm was considered to be incidental because normal reproduction results were obtained after re-mating with untreated animals. Moreover, general systemic toxicity was observed at this dose level.)",null,null,"No effect >30000 ",null,null,null,"No effect >30000 (Increased in F1 females at 1200 ppm, not treatment-related, no dose relation)",null,null,null,"No effect >30000 ","No effect >30000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 ","Increase 30000 (Rel. weight increased in F0+F1 males and females at 30000 ppm, treatment-related (abs. weight increased in females at 6000 ppm, considered to be not treatment-related))","No effect >30000 ","Increase 30000 (Rel. weight increased in F0+F1 males and females at 30000 ppm, treatment-related)",null,null,null,null,null,null,null,null,"Change 30000 (Distention of the caecum in F0 and F1 males and females at 30000 ppm, treatment-related)",null,null,null,null,null,null,null,null,"Decrease 30000 (Decreased in F0 and F1 males at 30000 ppm from treatment week 1 until necropsy, treatment-related (no treatment-related findings in females, increased mean body weight in F1 females at 30000 ppm on lactation day 0))",null,"Increase 30000 (Loose stool in F1 males during pre-mating and in F0 + F1 females during pre-mating and lactation at 30000 ppm, treatment-related (not treatment-related findings: hairloss in F0 males at ≥ 1200 ppm, considered to be incidental, malocclusion of the incisors, respiratory wheezing and red sebum in 1/24 F0 control males, 1/24 F0 control females and 1/24 F0 males at 6000 ppm and in 1/24 F1 males at 1200 ppm; distention of the abdomen in 1/24 F0 males at 6000 ppm))","No effect >30000 (No treatment-related findings (increased in F0 males at 1200 ppm in week 13; reduced in F1 males at 30000 ppm in week 4; increased in F0 females at 30000 ppm in weeks 2-4 and reduced in the same group on lactation days 7-14, no clear treatment-relation; increased in F1 females at 1200 and 6000 ppm on laction days 14-21, no dose relation, considered to be incidental))","No effect >30000 "]
[24,"DAR",1997,"Mammals","Two-generation reproduction toxicity test","Rat","1200; 6000; 30000","ppm","Oral","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Offspring (F1+F2)","Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 ","No effect >30000 ","Decrease 30000 (Decreased in F1 and F2 pups of both sexes at 30000 ppm, treatment-related)",null,"No effect >30000 ",null,null,null,null,null,null,"Increase 30000 (Distention of the caecum in F1 and F2 weeanlings at 30000 ppm, treatment-related)",null,"No effect >30000 ",null,"No effect >30000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 (No effects in offspring observed)"]
[24,"DAR",1997,"Mammals","Two-generation reproduction toxicity test","Rat","1200; 6000; 30000","ppm","Oral","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Adult (F1)","Organs weights were collected from each 10 randomly assigned males and females per group. Mean achieved test substance intake, F0: 83.6, 417 and 2150 mg/kg bw/day in males and 96.9, 485 and2532 mg/kg bw/day in females\nMean achieved test substance intake, F1: 91.7, 458 and 2411 mg/kg bw/day in males and 104.8, 530 and 2760 mg/kg bw/day in females","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 30000 (Statistically significant abs.+rel. prostate weight decreased in F1 males at 30000 ppm, treatment-related. No effects in F0 males.)"]
[25,"DAR",1993,"Mammals","Two-generation reproduction toxicity test","Rat","100; 1000; 10000","ppm","Oral","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F0+F1)","Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 ",null,"No effect >10000 ",null,null,null,null,null,null,null,"No effect >10000 ",null,"No effect >10000 ",null,"No effect >10000 ",null,null,null,null,"No effect >10000 (Gross necropsy findings: low incidences in hyperplasia/unilateral hyperplasia in 1/30 F0 control and 2/30 F0 males at 1000 ppm and in each 1/30 F1 males at 100 and 1000 ppm, not treatment-related\nHistopathology, F0 adults: degenerative changes in the seminiferous tubules in each 1/30  males at 100 and 10000 ppm, unequal in size at 1000 ppm, considered to be incidental and not related to treatment\nhistopathology, F1 adults: unilateral degenerative changes and giant cell formation in the seminiferous tubulus and chronic inflammation in each 1/30 F1 males at 100 and 1000 ppm, not treatment-related)",null,null,null,"No effect >10000 ",null,"No effect >10000 ","No effect >10000 ",null,null,null,null,"No effect >10000 (1/30 F0 females and 1/30 F1 females at 100 ppm died due to dystocia, not treatment-related)","No effect >10000 (Increased male fertility index in F0 animals at 100 and 10000 ppm, no dose relation, not treatment-related)",null,null,"No effect >10000 ",null,null,null,"No effect >10000 (Decreased no of implantations in F2 dams at 100 and 1000 ppm, considered to be incidental)",null,null,null,null,null,null,null,null,null,null,"No effect >10000 ",null,"No effect >10000 ",null,null,null,null,null,null,null,"No effect >10000 (Low incidences of cysts, dilated pelvis in F0 adults and low incidences of hydronephrosis in 2/60 F1 adults, considered to be incidental, not treatment-related)",null,"No effect >10000 ",null,"No effect >10000 (Gross pathology: Low incidences of consolidation, ecchymoses, collapse and/or emphysema in F0 and F1 adults, not dose- or treatment-related, 1/30 F0 females at 100 ppm died because of suppurative pneumonia)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 (No treatment-related findings (Initial bw of F0 males in treatment groups was higher than in control group, the trend continued during the entire treatment period but terminal body weight gain was comparable for all groups; increased bw in F1 males at 1000 ppm prior to and during treatment; decreased bw in F1 males at 10000 ppm at week 2 and 3; increased in females of all F1 treatment groups at selection and at 1000 and 10000 ppm up to week 10; increased in F1 females at 1000 ppm on Days 1 and 4 and in F1 females at 10000 ppm during the whole lactation period; reduced in F1 females at 1000 ppm during the lactation period))",null,"No effect >10000 (No treatment-related findings (nasal discharge and snuffling in both sexes of all treatment and control groups; rare instances of soft stool, biting injuries, urine incontinence and alopecia in single F0 and/or F1 animals; circling disease in 2/30 F1 females at 10000 ppm))",null,"No effect >10000 (No treatment-related deaths; 2/30 F0 females at 100 pppm (one distocia and one suppurative pneumonia), 1/30 F0 females at 10000 ppm (death not ascertained) and 1/30 F1 females at 100 ppm died)"]
[25,"DAR",1993,"Mammals","Two-generation reproduction toxicity test","Rat","100; 1000; 10000","ppm","Oral","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Adult (F1)","Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Change 10000 (Decreased in F1 males at ≥ 1000 ppm during weeks 0-2; increased in F1 females at 10000 ppm during gestation (not treatment-related findings: decreased in F0 females at 100 and 1000 ppm and in F1 females at 100 ppm during lactation; increased in F0 females at 10000 ppm during lactation))"]
[25,"DAR",1993,"Mammals","Two-generation reproduction toxicity test","Rat","100; 1000; 10000","ppm","Oral","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Offspring (F1+F2)","Treatment started at 8 weeks age and was continued for two successive generations until the second generation litters were weaned","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 (Mean number of F1 and F2 pups delivered and mean litter sizes in the 100, 1000 and 10000 ppm groups were comparable to the controls.)","No effect >10000 (The number of live pups on day 1 was reduced in F1 pups at 100 ppm,reduced in F2 pups at 1000 ppm and increased in F2 pups at 10000 ppm, not treatment-related)","No effect >10000 (No treatment-related findings (F1 pups: increased litter weight of combined sex and female pups on days 1 and 4, decreased litter weight of combined sex and males at 100 ppm on day 7, increased litter weight of combined sex and males at 10000 ppm on day 7, increased in complete litter and individual sex on day 21 at 1000 ppm, no dose-relation; F2 pups: increased litter weight of combined sex and female pups on days 1 and 4, increased combined sex litter weight at 100 and 1000 ppm and of males and females at 1000 ppm on day 4, decreased in males at 10000 ppm on days 14 and 21, no dose-relation))",null,"No effect >10000 (live-birth index increased in F1 pups at 1000 ppm, not treatment-related)",null,null,null,null,null,null,"No effect >10000 (No treatment-related findings (a few incidences of minor developmental abnormalities like kinky tail, rudimentary tail in F1 pups and of kidney hydronephrosis and dilated pelvis in F1 and F2 pups, no dose- or treatment-relationship))","No effect 1000 (No treatment and dose related consistent effects on number of pups born (combined and individual sex) and their growth were observed.)","No effect >10000 (No treatment-related findings (F1 pups: decreased survival at 100 ppm on days 4, 14 and 21, decreased at 1000 ppm on day 4 and increased at 1000 ppm on day 14, increased at 10000 ppm on days 14 and 21; F2 pups: no significant intergroup differences))",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 "]
[26,"DAR",1992,"Mammals","Two-generation reproduction toxicity test","Rat","1000; 3000; 10000","ppm","Oral","10 prior to mating, continued until termination","Weeks","Adult (F0+F1)","Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 ","No effect >10000 ",null,"No effect >10000 ",null,"No effect >10000 ",null,null,null,null,null,"No effect >10000 (No treatment-related findings (1/2 infertile F0 females at 1000 ppm had follicular cysts on ovaries, 1/3, 1/3, 1/7 and 0/3 infertile F1 females at 0, 1000, 3000 and 10000 ppm had no or a reduced number of corpora lutea in the ovaries))","No effect >10000 ","No effect >10000 ","No effect >10000 ","No effect >10000 ",null,null,null,null,"No effect >10000 ","No effect >10000 ","No effect >10000 ",null,"No effect >10000 (No treatment-related findings (luminal dilatation of the uterus in 2/3 infertile control females of the F1 generation))",null,"No effect >10000 ","No effect >10000 ","No effect >10000 (Enlarged  in one female at 10000 ppm found dead in week 23, not treatment-related)","No effect >10000 ","No effect >10000 (Pale tissue overlaying cranium and congested thickening meninges in one male at 10000 ppm which was sacrificed during week 23, not treatment-related)","No effect >10000 ",null,"No effect >10000 (No treatment-related findings (males failing to induce pregnangy were 1/28 at 10000 ppm in F0 males and 3/24, 1/24, 3/24 and 3/24 at 0, 1000, 3000 and 10000 ppm, histopathological findings only in 2/24 F1 males at 3000 ppm; females failing to mate: 1/28, 2/28, 0/28 and 1/28 in F0 females and 3/24, 3/24, 7/24 and 3/24 F1 females at 0, 1000, 3000 and 10000 ppm, explained by histopathological findings without treatment-relation))",null,null,"No effect >10000 ",null,null,null,"No effect >10000 (No treatment-related effect was observed on number of corpora lutea.)",null,null,null,"No effect >10000 (No treatment-related findings (1/3 infertile F1 females at 1000 ppm had cysts in pars anterior of the pituitary))",null,null,null,null,null,null,"No effect >10000 (In F1 generation, the pregnancy rate in all groups wass less than expected  (mate 1: 83%, 75%, 58% and 79%, mate 2: 67%, 78%, 67% and 74% at 0, 1000, 3000 and 10000 ppm, no dosage relationship))",null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 ","No effect >10000 ",null,null,null,"No effect >10000 (Pale and oedematous pancreas in 1/28 F0 males at 10000 ppm which died during the course of the study, not treatment-related)",null,"Change 3000 (Hypertrophy of acinar cells with prominent granular cytoplasms in the parotid salivary gland in F0 and F1 males and females at ≥ 3000 ppm and in the submaxillary salivary gland in F0 females at ≥ 3000 ppm, treatment-related (parotid: 2/27, 2/28, 3/28 and 12/26 F0 males and 1/24, 0/24, 4/23 and 10/23 F1 males and in 0/28, 2/27, 5/28 and 17/28 F0 females and 0/24, 0/23, 4/24 and 9/23 F1 females at 0, 1000, 3000 and 10000 ppm; submaxillary: 0/28, 1/27, 4/28 and 14/28 F0 females and 0/24, 0/23, 0/28 and 3/23 F1 females at 0, 1000, 3000 and 10000 ppm)\nhypertrophy of acinar cells with prominent granular cytoplasms in the submaxillary salivary gland in females at ≥ 3000 ppm, treatment-related (0/28, 1/27, 4/28 and 14/28 F0 females and in 0/24, 0/23, 0/24 and 3/23 F1 females at 0, 1000, 3000 and 10000 ppm))",null,null,null,"No effect >10000 ",null,null,"No effect >10000 (Thickened forestomach, invaginated stomach and abnormal contents in the gastrointestinal tract in one F0 female at 1000 ppm which was sacrificed on Day 2 post-partum, not treatment-related)",null,null,null,null,"Decrease 10000 (Absolute weight reduced in F1 males at 10000 ppm apparent at selection, overall weight gain was comparable to control, treatment-related (no clear adverse effects on bw gain during pregnancy and lactation, during the first mate of each generation bw gains during the initial stages of pregnancy were slightly lower than control at all dosage groups, no consistent dose-response))",null,"No effect >10000 (No treatment-related findings (occasional observations of skin ulceration, hair loss/scabbing, brown staining of the coat, red/brown eye discharge, dental abnormalities and soft faeces in F0 and F1 rats, no treatment relation))",null,"No effect >10000 (No treatment-related findings (mortalities observed: 1/28 F0 males at 0 ppm sacrificed, 1/28 F0 females at 1000 ppm sacrificed, 2/28 F0 males at 10000 ppm found dead/sacrificed, 1/24 F1 females at 1000 ppm sacrificed, 1/24 F1 males at 3000 ppm found dead, 1/24 F1 females at 10000 ppm found dead and 1/24 F1 males at 10000 ppm sacrificed))"]
[26,"DAR",1992,"Mammals","Two-generation reproduction toxicity test","Rat","1000; 3000; 10000","ppm","Oral","10 prior to mating, continued until termination","Weeks","Adult (F1)","Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Increase 10000 (Food consumption: slightly increased in F1 females at 10000 ppm during the latter stage of the first pre-mating period, not statistically significant\nFood efficiency: no clear consistent adverse effects observed across both generations\nWater consumption: slightly increased in F1 females at 10000 ppm with statistical significance in week 16)"]
[26,"DAR",1992,"Mammals","Two-generation reproduction toxicity test","Rat","1000; 3000; 10000","ppm","Oral","10 prior to mating, continued until termination","Weeks","Offspring (F1+F2)","Mean achieved test substance intake, F0, weeks 1-10: 66.4, 196.8 and 668.1 mg/kg bw/day in males and 75.3, 226.0 and 752.3 mg/kg bw in females\nMean achieved test substance intake, F1, weeks 5-16: 76.1, 230.2 and 771.3 mg/kg bw/day in males and 82.1, 244.9 and 841.1 mg/kg bw in females","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 ",null,"No effect >10000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10000 (Reduced at 10000 ppm (consistently but not significant) across all four matings and remained lower at day 4 in 3/4 matings, not conclusively attributable to treatment as the mean litter size at birth whithin each mating was not always the lowest litter size recorded)","No effect >10000 (Total litter loss was 2, 3, 1 and 1 at 0, 1000, 3000 and 10000 ppm across the four mates on the study, not treatment-related)","No effect >10000 (No treatment-related findings (litter weights were reduced in all treated groups first mating F0 generation from Day 16 post-partum with mean pup weights being lower from Day 8 post-partum, no dose-response, no findings in the 2nd mating of the F0 generation or in both matings of the F1 generation, considered unlikely to be  treatment-related))",null,"No effect >10000 ",null,null,null,null,null,null,"No effect >10000 ","No effect >10000 ","No effect >10000 ",null,"No effect >10000 ","No effect >10000 "]
[27,"DAR",1990,"Mammals","Two-generation reproduction toxicity test","Rat","2000; 10000; 30000","ppm","Oral","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F0+F1)","Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 ","No effect >30000 ",null,null,null,null,"No effect >30000 ","No effect >30000 ","No effect >30000 ","No effect >30000 ","No effect >30000 ",null,"No effect >30000 ",null,null,null,null,"No effect >30000 ","No effect >30000 (No effect on testes weight with epididymides was observed, except for a statistically significant increase in relative organ weight change in F1a adults of the high dose group which was attributed to the observed lower terminal body weight.)",null,null,"No effect >30000 ",null,"No effect >30000 ",null,null,null,null,null,null,"No effect >30000 (Mating rates for F0 and F1a treated dams were comparable and in some cases greater than for the control group. No adverse effect on precoital length were noted.)",null,null,"No effect >30000 (Gestation length was not affected in the F0 and F1 generation, including the second mating of the F1 generation.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 ",null,null,null,null,null,null,null,"No effect >30000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 30000 (Reduced in both sexes (F0+F1) at 30000 ppm throughout the study, treatment-related (F0: -8% and F1 -10% during pre-mating) (Not treatment-related findings: during gestation and lactation maternal bw at 30000 ppm tended to be lower than controls although bw gain was comparable to those of controls))",null,"Increase 30000 (Soft stool at 30000 ppm in F0 and F1 animals of both sexes, treatment-related (not treatment-related findings: red ocular discharge, result of overgrown / maloccluded teeth in both sexes, no dose-relation))","No effect 30000 (Food consumption: slightly decreased at 30000 ppm in F0 and F1 males and females during the first week of treatment and in F0 dams at 30000 ppm during the last week of lactation. However, in general food intake was not substantially affected during the study period.)","No effect >30000 (No treatment-related findings (one F0 female died before treatment, 2 F1a males and one F1a female died, one F1a female was sacrificed in extremis, causes of death were not due to toxicity of the test item))"]
[27,"DAR",1990,"Mammals","Two-generation reproduction toxicity test","Rat","2000; 10000; 30000","ppm","Oral","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Adult (F1)","Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 "]
[27,"DAR",1990,"Mammals","Two-generation reproduction toxicity test","Rat","2000; 10000; 30000","ppm","Oral","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Offspring (F1+F2)","Mean achieved test substance intake, F0: 132, 666 and 1983 mg/kg bw/day in males and 160, 777 and 2322 mg/kg bw in females\nMean achieved test substance intake, F1: 140, 711 and 2320 mg/kg bw/day in males and 163, 804 and 2536 mg/kg bw in females\nHistopathology perfromed for control and high dose groups","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 30000 (Slightly reduced (not statistically significant) in F1 pups and F2a pups at 30000 ppm, not reproduced in F2b pups, treatment relation equivocal)","No effect >30000 ","Decrease 30000 (Reduced (> -10%) by lactation Day 21 at 30000 ppm in F1, in F2 pups the effect appeared to occur earlier (Day 14 of lactctaion), consumption of prepared diet was considered responsibel for bw effect, treatment-related (Not treatment-related: slightly reduced at weaning in the 10000 ppm group, transient, not consistent for both sexes in all generations, toxicological relevance questionable))",null,"No effect >30000 ",null,null,null,null,null,null,"No effect >30000 ","No effect >30000 ","No effect >30000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 ",null,"No effect >30000 "]
[28,"DAR","1996 (Amendment 2002)","Mammals","Prenatal developmental toxicity study","Rat","250; 500; 1000","mg/kg bw/day","Oral","10 (GD 7-16)","Days","Adult","Treatment on gestation days 7-16, caesarian section on gestation day 22, no quantification of T3, T4, TSH hormones performed","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (Gravid uterus weight was not affected.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (Neither number of implantations nor corpora lutea was affected.)",null,null,null,null,null,"No effect >1000 ","No effect >1000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ",null,"No effect >1000 ","No effect >1000 (Food consumption: marginally reduced at 1000 mg/kg bw/day during dosing period, differences were not statistically significant)","No effect >1000 (One control animal was killed on Day 7 as a result of being misdosed, not treatment-related)"]
[28,"DAR","1996 (Amendment 2002)","Mammals","Prenatal developmental toxicity study","Rat","250; 500; 1000","mg/kg bw/day","Oral","10 (GD 7-16)","Days","Fetus","Treatment on gestation days 7-16, caesarian section on gestation day 22, no quantification of T3, T4, TSH hormones performed","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ",null,null,null,null,"No effect >1000 (Mean litter as well as foetal weight were not affected.)",null,null,null,"No effect >1000 (Neither early nor late intrauterine deaths were observed.)",null,null,null,null,"No effect >1000 (The incidence of fetuses with major defects was 1/284, 1/297, 1/301 and 2/296 at 0, 250, 500 and 1000 mg/kg bw/day, type or incidence gave no evidence for a treatment-related effect. The amount of fetuses with external/visceral variants and with skeletal variants were lower in the test item treated groups than in the controls.)",null,null,null,"No effect >1000 "]
[29,"DAR",1995,"Mammals","Prenatal developmental toxicity study","Rat","30; 300; 1000","mg/kg bw/day","Oral","10 (GD 6-15)","Days","Adult","Treatment on gestation days 7-16, caesarian section on gestation day 20, no quantification of T3, T4, TSH hormones performed","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (Gravid uterus weight as well as placental weight were not affected.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (Hair loss in 1/10 control females, not treatment-related)",null,null,"No effect >1000 ( Gross necropsy: No treatment-related findings. )",null,null,null,null,null,null,"No effect >1000 ",null,"Increase 1000 (Loose stool in 20/22 pregnant females at 1000 mg/kg bw/day during the dosing period and in 9/20 females one day after treatment (gestation day 16) (not treatment-related findings: hair loss or scabs in maternal rats at 30 and 300 mg/kg bw/day during the dosing period, within historical control data, hairloss in 1-2 maternal rats per group in each treated group))","Decrease 1000 (Decreased at 1000 mg/kg bw/day on gestation days 6-9, treatment-related (increase at 1000 mg/kg bw/day on gestation days 15-20 was considered to be due to the rebound effect against the reduced food consumption during the dosing period))","No effect >1000 "]
[29,"DAR",1995,"Mammals","Prenatal developmental toxicity study","Rat","30; 300; 1000","mg/kg bw/day","Oral","10 (GD 6-15)","Days","Fetus","Treatment on gestation days 7-16, caesarian section on gestation day 20, no quantification of T3, T4, TSH hormones performed","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ",null,null,null,"No effect >1000 (No effect on mean number of live fetuses, fetal deaths and resorptions was observed.)",null,null,null,null,"No effect >1000 (External malformations: no treatment-related findings (short tail in 1/361 fetus at 30 mg/kg bw/day, microphthalmia in 1/339 fetus at 1000 mg/kg bw/day)\nVisceral malformations: no treatment-related findings (right aortic arch in 1/173 fetus at 300 mg/kg bw/day, ventricular septical defects in 1/173 and in 1/164 fetuses each at 300 and 1000 mg/kg bw/day, considered to be incidental due to the low incidence; malformations such as thymic remnant in the neck, dilatation of the renal pelvis and left umbilical artery among all groups: 21/150, 28/174, 28/173 and 19/164 fetuses at 0, 30, 300 and 1000 mg/kg bw/day, not treatment-related)\nSkeletal malformations: no treatment-related findings (splitting of the ossification centers of the thoracic vertebral bodies in 2/164, 1/185 and 2/175 fetuses at 0, 300 and 1000 mg/kg bw/day; asymmetry of the sternebrae with sterno-costal joint displacement in 1/185 fetuses at 300 mg/kg bw/day, fusion of the sternebrae in 1/175 fetuses at 1000 mg/kg bw/day; malformations such as cervical ribs shortening, lumber ribs, sacralisation of the lumbar vertebra were observed in all groups: 9/164, 6/187, 11/185 and 14/175 fetuses at 0, 30, 300 and 1000 mg/kg bw/day))",null,null,null,"No effect >1000 "]
[42,"DAR",2012,"Mammals","Uterotrophic assay","Rat","100; 300; 1000","mg/kg bw/day","Oral",3,"Days","Adult",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 1000 (Mean uterine weights (wet and blotted, including luminal fluid) were not affetced.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 1000 (Mean body weights and body weight gains were not affected.)",null,"No effect > 1000 (Glyphosate was negative indicating lack of estrogenic activity. A single occurrence of red material around the nose in one animal of the 300 ppm group. )",null,"No effect > 1000 "]
[43,"DAR",2012,"Mammals","Hershberger assay","Rat","100; 300; 1000","mg/kg bw/day","Oral",10,"Days","Adult",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,"No effect > 1000 (All coefficient of variance (CV) values for the control and high-dose groups in this study are within the acceptable range.)",null,null,"No effect > 1000 (In the androgen agonist assay, the CV of the glans penis (19.44%) was slightly higher than the OECD CD of 17%; not considered significant.)","No effect > 1000 (All coefficient of variance (CV) values for the control and high-dose groups in this study are within the acceptable range.)",null,null,null,null,null,"No effect > 1000 (In the androgen agonist assay, the CV of the ventral prostate low dose (100 mg/kg/day) treated animals was slightly higher (43.74%) than the OECD CD value (40%); not considered significant.)","No effect > 1000 (All coefficient of variance (CV) values for the control and high-dose groups in this study are within the acceptable range.)",null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 1000 (All coefficient of variance (CV) values for the control and high-dose groups in this study are within the acceptable range.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 1000 ",null,"No effect > 1000 ",null,"No effect > 1000 "]
[44,"DAR",2012,"Mammals","Female pubertal assay (PP Female Assay)","Rat","100; 300; 1000","mg/kg bw/day","Oral","21 (PND 22-42)","Days","Juvenile",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 1000 (T4 levels were not affected.)",null,"No effect > 1000 (TSH levels were not affected.)",null,null,null,"No effect > 1000 ","No effect > 1000 (Control group (PND 36.4) was higher than the acceptable range of values in the performance criteria (30.67 days to 35.62 days; OPPTS 890.1450). However, the coefficient of variation (CV) value (6.52) fell within the acceptable range (0.00-6.52).)",null,null,null,null,null,null,"No effect > 1000 (Mean estrus cycle lengths were not affected.)",null,null,null,null,null,"No effect > 1000 ","No effect > 1000 (No evidence of glyphosate-related estrogenic or anti-estrogenic effects or effects on pubertal development or thyroid function ., absolute)",null,null,null,null,null,null,null,null,null,"No effect > 1000 ","No effect > 1000 (absolute)","No effect > 1000 ","No effect > 1000 (No effect on uterus weight wet (with luminal fluid) and blotted was observed., absolute)",null,null,null,"No effect > 1000 (absolute)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 1000 (absolute)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 1000 ","No effect > 1000 (absolute)",null,"No effect > 1000 (absolute)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 1000 ","No effect > 1000 (Lower AST in all three dose groups, lower potassium in the 100 and 300 mg/kg/day groups, higher chloride and ALP in the 1000 mg/kg/day group, and lower phosphorus in the 100 mg/kg/day group.  Since no histopathological changes were observed, the changes in clinical chemistry parameters were considered not toxicologically relevant.)","Increase 300 (Dose dependent rales were noted in 4/15 animals in the 300 mg/kg bw/day group and 13/15 animals in the 1000 mg/kg bw/day group.)",null,"No effect > 1000 "]
[45,"DAR",2012,"Mammals","Male pubertal assay (PP Male Assay)","Rat","100; 300; 1000","mg/kg bw/day","Oral","31 (PND 23-53)","Days","Juvenile",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 1000 (Mean serum hormone level (T4) were decreased from 100 mg/kg bw/day. However, the trend was not statistically significant. Moreover, no histological changes were observed in thyroid and thus, the observed decreasing trend is not considered toxicologically relevant.)","No effect > 1000 (Mean serum hormone level was not statistically significantly decreased at 1000 mg/kg bw/day; a dose showing overt toxicity (1 mortality, rales, body weight gain decrease >10%). No dose-response was observed and no histological changes were observed in testes.  Therefore, the decrease is considered not treatment-related. )","No effect > 1000 (Mean serum hormone level (TSH) were decreased from 100 mg/kg bw/day. However, the trend was not statistically significant. Moreover, no histological changes were observed in thyroid and thus, the observed decreasing trend is not considered toxicologically relevant.)",null,null,"Increase 1000 (A statistically non-significant delay in the mean age at attainment of balanopreputial separation was observed in the high dose group (48.0 days). However, the body weight on the day of attainment of complete balanopreputial separation in the 1000 mg/kg/day group was similar to the control group. Thus, the delay of BPS is considered an effect secondary to reduced body weight gain. Moreover, when adjusting the day of attainment for those males with three or more consecutive days of incomplete separation (persistent threads), no statistically significant delay in the mean age of attainment of preputial separation was noted for the 1000 mg/kg bw/day dose group when compared to the control group. There were 6, 11, 9, and 9 males in the control, 100, 300, and 1000 mg/kg bw/day dose group, respectively, with incomplete PSS for more than three days. No test substance related effects were observed at doses ≤300 mg/kg bw/day.\n)",null,null,null,null,null,null,"No effect > 1000 ","Decrease 300 (Lower mean absolute left and right epididymis weight (9.5-9.9% and 3.8-7.1% for 1000 and 300 mg/kg bw/day dose group, respectively) was observed (not statistically significant). The effect was considered secondary to body weight changes., absolute)",null,null,null,"Decrease 1000 (Statistically significantly lower mean absolute LABC weight (15.9%) were observed. The effect was considered secondary to body weight changes., absolute)",null,null,null,null,null,"Decrease 1000 (Statistically significantly lower mean absolute ventral prostate weight (22.6%) were observed. The effect was considered secondary to body weight changes., absolute)",null,"Decrease 1000 (Statistically significantly lower mean absolute seminal vesicle (with coagulating gland and fluid 18.5% and without 16.4%) weight were observed in the 1000 mg/kg/day group. The effect is considered to be a consequence of the lower mean body weights in this group. The effect was considered secondary to body weight changes., absolute)",null,null,null,"No effect > 1000 ","No effect > 1000 ","No effect > 1000 ","No effect > 1000 ",null,null,null,null,null,"Decrease 300 (Lower mean absolute adrenal gland (9.2%, 8.6% for 1000 and 300 mg/kg bw/day dose group, respectively) weight was observed (not statistically significant). The effect was considered secondary to body weight changes., absolute)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 1000 (Statistically significantly lower mean absolute pituitary weight (15.6%) was observed. The effect was considered secondary to body weight changes., absolute)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect > 1000 ","No effect 300 ",null,"Decrease 300 (Statistically significantly lower mean absolute liver weight (15.1% and 9.8% for 1000 and 300 mg/kg bw/day dose group, respectively) were observed. The effect was considered secondary to body weight changes., absolute)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 300 (Mean body weight gains for the 300 and 1000 mg/kg/day groups were decreased (7.5% and 12.4%, respectively) when the overall treatment period (PND 23-53) was evaluated, reaching statistical significance for the high dose group. Mean body weights for the 300 mg/kg/day group were 5.07% - 8.08% lower than the control group towards the end of the treatment period (PND 44-53), whereas mean body weights for the 1000 mg/kg/day group were 5.09% - 11.06% lower generally throughout the entire treatment period (PND 24-53). Final body weight was statistically significantly decreased by 12.4% and 7.5% for high and mid dose, respectively.  )","No effect > 1000 (Higher mean alanine aminotransferase (ALT) and sodium levels were noted in the 300 and 1000 mg/kg/day groups, respectively; higher mean albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), chloride, phosphorus, and total protein levels and a lower urea nitrogen level were noted in the 1000 mg/kg/day group compared to the control group. These effects are reported as toxicologically not significant.)","Increase 300 (Rales were noted in 9/15 animals in the 300 mg/kg bw/day group and 14/14 animals in the 1000 mg/kg bw/day group throughout the treatment period approximately 4 hours following dose administration.)",null,"Increase 1000 (One male in the 1000 mg/kg/day group was found dead prior to dose administration on PND 24.)"]
[49,"DAR","1991 (Amendment 1994)","Mammals","Subacute oral in rodent ","Rat","200; 2000; 20000","ppm","Oral",28,"Days","Adult","Urinalysis was not performed","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,null,null,null,null,null,null,null,null,"No effect >20000 ","No effect >20000 (Neither absolute nor relative organ weight was affected.)","No effect >20000 ",null,"No effect >20000 ",null,null,null,null,"No effect >20000 ","No effect >20000 (Neither absolute nor relative organ weight was affected.)","No effect >20000 ",null,"No effect >20000 ",null,null,null,"No effect >20000 ","No effect >20000 ","No effect >20000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,"No effect >20000 ",null,"No effect >20000 ","No effect >20000 (Neither absolute nor relative organ weight was affected.)","No effect >20000 ","No effect >20000 (Neither absolute nor relative organ weight was affected.)","No effect >20000 (Gross necropsy: Petechiae in 1/5 males and 2/5 recovery males at 20000 ppm, ecchymosis in 1/5 males at 20000 ppm, focal congestion in 1/5 males and 1/5 females at 20000 ppm; all findings were considered to be incidental\nHistopathology: Lymphoid hyperplasia in 1/5 and 5/5 males and in 2/5 and 1/5 females at 0 and 20000 ppm, considered to be incidental as the severity was not increased in the high dose group (increased incidences of congestion, atelectasis, interstitial pneumonia, perivascular leucocytic infiltration and perivascular lymphocytic aggregation were comparable between treated and control animals))","No effect >20000 ",null,"No effect >20000 ",null,null,null,null,"No effect >20000 (Histopathology colon: lymphoid hyperplasia in 1/5 and 2/5 females at 0 and 20000 ppm, considered to be incidental as the severitiy was not increased in the high dose group)",null,"No effect >20000 (Gross necropsy: thickening of capsule in 1/5 females at 20000 ppm in the recovery group, considered to be incidental as histopathological findings were absent)",null,null,null,null,null,null,"No effect >20000 ","Change 20000 (Haematology: No treatment-related findings. (Statistically significant decrease in haemoglobin in the high dose recovery animals; as the animals of the main group were not affected the effect was considered to be incidental.)\nClinical chemistry: Statistically significant increase in GPT and BUN at 20000 ppm in both sexes, which is reversible after 14 days of recovery (Non-treatment-related findings: statistically significant increase in BUN at 200 ppm, considered to be incidental due to the lack of a dose-relationship NOEAL for changes in BUN and GPT is 2000 mg/kg bw/d equivalent to 100 mg/kg bw; incidental decrease in Ca2+ at 200 ppm, increase in Ca2+ in 20000 ppm recovery group but not in the main group))","No effect >20000 (No treatment-related findings. (A few incidences of urine incontinence were observed at 2000 ppm (2/5 males) and 20000 ppm (2/5 females), but not in 20000 ppm recovery animals, therefore the findings wer considered to be incidental))","No effect >20000 ","No effect >20000 "]
[50,"DAR",1989,"Mammals","Subacute oral in rodent ","Rat","50; 250; 1000; 2500","mg/kg bw/day","Oral",28,"Days","Adult","Mean achieved doses: 49 ± 5.8, 255 ± 9.6, 1034 ± 58.2 and 2592 ± 226.9 mg/kg bw/day in males and 55 ± 7.9, 277 ± 17.1, 1047 ± 86.4 and 2614 ± 318.4 mg/kg bw/day in females; no recovery animals included, urinarlysis not performed","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >2500 (No effect on testes weight was observed (weighted together with epididymis).)",null,null,null,null,null,null,"No effect >2500 ","No effect >2500 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >2500 ",null,"Change 250 (Nephrocalcinosis (mineral deposition) in 2/5, 2/5 and 4/5 females at 250, 1000 and 2500 mg/kg bw/day, treatment-related)","No effect >2500 ","No effect >2500 ","No effect >2500 ",null,null,null,null,null,null,null,null,null,null,"No effect >2500 ",null,null,null,null,null,null,"No effect 2500 (Reduced total body weight gain at 2500 mg/kg bw/day in males (-9%) and females (-11%) throughout the dosing period, statistically not significant, not considered treatment-related)","Change 250 (Haematology: No treatment-related findings (statistically significantly decreased MCHC (-2%) in males at 50 mg/kg bw/day was considered to be incidental)\nClinical chemistry: statistically significantly increased ALT in males at ≥ 250 mg/kg bw/day and in females at 2500 mg/kg bw/day, increased ALP in males at ≥ 250 mg/kg bw/day (statistically significant at 250 and 2500 mg/kg bw/day) and in females at ≥ 1000 mg/kg bw/day (not significant) and bilirubin were regarded as normal responses to increased liver activity; increased phosphate levels in males at ≥ 1000 mg/kg bw/day, treatment-related (slightly increased Na in females at 50, 1000 and 2500 mg/kg bw/day and slighly decreased Cl in females at 50 mg/kg bw/day were considered to be incidental))","Increase 2500 (Soft faeces in 3/5 males at 2500 mg/kg bw/day during weeks 3 and 4, treatment-related)","No effect >2500 (Neither an efect on food not on water consumption was observed.)","No effect >2500 "]
[52,"DAR",1991,"Mammals","Repeated dose 90-day oral toxicity study in rodents","Rat","30; 300; 1000","mg/kg bw/day","Oral",90,"Days","Adult","No recovery group included","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ",null,null,null,null,null,"No effect >1000 ","No effect >1000 ","No effect >1000 (With fallopian tubes)","No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 ",null,null,null,null,"No effect >1000 ","No effect >1000 ","No effect >1000 ",null,"No effect >1000 ","No effect >1000 ",null,null,"No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ","No effect >1000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 (Mesenteric lymph nodes)",null,"No effect >1000 ",null,"Change 30 (Increased incidence of cellular alteration in the parotid salivary glands in both sexes at 30, 300 and 1000 mg/kg bw/day and increased severity of cellular alteration in the parotid salivary glands in both sexes at 1000 mg/kg bw/day and in males at 300 mg/kg bw/day, treatment-related, toxicological significance unclear)",null,null,null,null,"No effect >1000 ","No effect >1000 ",null,"No effect >1000 ","No effect >1000 ",null,null,"No effect >1000 ","Change 1000 (Haematology: statistically significant increase in eosinophils in males at 300 mg/kg bw/day, no dose relation, considered to be incidental\nClinical chemistry: statistically significantly increased glucose (11%), total protein (9%), albumin (9%) and creatinine (8%) in females at 1000 mg/kg bw/day, treatment-related (statistically significantly increased ALP in males (28%) at 300 mg/kg bw/day was considered to be incidental as it was not observed at the higher dose)\nUrinalysis: reduced pH in males at 1000 mg/kg bw/day, treatment-related)","No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 (Salivary gland weights were weighed.)"]
[53,"DAR",1993,"Mammals","Repeated dose 90-day oral toxicity study in rodents","Rat","2000; 6000; 20000","ppm","Oral",90,"Days","Adult","No recovery group included; mean achieved doses were 125.2, 371.9 and 1262.1 mg/kg bw/day in males and 156.3, 481.2 and 1686.5 mg/kg bw/day in females","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 (Cervix, uterus and vagina were fixed together. )",null,null,"No effect >20000 ","No effect >20000 (Testes and epididymis were weighed together.)",null,null,null,null,"No effect >20000 ","No effect >20000 ","No effect >20000 ","No effect >20000 ","No effect >20000 ",null,null,"No effect >20000 ",null,null,null,"No effect >20000 ","No effect >20000 (Testes and epididymis were weighed together.)","No effect >20000 ",null,"No effect >20000 (Cervix, uterus and vagina were fixed together. )",null,"No effect >20000 (Cervix, uterus and vagina were fixed together. )",null,"No effect >20000 (Minimal to mild cytoplasmic vacuolization of adrenal cortical cells was noted in 5/10 (50%) of the male rats included in the control group.)","Decrease 20000 (Abs. weight statistically signif. decreased in males at 2000 and 20000 ppm; as an effect at 6000 ppm was lacking the finding was questionable as toxicological effect, no findings in females\nrel. weight (to brain and body weight) statistically significantly decreased in high dose group in males.)",null,"No effect >20000 ",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 (Heart and aorta were subject to histopathology.)",null,"No effect >20000 (Urinary bladder histopathology was performed as well.)","No effect >20000 ","No effect >20000 (Minimal focal subacute inflammation in both sexes of all groups, common finding among laboratory rats, not attributed to treatment)","Decrease 6000 (Decreased abs. + rel weight at 20000 ppm in males only, statistically not significant, and decreased rel weight at 6000 ppm in males)","No effect >20000 (Focal mineralisation of the vascular intima was commonly observed in both sexes of all groups, general finding among laboratory rats, not regarded as treatment-related\nTrachea was analysed as well and no changes were observed.)","No effect >20000 ",null,"No effect >20000 ",null,null,null,null,"No effect >20000 (Esophagus and stomach were also analysed.)",null,"No effect >20000 ","Increase 20000 (Abs. weight increased in females only in all treatment groups (reaching statistical significance in high dose group only), rel. weight to body weight statistically signif. increased for the high dose group only; spleen weight increased relative to brain weight not statistically significant. However, no effect was observed during macroscopic and microscopic examination.)",null,"No effect >20000 ",null,null,null,"No effect >20000 (The total mean body weight gain was similar for all groups. \nStatistically sign. increased mean body weight gains in males on Day 43 at 6000 and 20000 ppm were attributed to decreased weight gain in the control group. Statistically signif. decreased body weight  at 20000 ppm in both sexes on Day 50 and in males on Day 85. )","Change 6000 (Haematology: No changes in haematological parameters observed.\nClinical chemistry: No treatment-related effects observed. (K was statistically signif. reduced in males at 2000 ppm, which was considered to be incidental because a dose-response relationship was lacking. Reduced ALT and increased bilirubin in males at 20000 ppm were considered to be without toxicological significance)\nUrinalysis: Treatment-related increase in RBC and detection of blood in females at ≥ 6000 ppm and in all treatment groups in males. Findings in males were not unequivocally attributed to treatment, as a mild elevation of RBC is commonly observed in male rats)","Increase 20000 (Diarrhea in 10/10 males and 9/10 females at 20000 ppm, treatment-related \nOphthalmic examinations: persistent pupillary membrane in the right eye of 1/10 control males and numerous corneal deposits in the right eye of 1/10 males at 20000 ppm, not treatment-related)","No effect >20000 ","No effect >20000 "]
[54,"DAR",1992,"Mammals","Repeated dose 90-day oral toxicity study in rodents","Rat","200; 2000; 20000","ppm","Oral",90,"Days","Adult","Mean achieved dosages were 14.0, 147.3 and 1358.6 mg/kg bw/day in males and 18.6, 195.7 and 2012.4 mg/kg bw/day in females","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,null,null,null,null,null,null,null,null,"No effect >20000 ","No effect >20000 (No effect on absolute and relative organ weight was observed.)","No effect >20000 (An instance of interstitial lymphoid cell infiltration in prostate was observed but cosnidered incidental.)",null,"No effect >20000 ",null,null,null,null,"No effect >20000 ","No effect >20000 (No effect on absolute and relative organ weight was observed.)","No effect >20000 (No effect on thyroid (including parathyroids) was observed.)",null,"No effect >20000 ",null,null,null,"No effect >20000 ","No effect >20000 (No effect on absolute and relative organ weight was observed.)","No effect >20000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ","No effect >20000 (No effect on absolute and relative organ weight was observed.)","No effect >20000 (A few gross lesions were observed at comparable incidences among all groups, no dose- or treatment-relation; focal chronic hepatitis in 1/10 males at 20000ppm, considered to be incidental)","No effect >20000 (No effect on absolute and relative organ weight was observed.)","No effect >20000 (A few gross and histopathological lesions were observed at comparable incidences among all groups, no dose- or treatment-relation)",null,null,"No effect >20000 ",null,null,null,null,"No effect >20000 (Intestine: hyperplasia of lymphoid nodules in the submucosa of the duodenum, ileum and colon with varying frequencies and severity were considered as spontaneous lesions; No effect was observed on stomach.)",null,"No effect >20000 ",null,null,"No effect >20000 ",null,null,null,"Decrease 20000 (Reduced body weight gain in females at 20000 ppm during study weeks 3-6 and thereafter, statistically signif. reduced body weight throughout the treatment period, treatment-related. Findings were restricted to females and were not evident in the high dose recovery group during the exposure period)","Change 200 (Haematology: No treatment-related findings (decreased RBC and HCT in males at 200 ppm and reduced RBC in males at 2000 ppm with concomitant increase in MCH and MCHC in the respective groups were not dose-related and considered to be incidental; decrease in eosinophils in males at 20000 ppm was not consistent with findings in high dose recovery group, increased MCH and MCHC in high dose recovery males were considered to be incidental)\nClinical chemistry: statistically signif. increase in ALP in males at 20000 ppm which remained high (not statistically signif.) at the end of the recovery period; decreased creatinine and Ca2+ levels in females in all dose groups (not reversible after recovery) and increased glucose levels in females at 20000 ppm (reversible after recovery), treatment-related\nUrinalysis: not performed in the study)","Increase 200 (Higher incidences of respiratory affections (nasal discharge, snuffling) in both sexes in all test item treated groups, persistent in males after recovery period, treatment-related)","No effect >20000 ","No effect >20000 "]
[55,"DAR",1987,"Mammals","Repeated dose 90-day oral toxicity study in rodents","Rat","1000; 5000; 20000","ppm","Oral",90,"Days","Adult","Mean achieved doses were 63, 317 and 1267 mg/kg bw/day in males and 84, 404 and 1623 mg/kg bw/day in females","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,null,"No effect >20000 ","No effect >20000 (Epididymides were weighed together with testes.)",null,null,null,null,"No effect >20000 ","No effect >20000 ","No effect >20000 ",null,"No effect >20000 ",null,"No effect >20000 ",null,null,null,null,"No effect >20000 ","No effect >20000 ","No effect >20000 ",null,"No effect >20000 ",null,null,null,"No effect >20000 ",null,"No effect >20000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,null,null,null,null,null,null,null,null,null,null,"No effect >20000 ",null,null,"No effect >20000 ",null,"No effect >20000 ","No effect >20000 ","No effect >20000 ","No effect >20000 ","No effect >20000 ","No effect >20000 ",null,"No effect >20000 ","No effect >20000 ",null,null,null,"No effect >20000 ","No effect >20000 ","No effect >20000 ",null,"No effect >20000 ","No effect >20000 ",null,"No effect >20000 ","No effect >20000 ","No effect >20000 ","No effect >20000 (Haematology: No adverse effects observed.\nClinical chemistry: No treatment-related findings. \n(Statistically significant increases in lymphocytes in males at 1000 and 5000 ppm and increased WBC in males at 5000 ppm were not dose-related and therefore not attributed to treatment; statistically signif. increased P and K in both sexes in all test item-treated groups and statistically signif. increased glucose levels in males at 5000 and 20000 ppm showed no dose-relation and/or where within or close to the upper levels of normal values and therefore considered to be without toxicological significance; increased BUN and AP (not siginificant) was attributed to extreme values of one rat)\nUrinalysis: Statistically signif. changes in specific gravity and pH at 5000 ppm in males were not considered to be related to treatment)","No effect >20000 ","No effect >20000 ","No effect >20000 "]
[60,"DAR",1993,"Mammals","Repeated dose dermal toxicity","Rat",1000,"mg/kg bw/day","Dermal",21,"Days","Adult","Treatment: 10% coverage body surface area, 6h/day under occlusive conditions; vehicle diethylphthalate","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ","No effect >1000 ",null,null,null,null,null,null,"No effect >1000 ",null,null,null,null,null,null,null,null,"No effect >1000 ","No effect >1000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (Gross necropsy: unilateral dilatation in 2/5 males at 1000 mg/kg bw/day, common finding in rats of this age, not considered related to treatment\nHistopathology: unilateral papillary necrosis in 1/5 males at 1000 mg/kg bw/day, urothelial hyperplasia in 2/5 males at 1000 mg/kg bw/day, pelvic dilatation in 3/5 males at 1000 mg/kg bw/day, common finding in rats of this age, not treatment-related)","No effect >1000 ","No effect 1000 ","No effect >1000 ",null,null,null,null,null,null,null,"No effect >1000 ",null,null,null,null,null,null,null,null,null,"No effect >1000 (Reduced body weight gain in males (-17%, statistically not significant) and statistically signifcant increased body weight gain in females (58%), due to the lack opf statistical significance, the wide variation between the sexes and the lack of similar observations in previous studies the changes were not attributed to treatment .)","Change 1000 (Haematology: statistically significant increase in MCH (4%) and MCV (4%) in females, reduced number of neutrophils (31%) in females. There was a decrease in monocytes (44%, P<0.05) and large unstained cells (62%, P<0.05) in the high dose males compared to\ncontrols. These findings have not been seen in previous studies and the decrease in monocytes may partly be due to higher values in concurrent control animals.\nClinical chemistry: no adverse effects observed\nUrinalysis: not performed)","Increase 1000 (Clinical signs of systemic toxicity: no adverse effects observed\nLocal skin reactions: 2/5 males and 3/5 females showed very slight erythema during Week 2, which remained apparent in 1/5 females in Week 3 at 1000 mg/kg bw/day, moderate to severe desquamation in 3/5 males and mild to severe desquamation in 5/5 females at 1000 mg/kg bw/day during Week2 and in 1/5 males and 1/5 females at 1000 mg/kg bw/day in Week 3, treatment-related)","No effect 1000 (Increased food consumption in females at 1000 mg/kg bw/day (14%), as findings in males and in previous studies were lacking the effect was considered to be by chance and not of toxicological importance)","No effect >1000 "]
[61,"DAR",1996,"Mammals","Repeated dose dermal toxicity","Rat","250; 500; 1000","mg/kg bw/day","Dermal",21,"Days","Adult","Treatment: area 7 cm x 7 cm, 6h/day for 5 days/week under occlusive conditions","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (Decreased abs. weight at 500 mg/kg bw/day, findings attributed to one (single) animal showing reduced and flaccid testes, not treatment-related)",null,null,null,null,null,null,null,"No effect >1000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ","No effect >1000 ","No effect >1000 ","No effect >1000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 ","Change 1000 (Haematology: statistically significant increase in Hb in females at 1000 mg/kg bw/day, treatment-related; statist. signif. decrease in RBC in females at 250 and 1000 mg/kg bw/day, considered not to be of tox. significance since no effect on the red cell parameters were observed\nClinical chemistry: statistically significant increase in plasma urea but not urea levels in females at 1000 mg/kg bw/day, considered to be not of tox significance; stat. signif. decrease in triglycerides in males at 500 mg/kg bw/day, no dose relation, considered to be not treatment-related\nUrinalysis: not performed)","No effect >1000 (No treatment-related signs of systemic toxicity or local skin reactions observed. 1/5 females at 500 mg/kg bw/day had desquamation during the latter part of the study, no dose-relation, toxicologically not significant)","No effect >1000 ","No effect >1000 "]
[64,"DAR",1991,"Mammals","Prenatal developmental toxicity study","Rat","300; 1000; 3500","mg/kg bw/day","Oral","10 (GD 6-15)","Days","Adult","Vehicle: 1% Methylcellulose; Pre-Study (study ID 41-90716) included in report, doses tested: 500; 1000; 3500 mg/kg bw/day","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >3500 (A total of 23, 23, 25 and 22 females had live young at Day 20 in control to high dose groups respectively. No treatment related effect on litter size.)",null,null,"No effect >3500 (No treatment-related effect on pre-treatment events (implantation rate, corpora lutea).)",null,null,"No effect >3500 (No treatment-related effect on embryonic losses and mean number of live fetuses.)",null,null,"No effect >3500 (No treatment-related effect on post-implantation loss.)","No effect 3500 (A significant increase in pre-implantation loss at 3500 mg/kg/day was observed. However, since treatment commences after implantation, this is not considered to be treatment-related.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 3500 (At 3500 mg/kg/day, the rate of bodyweight gain was markedly reduced during the first two days of treatment when compared to the concurrent control values. Thereafter, apart from a slight reduction in the rate of bodyweight gain during Days 12 to 14 of pregnancy, the rate of bodyweight gain was comparable with the controls, although absolute parity with the control group was not attained by Day 20.\nAt 1000 mg/kg/day, there was a marginal reduction in the rate of bodyweight gain during the first two days of treatment when compared with the concurrent control group. Thereafter, the pattern of bodyweight change was similar to the controls.)",null,"Change 1000 (3500 mg/kg: respiratory distress (noisy respiration/gasping (15/25)), post-dose salivation (22/22), wet coats (13/22), loose faeces from GD7-GD16 (22/22). 1000 mg/kg: noisy respiration on one occasion (2/25). Hair loss/scabbing in occasional animals, including controls, not treatment related.)","Change 3500 (Food: 3500 mg/kg: Food consumption was decreased throughout the treatment period, thereafter, food intake was comparable with controls to termination. At lower dosages, food consumption was comparable with controls throughout.\nWater: 3500 mg/kg: water consumption was increased following the start of treatment and continued to increase throughout the remainder of the treatment period. Thereafter, intake decreased, but was still slightly greater than controls at termination. At lower dosages, the pattern of water consumption did not indicate any clear effects, although at 1000 mg/kg/day, there was a suggestion of increased intake from Days 14 - 15 to termination, although at this stage no clear association with treatment can be made.\n)","Increase 3500 (One female was sacrificed on GD10 immediately after dosing following a probable intubation error (white fluid was found in the thoracic cavity). A further two females were sacrificed on GD7 and GD13 respectively following signs of respiratory distress (noisy respiration/gasping). Post mortem observation did not reveal the cause of distress but the marked signs were a continuation of the signs representative for this group and these two deaths are considered to be related to treatment. There were no further deaths.)"]
[64,"DAR",1991,"Mammals","Prenatal developmental toxicity study","Rat","300; 1000; 3500","mg/kg bw/day","Oral","10 (GD 6-15)","Days","Fetus","Vehicle: 1% Methylcellulose; Pre-Study (study ID 41-90716) included in report, doses tested: 500; 1000; 3500 mg/kg bw/day","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >3500 (No treatment-related effect on genitals was observed during sex determination, visceral examination, as well as gonadal inspection.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 3500 (At 3500 mg/kg, both litter and mean foetal weights were reduced compared to control (statistically significant for mean foetal weight).)",null,null,null,null,null,null,null,null,"Increase 3500 (Skeletal change: The incidence of rib distortion (wavy ribs) was markedly increased at 3500 mg/kg/day. The marginally higher incidence at 1000 mg/kg/day was of uncertain relationship to treatment.\nNo increase in incidence of malformed foetuses was observed (A total of 1, 2, 1 and 3 foetuses in control to high dose groups, respectively were malformed). Increased incidence of reduced ossification was observed in all treated groups compared to the concurrent control. However, compared to historical control data, the incidence of these skeletal changes at 3500 mg/kg/day was only slightly outside the range. Since no clear dosage-response was apparent, reduced ossification was not considered treatment-related.\nThe incidence of foetuses with visceral anomalies was low and did not indicate any adverse treatment-related effects.\n)",null,null,null,"No effect >3500 (No treatment-related effect on sex ratio.)"]
[65,"DAR",1991,"Mammals","Prenatal developmental toxicity study","Rat",1000,"mg/kg bw/day","Oral","10 (GD 6-15)","Days","Adult","Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (Gravid uterus weight along with ovaries was weighed. However, no further details were reported.)",null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (The intergroup comparison of litter data regarding \"litter size\" between control group and treatment group has not shown any statistically significant (p=0.5) difference.)",null,null,"No effect >1000 (The number of corpora lutea and implantations were similar in both control and treatment groups.)",null,null,null,null,null,"No effect >1000 (The number of post-implantation loss was similar in both control and treatment groups.)","No effect >1000 (The number of pre-implantation loss was similar in both control and treatment groups.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (Histopathology was not performed. During macroscopic examination (necropsy) no treatment-related findings were observed. )",null,"No effect >1000 (Histopathology was not performed. During macroscopic examination (necropsy) no treatment-related findings were observed. )",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (There were no significant intergroup differences in body weight at GD0; GD6; GD15; and GD20. The mean body weight gain during pre-treatment, treatment, post-treatment or overall gestation period did not show any statistical difference between the control and treatment groups. Similarly absolute body weight at the end of pregnancy had significantly (p=0.01) increased in both the study groups (control group and treatment group) as compared to GD0 weights.)",null,"No effect >1000 (No treatment-related clinical signs were observed.)","No effect >1000 (There was no intergroup differnce in feed intake between treatment and control group. )","No effect >1000 (No mortality was observed.)"]
[65,"DAR",1991,"Mammals","Prenatal developmental toxicity study","Rat",1000,"mg/kg bw/day","Oral","10 (GD 6-15)","Days","Fetus","Vehicle: Postman brand refined groundnut (peanut) oil; Pre-studies with non-pregnant and pregnant animals included. Based on the results of the pre-studies a limit test (one treatment group) was conducted in the main study.","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1000 (The intergroup comparison of litter data regarding \"mean fetal weight\" (combined sex and sex wise) between control group and treatment group has not shown any statistically significant (p=0.5) difference.)",null,null,null,"No effect >1000 (The number of embryonic and fetal resorptions was similar in both control and treatment groups. The number of dams with any resorption tended to decrease in treatment group which appears to be an incidential finding. The intergroup comparison of litter data regarding \"total number of fetuses\" and \"number of abnormal, dead and live fetuses\" between control group and treatment group has not shown any statistically significant (p=0.5) difference.)",null,null,null,null,"Increase 1000 (The intergroup comparison of litter data regarding \"number of abnormal, dead and live fetuses\" between control group and treatment group has not shown any statistically significant (p=0.5) difference. \nEXTERNAL MALFORMATIONS: No incidence of major external malformations was seen in either of the study groups. VISCERAL MALFORMATION: There was no incidence of major visceral malformations. SKELETAL MALFORMATIONS:  Indidence of minor and major skeletal malformations, did not show any statistically significant intergroup difference. The incidence of delayed ossification of caudal vertebral arch, forelimb-proximal phalange and hindlimb-distal phalange was significantly higher in the treatment group than in control. However, the incidence of incomplete to partial ossification of parietal and interparietal of the skull was less in the treatment group.)",null,null,null,"No effect >1000 (No statistically significant (p=0.5) effect on sex ration was observed.)"]
[69,"DAR",1991,"Mammals","One-generation reproduction toxicity study","Rat","3000; 10000; 30000","ppm","Oral","5.5 (GD 3 till 21 days post partum)","Weeks","Adult (F0)","This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 (The pregnancy rate was good, 90%, 100%, 100% and 90% in Groups 1 to 4 respectively. (Note, treatment started at GD 3.)\nThe duration of pregnancy was similar in all groups and not adversely affected by treatment.)","No effect >30000 (The implantation rates in all treated groups were higher than the controls. Since pup losses, both pre-birth and from birth to weaning, were generally similar among the groups, litter size of all treated groups was, as a consequence, generally greater than controls throughout weaning. These findings are not, however, considered to be an adverse effect of treatment. )",null,null,"No effect >30000 (The implantation rates in all treated groups were higher than the controls. Since pup losses, both pre-birth and from birth to weaning, were generally similar among the groups, litter size of all treated groups was, as a consequence, generally greater than controls throughout weaning. These findings are not, however, considered to be an adverse effect of treatment. )",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Change 3000 (Watery and/or dark contents in the gastro-intestinal tract were observed in 0, 2, 7 and 8 animals in Groups 1 to 4 respectively. Distended caecum was seen in 0, 0, 0 and 4 animals in Groups 1 to 4 respectively.These findings generally followed the trend noted in the clinical signs observed. No histopathology performed.)",null,null,null,"Change 3000 (Distended and/or congested stomach was seen in 0, 2, 5 and 4 animals in Groups 1 to 4 respectively. These findings generally followed the trend noted in the clinical signs observed. No histopathology performed.)",null,null,null,null,"Decrease 30000 (At 30000 ppm, the rate of bodyweight gain following the initiation of treatment was reduced to Day 14 of pregnancy: thereafter, the rate of bodyweight gain to Day 20 of pregnancy was similar to controls, however, absolute parity with controls at Day 20 was not achieved.\nAt both 3000 and 10000 ppm the pattern of bodyweight gain during pregnancy was essentially similar to controls throughout, although by Day 14 of pregnancy, bodyweights were slightly lower than controls.\nDuring the first week of lactation the pattern of bodyweight change in all groups was comparable. Thereafter, slight differences in the pattern of change were apparent to weaning at 10000 and 30000 ppm in so much as more weight loss occurred than in the control group. There were no further effects at 3000 ppm.)",null,"Change 10000 (Clinical signs  included soft faeces and yellow stained sawdust (considered to be caused by the urine) in both cages of animals at 10000 and 30000 ppm. Onset of these signs was earlier at 30000 ppm than at 10000 ppm (soft faeces occurred immediately dietary administration commenced at 30000 ppm but not until the third week post partum at 10000 ppm; yellow staining of the sawdust occurred on Day 26 post coitum at 30000 ppm but not until Day 28 post coitum at 10000 ppm), with signs still apparent in both groups at termination. There were no clinical signs at 3000 ppm considered to be attributable to treatment.)","No effect >30000 (WATER: At 30000 ppm, slight increases in water intake during gestation were apparent towards the end of pregnancy when compared with concurrent control values. At 3000 and 10000 ppm, no adverse effects on water consumption were observed.\nFOOD: Apart from a slight reduction in food intake during the first three days of treatment at 30000 ppm, food intake of all the treated groups was comparable with concurrent controls throughout pregnancy.)","No effect >30000 (There were two mortalities. One at 3000 ppm was sacrificed Day 22 of pregnancy due to poor condition. Post mortem examination did not reveal any reason for the apparent dystocia. Since no similar mortalities were seen at higher levels, this death is not considered to be attributed to treatment.\nA second animal at 30000 ppm was found dead Day 21 post partum (Day 43 of study). Post mortem examination or signs prior to sacrifice did not reveal the cause of death; it is difficult to relate this death to treatment or not.)"]
[69,"DAR",1991,"Mammals","One-generation reproduction toxicity study","Rat","3000; 10000; 30000","ppm","Oral","5.5 (GD 3 till 21 days post partum)","Weeks","Adult (F0+F1)","This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Change 3000 (F0: Macroscopic changes to the salivary glands (enlarged/firm/congested/swollen) were observed in 0, 2, 6 and 8 animals respectively in Groups 1 to 4 of F0 generation.\nDose-related incidence and degree of granular basophilic cytoplasm of acinar cells was seen with 0, 2, 0 and 0 animals showing minimal effects, 0, 0, 2 and 0 animals showing moderate effects and 0, 0, 8 and 9 animals showing marked effects in Groups 1 to 4, respectively. This change was associated with hypertrophy of acinar cells with 0, 2, 2 and 0 animals with minimal hypertrophy and 0, 0, 8 and 9 animals in Groups 1 to 4 respectively with moderate hypertrophy of the acinar cells. Prominent mitoses were also seen in 2 animals at 30000 ppm, but not in lower treatment levels or the controls.\nF1: Post mortem examination of F1 generation at PND 42 revealed swollen/enlarged parotid salivary glands in 5/10 males and 2/10 females at 30000 ppm, and in 1/10 males at 3000 ppm. No histopathological examinations were performed.)"]
[69,"DAR",1991,"Mammals","One-generation reproduction toxicity study","Rat","3000; 10000; 30000","ppm","Oral","only secondary exposure through milk from PND 0-21","Weeks","Offspring (F1)","This study is a range-finding study. Only pregnant rats were exposed to the test substance. Male parent animals were not included. Group mean achieved intakes of Glyphosate during gestation in the treatment groups ranged from 236 - 311 (3000 ppm), 799 - 1010 (10000 ppm) and 2515 - 2789 (30000 ppm) mg/kg/day. As expected, as the weight of the animals increased the actual intake of Glyphosate (expressed as mg/kg/day) generally declined. The 3-fold interval in fixed ppm, between the groups remains established when expressed as mg/kg/day.","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 (Pup losses, both pre-birth and from birth to weaning, were generally similar among the groups.)","Decrease 30000 (At birth, [total] litter weight of all treatment groups was increased compared to control - this is due to the increased litter sizes seen in the treatment groups.\nAt 30000 ppm litter weight converged towards control values to Day 8; thereafter litter weight became reduced and by Day 21 was only 78% of the concurrent control value. Mean pup weight was reduced at birth and diverged further away from controls through to Day 21 when mean pup weight at this level was only 62% of the controls.\nAt 3000 and 10000 ppm litter weight through to weaning was comparable with the controls even though litter size was increased. As a consequence mean pup weight diverged below control values to an extent that on Day 21 post partum mean pup weight at 3000 and 10000 ppm was 91% and 87% lower than the corresponding control value. These differences, however, can probably be attributed to the pivotal association between litter size, litter weight and mean pup weight and, at this stage, no conclusive treatment-related effects can be established.)",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30000 (Glyphosate did not selectively affect pups of one sex since, in all groups, sex ratios at birth and weaning were similar. )",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Change 3000 (Post mortem examination of weanlings at PND 21 revealed four pups with congested salivary glands at 10000 ppm and one pup with congested salivary glands at 3000 ppm. Since no similar findings were seen at 30000 ppm the significance of these incidences is unclear. No histopathological examinations were performed.)",null,null,"No effect >30000 (No effect observed at necropsy.)"]
[69,"DAR",1991,"Mammals","One-generation reproduction toxicity study","Rat","3000; 10000; 30000","ppm","Oral","3 (PND 21-42)","Weeks","Adult (F1)","Group achieved intakes of Glyphosate in Groups 2 to 4 respectively, recorded during Weeks 5 and 6, ranged from 368 - 390, 1291 - 1335 and 3918 - 4453 mg/kg/day for males and 355 - 402, 1191 - 1271 and 3961 - 4397 mg/kg/day for females.","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Change 30000 (Post mortem examination revealed: Soft gastro-intestinal contents were noted in 7/10 males and 9/10 females at 30000 ppm; grey/blue contents of the jejunum were noted in 2/10 females at this dosage. No histopathological examinations were performed.)",null,null,null,null,null,null,null,null,"Decrease 30000 (From weaning to termination (PND 21 - 42), males at 30000 ppm had a reduced rate of weight change. At lower dosages, and at all dosages among females, the rate of weight change was comparable with controls, however, differences inherent at weaning were still present by Week 6.)",null,"Change 30000 (Soft faeces were observed for all animals at 30000 ppm from Week 4 through to sacrifice at Week 6. No other clinical signs were observed at this or lower dosages.)","Decrease 30000 (Food consumption at 30000 ppm was lower than controls during Weeks 5 and 6 (males only). There were no other effects considered attributable to treatment for males or females at any dosage.\nThe food conversion ratio for males at 30000 ppm was slightly greater when compared to controls (Week 6 only), indicating a slightly lower efficiency of food utilisatian into bodyweight gain.\nThere were no other effects on food conversion ratios.)","No effect >30000 (There were no mortalities.)"]
[70,"DAR",1981,"Mammals","Multigenerational reproductive toxicity","Rat","3; 10; 30","mg/kg bw/day","Oral","life-time, all three generations","Weeks","Adult (F0+F1)",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30 (Preputial gland: No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)",null,null,null,null,null,null,null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)",null,null,null,null,null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2), for both sexes, were indicative of common incidental histological findings.)",null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (Mean ovary weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for females of all generations (F0, F1, and F2).)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)",null,null,null,null,null,null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (Mean testis weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for males from the F0, F1, and F2 generations.)","No effect >30 (THYROID: No microscopic findings were considered compound related.\nPARATHYROID: No microscopic findings were considered compound related.\nThe overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)",null,"No effect >30 (Uterus (Cervix not explicitly mentioned): No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)",null,null,null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (Mean adrenal weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females from each generation (F0, F1, and F2). For the F1 generation, some statistically significant differences were noted between control and mid-dose treatment group both in mean adrenal weight data and in the relative weight data; however, no trends were evident within dose levels or through the generations.)","No effect >30 (Investigated tissues were: two longitudinal sections of the brain, optic nerves, and Pineal gland (Pineal gland only in F2). No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (Mean brain weight data were considered comparable between the control and treated groups for both males and females for each generation (F0, F1, and F2).)",null,"No effect >30 (F0: Male and female mating indices and male fertility indices during both mating intervals of the F0 generation were considered comparable between the control and treated groups. During the second mating interval of the F0, pregnancy rates were lower than control in each of the treated groups; however, no indication of a dose-response relationship was evident as the lowest pregnancy rate was seen in the mid-dose group. This reduction in pregnancy rate for the mid-dose group was not statistically significant. In the absence of a dose-response relationship the reduction in pregnancy rate during this mating interval (F1b) in the treated groups was not considered treatment-related.\nF1: In the F1 generation, mating indices (males and females) for both litter intervals were comparable between the control and treated groups. It is note-worthy that for both mating intervals of this generation, mating indices for control and some treated groups were lower than normally encountered in multi-generation studies. The reason for the poorer mating performance in this generation is unclear but no treatment effect was indicated since mating indices were lowest in the control group. Pregnancy and male fertility indices for the first mating interval of the F1 were comparable between the control and treated groups. During the second litter interval, pregnancy rates were lower than those seen for the first interval in control and treated groups. The lowest pregnancy rate was seen, in the high-dose group; however, this difference from the control value was not statistically significant. Pregnancy rates for the low- and mid-dose groups, during the second mating interval, were considered comparable to control. Male fertility indices for this same mating interval were considered comparable between the control and treated groups.\nF2: In the F2 generation mating indices for the treated groups were lower than control for each mating interval. During the first mating interval of the F2 generation, the female mating indices were lower than control in each of the treated groups; however, only in the high-dose group was this difference from control statistically significant. The female mating index for the control group at this interval was 100%, which is higher than normally encountered. In general, the female mating indices observed for the control groups in this study have shown considerable variability ranging from 70.9 to 100%. The poor mating performance for the treated groups during the first mating interval is attributed to two males in each treatment group that did not mate either female in their mating unit (each mating unit is comprised of one male and two females). During the second mating interval of the F2 generation, male mating performance improved in the mid- and high-dose groups as both mid-dose males and one of two high-dose males that did not mate during the first mating interval, mated and impregnated at least one female. Male mating indices for the low-dose group remained unchanged as the same two males that did not mate during the first interval, failed to mate during the second interval.\nPregnancy and fertility indices for the treated groups were comparable to control for both litter intervals of the F2 generation.\nOver the entire study no consistent, dose-related effect was seen in mating, fertility or pregnancy indices to indicate an adverse effect of treatment.)",null,null,"No effect >30 (Mean gestation length was comparable between the control and treated groups for each pregnancy interval in each generation (F0, F1, and F2).)","No effect >30 (The mean numbers of live, dead and total pups at birth and pup viability at birth for each pregnancy interval were comparable between the control and treated groups for each generation (F0, F1, and F2). Likewise, mean litter size data on day 21 of lactation (weaning) was comparable between the control and treated groups for each litter interval throughout the study for each generation (F0, F1, and F2).)",null,null,null,"No effect >30 (The mean numbers of live, dead and toal pups at birth for each pregnancy interval were comparable between the control and treated groups for each generation (F0, F1, and F2).)",null,null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (Mean pituitary weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females for each generation (F0, F1, and F2).)",null,null,"No effect >30 (Gross postmortem examinations of the F0, F1 and F2 adults at terminal sacrifice (males and females) did not indicate an adverse effect of treatment.)",null,null,null,null,null,null,null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)",null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (Mean organ weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females from the F0, F1, and F2 generation.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (Mean organ weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females from the F0, F1, and F2 generation.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (Mean liver weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females from the F0, F1, and F2 generation. In the F2 female group, mean liver/body weight ratios were significantly lower than control in each of the treated groups; however, no clear dose-relationship was apparent. Mean liver/brain weight ratios for the treated F2 females were lower than control; however, these differences from control values were not statistically significant.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (Mesenteric, mandibular, and cervical lymph nodes: No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (Sciatic nerve: No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (Duodenum, Ileum, Colon: No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (In general, mean spleen weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females from the F0, F1, and F2 generation. Some statistically significant differences were noted between control and treated groups (mid dose) both in mean organ weight data and in the relative weight data (spleen); however, no trends were evident within dose levels or through the generations.  In the F2 female group, mean spleen weights (absolute and relative to brain and body weights) were significantly higher than the control value in the F2 mid-dose female group; however, mean spleen weight data for the low- and high-dose F2 females were comparable to control values. In the absence of an effect on spleen weight in the high-dose F2 female group, the change seen in spleen weight data for the mid-dose females was considered spurious and not biologically relevant.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)",null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)","No effect >30 (F0, F1, and F2: Mean body weight data during the growth and rest periods were comparable between the control and treated groups for each generation, throughout the study. Likewise, mean weight gain during the growth periods were comparable between these same groups for both sexes throughout all generations. No treatment effect on body weight data during the growth and rest periods was evident.\nMean body weight data during the gestation and lactation intervals and mean weight change during these same periods were considered comparable between the control and treated group for each pregnancy interval from each generation throughout the study.\nNo treatment effect was indicated in gestation - lactation body weight data throughout the study.\nAlso mean terminal body weight data were comparable between the control and treated groups for both males and females throughout the study.)",null,"No effect >30 (In-life physical observation data were considered comparable between the control and treated groups for each generation interval throughout the study. No adverse treatment-related effects were reported for adult F0, F1, and F2 animals.)","No effect >30 (F0, F1, and F2: Mean food consumption data were considered comparable between the control and treated groups (both sexes) during the growth and rest periods for each generation, throughout the study. No adverse effect of treatment on food consumption data was evident throughout the study.)","No effect >30 (In the F0 generation, no unscheduled mortality occurred in the control, low- or high-dose groups. In the mid-dose group, one female died on day 20 of lactation, during the first litter interval (F1a). A second mid-dose female died on day 7 during the lactation period of the second litter interval (F1b). None of the mid-dose males died during this interval of study.\nIn the F1 generation, no unscheduled mortality occurred in the control or low-dose groups. In the mid-dose group one female was killed in a moribund condition during the post-mating period for the second litters (F2b). This female had mated during the first mating interval but did not deliver a litter; this female had not mated during the second mating period. No other mortality occurred in the mid-dose group. In the high-dose group, one female died during the first week of the growth period; this animal was caught in the feeder jar and death was considered accidental. A second high-dose female died during the gestation period for the second (F2b) litters. This female died on Day 21 of gestation and the uterus contained 15 term fetuses. No other mortality  ccurred in the high-dose group.\nIn the F2 generation, no mortality occurred in the control or high-dose groups. In the low-dose group one female died during the F3a lactation period. This female delivered a litter containing only  dead pups (13 pups) and died the day after parturition. No other mortality occurred in the low-dose group. In the mid-dose group, one male was killed in a moribund condition during the period between mating of the first and second litters. This male had mated and impregnated both females during the first mating period. No other mortality occurred in the mid-dose group.)","No effect >30 (Harderian gland: No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings.)"]
[70,"DAR",1981,"Mammals","Multigenerational reproductive toxicity","Rat","3; 10; 30","mg/kg bw/day","Oral","life-time, all three generations","Weeks","Offspring (F1+F2)",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30 (Mean litter size data on day 21 of lactation (weaning) was comparable between the control and treated groups for each litter interval throughout the study for each generation (F0, F1, and F2).\nThe indices of litters weaned were comparable between the control and treated groups for each lactation interval in the F0, F1, and F2 generation.)","No effect >30 (Mean pup body weight data during each litter interval for each generation (F1, F2, and F3) were considered comparable between the control and treated groups. No adverse effects of treatment on pup weight data was evident. Accordingly, no treatment-related effect was evident in terminal body weight data for the F3b offspring.)",null,null,null,null,null,null,null,null,"No effect >30 (Gross postmortem observations of offspring at weaning (F1a, F2a,F3a F3b) on post-weaning (F1b, F2b) did not reveal an adverse effect of treatment. Likewise, evaluation of dead pups recovered at birth and during the 21-day lactation period did not reveal a treatment-related effect.)",null,"No effect >30 (In the F0 generation, postnatal survival indices for Days 0-4 and 4-21 were comparable between the control and treated groups for the first lactation interval (F1a). For the second litter interval of the F0 (F1b), postnatal survival indices for the Day 0-4 interval were comparable between the control and treated groups. During the day 4-21 interval, survival indices were significantlv lower than control in each treatment qroup. The increase in pup mortality during this interval (i.e. days 4-21) was attributed to high pup mortality within one or more litters at each treatment level. In the low-dose group the lower pup survival was attributed to one female that experienced complete litter mortality (litter contained 14 live pups at day 4). In the mid-dose group, one female died on Day 7 of lactation and all seven pups in her litter died during the Day 4-7 lactation interval. Additionally, three mid-dose litters lost five or more pups from their litters during the day 4-21 lactation interval. In the high-dose group, one female lost nine of 12 pups during the day 4-21 lactation interval.\nIn the F1, F2, and F3 generations postnatal survival indices for days 0-4 and 4-21 during both litter intervals were considered comparable between the control and treated groups. Some statistically significant differences in these indices were observed between the control and treated groups; however, no trend was evident through successive generations to indicate an adverse effect of treatment.)",null,"No effect >30 (Pup sex distributions ratios at day 0 were generally comparable between the control and treated groups for each litter interval for each generation (F1, F2, and F3). Pup sex distributions at day 21 (weaning) were similar to distributions noted at day 0 in both the control and treated groups for each generation (F1, F2, and F3). No adverse treatment effect on sex distribution data was evident.)"]
[70,"DAR",1981,"Mammals","Multigenerational reproductive toxicity","Rat","3; 10; 30","mg/kg bw/day","Oral","21 (PND0-21, exposure through milk)","Days","Offspring (F3)",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)",null,null,null,null,null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)",null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)",null,null,null,null,null,null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.)","No effect >30 (THYROID: No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.\nPARATHYROID: No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)",null,"No effect >30 (Uterus (Cervix not explicitly mentioned): No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)",null,null,null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.)","No effect >30 (Tissues investigated: two longitudinal sections of the brain and optic nerves. No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.)",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.)",null,null,null,null,null,null,null,null,null,null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)",null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (Mesenteric and cervical lymph nodes: No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (Sciatic nerve: No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (Duodenum, Ileum, Colon: No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)",null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)","No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)",null,null,null,null,null,"No effect >30 (Harderian gland: No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings.)"]
[70,"DAR",1981,"Mammals","Multigenerational reproductive toxicity","Rat","3; 10; 30","mg/kg bw/day","Oral","life-time, all three generations","Weeks","Adult (F0)",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30 (Clitoral gland investigated for F0 only. No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for generation F0 were indicative of common incidental histological findings.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >30 (No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study were indicative of common incidental histological findings.)"]
[71,"DAR",1989,"Mammals","Repeated dose 28-day oral toxicity study in rodents","Rat","30000; 40000; 50000","ppm","Oral",28,"Days","Adult","Dose-range finder","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ",null,"No effect >50000 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease >50000 (Cumulative body weight change treated vs. control: M 40000= -53%* (day 1 - 8); M 40000=-40%* (day 1-16); M 50000=-100%* (day 1-8); M 50000=-50%* (day 1-16); M 50000=-44%* (day 1-23); M50000=-44%* (day 1-28); F 50000=-64%* (day 1-8); F 50000=-46%* (day 1-16); F 50000=-47%* (day 1-23); F 50000=-46%* (day 1-28); F 30000= -38%* (day 1-23); F 50000=-33%* (day 1-28)\nBody weight reduction are considered secondary to gastrointestinal effects.)",null,"Increase 30000 (Significant incidences of soft stools and/or diarrhea were noted for both sexes at all three exposure levels with the highest dose group most affected (M/F 30000= Soft stool, diarrhea; M/F 40000= soft  stool/diarrhea; M/F 50000=marked diarrhea).)","No effect >50000 ","No effect >50000 "]
[74,"DAR",1988,"Mammals","Multigenerational reproductive toxicity","Rat","75; 150; 300","ppm","Oral","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F0)","Supportive only","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >300 (No effects in F0 observed.)",null,null,null,null,null,null,null,null,null,null,null,null,"No effect >300 (Pregnancy rate was not changed for F0 females.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >300 (Body weight was not affected in F0 adults.)",null,"No effect >300 (Signs of systemic toxicity were not observed in F0 generation.)","No effect >300 (Food consumption of F0 adults was not affected.)"]
[74,"DAR",1988,"Mammals","Multigenerational reproductive toxicity","Rat","75; 150; 300","ppm","Oral","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F1)","Supportive only","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >300 (No effects in F1 observed.)",null,null,null,"No effect >300 (No effects in F1 observed.)",null,null,null,null,"No effect >300 (No effects in F1 observed.)",null,"No effect >300 (No effects in F1 observed.)",null,"No effect >300 (No effects in F1 observed.)",null,null,null,"No effect >300 (No effects in F1 observed.)",null,"No effect >300 (No effects in F1 observed.)",null,null,"No effect >300 (Pregnancy rate was not changed for F1 females.)",null,null,null,null,null,null,null,null,null,null,"No effect >300 (No effects in F1 observed.)",null,null,null,null,null,null,null,null,null,"No effect >300 (No effects in F1 observed.)",null,null,"No effect >300 (No effects in F1 observed.)",null,"No effect >300 (No effects in F1 observed.)",null,"No effect >300 (No effects in F1 observed.)",null,"No effect >300 (No effects in F1 observed.)",null,"No effect >300 (No effects in F1 observed.)",null,"No effect >300 (No effects in F1 observed.)","No effect >300 (No effects in F1 observed.)",null,"No effect >300 (No effects in F1 observed.)",null,null,null,null,"No effect >300 (No effects in F1 observed.)",null,"No effect >300 (GI tract (stomach and intestines were exmined.)",null,null,null,"No effect >300 (No effects in F1 observed.)","No effect >300 (Body weight was not affected in F1 adults.)",null,"No effect >300 (Signs of systemic toxicity were not observed in F1 generation.)","No effect >300 (Food consumption of F1 adults was not affected.)"]
[74,"DAR",1988,"Mammals","Multigenerational reproductive toxicity","Rat","75; 150; 300","ppm","Oral","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Adult (F2)","Supportive only","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >300 (No effects in F2 observed.)",null,null,null,"No effect >300 (No effects in F2 observed.)",null,null,null,null,"No effect >300 (No effects in F2 observed.)",null,"No effect >300 (No effects in F2 observed.)",null,"No effect >300 (No effects in F2 observed.)",null,null,null,"No effect >300 (No effects in F2 observed.)",null,"No effect >300 (No effects in F2 observed.)",null,null,"No effect >300 (Pregnancy rate was not changed for F2 females.)",null,null,null,null,null,null,null,null,null,null,"No effect >300 (No effects in F2 observed.)",null,null,null,null,null,null,null,null,null,"No effect >300 (No effects in F2 observed.)",null,null,"No effect >300 (No effects in F2 observed.)",null,"No effect >300 (No effects in F2 observed.)",null,"No effect >300 (No effects in F2 observed.)",null,"No effect >300 (No effects in F2 observed.)",null,"No effect >300 (No effects in F2 observed.)",null,"No effect >300 (No effects in F2 observed.)","No effect >300 (No effects in F2 observed.)",null,"No effect >300 (No effects in F2 observed.)",null,null,null,null,"No effect >300 (No effects in F2 observed.)",null,"No effect >300 (F2: GI tract (stomach and intestines were exmined.))",null,null,null,"No effect >300 (No effects in F2 observed.)","No effect >300 (Body weight was not affected in F2 adults.)",null,"No effect >300 (Signs of systemic toxicity were not observed in F0 generation.)","No effect >300 (Food consumption of F2 adults was not affected.)"]
[74,"DAR",1988,"Mammals","Multigenerational reproductive toxicity","Rat","75; 150; 300","ppm","Oral","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Offspring (F1)","Supportive only","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >300 (No effect observed in F1 offspring.)","No effect >300 (No effect observed in F1 offspring.)","No effect >300 (No effect observed in F3 offspring.)"]
[74,"DAR",1988,"Mammals","Multigenerational reproductive toxicity","Rat","75; 150; 300","ppm","Oral","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Offspring (F2)","Supportive only","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >300 (No effect observed in F2 offspring.)","No effect >300 (No effect observed in F2 offspring.)"]
[74,"DAR",1988,"Mammals","Multigenerational reproductive toxicity","Rat","75; 150; 300","ppm","Oral","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Offspring (F3)","Supportive only","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >300 (No effect observed in F3 offspring.)","No effect >300 (No effect observed in F3 offspring.)"]
[75,"DAR",1988,"Mammals","One-generation reproduction toxicity study","Rat","5; 10","mg/kg bw/day","Oral","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Adult (F0)","Supportive only","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10 ",null,null,"No effect >10 (Number of corpora lutea and total implants in females killed at GD 13 were not affected.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10 ",null,null,"No effect >10 "]
[75,"DAR",1988,"Mammals","One-generation reproduction toxicity study","Rat","5; 10","mg/kg bw/day","Oral","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Offspring (F1)","Supportive only","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >10 (Growths rate of pups was not affected.)",null,null,null,null,"No effect >10 (Group mean pup weight was not affected.)",null,"No effect >10 ",null,"No effect >10 (Number of early and late in utero deaths in females killed at GD 13 were not affected.)",null,null,null,null,null,null,"No effect >10 "]
[76,"DAR",1990,"Mammals","Repeated dose 90-day oral toxicity study in rodents","Rat","2000; 5000; 7500","ppm","Oral","90-92","Days","Adult","Average substance intake over study period: M 2000ppm=5.506 g; M 5000ppm=13.83 g per rat; M 7500ppm=20.078 g per rat per rat; F 2000ppm=4.114 g per rat F 5000ppm=10.24 g per rat; F 7500ppm=14.707 g per rat; F","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >7500 ",null,null,null,null,null,null,null,null,"No effect >7500 ",null,"No effect >7500 ",null,"No effect >7500 ",null,null,null,null,null,null,"No effect >7500 ","No effect >7500 ","No effect >7500 ",null,"No effect >7500 ",null,null,null,"No effect >7500 ","No effect >7500 ","No effect >7500 ",null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >7500 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >7500 (Kidney and urinary bladder were examined.)","Decrease 2000 (Absolute: F 7500ppm=-8%*; F 5000ppm=-11%*; F 2000ppm=-13%*\nrelative: M 2000ppm=+12%* ; F 2000ppm=-9%* (not dose-dependent))","No effect >7500 ","No effect >7500 ","No effect >7500 ","No effect >7500 ",null,"No effect >7500 ",null,"No effect >7500 ",null,null,null,null,"No effect >7500 ",null,"No effect >7500 (The GI tract was examined (stomach and intestines).)","No effect >7500 ",null,"No effect >7500 ",null,"No effect >7500 ","Change 2000 (Hematology: RBC in F 2000ppm=+13.6%* and M 7500ppm=-1.4%* (males within normal range of historical controls); HCT in F 2000ppm=+13.2%* and M 7500ppm=-1.4%*; All values were close to the historical controls. \nSlight change in monocytes in males and females at 2000ppm however not considered treatment-related\nClincal chemistry: Ca in M 5000ppm increase; Na in M changed ; Cl in M 7500ppm increase (none of the clinical chemistry parameters is considered treatment-related))","No effect >7500 ","Decrease 7500 (Indication for slight decrease in males and females at 7500ppm)","No effect >7500 "]
[78,"DAR",1992,"Mammals","Repeated dose 90-day oral toxicity study in rodents","Rat","3125; 6250; 12500; 25000; 50000","ppm","Oral",90,"Days","Adult","Average substance intake over study period: M 3125 ppm=205 mg/kg bw/day; M 6250 ppm=410 mg/kg bw/day; M 12500 ppm= 811 mg/kg bw/day; M 25000 ppm=1678 mg/kg bw/day; M 50000ppm=3393 mg/kg bw/day; F 3125 ppm=213 mg/kg bw/day; F 6250 ppm=421 mg/kg bw/day; F 12500 ppm=844 mg/kg bw/day; F 25000 ppm=1690 mg/kg bw/day; F 50000 ppm= 3393 mg/kg bw/day","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ","Increase 50000 (Increased estrous cycle length was observed at 50000 ppm.)",null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ","No effect >50000 ","Decrease 25000 (A decrease in sperm numbers was observed from 25000 ppm. At the same dose level a significant reduction of body weight gain was observed (terminal body weight M 50000 ppm= -18% compared to control). Histopathology of testes was not performed within this study but a decrease in testes weight was not observed. The decreased count of sperm number is not considered to be endocrine-related but rather secondary to systemic toxicity.)",null,"Increase 50000 (An increase in relative but not absolute organ weight was observed at 25000 ppm and 50000 ppm. The increase was considered secondary to decreased body weights. Histopathology was not performed within this study. )",null,null,null,null,null,null,"No effect >50000 ",null,"No effect >50000 (Three sections frontal cortex and basal ganglia, parietal cortex and thalamus, cerebellum and pons were examined.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >50000 ","No effect >50000 ","No effect >50000 ",null,null,"No effect >50000 (No treatment-related effects)",null,"Increase 50000 (Relative: M at 25000 ppm and 50000 ppm; F no treatment-related effects)",null,"Increase 50000 (Relative: M at 6250 ppm; 12500 ppm; 25000 ppm and 50000 ppm; F no treament-related effects; F no treatment-related effects)",null,null,"No effect >50000 ",null,null,"Change 3125 (Parotid and submandibular salivary glands in M and F: Cytoplasmic alterations (basophilic change and hypertrophy of acinar cells) in M and F at 3125 ppm; 6250 ppm; 12500 ppm; 25000 ppm; 50000 ppm)",null,null,null,null,null,null,null,null,"Decrease 50000 (Relative: M 50000 ppm= -13%*; F no treatment-related effects)",null,null,"Decrease 25000 (Reduced weight gain in M at 25000 and 50000 ppm. Terminal body weight M 50000 ppm= -18% (in comparison to control)\nTerminal body weight F 50000 ppm= -5% (in comparison to control))","Change 12500 (Hematology: mild increase in hct and RBC in M at 12500 ppm; 25000 ppm; 50000 ppm; mild increase in hgb in M at 25000 ppm; 50000 ppm; mild increase in plts in M at 50000 ppm\nminimal but significant increase in lymphocyte and plts counts, WBC, MCH, MCV in F\nClinical chemistry: Changes in: ALP in M and F at all time points (except 90 days), total bile acids in M (days 23 and 90) and F (day 23), total protein in F at all time points; sporadic increases in urea nitrogen and albumin)","Increase 50000 (F and M at 50000 ppm = diarrhea during first 50 days was observed (normal thereafter).)","No effect >50000 ","No effect >50000 ","No effect >50000 (Lung)"]
[80,"Publication",2016,"Mammals","Subacute oral in rodent ","Rat","5; 50; 500","mg/kg bw/day","Oral",5,"Weeks","Adult",null,"Yes","N/A",null,null,null,null,null,null,null,null,null,null,"No effect >500 (Although there was a trend towards decreased serum (not dose-dependent), no statistically significant changes were noted.)",null,null,null,null,null,null,"No effect >500 (Although there was a trend towards decreased serum concentrations (not dose-dependent), no statistically significant changes were noted.)",null,null,null,null,null,"No effect >500 (Although there was a trend towards decreased serum concentrations with dose, no statistically significant changes were noted.)",null,null,null,null,null,null,null,null,null,"Decrease 500 (A significant decrease in absolute (but not relative) weight of the coagulating gland (weighed together with seminal vesicles) was observed, which may be attributed to the non statistically significant reduced final body weight.)","No effect >500 (No statistically significant changes were observed.)","No effect >500 ",null,null,null,null,null,null,null,null,null,"No effect >500 ","No effect >500 (No statistically significant changes were observed.)","Decrease 500 (A significant decrease in absolute (but not relative) weight of the seminal vesicle gland (weighed together with coagulating gland) was observed, which may be attributed to the non statistically significant reduced final body weight.)",null,null,"Decrease 500 (Total sperm count was decreased (epididymal sperm).)","No effect >500 (No statistically significant changes were observed. In addition, no statistically significant changes were observed in androgen receptor (AR) immunoreactivity localized in the nuclei of cells, including Sertoli cells, peritubular myoid cells and Leydig cells. Moreover, the levels of catalase (CAT, U/mg protein), superoxide dismutase (SOD, U/mg protein) and malondialdehyde (MDA, µmol/g protein) were determined in testes and no statistically significant changes were observed.)","No effect >500 ",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 50 (Although not statistically significant there was a dose-dependent decrease in daily weight gain. Mean terminal body weight was not statistically significantly changed. However, there was a ~10% reduction of mean body weights at 50 and 500 mg/kg bw groups providing an indication that the MTD was reached or exceeded.)",null,null,"No effect >500 (Average daily feed intake was significantly decreased at 50 mg/kg bw but not at 500 mg/kg bw. It is therefore suggested that the decrease of average daily feed intake is independent of glyphosate treatment. )"]
[91,"Publication",2018,"Mammals","Subacute oral in rodent ","Rat","2.5; 25","mg/kg bw/day","Oral",14,"Days","Adult","Reliable with restrictions: non-standard study design with a 14-day exposure by having two dose groups established for glyphosate and one for the formulation.","Yes","N/A",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >25 (The Leydig cell-specific steroidogenesis factors CYP11A1 and STAR were both expressed at comparative levels between the glyphosate treated animals and the controls. Also no difference in expression and distribution was noted between glyphosate treated groups and controls for the steroidogenic enzyme HSD3B1 and the germ cell-specific factor DDX4. )",null,"No effect >25 (Intra-testicular testosterone level was investigated.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >25 (No adverse histopathology in any of the glyphosate exposed groups was observed when compared with controls. The seminiferous tubules were intact and displayed active spermatogenesis with comparable spermatogenic cycling between examined specimens (qualitative assessment). Neither were there any differences between exposed and control animals with regard to missing germ cell layers or multinucleated germ cells. The interstitial space was comparable between glyphosate treated groups and controls. Moreover, the number of apoptotic cells was comparable between control testes and all glyphosate treated groups.)"]
[92,"Publication",2018,"Mammals","Subchronic oral toxicity in rodents","Rat","1,75","mg/kg bw/day","Oral","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0+F1)","The results are to be interpreted together with Study ID 93 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate and AMPA in urine and its validation were not fully reported.  ","Yes","N/A",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1.75 (There was no clinical evidence of alterations in activity or behavior, reflexes, eyes or skin, respiratory, gastrointestinal, genito-urinary and cardiovascular systems.)",null,"No effect >1.75 (All 24 dams and 108 rats from the 6-week and 13-week cohorts survived until sacrifice.)"]
[92,"Publication",2018,"Mammals","Subchronic oral toxicity in rodents","Rat","1,75","mg/kg bw/day","Oral","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0)","The results are to be interpreted together with Study ID 93 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate and AMPA in urine and its validation were not fully reported.  ","Yes","N/A",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1.75 (Body weight and body weight gain of the dams during gestation and lactation were not statistically different among groups.)",null,null,"No effect >1.75 (Water and feed consumption during gestation and lactation were not different across groups (dams).)"]
[92,"Publication",2018,"Mammals","Subchronic oral toxicity in rodents","Rat","1,75","mg/kg bw/day","Oral","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Offspring (F1)","The results are to be interpreted together with Study ID 93 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate and AMPA in urine and its validation were not fully reported.  ","Yes","N/A",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1.75 (Post-weaning body weight of female and male offspring was homogeneous and no statistically significant differences in body weight gain were observed among groups. )",null,null,"No effect >1.75 (Post weaning water and feed consumption were not affected by treatment (pups).)"]
[93,"Publication",2019,"Mammals","Subchronic oral toxicity in rodents","Rat","1,75","mg/kg bw/day","Oral","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F0)","Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1.75 (Total testosterone levels in dams were not affected.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1.75 (F0)",null,"No effect >1.75 (F0)","No effect >1.75 (F0: Absolute and relative weight was unaffected.)",null,null,null,null,null,null,null,null,null,null,null,"No effect >1.75 (F0)","No effect >1.75 (F0: Absolute and relative weight was unaffected.)","No effect >1.75 (F0)",null,"No effect >1.75 (F0)","No effect >1.75 (F0: Absolute and relative weight was unaffected.)",null,null,null,null,null,null,"No effect >1.75 (Gestational length did not differ significantly between groups.)"]
[93,"Publication",2019,"Mammals","Subchronic oral toxicity in rodents","Rat","1,75","mg/kg bw/day","Oral","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Offspring (F1)","Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1.75 (Age and body weight at PPS was not affected.)","No effect >1.75 (Female offspring in the control- and glyphosate-treated groups presented the FE within 6 days from the VO. (The female rats belonging to the developmental cohort (8F/group) were also monitored for the time to first estrous (FE), defined as the first day on which only cornified epithelial cells were observed on a vaginal smear, determined by vaginal cytology for 14 consecutive days, starting 3 days after vaginal opening was observed.))","No effect >1.75 (Age and body weight at VO was not affected.)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1.75 (Mean litter size (incuding dead and alive pups determined on PND 0, 1, 4, 7, 10, 13, 16, 19, 21, 25) did not differ significantly between groups.)","No effect 1,75 (Live birth index was calculated on PND 0. The mean live birth index was comparable between groups, although the number of dams with stillbirths was higher in the glyphosate (4/8) group compared to control (2/8).)",null,null,null,null,null,null,null,null,null,null,null,"No effect >1.75 (Survival index was calculated on PND 1, 4, 7, 10, 13, 16, 19, 21, 25.)",null,"No effect >1.75 (Sex ratio was determined on PND 1 and did not differ significantly between groups.)"]
[93,"Publication",2019,"Mammals","One-generation reproduction toxicity study","Rat","1,75","mg/kg bw/day","Oral","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Offspring (F1)","Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Increase >1.75 (AGD was measured on PND 4 (including bw determination). AGD was statistically significantly increased in males only (absolute values: 4.26 mm vs 4.02 mm in control) and the author also reports this for the AGD adjusted for body weight. However, the numbers for the AGD index are not provided. Moreover, when taking into account the provided box plots and dot plots regarding AGD and AGD index, a significant increase in AGD index is not obvious.)"]
[93,"Publication",2019,"Mammals","Subchronic oral toxicity in rodents","Rat","1,75","mg/kg bw/day","Oral","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Adult (F1)","Part of the study design is described in Study ID 92 (pilot study for EOGRTS).\nThis publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because only one dose level for glyphosate and MON 52276 was considered, only 8 animals were used per dose and per sex and the method of analysis of glyphosate in water and its validation were not fully reported.  ","Yes","N/A",null,null,null,null,null,null,null,null,null,null,"No effect >1.75 (F1: 17β-estradiol (E2). No statistically relevant effect observed in males (effect in females not possible to evaluate statistically due to insufficinet sample size considering the different stages of estrous cycle).)","No effect >1.75 (Using plasma samples from 40 pups (20 females and 20 males) randomly selected from the 6-week cohort (N = 48 total). FSH and LH were also assessed in 40 pups (20 females and 20 males) randomly selected from the 13-week cohort (N = 60 total).)",null,null,"No effect >1.75 (Using plasma samples from 40 pups (20 females and 20 males) randomly selected from the 6-week cohort (N = 48 total). FSH and LH were also assessed in 40 pups (20 females and 20 males) randomly selected from the 13-week cohort (N = 60 total).)","No effect >1.75 (Further hormones: sex hormone binding globuline (SHBG), growth hormone (GH), adrenocorticotropic hormone (ACTH), brain-derived neurotrophic factor (BDNF) levels were not affected in both F1 exposure groups.)",null,null,"No effect >1.75 (Using plasma samples from 40 pups (20 females and 20 males) randomly selected from the 6-week cohort (N = 48 total).)",null,null,null,null,"No effect >1.75 (F1: Serum concentration of free (fT) and total testosterone (TT), 5α-dihydrotestosterone (DHT) were analysed in both cohorts (6 and 13 weeks).\nNo statistically significant differences in serum TT, fT and DHT concentrations were observed in males or females belonging to both cohorts. A non-statistically significant increase in TT was observed in females of both cohorts only and fT was decreased after 6 weeks but not 13 weeks of exposure.)","Increase 1,75 (A statistically significant increase was observed in males of the 6 weeks exposure group only. No effect was observed after 13 weeks of exposure in males or in females. (Using plasma samples from 40 pups (20 females and 20 males) randomly selected from the 6-week cohort (N = 48 total).))",null,null,null,null,null,null,null,null,null,"No effect >1.75 (Assessed for both F1 exposure groups.)","No effect >1.75 (No effect was obsereved on absolute and relative organ weight of both exposure groups (6 and 13 weeks).)","No effect >1.75 (Starting on approximately PND 95 and for the duration of 3 weeks, daily vaginal lavage was performed on female rats belonging to the 13-week cohort (10 F/group).)",null,null,null,"No effect >1.75 (Assessed for both F1 exposure groups.)","No effect >1.75 (Assessed for both F1 exposure groups.)","No effect >1.75 (Assessed for both F1 exposure groups.)","No effect >1.75 (F1: No effect was obsereved on absolute and relative organ weight of both exposure groups (6 and 13 weeks).)","No effect >1.75 (Assessed for both F1 exposure groups.)","No effect >1.75 (No effect was observed on absolute and relative organ weight of both exposure groups (6 and 13 weeks; weighed together with bladder).)","No effect >1.75 (Seminal vesicles and coagulating gland (assessed for both F1 exposure groups).)","No effect >1.75 ( No effect was obsereved on absolute and relative organ weight (seminal vesicles and coagulating gland) of both exposure groups (6 and 13 weeks).)","No effect >1.75 (Assessed for both F1 exposure groups.)","No effect >1.75 (Sperm transit time was calculated (assessed for both F1 exposure groups).)","No effect >1.75 (Assessed for both F1 exposure groups.)","No effect >1.75 (Assessed for both F1 exposure groups.)","No effect >1.75 (No effect was obsereved on absolute and relative organ weight of both exposure groups (6 and 13 weeks).)","No effect >1.75 (Including parathyroid (assessed for both F1 exposure groups).)",null,"No effect >1.75 (Assessed for both F1 exposure groups.)","No effect >1.75 (F1: No effect was observed on absolute and relative organ weight (including cervix) of both exposure groups (6 and 13 weeks).)","No effect >1.75 (Assessed for both F1 exposure groups.)",null,"No effect >1.75 (Assessed for both F1 exposure groups.)","No effect >1.75 (F1: No effect was obsereved on absolute and relative organ weight of both exposure groups (6 and 13 weeks).)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect >1.75 (Bladder histopathology and weight was examined (assessed for both F1 exposure groups).)"]
[39,"DAR",2012,"InVitroAndrogen","AR Binding Assay","Rat, Sprague-Dawley, cytosol from prostate","10-10; 10-9; 10-8; 10-7; 10-6; 10-5; 10-4; 10-3","Molar","Uptake from the medium (in vitro)","16-20","Hours",null,null,"Yes","Yes","No effect >  10-03 (Glyphosate demonstrated no evidence for AR binding in the androgen receptor binding (rat prostate cytosol) screening assay since the test substance was identified as \"non-binder\" in three valid independent runs.)"]
[84,"Publication",2017,"InVitroEstrogen","ER Binding Assay","Human","10000 - 1000000","µg ai/L","Uptake from the medium (in vitro)","Multiple exposure times","Hours",null,null,"Yes","N/A",null,null,null,null,null,"No effect >2500 (Increased cell proliferation was observed in MCF-7 and T47D cells at 10,000 µg/L to 1,000,000 µg/L (but not in hormone-independent MDA-MB-231 cells) . Glyphosate stimulated ERE-mediated transcription of the luciferase reporter gene starting at a concentration of 1,000 µg/L. The analysis of gene ontology confirms that genes having their expression altered by treatment of MCF-7 cells with glyphosate were involved in cell cycle regulation, stimulation by steroid hormones and cell death through apoptosis. ONIOM binding energy assessment implies that binding of glyphosate to the ER is weak and unstable, suggesting that glyphosate is unlikely to bind to ERα. This study has demonstrated that glyphosate activates ERα through a ligand-independent pathway only at high concentrations that are not encountered at typical exposure levels. Glyphosate was reported to induce ERTA only at high concentrations (10,000 and 20,000 μg/L or 59 and 118 μM) and induction was concluded to result from an unknown ligand-independent ER mechanism. However, this result is inconsistent with the EDSP Tier 1 ERTA assay tested up to 1000 μM glyphosate.\n)"]
[85,"Publication",2013,"InVitroEstrogen","Other ER in vitro assay","Human","10^-6 - 1","µM","Uptake from the medium (in vitro)",24,"Hours",null,null,"Yes","N/A",null,null,null,null,null,"Change 0,000001 (The endpoints explored were the cell proliferation of hormone-dependent and hormone-independent cell lines with and without an ER antagonist, ERE-transcription activity with and without an ER antagonist, and expression of ERs. Glyphosate was found to produce cell proliferation in a hormone-dependent cancer cell line but not in a hormone-independent cancer cell line in the absence of E2. In the presence of a potent ER antagonist the cell proliferation caused by glyphosate in a hormone-dependent cancer cell line was reduced. The interaction of glyphosate with the ER was confirmed by ERE activation with and without an ER antagonist. When cells were co-incubated with glyphosate and E2, glyphosate suppressed the E2-induced ERE activation suggesting that glyphosate behaves as an antagonist in the presence of an endogenous agonist. It was demonstrated that glyphosate alters the expression of both ERα and ERβ in human breast cancer cells. However, Thongprakaisang et al., (2013) reported induction of 5 to 13-fold relative to controls for ER-driven transcriptional activity in T47D cells at the levels by glyphosate ranging from 1 10E-6 to 1 10E-12 M. Induction was blocked by the addition of 10 nM of the ER antagonist ICI 182780. In addition, proliferation in T47D cells after 5 d of exposure was reported to be 40% as measured by the MTT assay as an indirect assessment of cell number. Cell number in proliferations assays is best assessed by directly measuring cell number with flow cytometry. The increase in ER-driven transcriptional activity is highly inconsistent with the EDSP results and published studies using functionally equivalent test systems. Thongprakaisang et al., (2013) reported that glyphosate has greater estrogenic effect than a maximally inducing dose of 17β-estradiol, which is a highly questionable result based on what is known about structure and activity information for glyphosate. This finding led Mesnage et al. (2017) to conclude that the results of Thongprakaisang et al., (2013) are not biologically plausible and speculate that this result reflected an estrogenic contaminant in the assay.)"]
[89,"Publication",2016,"InVitroEstrogen","BG1Luc Estrogen Receptor Transactivation Assay","Human",10,"µM","Uptake from the medium (in vitro)",24,"Hours",null,null,"Yes","N/A",null,null,null,null,null,"No effect >10 (Glyphosate did not show any estrogenic activity at a concentration of 10 μM in two cell lines or via the two human estrogen receptor (hER) subtypes, hERα and hERβ. Based on the OECD 455 guideline for the BG1 assay, relative activity for the test substance that is <20% of the response of a maximally inducing concentration of E2 is considered to be negative. Therefore, glyphosate is conlcluded to have no ERα, ERβ agonistic activities, in vitro.\nIt needs to be noted that according to the published Corrigendum, the cell lines used were a variant of human breast cancer cell line MCF7. Thus, the recombinant cell lines are VM7Luc4E2 and VM7ERβc9.)"]
[38,"DAR",2012,"InVitroEstrogen","Stably Transfected Human ERα Transcriptional Activation Assay (ER STTA)","Human cell line (HeLa-9903)","10-10; 10-9, 10-8; 10-7; 10-6; 10-5; 10-4; 10-3","Molar","Uptake from the medium (in vitro)",24,"Hours",null,null,"Yes","Yes",null,null,null,null,null,"No effect >  10-03 (Based on the results of the two valid transcriptional activation assays, it can be concluded glyphosate is not an agonist of human estrogen receptor alpha (hERα) over the concentration range (maximum concentration 10-3 M) tested in the HeLa-9903 model system.)"]
[37,"DAR",2012,"InVitroEstrogen","ER Binding Assay","Rat, Sprague-Dawley, cytosol from uterus","10-10; 10-9; 10-8; 10-7; 10-6; 10-5; 10-4; 10-3","Molar","Uptake from the medium (in vitro)","16-20","Hours",null,null,"Yes","Yes",null,null,null,null,null,"No effect >  10-03 (Glyphosate demonstrated no evidence for ER binding in the estrogen receptor binding (rat uterine cytosol) screening assay since the test substance was identified as \"non-interacting\" in three valid independent runs.)"]
[88,"Publication",2017,"InVitroSteroidogenesis","Other Steroidogenesis in vitro assay","Cow","0.01; 0.3; 0.5; 1.7; 5","mg/L","Uptake from the medium (in vitro)","24 - 48","Hours",null,"This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate tested was not sufficiently characterized, no positive controls were used and the tests were conducted with only one or 2 test concentrations of glyphosate.","Yes","N/A",null,"No effect >5 (Glyphosate at 5 μg/mL had no effect on the theca cell (TC)  production of androstenedione. )","Change 0,5 (Statistically significant effects have been observed at 0.5 and 5 µg/mL on cell proliferation in FSH/IGF1 stimulated granulosa cells. (In the presence of FSH only, glyphosate had no effect on granulosa cell (GC) viability. In the presence of FSH and IGF1, glyphosate reduced GC proliferation without a dose-response at 0.5 and 5 μg/mL but not at lower test concentrations (0.01 and 0.3 μg/mL). Without FSH or IGF1, 1.7 μg/mL of glyphosate slightly increased GC proliferation in response to serum (≤11 %).) However, no effect on theca cell proliferation was observed.\n)","No effect >5 (The combined IGF1 plus FSH treatment increased (P<0.05) CYP19A1 and CYP11A1 mRNA abundance by threefold and twofold, respectively, above untreated control GC. Glyphosate (5μg/mL) had no significant effect on CYP19A1 or CYP11A1 mRNA in GC co-treated with FSH and IGF1.)","Decrease 5 (In the presence of FSH only, glyphosate had no effect on estradiol production. In the presence of FSH and IGF1, estradiol production was reduced at 5 μg/mL only, but not at any other dose in granulosa cells.\n)",null,"No effect >5 (Progesterone production was neither affected in granulosa nor in theca cells.)"]
[90,"Publication",2016,"InVitroSteroidogenesis","Aromatase Assay","Human","up to 10000","ppm","Uptake from the medium (in vitro)",24,"Hours",null,"3000 ppm (maximum concentration tested) is equivalent to a concentration of 17,741 μM which is way above the highest concentration to be tested under EPA Guideline (1000 µM).","Yes","N/A",null,null,null,"No effect >2000 (Glyphosate did not significantly inhibit aromatase activity at non-cytotoxic concentrations (up to approximately 2000 ppm [mg/L]).)"]
[40,"DAR",2012,"InVitroSteroidogenesis","Aromatase Assay","Human (CYP19 (aromatase) and P450 reductase Supersomes TM)","10-10; 10-9; 10-8; 10-7; 10-6; 10-5; 10-4; 10-3","Molar","Uptake from the medium (in vitro)",15,"Minutes",null,null,"Yes","Yes",null,null,null,"No effect >  10-03 (Based on 3 independent assay runs, glyphosate is classified as a \"non-inhibitor\" of aromatase activity in the human recombinant aromatase assay.)"]
[41,"DAR",2011,"InVitroSteroidogenesis","H295R steroidogenesis assay","Human cell line (H295R)"," 10 -10 - 10-3","Molar","Uptake from the medium (in vitro)",48,"Hours",null,null,"Yes","Yes",null,null,null,null,null,null,null,"No effect >  10-04 (Glyphosate did not alter 17ß-estradiol and testosterone production in the H295R steroidogenesis assay.)"]
[81,"Publication",2012,"InVitroSteroidogenesis","Other Steroidogenesis in vitro assay","Mouse",300,"µM","Uptake from the medium (in vitro)",4,"Hours",null,null,"Yes","N/A",null,null,null,null,null,null,null,null,"No effect >600 (Forgacs et al. (2012) evaluated the effect of 4 h exposures of glyphosate on testosterone production in BLTK1 murine Leydig cells in the presence and absence of an inducing dose of recombinant human chorionic gonadotropin (rhCG). Glyphosate at the maximum concentration of 300 μM did not alter rhCG induced testosterone concentrations in BLTK1 murine Leydig cells. Moreover, basal testosterone levels were not altered at a maximum concentration of 600 µM.)"]
[82,"Publication",2018,"InVitroSteroidogenesis","Other Steroidogenesis in vitro assay","Swine","0.2; 4; 16","µM","Uptake from the medium (in vitro)",48,"Hours",null,null,"Yes","N/A",null,null,"Decrease 0,2 (Glyphosate statistically signiﬁcantly decreased cell proliferation (p < 0.001) as evaluated by BrdU incorporation and cell viability (p < 0.05) as measured by ATP production without a concentration-response relationship. )",null,"Decrease 0,2 (17-ß-estradiol (E2) secretion was statistically signiﬁcantly inhibited (p < 0.05) at all tested concentrations but without a concentration-response relationship. )",null,"Increase 0,2 (Progesteron (P4) secretion was statistically significantly increased (p < 0.05) at all tested concentrations but without a concentration-response relationship. )"]
[86,"Publication",2018,"InVitroGeneral","In vitro method (general)","Mouse","10 - 10000","ppm","Uptake from the medium (in vitro)",24,"Hours",null,"No specific ED-related parameters were addressed. This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because the glyphosate used is not sufficiently characterized and no positive controls were used in any of the assays conducted. ","Yes","N/A",null,null,"No effect >10000 (In this study the effect of glyphosate on murine TM4 Sertoli cells was investigated in vitro. The endpoints were cytotoxicity, glutathione transferase activity and lipid accumulation. Glyphosate was found to have no impact on cell viability after 24 hours of exposure at concentrations ranging from 10 ppm to 10,000 ppm. Glyphosate reduced succinate dehydrogenase to some extent over the entire concentration range from 10 (approx. 85 % of control) to 10,000 ppm (approx.75 % of control) with no dose-effect relationship and was found to have no impact on glutathione transferase activity. Exposure of TM4 cells to glyphosate for 24 hours at 2,500 or 5,000 ppm induces an increase in cytoplasmic lipid droplets. These concentrations are far beyond what is physiologically feasible in vivo. )"]
[87,"Publication",2019,"InVitroGeneral","In vitro method (general)","Mouse","50; 100; 200; 500","µM","Uptake from the medium (in vitro)",14,"Hours",null,"No specific ED-related parameters were addressed. This publication is considered relevant for the risk assessment of glyphosate but reliable with restrictions because of the poor characterization of the glyphosate tested, no cytotoxicity testing,  the lack of a positive control and insufficient dose-response characterization at biologically relevant doses.","Yes","N/A",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Change 200 (200 µM glyphosate treatment negatively affected development of mouse oocytes as indicated by reduced rates of germinal vesicle breakdown (GVBD) and first polar body extrusion. Further, molecular analysis indicated increased reactive oxygen species and an influence of glyphosate on DNA stability and intracellular signaling pathways relevant for apoptosis. As only one concentration was applied in this study, no distinction between spontaneous or treatment-related causes is possible and hence, biological significance of these observations is rather difficult to evaluate.\nIn vitro intracellular changes in Kunming mice oocytes were evaluated after being cultured in medium supplemented with 500 μM glyphosate. Findings included: decreased germinal vesicle breakdown, decreased first polar body extrusion, increased mRNA expression of anti-oxidant enzyme-related genes, abnormal spindle morphology, increased DNA double strand breaks, aggregated mitochondria, decreased mitochondrial membrane potential, increased protein expression of apoptosis factors, increased mRNA expression of apoptosis related genes and decreased autophagy-related genes. \n\nNo dose-response could be determined as only one concentration was tested, far in excess of that considered biologically relevant. Whilst some evaluations were conducted on oocytes harvested from a wider data set of 24 mice (protein expression levels of apoptosis factors by Western blot analysis), a number of the assessments were conducted on oocytes from just 12 mice (mRNA expression of oxidative stress-related, apoptosis-related and autophagy-related genes) or 6 mice (mitochondrial staining, measurement of mitochondrial membrane potential). This narrow source of oocytes limits the robustness of certain conclusions. Furthermore, there are insufficient details reported in the methods to establish whether mice were of the same age before oocyte harvesting or the purity of the glyphosate tested.  )"]
[83,"Publication",2020,"InVitroGeneral","In vitro method (general)","Rat","10; 100","ppm","Uptake from the medium (in vitro)","Multiple exposure times","Hours",null,null,"Yes","N/A",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Change (In vitro exposure of Sertolli cells to glyphosate was reported to alter Sertoli cell junction barrier permeability and to decrease testosterone-stimulated TER. Further, a redistribution of claudin11 was observed.\nGlyphosate did not modify the expression of the androgen receptor or intercellular junction proteins (claudin11, occludin and ZO-1). Further, intracellular signalling via P-p38-MAPK and P-ERK1/2 pathways were not affected. Lactate production, glucose uptake, GLUT1, FA oxidation, or FAT/CD36 and CPT1 expression was unaffected by glyphosate. Thus, the conducted molecular and cell biological investigations indicate that glyphosate does not influence testicular function due to disturbances of nutritional function or metabolism in Sertolli cells. In vitro exposure to glyphosate at non-cytotoxic concentrations (10 - 100 ppm) altered Sertoli cell junction barrier permeability and decreased testosterone-stimulated TER. Further, redistribution of claudin11 at the zone of contact between cells was detected after glyphosate stimulation. If the effects observed on Sertolli cell junction barrier permeability may contribute to a postulated effect on male reproductive function cannot be finally assessed. In general, an evaluation of such highly specific cell biological endpoints for hazard assessment is rather difficult as they cannot be transferred easily to intact organisms. As the biological in vivo relevance of such “isolated” in vitro/ex vivo findings is not validated for intact organisms, an interpretation of the obtained results on the redistribution of one special protein and cell junction barrier permeability is difficlut and not considered sufficiently conclusive. )"]
[]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Androgen receptor","Androstenedione (in vitro)","Cellular proliferation","CYP19","Estradiol level (in vitro)","Estrogen receptor","Progesterone (in vitro)","Steroidogenesis (genes/enzyme changes) (in vitro)","Testosterone synthesis","Cowpers glands weight (Hershberger)","Estradiol level","Follicle Stimulating Hormone (FSH) level","Glans penis weight  (Hershberger)","LABC weight (Hershberger)","Luteinizing Hormone (LH) level","Other hormones","PPAR nuclear receptor (in vivo)","Progesterone","Prolactin","Prostate weight (Hershberger)","Seminal vesicles weight (Hershberger)","Steroidogenesis (genes/enzyme changes)","T3 and T4 level","Testosterone level","Thyroid-stimulating hormone level (TSH)","Uterus weight (UT assay)","Accessory sex organs histopathology","Age at balanopreputial separation","Age at first estrus","Age at Vaginal opening","Ano-Genital distance","Cervix histopathology","Coagulating gland histopathology","Coagulating gland weight","Epididymis histopathology","Epididymis weight","Estrus cyclicity","Genital abnormalities","HDL/LDL ratio (considered T-mediated only in combination with other thyroid endpoints)","LABC weight","Mammary gland histopathology (female)","Mammary gland histopathology (male)","Ovary histopathology","Ovary weight","Prostate histopathology (with seminal vesicles and coagulating glands)","Prostate weight","Seminal vesicles histopathology","Seminal vesicles weight","Sperm morphology","Sperm motility","Sperm numbers","Testis histopathology","Testis weight","Thyroid histopathology","Thyroid weight","Uterus histopathology (with cervix)","Uterus weight (with cervix)","Vagina histopathology","Vaginal smears","Adrenals histopathology","Adrenals weight","Brain histopathology examination","Brain weight","Dystocia","Fertility (mammals)","Fetal development","Functional observation battery","Gestation length","Litter size","Litter viability","Litter/pup weight","Number of implantations, corpora lutea","Number of live births","Number of ovarian follicles","Numbers of embryonic or foetal deaths and viable foetuses","Pituitary histopathology","Pituitary weight","Post implantation loss","Pre implantation loss","Presence of anomalies (external, visceral, skeletal","Pup development","Pup survival index","Reproduction","Sex ratio","Time to mating","Aorta histopathology","Bone histopathology","Bone marrow histopathology","Eyes histopathology","Gall bladder histopathology","Heart histopathology","Heart weight","Kidney histopathology","Kidney weight","Liver histopathology","Liver weight","Lung histopathology","Lymph nodes histopathology","Oesophagus histopathology","Pancreas histopathology","Peripheral nerve histopathology","Salivary glands histopathology","Skeletal muscle histopathology","Skin histopathology","Small and large intestines histopathology","Spinal cord histopathology","Spleen histopathology","Spleen weight","Stomach histopathology","Thymus histopathology","Thymus weight","Trachea histopathology","Urinary bladder histopathology","Body weight","Clinical chemistry and haematology","Clinical signs","Food consumption","Mortality","[Not in list]","No relevant effect observed"]
["Effect",null,null,null,null,null,null,null,null,null,null,null,null,null,null,0,0,2,0,2,1,1,0,0,0,0,0,0,0,0,0,1,0,0,0,0,0,0,1,1,0,0,2,0,0,1,0,0,1,0,1,1,0,1,1,0,0,0,0,2,3,0,2,0,0,2,0,6,0,1,1,0,0,0,0,5,0,3,0,0,0,0,0,1,0,7,0,0,0,2,0,3,1,0,5,0,0,0,0,0,0,1,1,0,0,0,3,3,10,3,12,0,0,0,0,0,8,0,1,8,0,0,3,2,0,3,0,1,39,26,33,25,13,7,1]
["No effect",null,null,null,null,null,null,null,null,null,null,null,null,null,null,1,1,1,3,0,4,1,1,1,1,2,1,1,1,1,1,0,1,1,1,1,2,2,5,2,1,3,3,2,5,1,22,14,3,42,23,7,4,0,0,34,22,50,35,40,13,28,7,6,6,6,54,46,43,13,48,23,18,5,47,40,25,34,2,10,4,1,9,19,12,19,21,8,2,14,41,17,13,10,16,4,7,3,19,5,5,8,9,12,6,19,13,48,39,48,38,29,21,12,25,11,12,7,10,18,9,26,14,18,18,6,8,14,43,16,48,49,60,13,0]
["Not classified",null,null,null,null,null,null,null,null,null,null,null,null,null,null,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0]

{"sheet":"LoE T","index":11,"n_rows":65,"n_cols":14,"rows_kept":65,"cut":false,"hidden":false,"merged":[[8,11,64,11],[8,12,64,12],[8,13,64,13],[1,12,7,12],[1,13,7,13],[2,11,7,11]]}
["Study ID Matrix","Effect classification","Effect target","Species","Duration of exposure","Duration unit","Route of administration","Lowest Effect dose","Dose unit","Effect direction","Observed effect (positive and negative)","Assessment of each line of evidence","Assessment on the integrated line of evidence","Modality"]
["n.a.","in silico","QSAR prediction T-modality","n.a.","n.a.","n.a.","n.a.","n.a.","n.a.","No effect","The molecular docking method (Endocrine Disruptome) indicates low probability of binding. The results (inconclusive and negative) from the two models available in the Danish QSAR database with regard to TPO are not reliable (out of applicability domain). Given the lack of other models the result should be considered with caution and thus as supporting information only.","No indication for T-related endocrine activity of the test substance is deduced from available in silico models.","Based on the available in vivo mechanistic data and supporting in silico information, it is concluded that the a.s. glyphosate does not posess any T-related endocrine activity.","T"]
[44,"In vivo mechanistic","T3 and T4 level","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect","Mean serum T4 levels were not affected in the female pubertal assay.","Thyroid hormones were analysed in the male and female pubertal assay as well as in a published pilot study for an EOGRTS. No relevant changes on hormone levels were observed within the pubertal assays. In the pilot study an increase in TSH was observed in F1 males only sacrificed after 6 weeks of exposure. Since no effect on TSH was observed after 13 weeks of exposure as well as in the pubertal assays, covering the same life stage as the 6 week period of the pilot study, the TSH increase is considered not biologically relevant (for more detail please refer to study ID 93). In conclusion, no indication for T-related endocrine activity of the test substance is deduced from available in vivo mechanistic data in male and female rat."]
[45,"In vivo mechanistic","T3 and T4 level","Rat","31 (PND 23-53)","Days","Oral","> 1000","mg/kg bw/day","No effect","No biologically relevant effect on mean serum T4 levels were observed in the male pubertal assay.  (Mean serum T4 were decreased in all treatment groups compared to the control. However, the change was not statistically significant and was not associated with any histological changes  such as follicular cell height. In addition, it was reported in literature (Laws et al., 2007; Trentacoste et al., 2001 ) that decreased hormone levels may be secondary to lower body weights as shown in feed restricted rats during pubertal development.  For further discussion please also refer to the respective study report and OECD summary.)"]
[44,"In vivo mechanistic","Thyroid-stimulating hormone level (TSH)","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect","Mean serum TSH levels were not affected in the female pubertal assay."]
[45,"In vivo mechanistic","Thyroid-stimulating hormone level (TSH)","Rat","31 (PND 23-53)","Days","Oral","> 1000","mg/kg bw/day","No effect","No biologically relevant effect on mean serum TSH levels was observed in the male pubertal assay. (Mean serum TSH levels were (not dose-dependently) decreased in all treatment groups compared to the control.  However, the change was not statistically significant and was not associated with any histological changes such as follicular cell height. In addition, it was reported in literature (Laws et al., 2007; Trentacoste et al., 2001 ) that decreased hormone levels may be secondary to lower body weights as shown in feed restricted rats during pubertal development. For further discussion please also refer to the respective study report and OECD summary.)"]
[93,"In vivo mechanistic","Thyroid-stimulating hormone level (TSH)","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",1.75,"mg/kg bw/day","Increase","A statistically significant increase was observed in male offspring of the 6 weeks exposure group only. No effect was observed after 13 weeks of exposure in males or in females. Moreover, histopathological changes in thyroid were observed neither in the 6 weeks nor in the 13 week exposure group. Moreover, the (male and female) pubertal assays, covering the same live stage as the 6 week period of the current study, did not show any increase in TSH or changes in thyroid weight and histopathology. In addition, no effects were observed in the FOB during the two-generation study (study ID 22). Based on the provided rationale as well as the results of the available repeated dose toxicity studies, no indication for thyroid disrupting effects is provided from this pilot study."]
[95,"In vivo mechanistic","HDL/LDL ratio (considered T-mediated only in combination with other thyroid endpoints)","Mouse","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Oral",5000,"mg/L","Increase","The following serum biochemical indexes were determined: TG, T-CHO, low- and high-density lipoprotein cholesterol (LDL-C and HDL-C) aspartate transaminase (AST), alanine transaminase (ALT). Additionally,  TG, T-CHO, LDL-C and HDL-C content was measured in liver homogenate. The concentrations of lipids such as triglycerides (TGs), total cholesterol (T-CHO), and low-density lipoprotein cholesterols (LDL-C) increased to a significant extent in both the serum and livers. \nChanges in HDL/LDL are considered T-mediated only in combination with other thyroid endpoints. Since no indication for T-related adversity nor activity is provided by the available in vivo studies, the observed increase in some lipid markers in serum and liver is not considered related to an endorine MoA.\n"]
[5,"EATS-mediated","Thyroid weight","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect",null,"Thyroid weight and thyroid histopathology were examined in 14 and 41 studies, respectively; including subcabute, subchronic, and chronic exposure periods. A toxicologically relevant effect on either T-mediated parameter was not observed in any study considering four species (dog, mouse, rabbit, rat) and different life stages in rat. Moreover, carcinogenicity in thyroid was not induced by the test substance in any study.\nIn conclusion, glyphosate does not induce adversity based on T-mediated parameters investigated in the available in vivo studies.","Based on the available in vivo data in four mammalian species after subacute, subchronic and chronic exposure to glyphosate, no T-mediated endocrine adversity was observed. Therefore, the ED criteria with regards to T-modality are not met. ","T"]
[6,"EATS-mediated","Thyroid weight","Dog",90,"Days","Oral",">10000","ppm","No effect"]
[7,"EATS-mediated","Thyroid weight","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"EATS-mediated","Thyroid weight","Dog",90,"Days","Oral",2000,"ppm","Decrease","Relative thyroid weight was reduced in females at 2000 and 10000 ppm. However, this effect showed no dose-response and no histopathological changes were observed in thyroid in dogs of this study. Moreover, no effect on organ weight at similar or higher doses was observed in dog after subchronic (study IDs 6-7) and chronic exposure (study IDs 9-11). Therefore, the reduction in thyroid weight in the current study is considered not toxicologically relevant."]
[9,"EATS-mediated","Thyroid weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"EATS-mediated","Thyroid weight","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"EATS-mediated","Thyroid weight","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[22,"EATS-mediated","Thyroid weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect","Absolute thyroid weight was increased in F0 females at 5000 ppm. Relative thyroid weight was decreased in F0 males at 1500 and 5000 ppm. Both changes were not considered treatment-related and no dose-reponse-relationship was deduced. \nHistotpathology was not performed for this study. However, when taking into account further repeated dose toxicity studies in rat, it is shown that no treatment-related histopathological changes were observed after subchronic and chronic exposure."]
[44,"EATS-mediated","Thyroid weight","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[45,"EATS-mediated","Thyroid weight","Rat","31 (PND 23-53)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[57,"EATS-mediated","Thyroid weight","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","Absolute weight was statistically significantly decreased in males at 60 mg/kg bw/day, relative weight was increased in females at 10 mg/kg bw/day (statistically not significant). No dose-response and no effect in thyroid histopathology were observed. Moreover, after 1 year exposure at similar doses no effects on thyroid weight were observed in dogs in other studies (e.g. study IDs 9, 10, 11, 58, 59). Therefore, the weight changes were considered not treatment-related."]
[58,"EATS-mediated","Thyroid weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[59,"EATS-mediated","Thyroid weight","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[62,"EATS-mediated","Thyroid weight","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[1,"EATS-mediated","Thyroid histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[2,"EATS-mediated","Thyroid histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[3,"EATS-mediated","Thyroid histopathology","Rat",90,"Days","Oral",">30000","ppm","No effect"]
[4,"EATS-mediated","Thyroid histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"EATS-mediated","Thyroid histopathology","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[6,"EATS-mediated","Thyroid histopathology","Dog",90,"Days","Oral",">10000","ppm","No effect"]
[7,"EATS-mediated","Thyroid histopathology","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"EATS-mediated","Thyroid histopathology","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"EATS-mediated","Thyroid histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"EATS-mediated","Thyroid histopathology","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"EATS-mediated","Thyroid histopathology","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"EATS-mediated","Thyroid histopathology","Rat",1,"Year","Oral",">20000","ppm","No effect"]
[13,"EATS-mediated","Thyroid histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No treatment-related histopathological changes were observed in thyroid. Moreover, an increase in neoplasia was not observed.\n(Neoplastic findings, dead/moribund animals: no treatment-related effect (C-cell adenoma in each 1/29 males and 1/17 females at 1000 ppm)\nNeoplastic findings, surviving animals: no treatment-related findings (C-cell adenoma in 2/19 and 1/29 males and 2/24 and 1/20 females at 0 and 10000 ppm))"]
[14,"EATS-mediated","Thyroid histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect","No treatment-related histopathological changes were observed in thyroid. Moreover, an increase in neoplasia was not observed.\n(Macroscopic: no abnormalities observed\nHistopathology, non-neoplastic: Animals found dead/killed in extremis: Decreased incidences of C-cell hyperplasia in females: 8/35, 6/31, 3/34 and 2/36 at 0, 3000, 10000 and 30000 ppm\nHistopathology, neoplastic: no treatment-related findings)"]
[15,"EATS-mediated","Thyroid histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[16,"EATS-mediated","Thyroid histopathology","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[17,"EATS-mediated","Thyroid histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"EATS-mediated","Thyroid histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No treatment-related histopathological changes were observed in thyroid. Moreover, an increase in neoplasia was not observed.\n(Histopathology, non-neoplastic: no treatment-related findings (C-cell hyperplasia among all rats of all groups, age-related; focal hyperplasia in the parathyroid glands of a few male rats)\nHistopathology, neoplastic: no treatment-related findings (follicular adenoma in 5/51, 1/51, 0/51 and 6/51 males and in 3/51, 0/51, 0/51 and 2/51 females at 0, 1500, 5000 and 15000 ppm; follicular adenocarcinoma in in 1/51 males at 5000 ppm and in 0/51 and 1/51 females at 0 and 1500 ppm; parafollicular adenoma in in 9/51, 1/51, 0/51 and 3/51 males and in 6/51, 1/51, 1/51 and 0/51 females at 0, 1500, 5000 and 15000 ppm; parafollicular adenocarcinoma in in 2/51and 1/51 males at 0 and 1500 ppm and in 1/51 female 1500 ppm and hibernoma in 1/51 males at 15000 ppm)"]
[19,"EATS-mediated","Thyroid histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No treatment-related histopathological changes were observed in thyroid. Moreover, an increase in neoplasia was not observed. \n(Histopathology, non-neoplastic findings dead/moribund animals: amyloidosis in 4/22, 3/20, 5/22 and 5/27 males and 3/16, 1/16, 1/20 and 2/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related)"]
[20,"EATS-mediated","Thyroid histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No treatment-related histopathological changes were observed in thyroid. Moreover, an increase in neoplasia was not observed. \n(Histopathology, non-neoplastic findings: no treatment-related findings; distention and coalescence of follicles, focal follicular cell hyperplasia, focal C-cell hyperplasia, vasculitis, focal inflammation, follicular cell hypertrophy and mononuclear cell foci occasionally observed)\nHistopathology, neoplastic findings: no tumours observed)"]
[21,"EATS-mediated","Thyroid histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect","No treatment-related histopathological changes were observed in thyroid. Moreover, an increase in neoplasia was not observed. \n(Histopathology, non-neoplastic findings: no treatment-related findings (reduced incidences of amyloid deposition in thyroid and parathyroid at 1600 and 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups)\nHistopathology, neoplastic findings: no treatment-related findings)"]
[26,"EATS-mediated","Thyroid histopathology","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[44,"EATS-mediated","Thyroid histopathology","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[45,"EATS-mediated","Thyroid histopathology","Rat","31 (PND 23-53)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[49,"EATS-mediated","Thyroid histopathology","Rat",28,"Days","Oral",">20000","ppm","No effect","No effects on histopathology of thyroid including parathyroid were observed."]
[52,"EATS-mediated","Thyroid histopathology","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"EATS-mediated","Thyroid histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[54,"EATS-mediated","Thyroid histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","No effects on histopathology of thyroid including parathyroid were observed."]
[55,"EATS-mediated","Thyroid histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","No effects on histopathology of thyroid including parathyroid were observed."]
[56,"EATS-mediated","Thyroid histopathology","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"EATS-mediated","Thyroid histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"EATS-mediated","Thyroid histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"EATS-mediated","Thyroid histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[63,"EATS-mediated","Thyroid histopathology","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect"]
[67,"EATS-mediated","Thyroid histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","No effects were observed in thyroid and parathyroid."]
[68,"EATS-mediated","Thyroid histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"EATS-mediated","Thyroid histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings for thyroid and parathyroid and not related to treatment (adults)."]
[70,"EATS-mediated","Thyroid histopathology","Rat","21 (PND 0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","The overall microscopic tissue alterations found throughout the study for each generation (Offspring F1, F2, F3) were indicative of common incidental histological findings for thyroid and parathyroid and not related to treatment (pups)."]
[73,"EATS-mediated","Thyroid histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[74,"EATS-mediated","Thyroid histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"EATS-mediated","Thyroid histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[76,"EATS-mediated","Thyroid histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[93,"EATS-mediated","Thyroid histopathology","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Including parathyroid (assessed for both F1 exposure groups)."]

{"sheet":"LoE EAS","index":12,"n_rows":638,"n_cols":14,"rows_kept":638,"cut":false,"hidden":false,"merged":[[274,11,291,11],[292,11,356,11],[582,11,637,11],[358,11,415,11],[453,11,460,11],[272,11,273,11],[578,11,581,11],[26,13,31,13],[33,11,46,11],[461,11,466,11],[473,11,577,11],[416,11,452,11],[467,11,472,11],[1,12,46,12],[32,13,46,13],[26,11,31,11],[2,11,7,11],[265,11,266,11],[47,13,637,13],[47,12,637,12],[267,11,271,11],[20,13,25,13],[147,11,240,11],[241,11,263,11],[52,11,53,11],[47,11,51,11],[62,11,146,11],[54,11,61,11],[1,13,7,13],[8,11,15,11],[17,11,19,11],[8,13,15,13],[17,13,19,13]]}
["Study ID Matrix","Effect classification","Effect target","Species","Duration of exposure","Duration unit","Route of administration","Lowest Effect dose","Dose unit","Effect direction","Observed effect (positive and negative)","Assessment of each line of evidence","Assessment on the integrated line of evidence","Modality"]
["n.a.","in silico","Estrogen receptor","n.a.","n.a.","n.a.","n.a.","n.a.","n.a.","No effect","Considering the results of the predictions in a weight of evidence approach, no indication for an estrogenic activity is observed. The overall weight of the CERAPP predictions is considered highest due a) the consensus approach and b) the extensive training and validation set derived within the CERAPP project. The CERAPP consensus predictions coincide well with the CERAPP potency for binding derived from Literature (https://comptox.epa.gov/dashboard/dsstoxdb/results?search=DTXSID1024122#bioactivity-toxcast-models). Furthermore, glyphosate is part of the training set of ER binding tests showing negative results. The results of inconclusive predictions (Danish QSAR DB) are considered less relevant because predictions are out of the applicability domain of the model. Otherwise, all other models also show no indication for an estrogenic activity potential (for a detailed description of the results please refer to the QSAR report). \n","No indication for E-related endocrine activity of the test substance is deduced from available in silico models.","In conclusion, no EAS-related endocrine activity is deduced for glyphosate based on in silico, in vitro as well as in vivo mechanistic data.","E"]
[37,"In vitro mechanistic","Estrogen receptor","Rat, Sprague-Dawley, cytosol from uterus","16-20","Hours","Uptake from the medium (in vitro)","> 10-03","Molar","No effect","Glyphosate demonstrated no evidence for ER binding in the estrogen receptor binding (rat uterine cytosol) screening assay since the test substance was identified as \"non-interacting\" in three valid independent runs.","Based on the results of 6 in vitro tests, including 2 Guideline studies (study IDs 37, 38), glyphosate does not show any relevant estrogenic activity."]
[38,"In vitro mechanistic","Estrogen receptor","Human cell line (HeLa-9903)",24,"Hours","Uptake from the medium (in vitro)","> 10-03","Molar","No effect","Based on the results of two valid transcriptional activation assays, it can be concluded that glyphosate is not an agonist of human estrogen receptor alpha (hERα) over the concentration range (maximum concentration 10-3 M) tested in the HeLa-9903 model system."]
[84,"in vitro mechanistic","Estrogen receptor","Human","Multiple exposure times","Hours","Uptake from the medium (in vitro)",">2500","µg a.i./L","No effect","Increased cell proliferation was observed in MCF-7 and T47D cells (but not in hormone-independent MDA-MB-231 cells) at 10,000 µg/L to 1,000,000 µg/L. Glyphosate stimulated ERE-mediated transcription of the luciferase reporter gene starting at a concentration of 1,000 µg/L. The analysis of gene ontology confirms that genes having their expression altered by treatment of MCF-7 cells with glyphosate were involved in cell cycle regulation, stimulation by steroid hormones and cell death through apoptosis. ONIOM binding energy assessment implies that binding of glyphosate to the ER is weak and unstable, suggesting that glyphosate is unlikely to bind to ERα. This study has demonstrated that glyphosate activates ERα through a ligand-independent pathway only at high concentrations that are not encountered at typical exposure levels. Glyphosate was reported to induce ERTA only at high concentrations (10,000 and 20,000 μg/L or 59 and 118 μM) and induction was concluded to result from an unknown ligand-independent ER mechanism. However, this result is inconsistent with the EDSP Tier 1 ERTA assay tested up to 1000 μM glyphosate.\n"]
[85,"in vitro mechanistic","Estrogen receptor",null,24,"Hours","Uptake from the medium (in vitro)",9.9999999999999995E-7,"µM","Change","A 5 to 13-fold relative induction to controls for ER-driven transcriptional activity in T47D cells was described at the levels by glyphosate ranging from 10^-6 to 10^-12 M. Induction was blocked by the addition of 10 nM of the ER antagonist ICI 182780. In addition, proliferation in T47D cells after 5 d of exposure was reported to be 40% as measured by the MTT assay as an indirect assessment of cell number whereas cell number in proliferations assays is best assessed by directly measuring cell number with flow cytometry. The increase in ER-driven transcriptional activity is highly inconsistent with the Uterotrophic Assay results and published studies. The current study reports that glyphosate has greater estrogenic effect than a maximally inducing dose of 17β-estradiol, which is a highly questionable result based on what is known about structure and activity information for glyphosate. This finding led Mesnage et al. (2017; study ID 84) to conclude that the results of the current study are not biologically plausible and speculate that this result reflected an estrogenic contaminant in the assay. Based on this rationale, the reported effect is considered not biologically relevant and no indication for E-related endocrine activity is deduced from this study."]
[89,"In vitro mechanistic","Estrogen receptor","Human in vitro",24,"Hours","Uptake from the medium (in vitro)",">10","µM","No effect","Glyphosate did not show any estrogenic activity at a concentration of 10 μM in two cell lines or via the two human estrogen receptor (hER) subtypes, hERα and hERβ. Based on the OECD 455 guideline for the BG1 assay, relative activity for the test substance that is <20% of the response of a maximally inducing concentration of E2 is considered to be negative. Therefore, glyphosate is conlcluded to have no ERα, ERβ agonistic activities, in vitro.\nIt needs to be noted that according to the published Corrigendum, the cell lines used were a variant of human breast cancer cell line MCF7. Thus, the recombinant cell lines are VM7Luc4E2 and VM7ERβc9."]
[87,"[Not in list]","[Not in list]","Mouse",14,"Hours","Uptake from the medium (in vitro)",500,"µM","Change","In vitro intracellular changes in Kunming mice oocytes were evaluated after being cultured in medium supplemented with 200 μM glyphosate. Findings included: decreased germinal vesicle breakdown, decreased first polar body extrusion, increased mRNA expression of anti-oxidant enzyme-related genes, abnormal spindle morphology, increased DNA double strand breaks, aggregated mitochondria, decreased mitochondrial membrane potential, increased protein expression of apoptosis factors, increased mRNA expression of apoptosis related genes and decreased autophagy-related genes. \nNo dose-response could be determined as only one concentration was tested, far in excess of that considered biologically relevant. Whilst some evaluations were conducted on oocytes harvested from a wider data set of 24 mice (protein expression levels of apoptosis factors by Western blot analysis), a number of the assessments were conducted on oocytes from just 12 mice (mRNA expression of oxidative stress-related, apoptosis-related and autophagy-related genes) or 6 mice (mitochondrial staining, measurement of mitochondrial membrane potential). This narrow source of oocytes limits the robustness of certain conclusions. Furthermore, there are insufficient details reported in the methods to establish whether mice were of the same age before oocyte harvesting or the purity of the glyphosate tested. Based on the rationale provided and also considering that the assessed endpoints are not considered EATS-related, no indication for endocrine-related activity is deduced from this in vitro assay.\n"]
[42,"In vivo mechanistic","Uterus weight (UT assay)","Rat",3,"Days","Oral","> 1000","mg/kg bw/day","No effect","Mean uterine weights (wet and blotted, including luminal fluid) were not affected.\nPotential endocrine activity was investigated in the Uterotrophic Assay (OECD TG 440; study ID 42). Glyphosate did not affect terminal body weight or body weight gains at any dose. The positive control group experienced a brief mean body weight loss (days 0-3), then recovered weight gain, resulting in a slightly reduced (5.2%) but not statistically significant terminal body weight. No treatment-related clinical and macroscopic findings were noted in uterus from either the glyphosate or positive control group. Mean uterine absolute and relative weights (wet and blotted) for the glyphosate group were similar the vehicle control. Significantly higher mean wet and blotted uterine weights (8.6- and 288 3.6-fold, respectively) compared to the vehicle control group were measured in the positive control group demonstrating the expected estrogenic effect. Based on these results, E-related endocrine activity is not deduced for glyphosate.","No EAS-related endocrine activity was observed in vivo, based on the results of an uterotrophic assay as well as in vivo hormone level measurements of published literature studies.",null,"E, A"]
[80,"In vivo mechanistic","Estradiol level","Rat",5,"Weeks","Oral",">500","mg/kg bw/day","No effect","Although there was a trend towards decreased serum (not dose-dependent), no statistically significant changes were noted."]
[93,"In vivo mechanistic","Estradiol level","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral","<1.75","mg/kg bw/day","No effect","F1: 17β-estradiol (E2). No statistically relevant effect observed in males (effect in females not possible to evaluate statistically due to insufficinet sample size considering the different stages of estrous cycle)."]
[80,"In vivo mechanistic","Progesterone level","Rat",5,"Weeks","Oral",">500","mg/kg bw/day","No effect","Although there was a trend towards decreased serum (not dose-dependent), no statistically significant changes were noted."]
[93,"In vivo mechanistic","Luteinizing Hormone (LH) level","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral","<1.75","mg/kg bw/day","No effect","Using plasma samples from 40 pups (20 females and 20 males) randomly selected from the 6-week cohort (N = 48 total). FSH and LH were also assessed in 40 pups (20 females and 20 males) randomly selected from the 13-week cohort (N = 60 total)."]
[93,"In vivo mechanistic","Follicle Stimulating Hormone (FSH) level","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral","<1.75","mg/kg bw/day","No effect","Using plasma samples from 40 pups (20 females and 20 males) randomly selected from the 6-week cohort (N = 48 total). FSH and LH were also assessed in 40 pups (20 females and 20 males) randomly selected from the 13-week cohort (N = 60 total)."]
[93,"In vivo mechanistic","Prolactin","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral","<1.75","mg/kg bw/day","No effect","Using plasma samples from 40 pups (20 females and 20 males) randomly selected from the 6-week cohort (N = 48 total)."]
[93,"In vivo mechanistic","Other hormones","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral","<1.75","mg/kg bw/day","No effect","Further hormones: sex hormone binding globuline (SHBG), growth hormone (GH), adrenocorticotropic hormone (ACTH), brain-derived neurotrophic factor (BDNF) levels were not affected in both F1 exposure groups."]
["n.a.","in silico","Androgen receptor","n.a.","n.a.","n.a.","n.a.","n.a.","n.a.","No effect","Considering the results of the predictions as provided above in a weight of evidence, glyphosate is considered to have no potential for androgenic activity. The overall weight of the CoMPARA predictions is considered highest due a) the consensus approach and b) the extensive training and validation set derived within the COMPARA project (https://comptox.epa.gov/dashboard/dsstoxdb/results?search=DTXSID1024122#bioactivity-toxcast-models). Furthermore, in the Danish (Q)SAR Database Glyphosate was included in the training set and tested negative for antagonistic effect on the human androgen receptor in vitro (for a detailed description of the results please refer to the QSAR report). \n","No indication for A-related endocrine activity of the test substance is deduced from available in silico models.",null,"A"]
[39,"In vitro mechanistic","Androgen receptor","Rat, Sprague-Dawley, cytosol from prostate","16-20","Hours","Uptake from the medium (in vitro)","> 10^-03","Molar","No effect","Glyphosate demonstrated no evidence for AR binding in the androgen receptor binding (rat prostate cytosol) screening assay since the test substance was identified as \"non-binder\" in three valid independent runs.","Based on the results of the available data, no androgenic activity was observed in vitro.",null,"A"]
[86,"In vitro mechanistic","Cellular proliferation","Mouse",24,"Hours","Uptake from the medium (in vitro)",">10000","ppm","No effect","In this study the effect of glyphosate on murine TM4 Sertoli cells was investigated in vitro. The endpoints were cytotoxicity, glutathione transferase activity and lipid accumulation. Glyphosate was found to have no impact on cell viability after 24 hours of exposure at concentrations ranging from 10 ppm to 10,000 ppm. Glyphosate reduced succinate dehydrogenase to some extent over the entire concentration range from 10 (approx. 85 % of control) to 10,000 ppm (approx.75 % of control) with no dose-effect relationship and was found to have no impact on glutathione transferase activity. Exposure of TM4 cells to glyphosate for 24 hours at 2,500 or 5,000 ppm induces an increase in cytoplasmic lipid droplets. These concentrations are far beyond what is physiologically feasible in vivo. "]
[83,"In vitro mechanistic","[Not in list]","Rat","Multiple exposure times","Hours","Uptake from the medium (in vitro)",null,"ppm","Change","In vitro exposure of Sertoli cells to glyphosate was reported to alter Sertolli cell junction barrier permeability and to decrease testosterone-stimulated TER. Further, a redistribution of claudin11 was observed. However, since this is an isolated finding in a single in vitro study which cannot easily be transferred to the in vivo situation and since and no effects on male fertility (e.g. sperm parameters) were observed in the available multi-generation studies, the result of this in vitro study is considered not biologically relevant (for further details please refer to the paragraph below).\n(Glyphosate did not modify the expression of the androgen receptor or intercellular junction proteins (claudin11, occludin and ZO-1). Further, intracellular signalling via P-p38-MAPK and P-ERK1/2 pathways were not affected. Lactate production, glucose uptake, GLUT1, FA oxidation, or FAT/CD36 and CPT1 expression was unaffected by glyphosate. Thus, the conducted molecular and cell biological investigations indicate that glyphosate does not influence testicular function due to disturbances of nutritional function or metabolism in Sertolli cells. In vitro exposure to glyphosate at non-cytotoxic concentrations (10 - 100 ppm) altered Sertoli cell junction barrier permeability and decreased testosterone-stimulated TER. Further, redistribution of claudin11 at the zone of contact between cells was detected after glyphosate stimulation. If the effects observed on Sertolli cell junction barrier permeability may contribute to a postulated effect on male reproductive function cannot be finally assessed. In general, an evaluation of such highly specific cell biological endpoints for hazard assessment is rather difficult as they cannot be transferred easily to intact organisms. As the biological in vivo relevance of such “isolated” in vitro/ex vivo findings is not validated for intact organisms, an interpretation of the obtained results on the redistribution of one special protein and cell junction barrier permeability is difficult and not considered sufficiently conclusive. In addition, when considering that no effects on male fertility were observed in the available multi-generation studies, the result of this single in vitro study is considered not biologically relevant.)"]
[43,"In vivo mechanistic","Cowpers glands weight (Hershberger)","Rat",10,"Days","Oral","> 1000","mg/kg bw/day","No effect","All coefficient of variance (CV) values for the control and high-dose groups in this study are within the acceptable range.","No A-related effect on Cowpers glands weight was observed.",null,"A"]
[43,"EATS-mediated","Coagulating gland weight","Rat",10,"Days","Oral","> 1000","mg/kg bw/day","No effect","All coefficient of variance (CV) values for the control and high-dose groups in this study are within the acceptable range and thus no effect on coagulating gland weight was observed.","No A-related effect on coagulating gland weight was observed."]
[43,"In vivo mechanistic","Glans penis weight  (Hershberger)","Rat",10,"Days","Oral","> 1000","mg/kg bw/day","No effect","In the androgen agonist assay, the CV of the glans penis (19.44%) was slightly higher than the OECD CD of 17%; not considered significant.","No A-related effect on glans penis weight was observed."]
[43,"In vivo mechanistic","LABC weight (Hershberger)","Rat",10,"Days","Oral","> 1000","mg/kg bw/day","No effect","All coefficient of variance (CV) values for the control and high-dose groups in this study are within the acceptable range.","No A-related effect on glans penis weight was observed."]
[43,"In vivo mechanistic","Prostate weight (Hershberger)","Rat",10,"Days","Oral","> 1000","mg/kg bw/day","No effect","In the androgen agonist assay, the CV of the ventral prostate low dose (100 mg/kg/day) treated animals was slightly higher (43.74%) than the OECD CD value (40%); not considered significant.","No A-related effect on prostate weight was observed."]
[43,"In vivo mechanistic","Seminal vesicles weight (Hershberger)","Rat",10,"Days","Oral","> 1000","mg/kg bw/day","No effect","All coefficient of variance (CV) values for the control and high-dose groups in this study are within the acceptable range.","No A-related effect on seminal vesicles weight was observed."]
[45,"In vivo mechanistic","Testosterone level","Rat","31 (PND 23-53)","Days","Oral",">1000","mg/kg bw/day","No effect","Mean serum hormone level was not statistically significantly decreased at 1000 mg/kg bw/day; a dose showing overt toxicity (1 mortality, rales, body weight gain decrease >10%) which confounds interpretation of reproductive system-related endpoints in the pubertal assay. No dose-response was observed and no histological changes were observed in testes. Therefore, the decrease is considered not treatment-related. ","Relevant and consistent treatment-related changes in serum testosterone levels in vivo were not observed in rat. A decrease in hormone testosterone level was observed in 35 day old male mouse offspring after exposure in utero. However, since no dose-response was observed and testosterone levels were not affected in 8 months old male mice of the same study, no indication of EAS-relates endocrine activity is derived.",null,"E, A, S"]
[80,"In vivo mechanistic","Testosterone level","Rat",5,"Weeks",null,">500","mg/kg bw/day","No effect","Although there was a trend towards decreased serum concentrations with dose, no statistically significant changes were noted."]
[91,"In vivo mechanistic","Testosterone level","Rat",14,"Days","Oral",">25","mg/kg bw/day","No effect","Intra-testicular testosterone level was investigated."]
[93,"In vivo mechanistic","Testosterone level","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral","<1.75","mg/kg bw/day","No effect","Total testosterone levels in dams were not affected."]
[93,"In vivo mechanistic","Testosterone level","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral","<1.75","mg/kg bw/day","No effect","F1: Serum concentration of free (fT) and total testosterone (TT), 5α-dihydrotestosterone (DHT) were analysed in both cohorts (6 and 13 weeks).\nNo statistically significant differences in serum TT, fT and DHT concentrations were observed in males or females belonging to both cohorts. A non-statistically significant increase in TT was observed in females of both cohorts only and fT was decreased after 6 weeks but not 13 weeks of exposure."]
[94,"In vivo mechanistic","Testosterone level","Mouse","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Oral",0.5,"mg/kg bw/day","Decrease","Serum testosterone level was statistically significantly decreased in the low and high dose group in 35 day old males. However, no dose-response was observed. No significant effect was observed in 8 months old rats."]
["n.a.","in silico","Steroidogenesis","n.a.","n.a.","n.a.","n.a.","n.a.","n.a.","No effect","There are three results available for steroid receptors: glucocorticoid receptor (GR), glucocorticoid receptor antagonism, and mineralocorticoid receptor (MR). No activity is predicted for these receptors by the molecular docking method (Endocrine Disruptome).\n","No indication for S-related endocrine activity of the test substance is deduced from available in silico models.",null,"S"]
[41,"In vitro mechanistic","Steroidogenesis (genes/enzyme changes) (in vitro)","Human cell line (H295R)",48,"Hours","Uptake from the medium (in vitro)","> 10^-04","Molar","No effect","Glyphosate did not alter 17ß-estradiol and testosterone production in the H295R steroidogenesis assay.","The observed increase in progesterone as well as decreases in in vitro estradiol levels, observed in single published non-TG studies, showed no dose-response. Based on this and on the fact that no effect on estradiol level was observed in an OECD TG 456 steroidogenesis assay, the non-dose-related effects in non-TG studies published in scientific literature provide no conclusive indication on S-related endocrine activity of glyphosate.\nThus, it is concluded that the results of two in vitro guideline tests as well as six published study addressing steroid hormone synthesis, do not show any relevant effect of glyphosate on steroidogenesis including aromatase."]
[81,"In vitro mechanistic","Testosterone synthesis","Mouse",4,"Hours","Uptake from the medium (in vitro)",">600","µM","No effect","Forgacs et al. (2012) evaluated the effect of 4 h exposures of glyphosate on testosterone production in BLTK1 murine Leydig cells in the presence and absence of an inducing dose of recombinant human chorionic gonadotropin (rhCG). Glyphosate at the maximum concentration of 300 μM did not alter rhCG induced testosterone concentrations in BLTK1 murine Leydig cells. Moreover, basal testosterone levels were not altered at a maximum concentration of 600 µM."]
[82,"In vitro mechanistic","Estradiol level (in vitro)","Swine",48,"Hours","Uptake from the medium (in vitro)",0.2,"µM","Decrease","17-ß-estradiol (E2) secretion was statistically signiﬁcantly inhibited (p < 0.05) at all tested concentrations but without a concentration-response relationship in swine granulosa cells."]
[88,"in vitro mechanistic","Estradiol level (in vitro)","Cow","24-48","Hours","Uptake from the medium (in vitro)",5,"mg/L","Decrease","In the presence of FSH only, glyphosate had no effect on estradiol production. In the presence of FSH and IGF1, estradiol production was reduced at 5 μg/mL only, but not at any other dose in granulosa cells."]
[82,"In vitro mechanistic","Progesterone level (in vitro)","Swine",48,"Hours","Uptake from the medium (in vitro)",0.2,"µM","Increase","Progesteron (P4) secretion was statistically significantly increased (p < 0.05) at all tested concentrations but without a concentration-response relationship in swine granulosa cells."]
[88,"In vitro mechanistic","Progesterone level (in vitro)","Cow","24-48","Hours","Uptake from the medium (in vitro)",">5","mg/L","No effect","Progesterone production was neither affected in granulosa nor in theca cells."]
[88,"In vitro mechanistic","Androstenedione (in vitro)","Cow","24-48","Hours","Uptake from the medium (in vitro)",">5","mg/L","No effect","Glyphosate at 5 μg/mL had no effect on the theca cell (TC)  production of androstenedione. "]
[82,"In vitro mechanistic","Cellular proliferation","Swine",48,"Hours","Uptake from the medium (in vitro)",0.2,"µM","Decrease","Glyphosate statistically signiﬁcantly decreased cell proliferation (p < 0.001) as evaluated by BrdU incorporation and cell viability (p < 0.05) as measured by ATP production without a concentration-response relationship in swine granulosa cells."]
[88,"in vitro mechanistic","Cellular proliferation","Cow","24-48","Hours","Uptake from the medium (in vitro)",0.5,"mg/L","Change","Statistically significant effects have been observed at 0.5 and 5 µg/mL on cell proliferation in FSH/IGF1 stimulated granulosa cells (In the presence of FSH only, glyphosate had no effect on granulosa cell (GC) viability. In the presence of FSH and IGF1, glyphosate reduced GC proliferation without a dose-response at 0.5 and 5 μg/mL but not at lower test concentrations. Without FSH or IGF1, 1.7 μg/mL of glyphosate slightly increased GC proliferation in response to serum (≤11 %).) However, no effect on theca cell proliferation was observed."]
[40,"In vitro mechanistic","CYP19","Human (CYP19 (aromatase) and P450 reductase Supersomes TM)",15,"Minutes","Uptake from the medium (in vitro)","> 10^-03","Molar","No effect","Based on 3 independent assay runs, glyphosate is classified as a \"non-inhibitor\" of aromatase activity in the human recombinant aromatase assay."]
[88,"in vitro mechanistic","CYP19","Cow","24-48","Hours","Uptake from the medium (in vitro)",">5","mg/L","No effect","The combined IGF1 plus FSH treatment increased (P<0.05) CYP19A1 and CYP11A1 mRNA abundance by threefold and twofold, respectively, above untreated control GC. Glyphosate (5μg/mL) had no significant effect on CYP19A1 or CYP11A1 mRNA in GC co-treated with FSH and IGF1."]
[90,"In vitro mechanistic","CYP19","Human",24,"Hours","Uptake from the medium (in vitro)",">2000","ppm","No effect","Glyphosate did not significantly inhibit aromatase activity at non-cytotoxic concentrations (up to approximately 2000 ppm [mg/L])."]
[91,"in vivo mechanistic","Steroidogenesis (genes/enzyme changes)","Rat",14,"Days","Oral",">25","mg/kg bw/day","No effect","The Leydig cell-specific steroidogenesis factors CYP11A1 and STAR were both expressed at comparative levels between the glyphosate treated animals and the controls. Also no difference in expression and distribution was noted between glyphosate treated groups and controls for the steroidogenic enzyme HSD3B1 and the germ cell-specific factor DDX4. "]
[94,"in vivo mechanistic","Steroidogenesis (genes/enzyme changes)","Mouse","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Oral",">50","mg/kg bw/day","No effect","Aromatase and Cyp11A1 mRNA levels were not affected."]
[22,"EATS-mediated","Age at Vaginal opening","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"No EAS-mediated effects on the age at vaginal opening were observed in three two-generation studies, a dose-reange finding study for an EOGRTS  as well as in a female pubertal assay in rat.\nIn conclusion, EAS-mediated adversity with regard to vaginal opening is not observed.","Under consideration of all available studies in four species up to chronic exposure period, adversity based on EAS-mediated parameters is not observed. In conclusion, glyphosate does not induce EAS-mediated adversity.","EAS"]
[23,"EATS-mediated","Age at Vaginal opening","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[26,"EATS-mediated","Age at Vaginal opening","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[44,"In vivo mechanistic","Age at Vaginal opening","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect","Control group (PND 36.4) was higher than the acceptable range of values in the performance criteria (30.67 days to 35.62 days; OPPTS 890.1450). However, the coefficient of variation (CV) value (6.52) fell within the acceptable range (0.00-6.52)."]
[93,"EATS-mediated","Age at Vaginal opening","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Age and body weight at vaginal opening was not affected."]
[44,"EATS-mediated","Age at first estrus  (female pubertal assay)","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect","Age of first estrus was not affected.","No EAS-related endocrine activity on the age at first estrus was observed in a female pubertal assay in rat as well as in a dose-range finding study for an EOGRTS."]
[93,"EATS-mediated","Age at first estrus ","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Female offspring in the control- and glyphosate-treated groups presented the FE within 6 days from the VO. (The female rats belonging to the developmental cohort (8F/group) were also monitored for the time to first estrous (FE), defined as the first day on which only cornified epithelial cells were observed on a vaginal smear, determined by vaginal cytology for 14 consecutive days, starting 3 days after vaginal opening was observed.)"]
[22,"EATS-mediated","Estrus cyclicity","Rat",10,"Weeks","Oral",">15000","ppm","No effect","No relevant effect was observed (higher number of irregular cycles in F1 females at ≥ 5000 ppm, which is not reflected in pre-coital intervals and thus, considered to be incidental and to be of no toxicological significance).","No relevant effect on estrous cyclicity was observed. The increased estrous cycle length observed in 1/8 studies (study ID 78) is attributed to general systemic toxicity (reduced body weight gain and diarrhea) and a dose exceeding the current applicable limit dose by a factor of three. Moreover, none of the other 7/8 studies (study IDs 22 – 24, 26, 79) including four two-generation studies did show any effects on fertility. In conclusion, no EAS-mediated adversity on estrous cyclicity is observed."]
[23,"EATS-mediated","Estrus cyclicity","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect","No treatment-related effects were observed. (The following effects were marginal and inconsistent and thus not considered treatment-related: higher number of cycles in F0 females observed at 10000 ppm and a lower cycle length in F1 females at 10000 ppm. There was no effect on pre-coital interval or the proportion of successful matings.)"]
[24,"EATS-mediated","Estrus cyclicity","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[26,"EATS-mediated","Estrus cyclicity","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[44,"EATS-mediated","Estrus cyclicity","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect","Mean estrus cycle lengths were not affected."]
[78,"EATS-mediated","Estrus cyclicity","Rat",90,"Days","Oral",50000,"ppm","Increase","Increased estrous cycle length was observed at 50000 ppm which is equivalent to 3393 mg/kg bw/day and thus, more than three times the limit dose of 1000 mg/kg bw/day. In addition general systemic toxicity was observed at this dose level (such as reduced body weight gain compared to control and diarrhea in the first 50 study days). No effect on estrous cyclicity was observed in further studies of subchronic exposure, including four two-generation studies (study IDs 22 - 24, 26) where no effects on fertility indices were observed. "]
[79,"EATS-mediated","Estrus cyclicity","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[93,"EATS-mediated","Estrus cyclicity","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Starting on approximately PND 95 and for the duration of 3 weeks, daily vaginal lavage was performed on female rats belonging to the 13-week cohort (10 F/group)."]
[1,"EATS-mediated","Ovary histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect",null,"Relevant effects on ovary weight were not observed in dog (8 studies), rabbit (2 studies), rat (18 studies), and mouse (6 studies). Moreover, no relevant effects with regard to histopathology were observed in dog (10 studies), rabbit (2 studies), rat (27 studies), and mouse (8 studies) after subchronic and chronic exposure as well as exposure over different life stages.\nIn conclusion, EAS-mediated adversity with regard to effects on ovaries is not observed."]
[2,"EATS-mediated","Ovary histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[3,"EATS-mediated","Ovary histopathology","Rat",90,"Days","Oral",">30000","ppm","No effect"]
[4,"EATS-mediated","Ovary histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"EATS-mediated","Ovary histopathology","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[6,"EATS-mediated","Ovary histopathology","Dog",90,"Days","Oral",">10000","ppm","No effect"]
[7,"EATS-mediated","Ovary histopathology","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"EATS-mediated","Ovary histopathology","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"EATS-mediated","Ovary histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"EATS-mediated","Ovary histopathology","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"EATS-mediated","Ovary histopathology","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"EATS-mediated","Ovary histopathology","Rat",1,"Years","Oral",">20000","ppm","No effect"]
[13,"EATS-mediated","Ovary histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No histopathological change compared to control group was observed.\n(Interim kill: cysts in 5/10 and 8/20 females of control and 10000 ppm at gross necropsy, not treatment-related;\nTerminal kill: cysts in 8/26, 3/24, 0/17 and 3/29 dead and moribund rats and 1/24, 4/26, 5/32 and 1/21 surviving rats of the 0, 100, 1000 and 10000 ppm group, age-related)"]
[14,"EATS-mediated","Ovary histopathology","Rat",24,"Months","Oral",">30000","ppm","No effect"]
[15,"EATS-mediated","Ovary histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[16,"EATS-mediated","Ovary histopathology","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[17,"EATS-mediated","Ovary histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"EATS-mediated","Ovary histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","Treatment-related non-neoplastic and neoplastic lesions were not observed.\n(Non-neoplastic: atrophy and absence of recent corpora lutea, follicular and non-follicular cysts, interstitial cell hyperplasia occasionally were observed in all groups including control and are considered age-related; isolated incidences of abscess formation, peripheral inflammatory cells and thrombus formation are considered spontaneous. Neoplastic: granulosa cell tumors, granulosa-theca cell tumors, anaplastic sacroma in 5/51, 3/51, 1/51 and 0/51 females at 0, 1500, 5000 and 15000 ppm.)"]
[19,"EATS-mediated","Ovary histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No effects were observed during gross pathology (bursal cysts in 13/34, 11/34, 11/30 and 13/30 females at 0, 100, 1000 and 10000 ppm)."]
[20,"EATS-mediated","Ovary histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","Treatment-related non-neoplastic and neoplastic lesions were not observed.\n(Non-neoplastic findings in treated and control animals: follicular and non-follicular cysts frequently observed, age-related; cystic and haemorrhagic follicles or corpora lutea in several control and high dose animals; interstitial cell hyperplasia, vasculitis, rete cyst formation, cystic distention of the oviducts, haemorrhagic cyst formation, necrosis and interstitial haemorrhage occasionally observed. Neoplastic findings: no treatment-related findings since diversity of tumor type did not suggest a treatment relation.)"]
[21,"EATS-mediated","Ovary histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect"]
[22,"EATS-mediated","Ovary histopathology","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"EATS-mediated","Ovary histopathology","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Ovary histopathology","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[25,"EATS-mediated","Ovary histopathology","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect"]
[26,"EATS-mediated","Ovary histopathology","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect","No treatment-related findings (1/2 infertile F0 females at 1000 ppm had follicular cysts on ovaries, 1/3, 1/3, 1/7 and 0/3 infertile F1 females at 0, 1000, 3000 and 10000 ppm had no or a reduced number of corpora lutea in the ovaries)"]
[27,"EATS-mediated","Ovary histopathology","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[44,"EATS-mediated","Ovary histopathology","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[49,"EATS-mediated","Ovary histopathology","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[52,"EATS-mediated","Ovary histopathology","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect","Fallopian tubes were also examined."]
[53,"EATS-mediated","Ovary histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[54,"EATS-mediated","Ovary histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"EATS-mediated","Ovary histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"EATS-mediated","Ovary histopathology","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"EATS-mediated","Ovary histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"EATS-mediated","Ovary histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"EATS-mediated","Ovary histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[60,"EATS-mediated","Ovary histopathology","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[62,"EATS-mediated","Ovary histopathology","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[63,"EATS-mediated","Ovary histopathology","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect"]
[67,"EATS-mediated","Ovary histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"EATS-mediated","Ovary histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"EATS-mediated","Ovary histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No treatment-related histopathological changes were observed. (The overall microscopic tissue alterations found throughout the study for each generation in dose and control group (F0, F1, and F2) were indicative of common incidental histological findings.)"]
[70,"EATS-mediated","Ovary histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","Offspring F3: No treatment-related histopathological changes were observed. (Microscopic tissue alterations in control and treatment groups were indicative of common incidental histological findings.)"]
[73,"EATS-mediated","Ovary histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[74,"EATS-mediated","Ovary histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"EATS-mediated","Ovary histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[76,"EATS-mediated","Ovary histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[93,"EATS-mediated","Ovary histopathology","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","F0"]
[93,"EATS-mediated","Ovary histopathology","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Assessed for both F1 exposure groups."]
[2,"EATS-mediated","Ovary weight","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[5,"EATS-mediated","Ovary weight","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[7,"EATS-mediated","Ovary weight","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"EATS-mediated","Ovary weight","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"EATS-mediated","Ovary weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"EATS-mediated","Ovary weight","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[13,"EATS-mediated","Ovary weight","Rat",2,"Years","Oral",">10000","ppm","No effect"]
[15,"EATS-mediated","Ovary weight","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[16,"EATS-mediated","Ovary weight","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[18,"EATS-mediated","Ovary weight","Rat",2,"Years","Oral",">15000","ppm","No effect"]
[19,"EATS-mediated","Ovary weight","Mouse",18,"Months","Oral",">10000","ppm","No effect"]
[20,"EATS-mediated","Ovary weight","Mouse",18,"Months","Oral",">5000","ppm","No effect"]
[22,"EATS-mediated","Ovary weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"EATS-mediated","Ovary weight","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Ovary weight","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect","An incidental decrease in relative organ weight was observed in F1 females at 1200 ppm. This finding is isolated and considered not treatment-related."]
[26,"EATS-mediated","Ovary weight","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[27,"EATS-mediated","Ovary weight","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[30,"EATS-mediated","Ovary weight","Rabbit","13 (GD 6-18)","Days","Oral",">300","mg/kg bw/day","No effect"]
[44,"EATS-mediated","Ovary weight","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect","No evidence of glyphosate-related estrogenic or anti-estrogenic effects or effects on pubertal development or thyroid function was observed."]
[49,"EATS-mediated","Ovary weight","Rat",28,"Days","Oral",">20000","ppm","No effect","Neither absolute nor relative organ weight was affected."]
[52,"EATS-mediated","Ovary weight","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"EATS-mediated","Ovary weight","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[54,"EATS-mediated","Ovary weight","Rat",90,"Days","Oral",">20000","ppm","No effect","No effect on absolute and relative organ weight was observed."]
[56,"EATS-mediated","Ovary weight","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"EATS-mediated","Ovary weight","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","No effect on relative and absolute organ weight was observed."]
[58,"EATS-mediated","Ovary weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[59,"EATS-mediated","Ovary weight","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[62,"EATS-mediated","Ovary weight","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[67,"EATS-mediated","Ovary weight","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Absolute organ weight was not affected."]
[68,"EATS-mediated","Ovary weight","Mouse",2,"Years","Oral","> 30000","ppm","No effect","No treatment-related effect was observed.\n(The mean absolute and relative (to body and brain weight) ovarian weights for the high-dose females were markedly elevated, although differences from control were not statistically significant. These differences were due to a single animal, whose ovarian weight was approximately six times the mean ovarian weight for the group. When this animal was excluded, differences compared to control were not apparent.)"]
[70,"EATS-mediated","Ovary weight","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","Mean organ weight data (absolute and relative to body weights or brain weights) were comparable for control and treated groups.\nNo treatment-related effect was evident in organ weight data for the F3b offspring."]
[70,"EATS-mediated","Ovary weight","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Mean ovary weight data (absolute and relative to body weights or brain weights) were comparable for control and treated groups of all generations (F0, F1, and F2)."]
[73,"EATS-mediated","Ovary weight","Mouse",90,"Days","Oral",">50000","ppm","No effect","Absolute and relative (to body and brain weight) organ weight was not affected."]
[93,"EATS-mediated","Ovary weight","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","F0: Absolute and relative weight was unaffected."]
[93,"EATS-mediated","Ovary weight","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","F1: No effect was obsereved on absolute and relative organ weight of both exposure groups (6 and 13 weeks)."]
[1,"EATS-mediated","Uterus histopathology (with cervix)","Rat",90,"Days","Oral",">20000","ppm","No effect",null,"Relevant effects on uterus weight were not observed in dog (3 studies), rabbit (4 studies), rat (13 studies), and mouse (2 studies). Moreover, no relevant effects with regard to histopathology of uterus and cervix were observed in dog (10 studies), rabbit (2 studies), rat (28 studies), and mouse (8 studies) after subchronic and chronic exposure as well as exposure over different life stages.\nIn conclusion, EAS-mediated adversity with regard to to effects on uterus and cervix is not observed."]
[2,"EATS-mediated","Uterus histopathology (with cervix)","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[3,"EATS-mediated","Uterus histopathology (with cervix)","Rat",90,"Days","Oral",">30000","ppm","No effect"]
[4,"EATS-mediated","Uterus histopathology (with cervix)","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"EATS-mediated","Uterus histopathology (with cervix)","Dog",90,"Days","Oral",1000,"mg/kg bw/day","Change","Decreased uterus size at macroscopical examination at 1000 mg/kg bw/day was observed: uterine atrophy in 3/3 females.\nHowever this finding was judged to be secondary to systemic toxicity as reduced body weight and body weight gain, reduced food consumption and diarrhea were observed at 1000 mg/kg. Furthermore, studies performed in the same species with similar or even higher dose groups for the same period of time, did not reveal any effects on uterus size. Moreover, no effect on uterine size was observed after an exposure period of 1 year at similar doses in the same species. In conclusion, the observed macroscopic effect is an isolated finding, not toxicologically relevant."]
[6,"EATS-mediated","Uterus histopathology (with cervix)","Dog",90,"Days","Oral",">10000","ppm","No effect"]
[7,"EATS-mediated","Uterus histopathology (with cervix)","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"EATS-mediated","Uterus histopathology (with cervix)","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"EATS-mediated","Uterus histopathology (with cervix)","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"EATS-mediated","Uterus histopathology (with cervix)","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"EATS-mediated","Uterus histopathology (with cervix)","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"EATS-mediated","Uterus histopathology (with cervix)","Rat",1,"Years","Oral",">20000","ppm","No effect"]
[13,"EATS-mediated","Uterus histopathology (with cervix)","Rat",2,"Years","Oral",">10000","ppm","No effect","No treatment-related histopathological changes were observed. (Interim kill: small masses or polyps in 3/10 and 3/20 females at 0 and 10000 ppm at gross necropsy, not treatment-related; terminal kill: focal irregular thickening in 7/24, 3/26, 12/33 and 6/21 females at gross necropsy, treatment-related but without dose-relation; Neoplastic findings, dead/moribund animals: no treatment-related findings: adenocarcinoma in 1/17 females at 1000 ppm; anaplastic carcinoma in 1/24 females at 100 ppm; leiomyosarcoma in 1/29 females at 10000 ppm; neoplastic findings, surviving animals: no treatment-related findings)"]
[14,"EATS-mediated","Uterus histopathology (with cervix)","Rat",2,"Years","Oral",">30000","ppm","No effect"]
[15,"EATS-mediated","Uterus histopathology (with cervix)","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[16,"EATS-mediated","Uterus histopathology (with cervix)","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[17,"EATS-mediated","Uterus histopathology (with cervix)","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"EATS-mediated","Uterus histopathology (with cervix)","Rat",2,"Years","Oral",">15000","ppm","No effect","No treatment-related histopathological changes were observed. (Histopathology, non-neoplastic: no treatment-related findings: cystic endometrial hyperplasia in control and treatment-groups, age-related; uterine dilatation statistically significantly increased in high dose females, considered to be without toxicological significance; rare instances of keratinisation of the cervix, haemorrhage, pyometra, keratin cyst formation, abscess formation and squamous cell carcinoma; Neoplastic: no treatment-related findings (52 uterine tumours in 46 rats, 7/46 rats had more than 1 tumour type, 24/52 incidences of endometrial stromal polyps, 21/52 incidences of adenocarcinomas and 7/52 incidences of leiomyoma, stromal sarcoma or angiosarcoma in females over all groups (16/51, 12/51, 9/51 and 15/51 females at 0, 1500, 5000 and 15000 ppm))"]
[19,"EATS-mediated","Uterus histopathology (with cervix)","Mouse",18,"Months","Oral",">10000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic findings dead/moribund animals: cystic glands in 5/16, 3/16, 2/20 and 7/20 females at 0, 100, 1000 and 10000 ppm, non-neoplastic findings terminal kill: cystic endometrial hyperplasia in 17/34, 5/34, 4/30 and 8/30 females at 0, 100, 1000 and 10000 ppm; neoplastic findings: 10 tumours observed, mostly endometrial stromal sarcomas. No dose- or treatment-relation identified.)"]
[20,"EATS-mediated","Uterus histopathology (with cervix)","Mouse",18,"Months","Oral",">5000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic findings: no treatment-related findings: cystic endometrial hyperplasia in most mice and uterine atrophy, age-related; instances of vasculitis, lymphoid foci, haemorrhagic cyst formation and angiectasis; neoplastic findings: tumours observed in 20 mice, but group distribution was unrelated to treatment, 6 different tumour types; most frequently observed tumour was endometrial stromal polyp; histiocytic sarcomas in 5 animals)"]
[21,"EATS-mediated","Uterus histopathology (with cervix)","Mouse",18,"Months","Oral",">40000","ppm","No effect","No treatment-related histopathological changes were observed. "]
[22,"EATS-mediated","Uterus histopathology (with cervix)","Rat",10,"Weeks","Oral",">15000","ppm","No effect","No treatment-related histopathological changes were observed (focal haemorrhage, foam cell accumulations and haemosiderin pigment deposition in the peripheral uterine tissue of pregnant rats, commonly encountered consequences of pregnancy and parturition)."]
[23,"EATS-mediated","Uterus histopathology (with cervix)","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Uterus histopathology (with cervix)","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[25,"EATS-mediated","Uterus histopathology (with cervix)","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect"]
[26,"EATS-mediated","Uterus histopathology (with cervix)","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect","No treatment-related findings (luminal dilatation of the uterus in 2/3 infertile control females of the F1 generation)"]
[27,"EATS-mediated","Uterus histopathology (with cervix)","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[31,"EATS-mediated","Uterus histopathology (with cervix)","Rabbit","13 (GD 7-19)","Days","Oral",400,"mg/kg bw/day","No effect","Histopathological findings were not observed. (Gross necropsy: blood and dead fetuses in 1/2 dead females at 400 mg/kg bw/day)"]
[44,"EATS-mediated","Uterus histopathology (with cervix)","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[49,"EATS-mediated","Uterus histopathology (with cervix)","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[52,"EATS-mediated","Uterus histopathology (with cervix)","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"EATS-mediated","Uterus histopathology (with cervix)","Rat",90,"Days","Oral",">20000","ppm","No effect","Cervix, uterus and vagina were fixed together. "]
[54,"EATS-mediated","Uterus histopathology (with cervix)","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"EATS-mediated","Uterus histopathology (with cervix)","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"EATS-mediated","Uterus histopathology (with cervix)","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"EATS-mediated","Uterus histopathology (with cervix)","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"EATS-mediated","Uterus histopathology (with cervix)","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"EATS-mediated","Uterus histopathology (with cervix)","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[62,"EATS-mediated","Uterus histopathology (with cervix)","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[67,"EATS-mediated","Uterus histopathology (with cervix)","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"EATS-mediated","Uterus histopathology (with cervix)","Mouse",2,"Years","Oral","> 30000","ppm","No effect","Uterus histopathology was performed including uterine horns and cervix."]
[70,"EATS-mediated","Uterus histopathology (with cervix)","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered treatment-related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"EATS-mediated","Uterus histopathology (with cervix)","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","Offspring: No microscopic findings were considered treatment-related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"EATS-mediated","Uterus histopathology (with cervix)","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[74,"EATS-mediated","Uterus histopathology (with cervix)","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"EATS-mediated","Uterus histopathology (with cervix)","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[76,"EATS-mediated","Uterus histopathology (with cervix)","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[93,"EATS-mediated","Uterus histopathology (with cervix)","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","F0: Absolute and relative weight was unaffected."]
[93,"EATS-mediated","Uterus histopathology (with cervix)","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Assessed for both F1 exposure groups."]
[5,"EATS-mediated","Uterus weight (with cervix)","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[9,"EATS-mediated","Uterus weight (with cervix)","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[15,"EATS-mediated","Uterus weight (with cervix)","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[16,"EATS-mediated","Uterus weight (with cervix)","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[18,"EATS-mediated","Uterus weight (with cervix)","Rat",2,"Years","Oral",">15000","ppm","No effect"]
[22,"EATS-mediated","Uterus weight (with cervix)","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[22,"EATS-mediated","Uterus weight (with cervix)","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"EATS-mediated","Uterus weight (with cervix)","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Uterus weight (with cervix)","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[28,"EATS-mediated","Uterus weight (with cervix)","Rat","10 (GD 7-16)","Days","Oral",">1000","mg/kg bw/day","No effect","Gravid uterus weight was not affected."]
[29,"EATS-mediated","Uterus weight (with cervix)","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","Gravid uterus weight as well as placental weight were not affected."]
[30,"EATS-mediated","Uterus weight (with cervix)","Rabbit","13 (GD 6-18)","Days","Oral",">300","mg/kg bw/day","No effect","Gravid uterus weight was not affected."]
[32,"EATS-mediated","Uterus weight (with cervix)","Rabbit","13 (GD 8-20)","Days","Oral","> 300","mg/kg bw/day","No effect","Gravid uterus weight was not affected."]
[34,"EATS-mediated","Uterus weight (with cervix)","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect"]
[35,"EATS-mediated","Uterus weight (with cervix)","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect"]
[44,"EATS-mediated","Uterus weight (with cervix)","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect","No effect on uterus weight wet (with luminal fluid) and blotted was observed."]
[52,"EATS-mediated","Uterus weight (with cervix)","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[56,"EATS-mediated","Uterus weight (with cervix)","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[59,"EATS-mediated","Uterus weight (with cervix)","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[65,"EATS-mediated","Uterus weight (with cervix)","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","Gravid uterus weight along with ovaries was weighed. However, no further details were reported."]
[67,"EATS-mediated","Uterus weight (with cervix)","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Absolute organ weight was not affected."]
[93,"EATS-mediated","Uterus weight (with cervix)","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","F0: Absolute and relative weight was unaffected."]
[93,"EATS-mediated","Uterus weight (with cervix)","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","F1: No effect was observed on absolute and relative organ weight (including cervix) of both exposure groups (6 and 13 weeks)."]
[1,"EATS-mediated","Cervix histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[2,"EATS-mediated","Cervix histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[3,"EATS-mediated","Cervix histopathology","Rat",90,"Days","Oral",">30000","ppm","No effect"]
[4,"EATS-mediated","Cervix histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"EATS-mediated","Cervix histopathology","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[8,"EATS-mediated","Cervix histopathology","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[11,"EATS-mediated","Cervix histopathology","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"EATS-mediated","Cervix histopathology","Rat",1,"Years","Oral",">20000","ppm","No effect"]
[15,"EATS-mediated","Cervix histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[17,"EATS-mediated","Cervix histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"EATS-mediated","Cervix histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect"]
[19,"EATS-mediated","Cervix histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect"]
[21,"EATS-mediated","Cervix histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect"]
[22,"EATS-mediated","Cervix histopathology","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"EATS-mediated","Cervix histopathology","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Cervix histopathology","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[26,"EATS-mediated","Cervix histopathology","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[53,"EATS-mediated","Cervix histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","Cervix, uterus and vagina were fixed together. "]
[55,"EATS-mediated","Cervix histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","Cervix was examined together with uterus."]
[56,"EATS-mediated","Cervix histopathology","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[58,"EATS-mediated","Cervix histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Cervix examined together with uterus. "]
[76,"EATS-mediated","Cervix histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[2,"EATS-mediated","Vagina histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect",null,"No relevant effects with regard to histopathology of vagina were observed in dog (1 study), rat (12 studies), and mouse (3 studies) after subchronic and chronic exposure as well as exposure over different life stages. Moreover, no changes were observed in vaginal smears.\nIn conclusion, EAS-mediated adversity with regard to effects on vagina is not observed.\n"]
[3,"EATS-mediated","Vagina histopathology","Rat",90,"Days","Oral",">30000","ppm","No effect"]
[4,"EATS-mediated","Vagina histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[9,"EATS-mediated","Vagina histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[14,"EATS-mediated","Vagina histopathology","Rat",24,"Months","Oral",">30000","ppm","No effect"]
[17,"EATS-mediated","Vagina histopathology","Rat",24,"Months","Oral",">20000","ppm","No effect"]
[18,"EATS-mediated","Vagina histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect"]
[20,"EATS-mediated","Vagina histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic findings: no treatment-related findings: epithelial keratinisation as normal cyclical change; one case of peripheral lymphocyte infiltration; neoplastic findings: no neoplastic changes)"]
[21,"EATS-mediated","Vagina histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect"]
[22,"EATS-mediated","Vagina histopathology","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"EATS-mediated","Vagina histopathology","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Vagina histopathology","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[25,"EATS-mediated","Vagina histopathology","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect"]
[26,"EATS-mediated","Vagina histopathology","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[27,"EATS-mediated","Vagina histopathology","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[53,"EATS-mediated","Vagina histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","Cervix, uterus and vagina were fixed together. "]
[93,"EATS-mediated","Vagina histopathology","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","F0"]
[93,"EATS-mediated","Vagina histopathology","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Assessed for both F1 exposure groups."]
[22,"EATS-mediated","Vaginal smears","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"EATS-mediated","Vaginal smears","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Vaginal smears","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[25,"EATS-mediated","Vaginal smears","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect"]
[26,"EATS-mediated","Vaginal smears","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[70,"EATS-mediated","Accessory sex organs histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Clitoral gland investigated for F0 only. No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for generation F0 were indicative of common incidental histological findings.","In conclusion, EAS-mediated adversity with regard to effects on clitoral gland is not observed."]
[22,"EATS-mediated","Ano-Genital distance","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"The AGD was assessed in a two-generation study and was not affected by glyphosate exposure (study ID 22). The AGD was not investigated in further available two-generation studies since those were performed according to former test guideline versions and no effect on sex ratio was observed (study ID 23).\nThe increase in AGD observed in males in one published study is considered not related to an endocrine pathway, since no other male parameters (e.g., age at PPS, testes weight, accessory sexual tissue weights, sperm parameters) were affected in this study. Moreover, there is no consistency with regard to a potential androgenic effect when also considering the results of the in vivo mechanistic as well as the multi-generation studies.\nIn conclusion, EAS-mediated adversity with regard to effects on anogenital distance is not observed."]
[93,"EATS-mediated","Ano-Genital distance","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",1.75,"mg/kg bw/day","Increase","AGD was measured on PND 4 (including bw determination). AGD was statistically significantly increased in males only (absolute values: 4.26 mm vs 4.02 mm in control) and the author also reports this for the AGD adjusted for body weight. However, the numbers for the AGD index as well as the body weight data are not provided. Moreover, when taking into account the provided box plots and dot plots regarding AGD and AGD index, a significant increase in AGD index is not obvious. Moreover, the increase in anogenital distance was not correlated with increased testosterone levels or changes in any male reproductive endpoints (e.g., age at PPS, testes weight, accessory sexual tissue weights, sperm parameters). No endpoints were statistically significant with female rats. In the in vivo mechanistic and multi-generational studies there were no indication of effects on the androgen pathway that would result in an increase on anogenital distance in male rats. Therefore, the reported increase in AGD in males only is considered toxicologically not related to an endocrine pathway."]
[22,"EATS-mediated","Age at balanopreputial separation","Rat",10,"Weeks","Oral",15000,"ppm","Increase","Preputial separation (PPS) was statistically significantly delayed at 15000 ppm  (about 1000 mg/kg bw/d), which is  the limit dose of the test system according to OECD TG 416. The age at PPS was increased to  45.9 ± 3.1 days versus 43.0 ± 2.3 days in control group with no further signs of developmental retardation, hence, a higher mean bodyweight was noted at attainment of PPS. The delay of PPS is of marginal magnitude and considered to be based on biological variation. There were no differences in mating performance, sperm parameters and histopathological examinations did not reveal any changes in the testis or epididymis. Therefore, in isolation, this finding was considered to be unrelated to treatment which is supported by two futher studies performed in rats at similar doses (study IDs 23, 26) which did not show a delay in PPS. Moreover, the PPS observed in the high dose group is only slightly above the range provided in OECD GD 43 and 151, according to which onset of puberty in the rat occurs around postnatal days 40-45. In addition, a delay in PPS was not reproduced in the second generation (F2 generation). Therefore, the increase in age at PPS in the F1 generation is not considered an anti-androgenic effect.","2/5 studies investigating balanopreputial separation (PPS) did not show any effect of glyphosate exposure including one two-generation study tested up to the limit dose of 1000 mg/kg bw/day (study ID 23) and conducted similar to OECD TG 416 (2001).  \nWithin the male pubertal assay (study ID 45), a delayed age at PPS was shown only at the high dose where also overt toxicity (one mortality, lung rales, body weight gain decrease >10%) was observed. Since overt toxicity confounds interpretatoin of reproductive system-related endpoints in the pubertal assay, the delay in PPS is not considered an antiandrogenic effect (further details please refer to study ID 45).\nIn one two-generation study (study ID 22) a marginal but statistically significant delay in PPS was observed at the limit test dose of 1000 mg/kg bw/day in the F1 but not the F2 generation. Since further parameters, such as mating performance, sperm parameters and histopathological examinations of testis or epididymis did not reveal any changes and the effect was not reproduced in two further two-generation studies at similar doses, the delay of PPS was considered an isolated finding, not relevant for deducing an antiandrogenic effect of glyphosate. This rationale is in line with the conclusion of the EFSA Peer Review (EFSA Journal 2017;15(9):4979) as well as with the conclusion of EPA on the Endocrine Screening Program (EDSP) Tier l (US EPA, 2015). \nIn conclusion, glyphosate does not induce an adverse EAS-mediated effect on PPS."]
[23,"EATS-mediated","Age at balanopreputial separation","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[26,"EATS-mediated","Age at balanopreputial separation","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[45,"EATS-mediated","Age at balanopreputial separation","Rat","31 (PND 23-53)","Days","Oral",1000,"mg/kg bw/day","Increase","A statistically non-significant delay in the mean age at attainment of balanopreputial separation was observed in the high dose group (48.0 days). However, the body weight on the day of attainment of complete balanopreputial separation (PPS) in the 1000 mg/kg/day group was similar to the control group. However, the body weight was decreased at several time points by about 10% and the overall body weight change was reduced by 12.4% at 1000 mg/kg bw/day. Thus, the delay of PPS is considered an effect secondary to reduced body weight gain. Moreover, when adjusting the day of attainment for those males with three or more consecutive days of incomplete separation (persistent threads), no statistically significant delay in the mean age of attainment of preputial separation was noted for the 1000 mg/kg bw/day dose group when compared to the control group. There were 6, 11, 9, and 9 males in the control, 100, 300, and 1000 mg/kg bw/day dose group, respectively, with incomplete PSS for more than three days. No test substance related effects were observed at doses not causing overt toxicity. Therefore, the increase in age at PPS is not considered and anti-androgenic effect."]
[93,"EATS-mediated","Age at balanopreputial separation","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Age and body weight at PPS was not affected."]
[20,"EATS-mediated","Accessory sex organs histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No effect on the preputial gland was observed. (No treatment-related findings: inflammatory and atrophic lesions, age-related; abscess formation occasionally observed, one instance of keratin cyst formation.)","In conclusion, EAS-mediated adversity with regard to effects on the preputial gland is not observed."]
[70,"EATS-mediated","Accessory sex organs histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No effect on the preputial gland was observed. No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[3,"EATS-mediated","Coagulating gland histopathology","Rat",90,"Days","Oral",">30000","ppm","No effect",null,"In 1/3 studies, relative but not absolute coagulating gland weight was reduced. No effect on coagulating gland weight was observed in 2/3 toxicity studies in rat with higher doses (e.g. study ID 22, 23). Moreover, no relevant effects with regard to histopathology of coagulating gland were observed in rat (11 studies), and mouse (4 studies) after subchronic and chronic exposure as well as exposure over different life stages. \nIn conclusion, EAS-mediated adversity with regard to effects on coagulating gland is not observed."]
[4,"EATS-mediated","Coagulating gland histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[13,"EATS-mediated","Coagulating gland histopathology","Rat",24,"Months","Oral",">10000","ppm","No effect"]
[14,"EATS-mediated","Coagulating gland histopathology","Rat",24,"Months","Oral",">30000","ppm","No effect"]
[19,"EATS-mediated","Coagulating gland histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect"]
[20,"EATS-mediated","Coagulating gland histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No treatment-related histopathological changes were observed.\n(Non-neoplastic findings: no treatment-related findings (focal epithelial hyperplastic and atrophic changes frequently observed, age-related; mononuclear cell foci, mixed inflammatory cell infiltrates, interstitial fibrosis and abscess formation occasionally more rarely observed - not treatment-related; no neoplastic lesions observed.)"]
[21,"EATS-mediated","Coagulating gland histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect"]
[22,"EATS-mediated","Coagulating gland histopathology","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"EATS-mediated","Coagulating gland histopathology","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Coagulating gland histopathology","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[25,"EATS-mediated","Coagulating gland histopathology","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect"]
[26,"EATS-mediated","Coagulating gland histopathology","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[49,"EATS-mediated","Coagulating gland histopathology","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[54,"EATS-mediated","Coagulating gland histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[93,"EATS-mediated","Coagulating gland histopathology","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Seminal vesicles and coagulating gland (assessed for both F1 exposure groups)."]
[22,"EATS-mediated","Coagulating gland weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"EATS-mediated","Coagulating gland weight","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[80,"EATS-mediated","Coagulating gland weight","Rat",5,"Weeks","Oral",500,"mg/kg bw/day","Decrease","A significant decrease in absolute (but not relative) weight of the coagulating gland(weighed together with seminal vesicles) was observed, which may be attributed to the non statistically significant reduced final body weight. Since no effect on coagulating gland weight and histopathology was observed  in further toxicity studies in rat with higher doses (e.g. study ID 22, 23), and no effect on relative organ weight was observed in the current study, the decrease in absolute organ weight is not considered toxicologically relevant."]
[1,"EATS-mediated","Epididymis histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect",null,"Relevant effects on epididymis weights were not observed in dog (6 studies), rat (14 studies), and mouse (3 studies). Moreover, no relevant effects with regard to histopathology of epididymis were observed in dog (9 studies), rabbit (1 study), rat (23 studies), and mouse (9 studies) after subchronic and chronic exposure as well as exposure over different life stages (for rat).\nIn conclusion, EAS-mediated adversity with regard to effects on epididymis is not observed."]
[3,"EATS-mediated","Epididymis histopathology","Rat",90,"Days","Oral",">30000","ppm","No effect"]
[4,"EATS-mediated","Epididymis histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"EATS-mediated","Epididymis histopathology","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[7,"EATS-mediated","Epididymis histopathology","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"EATS-mediated","Epididymis histopathology","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"EATS-mediated","Epididymis histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"EATS-mediated","Epididymis histopathology","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"EATS-mediated","Epididymis histopathology","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"EATS-mediated","Epididymis histopathology","Rat",1,"Years","Oral",">20000","ppm","No effect"]
[13,"EATS-mediated","Epididymis histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","Neoplastic findings: no treatment-related findings (undifferentiated sarcoma in 1/32 males at 1000 ppm)"]
[14,"EATS-mediated","Epididymis histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect"]
[15,"EATS-mediated","Epididymis histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[16,"EATS-mediated","Epididymis histopathology","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[17,"EATS-mediated","Epididymis histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"EATS-mediated","Epididymis histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No treatment-related histopathological changes were observed.\n(Non-neoplastic: age-related changes observed only such as reduced sperm count, spermatozoal granuloma formation, abscess formation and sclerotic nodule observed with low incidences; neoplastic: mesothelioma in 1/51 control and 2/51 males at 1500 ppm)"]
[19,"EATS-mediated","Epididymis histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No treatment-related histopathological changes were observed.\n(Non-neoplastic in dead/moribund animals: lymphocyte infiltration in 4/22, 1/20, 0/22 and 3/27 males and cell debris in tubules in 0/22, 1/20, 4/22 and 0/27 males at 0, 100, 1000 and 10000 ppm)"]
[20,"EATS-mediated","Epididymis histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic: age-related changes observed only such as reduced spermatozoal content, spermatocoel and spermatocoel granuloma formation, eosinophilic contents, interstitial mononuclear cells and fibrosis, distention of ducts observed with low incidences; neoplastic: no neoplastic changes)"]
[21,"EATS-mediated","Epididymis histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect"]
[22,"EATS-mediated","Epididymis histopathology","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"EATS-mediated","Epididymis histopathology","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Epididymis histopathology","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[25,"EATS-mediated","Epididymis histopathology","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect"]
[26,"EATS-mediated","Epididymis histopathology","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[27,"EATS-mediated","Epididymis histopathology","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[45,"EATS-mediated","Epididymis histopathology","Rat","31 (PND 23-53)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[52,"EATS-mediated","Epididymis histopathology","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"EATS-mediated","Epididymis histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"EATS-mediated","Epididymis histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","Epididymides were examined together with testes."]
[56,"EATS-mediated","Epididymis histopathology","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"EATS-mediated","Epididymis histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","Examined together with testes."]
[58,"EATS-mediated","Epididymis histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"EATS-mediated","Epididymis histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[60,"EATS-mediated","Epididymis histopathology","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[62,"EATS-mediated","Epididymis histopathology","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[67,"EATS-mediated","Epididymis histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"EATS-mediated","Epididymis histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"EATS-mediated","Epididymis histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"EATS-mediated","Epididymis histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"EATS-mediated","Epididymis histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[80,"EATS-mediated","Epididymis histopathology","Rat",5,"Weeks","Oral",">500","mg/kg bw/day","No effect","No statistically significant changes were observed."]
[93,"EATS-mediated","Epididymis histopathology","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Assessed for both F1 exposure groups."]
[5,"EATS-mediated","Epididymis weight","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[8,"EATS-mediated","Epididymis weight","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"EATS-mediated","Epididymis weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[11,"EATS-mediated","Epididymis weight","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"EATS-mediated","Epididymis weight","Rat",1,"Years","Oral",">20000","ppm","No effect","Absolute and relative organ weights were reduced at 2000 ppm only. This was considered an incidental finding since no dose-relationship was observed."]
[15,"EATS-mediated","Epididymis weight","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"EATS-mediated","Epididymis weight","Rat",2,"Years","Oral",">15000","ppm","No effect"]
[20,"EATS-mediated","Epididymis weight","Mouse",18,"Months","Oral",">5000","ppm","No effect"]
[22,"EATS-mediated","Epididymis weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"EATS-mediated","Epididymis weight","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Epididymis weight","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[27,"EATS-mediated","Epididymis weight","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[45,"EATS-mediated","Epididymis weight","Rat","31 (PND 23-53)","Days","Oral",300,"mg/kg bw/day","Decrease","Lower mean absolute left and right epididymis weight (9.5-9.9% and 3.8-7.1% for 1000 and 300 mg/kg bw/day dose group, respectively) was observed (not statistically significant). The effect was considered secondary to body weight decreases. For the high dose overt toxicity (1 mortality, rales, body weight gain decrease >10%) was observed. Body weight decreases > 10% have been shown to confound the interpretation of reproductive system-related endpoints in the pubertal assays (Fed Reg. 74(71):17570-17585). Therefore, for the 1000 mg/kg bw/day dose group, interpretation of endocrine endpoints was confounded by overt and systemic toxicity and considered not relevant for a WoE analysis for the androgen pathway as per the USEPA and EFSA guidance. In addition, no histopathological changes were observed in the current study and no effects on reproduction were observed in one-, two- and three-generation studies. Thus, decreased organ weight is not considered relevant for EAS-mediated adversity."]
[53,"EATS-mediated","Epididymis weight","Rat",90,"Days","Oral",">20000","ppm","No effect","Testes and epididymis were weighed together. Absolute and relative organ weights were not affected."]
[55,"EATS-mediated","Epididymis weight","Rat",90,"Days","Oral",">20000","ppm","No effect","Testes and epididymis were weighed together. Absolute and relative organ weights were not affected."]
[56,"EATS-mediated","Epididymis weight","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect","Testes and epididymis were weighed together. Absolute and relative organ weights were not affected."]
[58,"EATS-mediated","Epididymis weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Testes and epididymis were weighed together. Absolute and relative organ weights were not affected."]
[59,"EATS-mediated","Epididymis weight","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Testes and epididymis were weighed together. Absolute and relative organ weights were not affected."]
[60,"EATS-mediated","Epididymis weight","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[67,"EATS-mediated","Epididymis weight","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Testes and epididymis were weighed together. Absolute organ weight was not affected."]
[78,"EATS-mediated","Epididymis weight","Rat",90,"Days","Oral",">50000","ppm","No effect","Absolute organ weight was not affected."]
[93,"EATS-mediated","Epididymis weight","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral","<1.75","mg/kg bw/day","No effect","No effect was obsereved on absolute and relative organ weight of both exposure groups (6 and 13 weeks)."]
[94,"In vivo mechanistic","Epididymis weight","Mouse","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Oral",">50","mg/kg bw/day","No effect","Epididymides weights were determined in 35 day and 8 months old males and no statistically significant effect was observed."]
[45,"EATS-mediated","LABC weight","Rat","31 (PND 23-53)","Days","Oral",1000,"mg/kg bw/day","Decrease","Statistically significantly decreased mean absolute LABC weight (15.9%) was observed at the high dose showing overt toxicity (1 mortality, rales, body weight gain decrease >10%). Body weight decreases > 10% have been shown to confound the interpretation of reproductive system-related endpoints in the pubertal assays (Fed Reg. 74(71):17570-17585). Therefore, for the 1000 mg/kg bw/day dose group, interpretation of endocrine endpoints was confounded by overt and systemic toxicity and considered not relevant for a WoE analysis for the androgen pathway as per the USEPA and EFSA guidance. In addition, no effects on reproduction were observed in one-, two- and three-generation studies.","An effect on LABC weight was observed at overt systemic toxicity only. Therefore, no indication for endocrine-related adversity can be deduced."]
[2,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat",90,"Days","Oral",">50000","ppm","No effect",null,"Relevant effects on prostate weight were not observed in dog (5 studies), rat (9 studies), and mouse (2 studies). Moreover, no relevant effects with regard to histopathology of prostate were observed in dog (9 studies), rabbit (1 study), rat (22 studies), and mouse (8 studies) after subchronic and chronic exposure as well as exposure over different life stages (for rat).\nNo EAS-mediated adversity was observed for the prostate in four species."]
[3,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat",90,"Days","Oral",">30000","ppm","No effect"]
[4,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Dog",90,"Days","Oral",1000,"mg/kg bw/day","Change","Prostate atrophy was observed in 2/3 animals at 1000 mg/kg bw/day. However, at the same dose reduced mean body weight (-28%) and lower weight gain (+4% vs +31% in controls) was observed. Moreover, clinical signs such as diarrhea were observed and one animal was sacrificed prior to study termination. \nFurthermore, chronic toxicity studies in dogs, using similar dose groups did not reveal any effects on the histopathology of the prostate (study IDs 7-11). Therefore, the observed effect on prostate is considered secondary to general toxicity at this dose level and not related to an endocrine MoA. "]
[7,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Dog",90,"Days","Oral",">50000","ppm","No effect","No treatment-related histopathological changes were observed (imperfect spermatogenesis and minimal secretory activity in 1/4, 1/4, 1/4 and 2/4 males at 0, 2000, 10000 and 50000 ppm)."]
[9,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat",1,"Year","Oral",">20000","ppm","No effect"]
[13,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat",2,"Years","Oral",">10000","ppm","No effect","No treatment-related histopathological changes were observed. (Cysts in 16/30, 13/30, 18/32 and 12/21 dead or moribund males and 16/20, 0/20, 0/18 and 22/29 surviving males in the 0, 100, 1000 and 10000 ppm group.)"]
[14,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat",2,"Years","Oral",">30000","ppm","No effect","No treatment-related histopathological changes were observed. (Gross necropsy: no abnormalities observed; Histopathology, non-neoplastic: decreased incidences of inflammation: 6/18, 5/20, 2/18 and 2/29 at 0, 3000, 10000 and 30000 ppm; neoplastic: no treatment-related findings.)\n"]
[15,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat",2,"Years","Oral",20000,"ppm","Change","Gross necropsy: increased (3/64) firmness at 20000 ppm\nHistopathology, non-neoplastic findings: Prostatitis at 20000 ppm, increased incidences compared to concurrent control but within historical control range.\nHistopathology, neoplastic findings: no treatment-related findings\nThe findings during gross necropsy are of very low magnitude and are therefore considered as a result of normal biological variation. In addition, histopathological changes were within the range of historical control data. Moreover, further chronic studies in rat exposed to similar doses did not show any effect on prostate (study IDs 13, 14). In conclusion, prostatitis as well as the increased firmness were not considered treatment-related."]
[16,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[17,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat",2,"Years","Oral",">15000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic: atrophic changes commonly observed in control and treated groups, age-related; focal epithelial hyperplasia, inflammatory cell infiltrates, interstitial fibrosis, interstitial haemorrhage and prostatis occasionally observed, considered as spontaneous changes; neoplastic: no neoplastic lesions observed.)"]
[19,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Mouse",18,"Months","Oral",">10000","ppm","No effect"]
[20,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Mouse",18,"Months","Oral",">5000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic: focal epithelial hyperplastic and atrophic changes frequently observed, age-related; mononuclear cell foci, mixed inflammatory cell infiltrates, interstitial fibrosis and abscess formation occasionally ore rarely observed; neoplastic findings: no neoplastic lesions observed.)"]
[21,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Mouse",18,"Months","Oral",">40000","ppm","No effect"]
[22,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat",10,"Weeks","Oral",">15000","ppm","No effect","No treatment-related histopathological changes were observed (interstitial chronic inflammatory cell infiltrates which is a common background finding were observed in dose and control groups)."]
[23,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[25,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect"]
[26,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[27,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[49,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[52,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[54,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat",90,"Days","Oral",">20000","ppm","No effect","An incidence of interstitial lymphoid cell infiltration in prostate was observed at 20000 ppm but considered incidental.\nGeneral toxicity was also observed in males manifested in decreased food consumption and body weights at 20000 ppm. Due to the low incidence and general systemic toxicity observed, this inflammation reaction is not considered to be treatment-related. Moreover, no effect on histopathology in rat is observed in further 90 day studies at similar doses (study IDs 52, 53) or after chronic exposure (study IDs 13, 14)."]
[55,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[62,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[67,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No treatment-related histopathological changes were observed. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No treatment-related histopathological changes were observed. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[76,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[93,"EATS-mediated","Prostate histopathology (with seminal vesicles and coagulating glands)","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Assessed for both F1 exposure groups."]
[5,"EATS-mediated","Prostate weight","Dog",90,"Days","Oral",1000,"mg/kg bw/day","Decrease","Absolute and relative organ weights were decreased at 1000 mg/kg bw/day (-68 and -56%; statistical significance only for absolute weight). The weight reduction  correlates with the observed atrophy. However, at the same dose reduced mean body weight (-28%) and lower weight gain (+4% vs +31% in controls) was observed. Moreover, clinical signs such as diarrhea were observed and one animal was sacrificed prior to study termination. \nFurthermore, chronic toxicity studies in dogs, using similar dose groups did not reveal any effects on the histopathology or weight of the prostate (study IDs 7-11). Therefore, the observed organ weight decrease is considered secondary to general toxicity at this dose level and not related to an endocrine MoA. "]
[7,"EATS-mediated","Prostate weight","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[9,"EATS-mediated","Prostate weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"EATS-mediated","Prostate weight","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[16,"EATS-mediated","Prostate weight","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[22,"EATS-mediated","Prostate weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"EATS-mediated","Prostate weight","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Prostate weight","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",30000,"ppm","Decrease","Statistically significant decrease in  absolute and relative prostate weight was observed at 30000 ppm in F1 males only (no effect in F0 males).\nThe histopathological examination of the prostate in F1 males did not reveal any effects. Moroever, signs of general toxicity such as decreased body weight gain and loose stool was observed at this dose level.  Moreover, in further two-generation studies (study IDs 22, 23, 26 ) prostate weight was not affected. Therefore, changes in prostate weight are attributed to systemic toxicity and not related to an endocrine MoA.  "]
[26,"EATS-mediated","Prostate weight","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[45,"EATS-mediated","Prostate weight","Rat","31 (PND 23-53)","Days","Oral",1000,"mg/kg bw/day","Decrease","Statistically significantly lower mean absolute ventral prostate weight (22.6%) were observed in the high dose group. \nWeight change of the ventral prostate was only observed at the high dose also inducing overt toxicity (significant body wight decrease >10% and clinical signs) and thus, was considered secondary to general toxicity not related to EAS-mediated adversity. \nMean dorsolateral prostate weight was significantly reduced with glyphosate at the mid-dose group, 300 mg/kg bw/day, compared to control. However, this change was not observed at the high or low dose groups, so in the absence of a dose-response and coupled with none of the other reproductive organ weights were altered, this isolated finding is not considered to be endocrine-mediated."]
[52,"EATS-mediated","Prostate weight","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[56,"EATS-mediated","Prostate weight","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect","Observed increased absolute (statistically not significant) and statistically significant increased relative weight at 1000 mg/kg bw/day, were considered incidental since no effect was observed in the high dose group. Moreover, no histopathological changes were observed and no effect on organ weight was observed in a chronic study in mouse (study ID 67)."]
[59,"EATS-mediated","Prostate weight","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[67,"In vivo mechanistic","Prostate weight","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Absolute organ weight was not affected."]
[80,"EATS-mediated","Prostate weight","Rat",5,"Weeks","Oral",">500","mg/kg bw/day","No effect"]
[93,"EATS-mediated","Prostate weight","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","No effect was observed on absolute and relative organ weight of both exposure groups (6 and 13 weeks; weighed together with bladder)."]
[2,"EATS-mediated","Seminal vesicles histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect",null,"Relevant effects on seminal vesicles weight were not observed in rat and mouse. In 2/8 rat studies a decrease in absolute organ weight was observed. In both cases, the effect cannot be attributed to glyphosate treatment: 1) Within the pubertal assay overt toxicity is observed at the same dose level; 2) Only relative but not absolute organ weight was significantly decreased without corresponding histopathological changes. In addition, organ weight was not decreased in further studies in rat at higher doses and longer exposure period (e.g. study ID 22, 23). Moreover, no relevant effects with regard to histopathology of seminal vesicles were observed in rabbit (1 study), rat (23 studies), and mouse (8 studies) after subchronic and chronic exposure as well as exposure over different life stages (for rat).\nNo EAS-mediated adversity was observed on seminal vesicles in three species."]
[3,"EATS-mediated","Seminal vesicles histopathology","Rat",90,"Days","Oral",">30000","ppm","No effect"]
[4,"EATS-mediated","Seminal vesicles histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[12,"EATS-mediated","Seminal vesicles histopathology","Rat",1,"Years","Oral",">20000","ppm","No effect"]
[13,"EATS-mediated","Seminal vesicles histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect"]
[14,"EATS-mediated","Seminal vesicles histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect"]
[15,"EATS-mediated","Seminal vesicles histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[17,"EATS-mediated","Seminal vesicles histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"EATS-mediated","Seminal vesicles histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic: reduced secretory content of one or both vesicles occasionally observed among all groups, increased incidences of bilateral secretory reduction in high dose males, not considered treatment-related; isolated instances of secretory distention, generalised atrophy of vesicles and atrophy or degeneration of the secretory content, age-related; peripheral and luminal inflammatory cells and abscess formation rarely observed in all groups; neoplastic: no neoplastic lesions observed.)"]
[19,"EATS-mediated","Seminal vesicles histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic findings dead/moribund animals: atrophy in 3/22, 3/20, 5/22 and 5/27 males at 0, 100, 1000 and 10000 ppm, not treatment-related.)"]
[20,"EATS-mediated","Seminal vesicles histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic findings in all groups: variations in secretory content, instances of cystic distention, focal hyperplasia of the epithelial lining of the vesicles, mononuclear cell foci, mixed inflammatory cell infiltrates, fibrous thickening, atrophy and abscess formation; neoplastic findings: adenoma of the vesicular epithelium in 2/51 control males and leiomyosarcoma in 1/51 high dose males.)"]
[21,"EATS-mediated","Seminal vesicles histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect"]
[22,"EATS-mediated","Seminal vesicles histopathology","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"EATS-mediated","Seminal vesicles histopathology","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Seminal vesicles histopathology","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[25,"EATS-mediated","Seminal vesicles histopathology","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect"]
[26,"EATS-mediated","Seminal vesicles histopathology","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[27,"EATS-mediated","Seminal vesicles histopathology","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[49,"EATS-mediated","Seminal vesicles histopathology","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[52,"EATS-mediated","Seminal vesicles histopathology","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[54,"EATS-mediated","Seminal vesicles histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"EATS-mediated","Seminal vesicles histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"EATS-mediated","Seminal vesicles histopathology","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[62,"EATS-mediated","Seminal vesicles histopathology","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[74,"EATS-mediated","Seminal vesicles histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"EATS-mediated","Seminal vesicles histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[80,"EATS-mediated","Seminal vesicles histopathology","Rat",5,"Weeks","Oral",">500","mg/kg bw/day","No effect","No statistically significant changes were observed."]
[93,"EATS-mediated","Seminal vesicles histopathology","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Seminal vesicles and coagulating gland (assessed for both F1 exposure groups)."]
[2,"EATS-mediated","Seminal vesicles weight","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[22,"EATS-mediated","Seminal vesicles weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"EATS-mediated","Seminal vesicles weight","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Seminal vesicles weight","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[45,"EATS-mediated","Seminal vesicles weight","Rat","31 (PND 23-53)","Days","Oral",1000,"mg/kg bw/day","Decrease","Statistically significantly lower mean absolute seminal vesicle (with coagulating gland and fluid 18.5% and without 16.4%) weight were observed in the 1000 mg/kg/day group also showing overt toxicity (1 mortality, rales, body weight gain decrease >10%). Body weight decreases > 10% have been shown to confound the interpretation of reproductive system-related endpoints in the pubertal assays (Fed Reg. 74(71):17570-17585). Therefore, for the 1000 mg/kg bw/day dose group, interpretation of endocrine endpoints was confounded by overt and systemic toxicity and considered not relevant for a WoE analysis for the androgen pathway as per the USEPA and EFSA guidance. In addition, no effects on reproduction were observed in one-, two- and three-generation studies."]
[53,"EATS-mediated","Seminal vesicles weight","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[80,"EATS-mediated","Seminal vesicles weight","Rat",5,"Weeks","Oral",500,"mg/kg bw/day","Decrease","A significant decrease in absolute (but not relative) weight of the seminal vesicle gland (weighed together with coagulating gland) was observed, which was reported together with non statistically significant reduced final body weight. Histopathological changes on seminal vesicles were not observed within the current study. In addition, further studies with higher and longer exposure to glyphosate (e.g. study ID 22, 23) did not result in reduction of seminal vesicles weight. Based on the rationale provided and the lacking consistent effect on organ weight, the reduction of absolute seminal vesicles weigh only, is not considered endocrine-related."]
[93,"EATS-mediated","Seminal vesicles weight","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","No effect was obsereved on absolute and relative organ weight (seminal vesicles and coagulating gland) of both exposure groups (6 and 13 weeks)."]
[94,"EATS-mediated","Seminal vesicles weight","Mouse","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Oral",">50","mg/kg bw/day","No effect","Seminal vesicles weights were determined in 35 day and 8 months old males and no statistically significant effect was observed."]
[22,"EATS-mediated","Sperm numbers","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"No relevant effect on sperm numbers was observed in rat and mouse (stud ID 94). A decrease in sperm numbers was observed in 2/6 studies. The decreased number in the subchronic study (study ID 78) is attributed to overt systemic toxicity and not associated with any decrease in testes weights. The decrease in epididymal sperm count observed in a literature study is considered incidental since no effects on testis weight and histopathology were observed in the same study. Moreover, none of the other six studies (study IDs 22 – 24, 79, 93, 94) including two-generation studies did show any effects on sperm or fertility parameters. In conclusion, no EAS-mediated adversity on sperm numbers is observed."]
[23,"EATS-mediated","Sperm numbers","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Sperm numbers","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[78,"EATS-mediated","Sperm numbers","Rat",90,"Days","Oral",25000,"ppm","Decrease","A decrease in sperm numbers was observed from 25000 ppm. At the same dose level a significant reduction of body weight gain was observed (terminal body weight M 50000 ppm= -18% compared to control). Histopathology of testes was not performed within this study but a decrease in testes weight was not observed.\nThe decreased count of sperm number is not considered to be endocrine-related but rather secondary to systemic toxicity. Furthermore, studies at similar doses did not show any effects on sperm parameters. In addition, no effects on fertility were observed in the available two-generation studies."]
[79,"EATS-mediated","Sperm numbers","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[80,"EATS-mediated","Sperm numbers","Rat",5,"Weeks","Oral",500,"mg/kg bw/day","Decrease","Total sperm count was decreased (epididymal sperm) which is considered incidental since no effects on testis weight and histopathology were observed."]
[93,"EATS-mediated","Sperm numbers","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Assessed for both F1 exposure groups."]
[94,"In vivo mechanistic","Sperm numbers","Mouse","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Oral",">50","mg/kg bw/day","No effect","Spermatozoa number was not statistically significantly affected."]
[22,"EATS-mediated","Sperm motility","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"No EAS-mediated adversity on sperm motility is observed in rat (5 studies including two 2-generation studies and mouse (1 study) after subchronic exposure."]
[23,"EATS-mediated","Sperm motility","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Sperm motility","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[78,"EATS-mediated","Sperm motility","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[79,"EATS-mediated","Sperm motility","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[93,"EATS-mediated","Sperm motility","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Sperm transit time was calculated (assessed for both F1 exposure groups)."]
[22,"EATS-mediated","Sperm morphology","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"No EAS-mediated adversity on sperm morphology is observed in rat (5 studies including 2  2-generation studies and mouse (1 study) after subchronic exposure."]
[23,"EATS-mediated","Sperm morphology","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Sperm morphology","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[78,"EATS-mediated","Sperm morphology","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[79,"EATS-mediated","Sperm morphology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[93,"EATS-mediated","Sperm morphology","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Assessed for both F1 exposure groups."]
[1,"EATS-mediated","Testis histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect",null,"Relevant effects on testis weight were not observed in dog (10 studies), rabbit (2 studies), rat (30 studies), and mouse (10 studies). In isolated studies testes weight increases were observed in rat. However, these were mostly attributed to body weight decreases.  A decrease in relative weight was observed in one published non-TG study in mouse. The isolated weight changes were neither consistent within one species over different exposure periods (no time coherence) nor in the four species investigated. Moreover, no relevant effects with regard to histopathology were observed in dog (10 studies), rabbit (2 studies), rat (32 studies), and mouse (9 studies) after subchronic and chronic exposure as well as exposure over different life stages.\nIn conclusion, EAS-mediated adversity with regard to effects on testis is not observed."]
[2,"EATS-mediated","Testis histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[3,"EATS-mediated","Testis histopathology","Rat",90,"Days","Oral",">30000","ppm","No effect"]
[4,"EATS-mediated","Testis histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"EATS-mediated","Testis histopathology","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[6,"EATS-mediated","Testis histopathology","Dog",90,"Days","Oral",">10000","ppm","No effect"]
[7,"EATS-mediated","Testis histopathology","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"EATS-mediated","Testis histopathology","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"EATS-mediated","Testis histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"EATS-mediated","Testis histopathology","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"EATS-mediated","Testis histopathology","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"EATS-mediated","Testis histopathology","Rat",1,"Years","Oral",">20000","ppm","No effect"]
[13,"EATS-mediated","Testis histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No treatment-related histopathological changes were observed. (Interim kill: no changes observed; terminal kill:  neoplastic findings, dead/moribund animals: no treatment-related findings (Leydig cell tumor in 2/31 males at 1000 ppm; seminoma in 1/31 males at 1000 ppm; neoplastic findings, surviving rats: Leydig cell tumor in 2/20 and 3/29 males at 0 and 10000 ppm)"]
[14,"EATS-mediated","Testis histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect","No treatment-related histopathological changes were observed. (Gross necropsy: no abnormalities observed; histopathology, non-neoplastic: animals at terminal kill: increased incidence of arteritis at 3000 ppm: 1/18, 7/20, 3/18 and 2/29 at 0, 3000, 10000 and 30000 ppm; neoplastic: no changes observed)\n"]
[15,"EATS-mediated","Testis histopathology","Rat",2,"Years","Oral",20000,"ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic findings: decreased incidence of tubular degeneration at 20000 ppm, not toxicologically relevant; neoplastic: no changes observed.)"]
[16,"EATS-mediated","Testis histopathology","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[17,"EATS-mediated","Testis histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"EATS-mediated","Testis histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No treatment-related histopathological changes were observed."]
[19,"EATS-mediated","Testis histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic dead/moribund animals: atrophy/degenerative changes in 9/22, 4/20, 11/22 and 9/27 males at 0, 100, 1000 and 10000 ppm, not treatment-related.)"]
[20,"EATS-mediated","Testis histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic: bilateral testicular atrophy, statistically significant in males at 5000 ppm, considered not toxicologically significant; interstitial (Leydig) cell hyperplasia in most animals, age-related; incidental findings included spermatocoel formation, focal mineralisation of tubules, focal hyperplasia of the rete tubular epithelium, cyst formation; neoplastic: no treatment-related findings (benign interstitial (Leydig) cell tumours in 2/51 control males.)"]
[21,"EATS-mediated","Testis histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect","No treatment-related histopathological changes were observed. (Gross pathology: reduced incidence of atrophy at 40000 ppm, considered incidental; histopathology, non-neoplastic and neoplastic: no treatment-related changes observed.)"]
[22,"EATS-mediated","Testis histopathology","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"EATS-mediated","Testis histopathology","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Testis histopathology","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[25,"EATS-mediated","Testis histopathology","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect","No treatment-related histopathological changes were observed. (F1 adults: Unilateral degenerative changes and giant cell formation in the seminiferous tubulus and chronic inflammation in each 1/30 F1 males at 100 and 1000 ppm, which are considered incidental findings.)"]
[26,"EATS-mediated","Testis histopathology","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[27,"EATS-mediated","Testis histopathology","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[45,"EATS-mediated","Testis histopathology","Rat","31 (PND 23-53)","Days","Oral","> 1000","mg/kg bw/day","No effect","No effect on testes histopathology was observed."]
[49,"EATS-mediated","Testis histopathology","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[52,"EATS-mediated","Testis histopathology","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"EATS-mediated","Testis histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[54,"EATS-mediated","Testis histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"EATS-mediated","Testis histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"EATS-mediated","Testis histopathology","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"EATS-mediated","Testis histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"EATS-mediated","Testis histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"EATS-mediated","Testis histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[60,"EATS-mediated","Testis histopathology","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[62,"EATS-mediated","Testis histopathology","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect","No treatment-related histopathological changes were observed.  (Traces of mild degeneration of seminiferous tubules were observed in control and treatment groups which were attributed to non-specific stress caused by treatment procedures.)\n"]
[63,"EATS-mediated","Testis histopathology","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect","No treatment-related histopathological changes were observed."]
[67,"EATS-mediated","Testis histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"EATS-mediated","Testis histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"EATS-mediated","Testis histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"EATS-mediated","Testis histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"EATS-mediated","Testis histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[74,"EATS-mediated","Testis histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F0 observed."]
[74,"EATS-mediated","Testis histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"EATS-mediated","Testis histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[75,"EATS-mediated","Testis histopathology","Rat","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Oral",">10","mg/kg bw/day","No effect"]
[76,"EATS-mediated","Testis histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[80,"EATS-mediated","Testis histopathology","Rat",5,"Weeks","Oral",500,"mg/kg bw/day","No effect","No statistically significant changes were observed. In addition, no statistically significant changes were observed in androgen receptor (AR) immunoreactivity localized in the nuclei of cells, including Sertoli cells, peritubular myoid cells and Leydig cells."]
[93,"EATS-mediated","Testis histopathology","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Assessed for both F1 exposure groups."]
[94,"EATS-mediated","Testis histopathology","Mouse","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Oral",">50","mg/kg bw/day","No effect","Number of germ and Sertoli cells as well as undifferentiated spermatogonia were determined via immunostaining. No effect was observed in the number of Sertoli cells. A decrease in spermatogonia was observed in the mid dose group (no information on statistical significance; tested in 35 day old rats). Since no dose-relationship was observed, the effect is considered biologically not relevant.\nAn increase in vacuoles in the seminiferous epithelium of the testis and empty tubules were observed in glyphosate groups compared with control. However, this was only observed in 20 day old animals and not in animals aged 35 days. Therefore, this is considered a reversible finding and not adverse."]
[1,"EATS-mediated","Testis weight","Rat",90,"Days","Oral",">20000","ppm","No effect","Reduced organ weight (not statistically significant) compared to concurrent control was observed for all treatment groups which was elicited by a high value of a single male in the control group. Therefore the effect is considered not treatment-related."]
[2,"EATS-mediated","Testis weight","Rat",90,"Days","Oral",50000,"ppm","Increase","Relative testes weight was increased in all treatment groups. This was attributed to decreased body weight at this dose level (partially reversible towards the end of the study period). The increased relative weight in the other dose groups is considered a result of low control group means. In addition, no histopathological changes were observed in this study. Changes in relative testes weight are therefore not considered relevant for EAS-mediated adversity assessment."]
[3,"EATS-mediated","Testis weight","Rat",90,"Days","Oral",">30000","ppm","No effect"]
[4,"EATS-mediated","Testis weight","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"EATS-mediated","Testis weight","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[6,"EATS-mediated","Testis weight","Dog",90,"Days","Oral",">10000","ppm","No effect"]
[7,"EATS-mediated","Testis weight","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"EATS-mediated","Testis weight","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"EATS-mediated","Testis weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"EATS-mediated","Testis weight","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"EATS-mediated","Testis weight","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"EATS-mediated","Testis weight","Rat",1,"Years","Oral",">20000","ppm","No effect"]
[13,"EATS-mediated","Testis weight","Rat",2,"Years","Oral",">10000","ppm","No effect"]
[14,"EATS-mediated","Testis weight","Rat",2,"Years","Oral",">30000","ppm","Increase","Increased relative weight was observed in males at 30000 ppm in week 26 which is considered secondary to decreased body weight. In addition general systemic toxicity such as decreased food consumtion and decreased motoractivity were observed. Moreover, no histopathological changes were observed in testes. Therefore, the decreased relative weight is not considered relevant for EAS-mediated adversity assessment."]
[15,"EATS-mediated","Testis weight","Rat",2,"Years","Oral",2000,"ppm","No effect","Absolute and relative testis weight was reduced in all treated groups at terminal kill. This decrease was not considered treatment-related as a dose-response was lacking. In addition, as no effect was seen at the interim kill (week 53) and no histopathological changes were observed. "]
[16,"EATS-mediated","Testis weight","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[17,"EATS-mediated","Testis weight","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"EATS-mediated","Testis weight","Rat",2,"Years","Oral",">15000","ppm","No effect"]
[19,"EATS-mediated","Testis weight","Mouse",18,"Months","Oral",">10000","ppm","No effect"]
[20,"EATS-mediated","Testis weight","Mouse",18,"Months","Oral",">5000","ppm","No effect"]
[21,"EATS-mediated","Testis weight","Mouse",18,"Months","Oral",">40000","ppm","No effect"]
[22,"EATS-mediated","Testis weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"EATS-mediated","Testis weight","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"EATS-mediated","Testis weight","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[26,"EATS-mediated","Testis weight","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[27,"EATS-mediated","Testis weight","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect","No effect on testes weight with epididymides was observed, except for a statistically significant increase in relative organ weight in F1a adults of the high dose group which was attributed to the observed lower terminal body weight. In addition, no histopathological changes were observed in this study for F0 and F1 males."]
[45,"EATS-mediated","Testis weight","Rat","31 (PND 23-53)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[49,"EATS-mediated","Testis weight","Rat",28,"Days","Oral",">20000","ppm","No effect","Neither absolute nor relative organ weight was affected."]
[50,"EATS-mediated","Testis weight","Rat",28,"Days","Oral",">2500","mg/kg bw/day","No effect","No effect on testes weight was observed (weighted together with epididymis)."]
[52,"EATS-mediated","Testis weight","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"EATS-mediated","Testis weight","Rat",90,"Days","Oral",">20000","ppm","No effect","Testes and epididymis were weighed together."]
[54,"EATS-mediated","Testis weight","Rat",90,"Days","Oral",">20000","ppm","No effect","No effect on absolute and relative organ weight was observed."]
[55,"EATS-mediated","Testis weight","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"EATS-mediated","Testis weight","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect","Statistically significantly increased abolute and relative organ weight at 200 and 1000 mg/kg bw/day. This finding is considered incidental since no dose-relation was established and histopathological changes were not observed."]
[57,"EATS-mediated","Testis weight","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","Non-statistically significant increase in absolute organ weight at 300 mg/kg bw/day which was attributed to one animal. No histopathological changes were observed and thus, the increase is considered not treatment-related."]
[58,"EATS-mediated","Testis weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[59,"EATS-mediated","Testis weight","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[60,"EATS-mediated","Testis weight","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[61,"EATS-mediated","Testis weight","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect","Decreased absolute organ weight at 500 mg/kg bw/day, which is  attributed to one (single) animal showing reduced and flaccid testes. Therefore, the decrease is considered not treatment-related."]
[62,"EATS-mediated","Testis weight","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[63,"EATS-mediated","Testis weight","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect","Absolute and organ weight relative to brain weight was assessed."]
[67,"EATS-mediated","Testis weight","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Testes were weighed with epididymides. Absolute organ weight was not affected."]
[68,"EATS-mediated","Testis weight","Mouse",2,"Years","Oral",30000,"ppm","Increase","At terminal sacrifice, the mean absolute and relative weights (to brain and body weight) of the testes were elevated at 30000 ppm (5342.4 mg/kg bw current limit dose would be 1000 mg/kg bw/day). (Epididymis was not weighed.) No histopathological changes were observed . Two further studies in mice using similar doses for 90 days and 2 years (study IDs 67 and 56) did not reveal any effects on testes weight. Since the effect is not reproducibel neither in mouse nor in any other species, the increased organ weight is not considered relevant for EAS-mediated adversity assessment."]
[70,"EATS-mediated","Testis weight","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring."]
[70,"EATS-mediated","Testis weight","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Mean testis weight data (absolute and relative to body weights or brain weights) were considered comparable between control and treatment groups for males of the F0, F1, and F2 generations."]
[73,"EATS-mediated","Testis weight","Mouse",90,"Days","Oral",">50000","ppm","No effect","Absolute and relative (to body and brain weight) organ weight was not affected."]
[76,"EATS-mediated","Testis weight","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[78,"EATS-mediated","Testis weight","Rat",90,"Days","Oral",25000,"ppm","Increase","An increase in relative but not absolute organ weight was observed at 25000 ppm and 50000 ppm. The increase was considered secondary to extensively decreased body weights (-18%). Histopathology was not performed within this study. However, in another subchronic toxicity study (study ID 2) , no histopathological changes were observed. Moreover, no effects on  histopathology were observed in testes after chronic exposure (study IDs 13-18). In addition, the assessment of absolute testes weight is of more relevance, since testis weight is normally conserved despite body weight loss (JRC (2016) Screening methodology to identify potential endocrine disruptors according to different options in the context of an impact assessment.). Therefore, the increase of relative testes weight is considered not relevant for EAS-mediated adversity."]
[79,"EATS-mediated","Testis weight","Mouse",90,"Days","Oral",25000,"ppm","Increase","An increase in relative but not absolute organ weight was observed at 25000 ppm and 50000 ppm. The increase was considered secondary to decreased body weights (>10%). Histopathology was not performed within this study. However, in another subchronic toxicity study (study ID 4) , no histopathological changes were observed. Moreover, no effects on  histopathology were observed in testes after chronic exposure (study IDs 19-21). In addition, the assessment of absolute testes weight is of more relevance, since testis weight is normally conserved despite body weight loss (JRC (2016) Screening methodology to identify potential endocrine disruptors according to different options in the context of an impact assessment.). Therefore, the increase of relative testes weight is considered not relevant for EAS-mediated adversity."]
[80,"EATS-mediated","Testis weight","Rat",5,"Weeks","Oral",500,"mg/kg bw/day","No effect"]
[93,"EATS-mediated","Testis weight","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","No effect was obsereved on absolute and relative organ weight of both exposure groups (6 and 13 weeks)."]
[94,"EATS-mediated","Testis weight","Mouse","Dams: Day of vaginal plug detection (embryonic day 10.5) to 20 days post-partum\nOffspring termination: PND 5, 20, 35 and 8 months old animals","Days","Oral",0.5,"mg/kg bw/day","Decrease","Relative testes weight was not affected in 20 day old males. A decrease in relative weight was observed in the low and mid dose group aged 35 days reaching statistical significance for the low dose only. In 8 months old rats a decrease in relative testes weight was observed for the low and the high dose group achieving statistical significance for the low dose only. Since no dose-response was observed and the absolute testes weight is not provided (which would be more relevant based on OECD GD 151 (2013)), the effects on testes weight are considered isolated findings. "]
[22,"EATS-mediated","Genital abnormalities","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"Genital abnormalities were not observed in rat and rabbit in prenatal developmental or 2-generation studies. In conclusion, EAS-mediated adversity inducing genital abnormalities is not observed."]
[24,"EATS-mediated","Genital abnormalities","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[64,"EATS-mediated","Genital abnormalities","Rat","10 (GD 6-15)","Days","Oral",">3500","mg/kg bw/day","No effect","No treatment-related effect on genitals was observed during sex determination, visceral examination, as well as gonadal inspection."]
[66,"EATS-mediated","Genital abnormalities","Rabbit","22 (GD 6-27)","Days","Oral",">350","mg/kg bw/day","No effect","Each fetus was first examined for external malformations and variations and subsequently dissected, internally sexed, and examined for visceral malformations and variations. No genital abnormalities were reported."]
[2,"EATS-mediated","Mammary gland histopathology (female)","Rat",90,"Days","Oral",">50000","ppm","No effect",null,"Relevant effects on mammary gland histopathology of male and female animals were not observed in dog (9 studies), rat (16 studies), and mouse (7 studies) after subchronic and chronic exposure as well as exposure over different life stages.\nIn conclusion, EAS-mediated adversity with regard to effects on mammary gland is not observed."]
[3,"EATS-mediated","Mammary gland histopathology (female)","Rat",90,"Days","Oral",">30000","ppm","No effect"]
[4,"EATS-mediated","Mammary gland histopathology (female)","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"EATS-mediated","Mammary gland histopathology (female)","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[7,"EATS-mediated","Mammary gland histopathology (female)","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"EATS-mediated","Mammary gland histopathology (female)","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"EATS-mediated","Mammary gland histopathology (female)","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"EATS-mediated","Mammary gland histopathology (female)","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"EATS-mediated","Mammary gland histopathology (female)","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"EATS-mediated","Mammary gland histopathology (female)","Rat",1,"Years","Oral",">20000","ppm","No effect"]
[13,"EATS-mediated","Mammary gland histopathology (female)","Rat",2,"Years","Oral",">10000","ppm","No effect","No treatment-related histopathological changes were observed. (Interim kill: no abnormal findings; terminal kill: ductectasia and acinectasia in 4/26, 1/24, 4/17 and 6/29 dead and moribund rats and 4/24, 2/26, 10/32 and 1/21 surviving rats of the 0, 100, 1000 and 10000 ppm group, statistically not significant, no dose-relation; main group neoplastic dead/moribund animals: adenoma in 1/23, 1/22, 3/16 and 3/28 females at 0, 100, 1000 and 10000 ppm; neoplastic surviving animals: adenoma in 1/17, 2/8, 5/17 and 2/20 females at 0, 100, 1000 and 10000 ppm; adenocarcinoma in 1/17 females at 0 ppm)"]
[14,"EATS-mediated","Mammary gland histopathology (female)","Rat",2,"Years","Oral",">30000","ppm","No effect"]
[15,"EATS-mediated","Mammary gland histopathology (female)","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[16,"EATS-mediated","Mammary gland histopathology (female)","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[17,"EATS-mediated","Mammary gland histopathology (female)","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"EATS-mediated","Mammary gland histopathology (female)","Rat",2,"Years","Oral",">15000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic: secretory glandular hyperplasia in the majority of females examined with lower incidence in high dose females; secretory distention of ducts and galactocoel formation occasionally seen, common findings in aging rats, isolated findings of keratin cyst formation and acute inflammatory cell infiltrates; neoplastic: fibroadenoma, adenoma, adenocarcinoma in 9/51, 12/51, 8/51 and 13/51 females at 0, 1500, 5000 and 15000 ppm, attributed to aging.)"]
[19,"EATS-mediated","Mammary gland histopathology (female)","Mouse",18,"Months","Oral",">10000","ppm","No effect"]
[20,"EATS-mediated","Mammary gland histopathology (female)","Mouse",18,"Months","Oral",">5000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic findings: secretory distention of ducts frequently observed, glandular hyperplasia occasionally observed, both findings in control and treatment groups are age-related)\nneoplastic findings: adenocarcinomas or adenosquamous carcinomas in 2/51, 3/51 and 1/51 females at 500, 1500 and 5000 ppm.)"]
[21,"EATS-mediated","Mammary gland histopathology (female)","Mouse",18,"Months","Oral",">40000","ppm","No effect"]
[27,"EATS-mediated","Mammary gland histopathology (female)","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[52,"EATS-mediated","Mammary gland histopathology (female)","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"EATS-mediated","Mammary gland histopathology (female)","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"EATS-mediated","Mammary gland histopathology (female)","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"EATS-mediated","Mammary gland histopathology (female)","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"EATS-mediated","Mammary gland histopathology (female)","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"EATS-mediated","Mammary gland histopathology (female)","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"EATS-mediated","Mammary gland histopathology (female)","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[67,"EATS-mediated","Mammary gland histopathology (female)","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"EATS-mediated","Mammary gland histopathology (female)","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"EATS-mediated","Mammary gland histopathology (female)","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No treatment-related histopathological changes were observed. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2), for both sexes, were indicative of common incidental histological findings."]
[70,"EATS-mediated","Mammary gland histopathology (female)","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No treatment-related histopathological changes were observed. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[76,"EATS-mediated","Mammary gland histopathology (female)","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[93,"EATS-mediated","Mammary gland histopathology (female)","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","F0"]
[93,"EATS-mediated","Mammary gland histopathology (female)","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Assessed for both F1 exposure groups."]
[2,"EATS-mediated","Mammary gland histopathology (male)","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[3,"EATS-mediated","Mammary gland histopathology (male)","Rat",90,"Days","Oral",">30000","ppm","No effect"]
[5,"EATS-mediated","Mammary gland histopathology (male)","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[7,"EATS-mediated","Mammary gland histopathology (male)","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[9,"EATS-mediated","Mammary gland histopathology (male)","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"EATS-mediated","Mammary gland histopathology (male)","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[14,"EATS-mediated","Mammary gland histopathology (male)","Rat",2,"Years","Oral",">30000","ppm","No effect"]
[16,"EATS-mediated","Mammary gland histopathology (male)","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[17,"EATS-mediated","Mammary gland histopathology (male)","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"EATS-mediated","Mammary gland histopathology (male)","Rat",2,"Years","Oral",">15000","ppm","No effect","No treatment-related histopathological changes were observed (neither non-neoplastic nor neoplastic)."]
[20,"EATS-mediated","Mammary gland histopathology (male)","Mouse",18,"Months","Oral",">5000","ppm","No effect","(Only two animals were examined.)"]
[27,"EATS-mediated","Mammary gland histopathology (male)","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[52,"EATS-mediated","Mammary gland histopathology (male)","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"EATS-mediated","Mammary gland histopathology (male)","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"EATS-mediated","Mammary gland histopathology (male)","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"EATS-mediated","Mammary gland histopathology (male)","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"EATS-mediated","Mammary gland histopathology (male)","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"EATS-mediated","Mammary gland histopathology (male)","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"EATS-mediated","Mammary gland histopathology (male)","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[67,"EATS-mediated","Mammary gland histopathology (male)","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"EATS-mediated","Mammary gland histopathology (male)","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[93,"EATS-mediated","Mammary gland histopathology (male)","Rat","F0: from GD 6 to end of lactation; Offsping: up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Assessed for both F1 exposure groups."]

{"sheet":"LoE sensitive to EATS","index":13,"n_rows":430,"n_cols":14,"rows_kept":430,"cut":false,"hidden":false,"merged":[[93,11,154,11],[332,11,343,11],[403,11,409,11],[155,11,215,11],[218,11,227,11],[344,11,369,11],[312,11,331,11],[1,11,92,11],[1,12,429,12],[1,13,429,13],[370,11,377,11],[378,11,398,11],[399,11,402,11],[279,11,299,11],[300,11,302,11],[303,11,307,11],[308,11,311,11],[216,11,217,11],[237,11,238,11],[239,11,254,11],[410,11,428,11],[228,11,236,11],[255,11,278,11]]}
["Study ID Matrix","Effect classification","Effect target","Species","Duration of exposure","Duration unit","Route of administration","Lowest Effect dose","Dose unit","Effect direction","Observed effect (positive and negative)","Assessment of each line of evidence","Assessment on the integrated line of evidence","Modality"]
[1,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect",null,"There were no effects observed on histopathology of adrenals in dogs, rabbits, rats, and mice. \nThere are 4/25 studies indicating changes in adrenal weight of rats. However, no consistent weight change is apparent and without any histopathological correlate, weight changes are considered incidental. An increase in absolute and relative organ weight was observed in male dogs in 1/10 studies (study ID 5) only after sub-chronic exposure. However, without any histopathological correlate and no effect on weight in chronic studies at similar and higher doses in dog, the weight change is considered incidental. An effect on organ weight was not observed in rabbit and mouse.\nIn conclusion, glyphosate does not induce adverse effects on adrenals.","Under consideration of all available studies in four species up to chronic exposure period, adversity based on \"parameters sensitive to, but not diagnostic of EATS\" is not observed.","N"]
[2,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[3,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",90,"Days","Oral",">30000","ppm","No effect"]
[4,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[6,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Dog",90,"Days","Oral",">10000","ppm","No effect"]
[7,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",1,"Year","Oral",">20000","ppm","No effect"]
[13,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic interim kill: no abnormal findings; non-neoplastic terminal kill: vacuolar degeneration in dead/moribund and surviving rats among all treatment and control groups, blood filled cystic spaces in dead/moribund rats and medullary cell hyperplasia in surviving rats at similar incidences, not treatment-related; Neoplastic dead/moribund animals: no treatment-related findings (cortical cell adenoma in 2/30 males at 0 ppm and in 1/17 females at 1000 ppm; pheochromocytoma in 7/30, 3/30, 4/32 and 4/21 males at 0, 100, 1000 and 10000 ppm and in 2/29 females at 10000 ppm; Neoplastic surviving rats:cortical cell adenoma in 1/20 and 1/4 males at 0 and 1000 ppm and in 2/7 and 1/21 females at 1000 and 10000 ppm; pheochromocytoma in 6/20, 2/3, 2/4 and 12/29 males and 1/24, 0/4, 4/7 and 2/21 females at 0, 100, 1000 and 10000 ppm; malignant pheochromocytoma in 1/4 and 1/29 males at 1000 and 10000 ppm)"]
[14,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect","No treatment-related histopathological changes were observed. (Gross necropsy all animals: decrease in masses in females at 30000 ppm (5/78, 3/79, 6/78 and 0/78 females at 0, 3000, 10000 and 30000 ppm; animals found dead/killed in extremis: enlarged organ in 8/35, 3/31, 1/34 and 2/36 females at 0, 3000, 10000 and 30000 ppm; histopathology, non-neoplastic: animals found dead/killed in extremis: decreased incidence of peliosis adrenalis in females at 3000 ppm: 18/35, 8/31, 13/34 and 10/36 at 0, 3000, 10000 and 30000 ppm; neoplastic: pheochromocytoma in 8/18, 4/20, 3/18 and 4/29 terminally killed males and in 14/76, 9/75, 5/80 and 10/78 in all males at 0, 3000, 10000 and 30000 ppm.)\n"]
[15,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[16,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[17,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic: foci of altered cortical cells (hypertrophic or vacuolated) were frequently observed in both sexes among all groups, haemocysts in females of all groups, no dose-relation, attributed to aging; mononuclear cell foci, focal hyperplasia of medullary and cortical cells, focal extramedullary hematopoesis, focal necrosis, complete atrophy and congestion were occasionally observed; neoplastic: tumors of adrenal gland (cortical tumors, phaeochromocytomas, ganglioneuroma) in 4/51, 1/51, 3/51 and 2/51 males and  1/51, 1/51, 0/51 and 1/51 females at 0, 1500, 5000 and 15000 ppm.)"]
[19,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic findings dead/moribund animals: subcapsular cell hyperplasia in 3/22, 8/20, 7/22 and 10/27 males and 12/16, 11/16, 13/20 and 15/20 females at 0, 100, 1000 and 10000 ppm; amyloidosis in 7/22, 9/20, 10/22 and 11/27 males and 3/16, 0/16, 1/20 and 3/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related\nhistopathology, non-neoplastic findings terminal kill animals: subcapsular cell hyperplasia in 15/28 and 13/23 males and 27/34 and 22/30 females at 0 and 10000 ppm and amyloidosis in 7/28 and 8/23 males and 1/27 and 3/30 females at 0 and 10000 ppm, not treatment-related)"]
[20,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic: focal hyperplasia of subcapsular cortical cells and focal hyperplasia of medullary cells in both sexes among all groups and focal cortical hypertrophy in males, age-related findings; focal hyperplasia of cortical cells and cortical atrophy were rarely observed; neoplastic: cortical adenoma in 3/51 and 3/51 males at 0 and 5000 ppm, cortical carcinoma in 1/51 control males.)"]
[21,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect"]
[22,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",10,"Weeks","Oral",15000,"ppm","No effect","No treatment-related, toxicologically relevant histopathological changes were observed (lower incidence of vacoulation in all F1 male treated rats, treatment relation cannot be excluded, non-adverse, abscence of a dose response suggests that the range of the controls was high and caused the effect; incidental finding: bilateral extensice necrosis of the renal cortex in the single dead F1 control female)."]
[23,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[26,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect","An enlarged organ was observed in one female at 10000 ppm found dead in week 23, which was considered an incidental finding."]
[49,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[50,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",28,"Days","Oral",">2500","mg/kg bw/day","No effect"]
[52,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","Minimal to mild cytoplasmic vacuolization of adrenal cortical cells was noted in 5/10 (50%) of the male rats included in the control group which is this considered not treatment-related."]
[54,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[63,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect","No treatment-related histopathological changes were observed. (Atrophy, congestion and focal fatty degeneration was observed in 1/5 and 1/5 males of control and high dose group, respectively and thus is considered incidental.)"]
[67,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No treatment-related histopathological changes were observed. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No treatment-related histopathological changes were observed. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect","No treatment-related histopathological changes were observed (cortical hyperplasia in 3/8 males (control), 5/10 females (control), 1/10 females (50000 ppm); vacuolation 4/10 females (control) and 3/10 females (50000 ppm))."]
[74,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No treatment-related histopathological changes were observed in F1."]
[74,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No treatment-related histopathological changes were observed in F2."]
[76,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[78,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[79,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[93,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","F0"]
[93,"Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Assessed for both F1 exposure groups."]
[1,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[2,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",90,"Days","Oral",50000,"ppm","Increase","Relative weight was increased in males at 50000 ppm (minimal effect) where also signs of general toxicity (reduced body weight gain during week 1-4, diarrhea) were observed. In the absence of histopathological findings, the relative increased organ weight is attributed to the decreased body weight. Moreover, without any histopathological correlate, the relative organ weight decrease is considered an isolated finding and thus, not relevant for assessment of potential EATS-related adversity."]
[3,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",90,"Days","Oral",">30000","ppm","No effect"]
[4,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Dog",90,"Days","Oral",300,"mg/kg bw/day","Increase","Absolute and relative weight were increased in males at 300 mg/kg bw/day (+18 and +25%) and 1000 mg/kg bw/day (+21 and +70%). Statistical significance was reached for relative weight at 1000 mg/kg bw/day only. In absence of any histopathological changes and since the weight change was not reproducible in other chronic (study IDs 9-11, 57, 58, 59) as well as subchronic (study IDs 6, 7, 8) studies at similar doses, the observed increase is considered incidental and thus, not relevant for assessment of potential EATS-related adversity."]
[6,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Dog",90,"Days","Oral",">10000","ppm","No effect"]
[7,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Dog",1,"Year","Oral",">30000","ppm","No effect","Absolute and relative organ weights were slightly increased in males at 3000 ppm which is considered to be due to a very low value within the control group and thus not treatment-related. Moreover, no dose-response was observed since no effect was observed in the high dose group."]
[12,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",1,"Year","Oral",">20000","ppm","No effect"]
[13,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",2,"Years","Oral",">10000","ppm","No effect"]
[14,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",2,"Years","Oral",">30000","ppm","No effect"]
[15,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",2,"Years","Oral",6000,"ppm","Decrease","Absolute and relative weights were decreased in females at ≥ 6000 ppm which was partly statistically significant but mainly within historical control data. Based on the fact that histopathological changes were not observed and no effects on organ weight were observed in further chronic studies in rat at similar or even higher doses (study IDs 13, 14, 16), the decreased organ weight is considered not toxicologically relevant."]
[16,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect","Absolute organ weight was decreased in interim kill males at ≥ 300 mg/kg bw/day. The effect was considered not toxicologically relevant, since organ weight at terminal kill was not affected. This is substantiated by the 1-year study (study ID 12), where no histopathological changes were observed at a similar dose (>1000 mg/kg bw/day)."]
[18,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",2,"Years","Oral",">15000","ppm","No effect"]
[19,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Mouse",18,"Months","Oral",">10000","ppm","No effect"]
[20,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Mouse",18,"Months","Oral",">5000","ppm","No effect"]
[21,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Mouse",18,"Months","Oral",">40000","ppm","No effect"]
[22,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[26,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[44,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[45,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat","31 (PND 23-53)","Days","Oral",300,"mg/kg bw/day","Decrease","Not statistically significantly lower mean absolute adrenal gland (9.2%, 8.6% for 1000 and 300 mg/kg bw/day, respectively) weight was observed. However, at the same dose, signs of general systemic toxicity such as decreased body weight gain and rales were observed. Since the relative organ weights were not affected, the non-significant decrease in absolute adrenal weights is considered to be an effect of general systemic toxicity and thus,s not considered relevant for EAS-mediated adversity."]
[49,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[50,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",28,"Days","Oral",">2500","mg/kg bw/day","No effect"]
[52,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",90,"Days","Oral",20000,"ppm","Decrease","Absolute organ weight was statistically significantly decreased in males only at 2000 and 20000 ppm but not at 6000 ppm. Since no dose-repsonse was observed, the toxicological relevance is questionable.\nRelative organ weight (to brain and body weight) was statistically significantly decreased in high dose group in males where also signs of general toxicity (diarrhea) were observed.\nSignificant organ weight changes were not obsereved in further sub-chronic studies in rat at similar doses (study IDs 1, 3, 52, 54) and no histopathological changes were observed in the current study. Therefore, the decreased organ weight was considered not relevant for EATS-related effects."]
[54,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",90,"Days","Oral",">20000","ppm","No effect","Absolute and relative organ weights were not affected."]
[56,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[58,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[59,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[61,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[62,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[63,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect","Absolute and organ weight relative to brain weight was assessed."]
[67,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Absolute organ weight was not affected."]
[68,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Mouse",2,"Years","Oral","> 30000","ppm","No effect","The mean absolute and relative (to body and brain weight) adrenal weights were not affected."]
[70,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring."]
[70,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Mean adrenal weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females from each generation (F0, F1, and F2). For the F1 generation, some statistically significant differences were noted between control and mid-dose treatment group both in mean adrenal weight data and in the relative weight data; however, no trends were evident within dose levels or through the generations and no histopathological changes were observed."]
[76,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[93,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","F0: Absolute and relative weight was unaffected."]
[93,"Sensitive to, but not diagnostic of, EATS","Adrenals weight","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","F1: No effect was obsereved on absolute and relative organ weight of both exposure groups (6 and 13 weeks)."]
[3,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat",90,"Days","Oral",">30000","ppm","No effect",null,"No toxicologically relevant effects on brain weight and histopathology were observed in four species in adult animals (dog, mouse, rabbit, rat). \nIncreased brain weights were observed in 3/17 rat studies. In 14/17 rat studies including chronic exposure period, no effect was observed. Considering this as well as the lack of any histopathological correlate, intra- and inter-species consistency (no effects were observed in dog, mouse, and rabbit), brain weight changes are considered incidental and thus, not toxicologically relevant.\nIn addition, no effects on brain were observed in two-, and three-generation studies in rat (study IDs 22, 26, 70, 74). \nIn conclusion, glyphosate does not induce adverse effects on brain."]
[13,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat",2,"Years","Oral",">10000","ppm","No effect","No treatment-related histopathological changes were observed. (Neoplastic dead/moribund animals: metastatic squamous cell carcinoma in 1/21 males at 10000 ppm; surviving rats: no treatment-related findings.)"]
[14,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat",2,"Years","Oral",">30000","ppm","No effect"]
[15,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat",2,"Years","Oral",">20000","ppm","No effect","No treatment-related histopathological changes were observed. "]
[18,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat",2,"Years","Oral",">15000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic: isolated necrotic, degenerative or inflammatory lesions occasionally observed, no toxicological significance; occasional instances of distortion of the brain and dilatation of the lateral ventricles, consequence of expansive pituitary neoplasia in either sex; neoplastic: astrocytoma, meningeal granular cell tumor, oligodendroglioma or ependymoma in 1/51, 1/51, 0/51 and 2/51 males and 2/51, 1/51, 0/51 and 0/51 females at 0, 1500, 5000 and 15000 ppm.)"]
[20,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Mouse",18,"Months","Oral",">5000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic: isolated instances of dilatation of the lateral ventricles, crystalline clefts/ granuloma formation, focal mineralisation, vacuolation of the cerebral cortex and mononuclear cell foci; extensive abscess formation with areas of necrosis in 1/51 control males; neoplastic: meningeal sarcoma in 1/51 males at 5000 ppm, oligodenroglioma in 1/51 and 1/51 control male and control female mouse.)"]
[22,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat",10,"Weeks","Oral",">15000","ppm","No effect","Gross necropsy: no treatment-related findings (pallor in the dead F0 female at 15000 ppm, pallor of the medulla at low incidences in terminal kill animals of the F1 generation)"]
[26,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect","Pale tissue overlaying cranium and congested thickening meninges in one male at 10000 ppm which was sacrificed during week 23, not treatment-related"]
[49,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[52,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[54,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[57,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[59,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","The brain was sectioned at 3 levels (cerebral cortex, mid-brain and cerebellum with medulla) for histopathological examination. No treatment-related histopathological changes were observed. "]
[63,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect"]
[67,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Mouse",2,"Years","Oral",1000,"mg/kg bw/day","No effect"]
[68,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Investigated tissues were: two longitudinal sections of the brain, optic nerves, and Pineal gland (Pineal gland only in F2). No treatment-related histopathological changes were observed. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","Tissues investigated: two longitudinal sections of the brain and optic nerves. No treatment-related histopathological changes were observed. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[74,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No treatment-related histopathological changes were observed in F1."]
[74,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No treatment-related histopathological changes were observed in F2."]
[76,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[78,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Rat",90,"Days","Oral",null,"ppm","No effect","Three sections frontal cortex and basal ganglia, parietal cortex and thalamus, cerebellum and pons were examined. No treatment-related histopathological changes were observed. "]
[79,"Sensitive to, but not diagnostic of, EATS","Brain histopathology examination","Mouse",90,"Days","Oral",null,"ppm","No effect","Three sections frontal cortex and basal ganglia, parietal cortex and thalamus, cerebellum and pons were examined. No treatment-related histopathological changes were observed. "]
[1,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[2,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat",90,"Days","Oral",10000,"ppm","Increase","Relative weight was increased in males at ≥ 10000 ppm which is considered incidental and attributed reduced body weight. Since no effect on absolute adrenal weights and no relevant histopathological changes were observed at similar doses (study ID 3), also after chronic  exposure (study ID 12-18), the increase in relative organ weight in the present study is considered not toxicologically relevant."]
[3,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat",90,"Days","Oral",30000,"ppm","Increase","Relative weight increased in females at 30000 ppm, considered to be secondary attributed to decreased body weight (no change in males)\nSince no relevant histopathological changes were observed,  the increase in relative organ weight in one sex only is considered not toxicologically relevant. This is supported by chronic toxicity studies (study ID 12-18) where no toxicologically relevant effects on brain weights were oberved."]
[4,"Sensitive to, but not diagnostic of, EATS","Brain weight","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"Sensitive to, but not diagnostic of, EATS","Brain weight","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[7,"Sensitive to, but not diagnostic of, EATS","Brain weight","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"Sensitive to, but not diagnostic of, EATS","Brain weight","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"Sensitive to, but not diagnostic of, EATS","Brain weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Absolute weight was statistically significantly reduced in males at 125 mg/kg bw/day. Since neither dose-relation (no effect in high dose) nor macroscopic/microscopic findings were observed, the effect is considered incidental."]
[10,"Sensitive to, but not diagnostic of, EATS","Brain weight","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"Sensitive to, but not diagnostic of, EATS","Brain weight","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat",1,"Year","Oral",">20000","ppm","No effect"]
[13,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat",2,"Years","Oral",">10000","ppm","No effect"]
[14,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat",2,"Years","Oral",">30000","ppm","No effect","Increased relative weight in males at 30000 ppm in week 26 is considered incidental."]
[15,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[16,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[17,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat",2,"Years","Oral",">15000","ppm","No effect"]
[20,"Sensitive to, but not diagnostic of, EATS","Brain weight","Mouse",18,"Months","Oral",">5000","ppm","No effect"]
[21,"Sensitive to, but not diagnostic of, EATS","Brain weight","Mouse",18,"Months","Oral",">40000","ppm","No effect"]
[22,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat","10 (pre-mating)","Weeks","Oral",">15000","ppm","No effect","Absolute weight was reduced in F1 males at 15000 ppm only which was considered an incidental finding."]
[22,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect","No effect was observed in offspring (F1 + F2)."]
[23,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect","Relative weight increased in F0 males at ≥ 3000 ppm, absolute weight comparable to control group, considered to be incidental (no effect in high dose group)"]
[23,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect","No effect was observed in offspring (F1 + F2)."]
[24,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",30000,"ppm","Increase","Relative brain weight was increased in F0 males at 30000 ppm. Since at this dose body weight change was decreased and absolute organ weight was not affected, the effect is not considered EATS-related but due to general systemic toxicity."]
[26,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[52,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"Sensitive to, but not diagnostic of, EATS","Brain weight","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"Sensitive to, but not diagnostic of, EATS","Brain weight","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","No effect on relative and absolute organ weight was observed."]
[58,"Sensitive to, but not diagnostic of, EATS","Brain weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Absolute brain weight was statistically significantly reduced in males at 100 mg/kg bw/day. Since neither dose-relation nor macroscopic/microscopic findings were observed, the effect is considered incidental."]
[59,"Sensitive to, but not diagnostic of, EATS","Brain weight","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[63,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect","Fresh brain weight was recorded."]
[67,"Sensitive to, but not diagnostic of, EATS","Brain weight","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Absolute organ weight was not affected."]
[68,"Sensitive to, but not diagnostic of, EATS","Brain weight","Mouse",2,"Years","Oral","> 30000","ppm","No effect","The mean absolute and relative (to body weight) brain weight were not affected."]
[70,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","Mean brain weight data (absolute and relative to body weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring."]
[70,"Sensitive to, but not diagnostic of, EATS","Brain weight","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Mean brain weight data were considered comparable between the control and treated groups for both males and females for each generation (F0, F1, and F2)."]
[73,"Sensitive to, but not diagnostic of, EATS","Brain weight","Mouse",90,"Days","Oral",">50000","ppm","No effect","Relative organ weight (relative to body weight) was increased (M 50000 ppm =+11%*) which was attributed to lower terminal body weight and thus considered not of toxicological relevance. No effects on absolute organ weight were observed. Moreover, no histopathological changes were observed."]
[1,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect",null,"No toxicologically relevant effects on pituitary weight and histopathology were observed in four species in adult animals (dog, mouse, rabbit, rat). \nDecreased pituitary weights were observed in single studies in rat (2/9) and dog (1/7) were also general systemic toxicity (decreased body weight gain) was evident. Since no histopathological correlate and no intra- and inter-species consistency was observed (no effect in mouse and rabbit), organ weight changes are considered isolated and incidental, not toxicologically relevant findings. Moreover, not effect on pituitary weight was observed in three two-generation studies (study IDs 22-24), thus showing no indication for an effect on different life stages.\nIn conclusion, glyphosate does not induce adverse effects on pituitary.\n"]
[2,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[4,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[6,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Dog",90,"Days","Oral",">10000","ppm","No effect"]
[7,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat",1,"Year","Oral",">20000","ppm","No effect"]
[13,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No treatment-related histopathological changes were observed. (Gross necropsy: interim kill: no abnormal findings; terminal kill: incidences of enlargement in 5/44, 12/46, 7/51 and 3/50 rats at gross necropsy at 0, 100, 1000 and 10000 ppm; histopathology: neoplastic dead/moribund animals: adenocarcinoma in 1/27 males at 100 ppm, adenoma in 2/29, 2/27, 3/30 and 1/20 males and in 5/25, 8/22, 3/16 and 5/29 females at 0, 100, 1000 and 10000 ppm; neoplastic surviving rats: adenocarcinoma in 1/24 females at 0 ppm; adenoma in 1/20, 2/3, 0/1 and 4/29 males and 2/24, 5/11, 4/7 and 1/21 females at 0, 100, 1000 and 10000 ppm.)"]
[14,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect","No treatment-related histopathological changes were observed. (Gross necropsy: reduced masses in males found dead/killed in extremis at 10000 ppm; histopathology, non-neoplastic: no findings; neoplastic: lower incidences of anterior adenoma in males at 10000 ppm (22/32, 21/30, 14/32 and 18/21 decedent males and 34/35, 29/31, 28/33 and 31/36 decedent females at 0, 3000, 10000 and 30000 ppm.)\n"]
[16,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[17,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic: focal hyperplasia, focal haemorrhage and cyst formation occasionally without differences in groups; neoplastic: age related adenoma and adenocarcinoma observed in both sexes without differences in groups.)"]
[19,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect"]
[20,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No treatment-related histopathological changes were observed. (Non-neoplastic: isolated incidences of focal hyperplasia, cysts or mononuclear cell foci; neoplastic: no inter-group differences.)"]
[21,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect"]
[22,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[26,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect","No treatment-related findings (1/3 infertile F1 females at 1000 ppm had cysts in pars anterior of the pituitary)."]
[27,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[49,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[52,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[54,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[67,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No treatment-related histopathological changes were observed. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No treatment-related histopathological changes were observed. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[74,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No treatment-related histopathological changes were observed in F1."]
[74,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No treatment-related histopathological changes were observed in F2."]
[76,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[2,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Rat",90,"Days","Oral",50000,"ppm","Decrease","Absolute weight was decreased in males at 50000 ppm which was attributed to the reduced body weight. Moreover mean absolute weight of females was decreased from 10000 ppm, which was attributed to the extreme high value of 1 control group animal. Since no dose-response was observed and histopathological effects were neither observed in the current study nor in further sub-chronic and chronic rat studies at similar doses, the decrease in absolute organ weight is considered toxicologically not relevant.\n"]
[5,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[7,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[9,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Dog",1,"Year","Oral",">50000","ppm","No effect","Absolute and relative weights were decreased in males at 1600 ppm which was considered incidental. This is substantiated by the fact that neither dose-relation (no effect in high dose) nor histopathological changes were observed."]
[16,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[22,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[44,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[45,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Rat","31 (PND 23-53)","Days","Oral",1000,"mg/kg bw/day","Decrease","Statistically significantly lower mean absolute pituitary weight (15.6%) was observed. However, at the same dose, signs of general systemic toxicity such as (stat.sign.) decreased body weight gain and rales were observed. Thus, decreased organ weight is not considered not toxicologically relevant."]
[52,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[56,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect","Statistically significant increased absolute weight in females only at 4500 mg/kg bw/day, considered incidental due to the variability seen in the other dose groups. Moreover, no histopathological changes were observed."]
[57,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","No effect on relative and absolute organ weight was observed."]
[58,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Dog",1,"Year","Oral",100,"mg/kg bw/day","Decrease","Absolute and relative weight were decreased in males at 100 and 500 mg/kg bw/day. No histopathological changes were observed, neither in the current study nor in two similar studies in dog (study IDs 9, 59). Therefore, the organ weight change is considered not toxicologically relevant."]
[59,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[62,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[67,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Absolute organ weight was not affected."]
[70,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring."]
[70,"Sensitive to, but not diagnostic of, EATS","Pituitary weight","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Mean pituitary weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females for each generation (F0, F1, and F2)."]
[24,"Sensitive to, but not diagnostic of, EATS","Dystocia","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect",null,"Increased incidences of dystocia were not observed in reproductive toxicity studies. \nIn conclusion, glyphosate did not induce dystocia. "]
[25,"Sensitive to, but not diagnostic of, EATS","Dystocia","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect","1/30 F0 females and 1/30 F1 females at 100 ppm died due to dystocia. However, these single findings are considered incidental, since no dose-response-relationship was observed and dystocia was not reported in further 2-generation reproduction toxicity studies (study IDs 22-27)."]
[22,"Sensitive to, but not diagnostic of, EATS","Fertility (mammals)","Rat",10,"Weeks","Oral",">15000","ppm","No effect","No treatment-related findings (the following females failed to achieve pregnancy: 1/28 F0 control, 1/28 F0 1500 ppm, 1/24 and 1/24 F1 control and F1 at 1500 ppm, 1/24 F1 at 15000 ppm, no dose relation, normal variation).","No toxicologically relevant effects on fertility have been observed in rat. \nA non-significant decrease in gestation index (F1 only) was observed in 1/7 multi-generation studies. However, this was considered an incidental finding, since no effects were observed after re-mating. Moreover, no effects on fertility parameters were observed in six further multigeneration studies. Therefore, the reduction in gestation index in the F1 generation of one study only, is considered not toxicologically relevant.\nIn conclusion, glyphosate does not induce adverse effects on fertility.\n"]
[23,"Sensitive to, but not diagnostic of, EATS","Fertility (mammals)","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect","There was no effect on pre-coital interval or the proportion of successful matings."]
[24,"Sensitive to, but not diagnostic of, EATS","Fertility (mammals)","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",30000,"ppm","Decrease","F0 males and females\nReproductive performance of F0 parental animals was not adversely affected by test substance treatment, and no significant differences were observed in such parameters as percentage of females having normal oestrous cycle, mating index, fertility index, gestation index, duration of gestation, number of implantation sites, and number, motility and morphology of epididymal sperm between the control group and the treated groups.\nF1 females\nThe gestation indices in the control, 1200, 6000 and 30000 ppm groups were 95.8 (23/24), 95.8 (23/24), 87.5 (21/24) and 79.2% (23/24), respectively, with somewhat low values in the 2 higher dose groups. However, these decreases were considered to be incidental because the differences between the control and treated groups were not statistically significant, and normal reproduction results were obtained in the F1 maternal animals, which had failed to produce offspring in this study, after remating with untreated animals (no Guideline-conform procedure).\nMoreover, no effects on sperm number and morphology have been observed for F0 and F1 males."]
[25,"Sensitive to, but not diagnostic of, EATS","Fertility (mammals)","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect","Increased male fertility index in F0 animals at 100 and 10000 ppm, no dose relation, not treatment-related, non-adverse"]
[26,"Sensitive to, but not diagnostic of, EATS","Fertility (mammals)","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[27,"Sensitive to, but not diagnostic of, EATS","Fertility (mammals)","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect","Mating rates for F0 and F1a treated dams were comparable and in some cases greater than for the control group. No adverse effect on precoital length were noted."]
[70,"Sensitive to, but not diagnostic of, EATS","Fertility (mammals)","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Over the entire study no consistent, dose-related effect was seen in mating, fertility or pregnancy indices indicating an adverse effect of treatment.\n(F0: Male and female mating indices and male fertility indices during both mating intervals of the F0 generation were considered comparable between the control and treated groups. During the second mating interval of the F0, pregnancy rates were lower than control in each of the treated groups; however, no indication of a dose-response relationship was evident as the lowest pregnancy rate was seen in the mid-dose group. This reduction in pregnancy rate for the mid-dose group was not statistically significant. In the absence of a dose-response relationship the reduction in pregnancy rate during this mating interval (F1b) in the treated groups was not considered treatment-related.\nF1: In the F1 generation, mating indices (males and females) for both litter intervals were comparable between the control and treated groups. It is note-worthy that for both mating intervals of this generation, mating indices for control and some treated groups were lower than normally encountered in multi-generation studies. The reason for the poorer mating performance in this generation is unclear but no treatment effect was indicated since mating indices were lowest in the control group. Pregnancy and male fertility indices for the first mating interval of the F1 were comparable between the control and treated groups. During the second litter interval, pregnancy rates were lower than those seen for the first interval in control and treated groups. The lowest pregnancy rate was seen, in the high-dose group; however, this difference from the control value was not statistically significant. Pregnancy rates for the low- and mid-dose groups, during the second mating interval, were considered comparable to control. Male fertility indices for this same mating interval were considered comparable between the control and treated groups.\nF2: In the F2 generation mating indices for the treated groups were lower than control for each mating interval. During the first mating interval of the F2 generation, the female mating indices were lower than control in each of the treated groups; however, only in the high-dose group was this difference from control statistically significant. The female mating index for the control group at this interval was 100%, which is higher than normally encountered. In general, the female mating indices observed for the control groups in this study have shown considerable variability ranging from 70.9 to 100%. The poor mating performance for the treated groups during the first mating interval is attributed to two males in each treatment group that did not mate either female in their mating unit (each mating unit is comprised of one male and two females). During the second mating interval of the F2 generation, male mating performance improved in the mid- and high-dose groups as both mid-dose males and one of two high-dose males that did not mate during the first mating interval, mated and impregnated at least one female. Male mating indices for the low-dose group remained unchanged as the same two males that did not mate during the first interval, failed to mate during the second interval.\nPregnancy and fertility indices for the treated groups were comparable to control for both litter intervals of the F2 generation.)"]
[74,"Sensitive to, but not diagnostic of, EATS","Fertility (mammals)","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","Pregnancy rate was not changed for F0 females."]
[74,"Sensitive to, but not diagnostic of, EATS","Fertility (mammals)","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","Pregnancy rate was not changed for F1 females."]
[74,"Sensitive to, but not diagnostic of, EATS","Fertility (mammals)","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","Pregnancy rate was not changed for F2 females."]
[22,"Sensitive to, but not diagnostic of, EATS","Gestation length","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"No effect on gestation length in rat was observed in two- and three--generation studies (study IDs 22 – 27, 70, 74) as well as in a range finding study for an EOGRTS (study ID 93).  In conclusion, no EATS-related adversity with regards togestation length is observed."]
[23,"Sensitive to, but not diagnostic of, EATS","Gestation length","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"Sensitive to, but not diagnostic of, EATS","Gestation length","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[25,"Sensitive to, but not diagnostic of, EATS","Gestation length","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect"]
[26,"Sensitive to, but not diagnostic of, EATS","Gestation length","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[27,"Sensitive to, but not diagnostic of, EATS","Gestation length","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect","Gestation length was not affected in the F0 and F1 generation, including the second mating of the F1 generation."]
[69,"Sensitive to, but not diagnostic of, EATS","Gestation length","Rat","5.5 (GD 3 till 21 days post partum)","Weeks","Oral",">30000","ppm","No effect","The pregnancy rate was good, 90%, 100%, 100% and 90% in Groups 1 to 4 respectively. (Note, treatment started at GD 3.)\nThe duration of pregnancy was similar in all groups and not adversely affected by treatment."]
[70,"Sensitive to, but not diagnostic of, EATS","Gestation length","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Mean gestation length was comparable between the control and treated groups for each pregnancy interval in each generation (F0, F1, and F2)."]
[93,"Sensitive to, but not diagnostic of, EATS","Gestation length","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Gestational length did not differ significantly between groups."]
[22,"Sensitive to, but not diagnostic of, EATS","Number of ovarian follicles","Rat",10,"Weeks","Oral",">15000","ppm","No effect","Increased number of large follicles in F1 females at 15000 ppm, in the absence of supporting data from uterine examination and any differences in the number of offspring the increase was indicative of normal biological variation, toxicologically not relevant","No EATS-related adversity was caused with regards to the number of ovarian follicles"]
[23,"Sensitive to, but not diagnostic of, EATS","Number of ovarian follicles","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[28,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rat","10 (GD 7-16)","Days","Oral",">1000","mg/kg bw/day","No effect","Neither early nor late intra-uterine deaths were observed.","No toxicologically relevant effects on embryonic and foetal viability were observed in rat and rabbit. 5/5 and 9/11 studies in rat and rabbit, respectively, showed no change. Isolated findings of abortions (2/11 studies) and late foetal deaths (1/11 studies) were observed only at doses of maternal toxicity and thus, are not considered EATS-related.\nIn conclusion no EATS-related adversity with regards to the number of embryonic or fetal deaths is observed."]
[29,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","No effect on mean number of live fetuses, fetal deaths and resorptions was observed."]
[30,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rabbit","13 (GD 6-18)","Days","Oral",">300","mg/kg bw/day","No effect","1/17 and 1/17 females at 10 and 300 mg/kg bw/day aborted and 1/17 and 1/17 females at 10 and 300 mg/kg bw/day prematurely delivered. Effects were not significant and considered incidental since abortions were isolated findings and were not observed in further prenatal toxicity studies in the rabbit (study IDs 31-34, 46, 47)."]
[31,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rabbit","13 (GD 7-19)","Days","Oral",200,"mg/kg bw/day","Increase","Slight increase in late foetal deaths at 400 mg/kg bw/day leading to an increase of total foetal deaths. This effect is attributed to one animal with nine late deaths resulting in post-implantation loss of 69.2%, which is considered not treatment-related since it is based on the effect on a single animal. An increase in early foetal deaths leading to an increase in total foetal death at 200 mg/kg bw/day, was observed but not considered treatment-related according to the study report. Moreover, maternal toxicity was observed from 200 mg/kg bw/day (reduced body weight gain) and thus, a potential effect on foetal deaths would be related to maternal toxicity rather than to EATS-related adversity."]
[32,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rabbit","13 (GD 8-20)","Days","Oral",300,"mg/kg bw/day","No effect","No effect on numer of viable fetuses, early and late intra-uterine deaths. "]
[33,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rabbit","22 (GD 6-27)","Days","Oral","> 350","mg/kg bw/day","No effect","An increase in the mean number of viable fetuses in the 75 mg/kg bw/day was considered as not toxicologically relevant."]
[34,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect","Resorptions: one dam of the high dose group showed complete resorptions;  no dose-relationship in the incidence of resorptions among the treatment groups and control group"]
[34,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect"]
[35,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rabbit","13 (GD 6-18)","Days","Oral",500,"mg/kg bw/day","Increase","Two animals of the high dose group aborted. This effect is attributed to maternal toxicity (decreased body weight gain and food consumption)."]
[46,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rabbit","13 (GD 7-19)","Days","Oral","> 450","mg/kg bw/day","No effect","No effect on abortions was observed. Number of embryonic deaths in treated groups was increased compared to concurrent control. However, this effect is not considered treatment-related since the concurrent control values were atypically low and observed incidences in treatment groups were within the  range of historic control data. Consequently viable fetuses at GD 29 and weight of fetuses were reduced in treated groups. (A total of 18, 12, 15 and 13 pregnant females (and 163, 104, 112 and 95 foetuses) in control, 50, 150, 450 mg/kg bw/d group, respectively have been included in assessment.)"]
[47,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rabbit","13 (GD 7-19)","Days","Oral","> 625","mg/kg bw/day","No effect","No effect on embryonic deaths was observed."]
[64,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rat","10 (GD 6-15)","Days","Oral",">3500","mg/kg bw/day","No effect","No treatment-related effect on embryonic losses and mean number of live fetuses."]
[65,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","The number of embryonic and fetal resorptions was similar in both control and treatment groups. The number of dams with any resorption tended to decrease in treatment group which appears to be an incidential finding. The intergroup comparison of litter data regarding \"total number of fetuses\" and \"number of abnormal, dead and live fetuses\" between control group and treatment group has not shown any statistically significant (p=0.5) difference."]
[66,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rabbit","22 (GD 6-27)","Days","Oral",">350","mg/kg bw/day","No effect","Non-viable fetuses were not present in any group and there were no biologically relevant or statistically significant differences in the mean numbers of early or late resorptions in any of the treatment groups when compared to the control group. A statistically significant, though not biologically relevant increase was noted in the mean number of viable fetuses in the 75 mg/kg/day dosage group which was considered incidental. There were no biologically relevant or statistically significant differences in the mean numbers of total implantations or corpora lutea in any of the treatment groups when compared to the control group.\nABORTIONS: Two rabbits in the control group aborted and were sacrificed, both on gestation day 22. In the 175 mg/kg/day dosage group, one rabbit aborted and was sacrificed on gestation day 27. One rabbit in the 350 mg/kg/day dosage group aborted and was sacrificed on gestation day 23. Therefore, no treatment-related increase in the incidence of abortions was noted."]
[75,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rat","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Oral",">10","mg/kg bw/day","No effect","Number of early and late in utero deaths in females sacrificed at GD 13 were not affected."]
[77,"Sensitive to, but not diagnostic of, EATS","Numbers of embryonic or foetal deaths and viable foetuses","Rabbit","22 (GD 6-27)","Days","Oral",250,"mg/kg bw/day","No effect"]
[22,"Sensitive to, but not diagnostic of, EATS","Post implantation loss","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"No toxicologically relevant effects on post-implantation loss were observed in rat (5/5) and rabbit (9/9) in reproduction and prenatal developmental toxicity (PDT) studies at non maternally toxic doses. Pre-implantation loss is reported for PDT studies, however, for potential substance-related effects only multi-generation studies are considered relevant since dosing in PDT studies starts after implantation. No effect on pre-implantation loss was observed in one two-generation study in rat.\nIn conclusion, glyphosate does not induce EATS-related pre- and post-implantation loss.\n"]
[23,"Sensitive to, but not diagnostic of, EATS","Post implantation loss","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[28,"Sensitive to, but not diagnostic of, EATS","Post implantation loss","Rat","10 (GD 7-16)","Days","Oral",">1000","mg/kg bw/day","No effect"]
[31,"Sensitive to, but not diagnostic of, EATS","Post implantation loss","Rabbit","13 (GD 7-19)","Days","Oral",400,"mg/kg bw/day","No effect","Increased at 400 mg/kg bw/day due to 1/18 females with nine late deaths (69.2%), not treatment-related since this is considered an isolated finding; increased at 200 mg/kg bw/day due to early fetal deaths, no dose relation, considered to be not treatment-related"]
[32,"Sensitive to, but not diagnostic of, EATS","Post implantation loss","Rabbit","13 (GD 8-20)","Days","Oral",">300","mg/kg bw/day","No effect"]
[33,"Sensitive to, but not diagnostic of, EATS","Post implantation loss","Rabbit","22 (GD 6-27)","Days","Oral","> 350","mg/kg bw/day","No effect"]
[34,"Sensitive to, but not diagnostic of, EATS","Post implantation loss","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect"]
[35,"Sensitive to, but not diagnostic of, EATS","Post implantation loss","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect"]
[46,"Sensitive to, but not diagnostic of, EATS","Post implantation loss","Rabbit","13 (GD 7-19)","Days","Oral","> 450","mg/kg bw/day","No effect","An increase compared to concurrent control group was observed based on the increase of embryonic deaths. However, this effect was considered not treatment-related since the concurrent control group values were very low, no dose-response was observed, and incidence was only slightly above the historic control."]
[47,"Sensitive to, but not diagnostic of, EATS","Post implantation loss","Rabbit","13 (GD 7-19)","Days","Oral","> 625","mg/kg bw/day","No effect"]
[64,"Sensitive to, but not diagnostic of, EATS","Post implantation loss","Rat","10 (GD 6-15)","Days","Oral",">3500","mg/kg bw/day","No effect","No treatment-related effect on post-implantation loss."]
[65,"Sensitive to, but not diagnostic of, EATS","Post implantation loss","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","The number of post-implantation loss was similar in both control and treatment groups."]
[66,"Sensitive to, but not diagnostic of, EATS","Post implantation loss","Rabbit","22 (GD 6-27)","Days","Oral",">350","mg/kg bw/day","No effect","There were no biologically relevant or statistically significant differences in the mean numbers of early or late resorptions in any of the treatment groups when compared to the control group."]
[77,"Sensitive to, but not diagnostic of, EATS","Post implantation loss","Rabbit","22 (GD 6-27)","Days","Oral",250,"mg/kg bw/day","Increase","A slight increase in post-implantation loss was observed in animals of the 250 mg/kg bw/d dose group. Higher doses cannot be evaluated due to excessive maternal toxicity. However, in further prenatal developmental toxicity studies in rabbit, no effect was observed (study IDs 32-35, 47, 66) and thus, the effect is not reproducible."]
[22,"Sensitive to, but not diagnostic of, EATS","Pre implantation loss","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[28,"Sensitive to, but not diagnostic of, EATS","Pre implantation loss","Rat","10 (GD 7-16)","Days","Oral",">1000","mg/kg bw/day","No effect"]
[31,"Sensitive to, but not diagnostic of, EATS","Pre implantation loss","Rabbit","13 (GD 7-19)","Days","Oral","> 400","mg/kg bw/day","No effect"]
[32,"Sensitive to, but not diagnostic of, EATS","Pre implantation loss","Rabbit","13 (GD 8-20)","Days","Oral",">300","mg/kg bw/day","No effect"]
[34,"Sensitive to, but not diagnostic of, EATS","Pre implantation loss","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect"]
[35,"Sensitive to, but not diagnostic of, EATS","Pre implantation loss","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect"]
[46,"Sensitive to, but not diagnostic of, EATS","Pre implantation loss","Rabbit","13 (GD 7-19)","Days","Oral","> 450","mg/kg bw/day","No effect","No effect on pre-implantation loss was observed. However, treatment was started after implantation."]
[47,"Sensitive to, but not diagnostic of, EATS","Pre implantation loss","Rabbit","13 (GD 7-19)","Days","Oral","> 625","mg/kg bw/day","No effect"]
[64,"Sensitive to, but not diagnostic of, EATS","Pre implantation loss","Rat","10 (GD 6-15)","Days","Oral",3500,"mg/kg bw/day","No effect","A significant increase in pre-implantation loss at 3500 mg/kg/day was observed. However, since treatment commences after implantation, this is not considered to be treatment-related."]
[65,"Sensitive to, but not diagnostic of, EATS","Pre implantation loss","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","The number of pre-implantation loss was similar in both control and treatment groups."]
[22,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rat",10,"Weeks","Oral",">15000","ppm","No effect","Macroscopical abnormalities detected were considered to be normal low incidence findings in offspring of the age and strain","Some anomalies and retarded ossification were observed in rat and rabbit. However, in most cases, this could be related to maternal toxicity. Moreover, no specific anomaly or malformation could be attributed to glyphosate treatment and thus, partially observed retarded development is attributed to general systemic toxicity not related to EATS. In conclusion, no indication for EATS-related adversity was observed based on the presence of anomalies (external, visceral, skeletal) in foetuses."]
[23,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect","Increased pelvis dilatation in F2A females at 10000 ppm (3/58, 1/59, 2/57 and 9/69 at 0, 1000, 3000 and 10000 ppm), common spontaneous change, considered to be incidental"]
[24,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",30000,"ppm","Increase","Distention of the caecum in F1 and F2 weanlings at 30000 ppm was observed."]
[25,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect","No treatment-related findings (a few incidences of minor developmental abnormalities like kinky tail, rudimentary tail in F1 pups and of kidney hydronephrosis and dilated pelvis in F1 and F2 pups, no dose- or treatment-relationship)"]
[26,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[27,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[28,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rat","10 (GD 7-16)","Days","Oral",">1000","mg/kg bw/day","No effect","The incidence of fetuses with major defects was 1/284, 1/297, 1/301 and 2/296 at 0, 250, 500 and 1000 mg/kg bw/day, type or incidence gave no evidence for a treatment-related effect. The amount of fetuses with external/visceral variants and with skeletal variants were lower in the test item treated groups than in the controls."]
[29,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","External malformations: no treatment-related findings (short tail in 1/361 fetus at 30 mg/kg bw/day, microphthalmia in 1/339 fetus at 1000 mg/kg bw/day)\nVisceral malformations: no treatment-related findings (right aortic arch in 1/173 fetus at 300 mg/kg bw/day, ventricular septical defects in 1/173 and in 1/164 fetuses each at 300 and 1000 mg/kg bw/day, considered to be incidental due to the low incidence; malformations such as thymic remnant in the neck, dilatation of the renal pelvis and left umbilical artery among all groups: 21/150, 28/174, 28/173 and 19/164 fetuses at 0, 30, 300 and 1000 mg/kg bw/day, not treatment-related)\nSkeletal malformations: no treatment-related findings (splitting of the ossification centers of the thoracic vertebral bodies in 2/164, 1/185 and 2/175 fetuses at 0, 300 and 1000 mg/kg bw/day; asymmetry of the sternebrae with sterno-costal joint displacement in 1/185 fetuses at 300 mg/kg bw/day, fusion of the sternebrae in 1/175 fetuses at 1000 mg/kg bw/day; malformations such as cervical ribs shortening, lumber ribs, sacralisation of the lumbar vertebra were observed in all groups: 9/164, 6/187, 11/185 and 14/175 fetuses at 0, 30, 300 and 1000 mg/kg bw/day)"]
[30,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rabbit","13 (GD 6-18)","Days","Oral",">300","mg/kg bw/day","No effect","High incidence of maternal rabbits with fetuses with any malformation at 300 mg/kg bw/day, malformations were of inconsistent type and comprised external, visceral and skeletal malformations in single animals, considered to be sporadic"]
[31,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rabbit","13 (GD 7-19)","Days","Oral","> 400","mg/kg bw/day","No effect","No treatment-related findings. Incidences of external and visceral malformations observed in single animals, no dose relation. Incidences of skeletal malformations of different types were higher but comparable between treatment and control animals and therefore not attributed to treatment."]
[32,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rabbit","13 (GD 8-20)","Days","Oral",">300","mg/kg bw/day","No effect","Only very minor changes in ossification were observed in the 300 mg/kg bw/day group but not considered treatment-related but due to lower bodyweight of the foetuses"]
[33,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rabbit","22 (GD 6-27)","Days","Oral","> 350","mg/kg bw/day","No effect","Malformations were noted only in treatment groups but not considered to be treatment-related due to a lack of a dose-related pattern and because the frequency did not exceed the historical control data."]
[34,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rabbit","13 (GD 6-18)","Days","Oral",20,"mg/kg bw/day","Increase","A significant increase in dilated heart was observed in all treatment groups while other incidences of visceral malformations were not considered treatment-related; no treatment and dose-related significant major skeletal malformations; no significant or dose-relationship of the incidences of external malformations"]
[35,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rabbit","13 (GD 6-18)","Days","Oral",500,"mg/kg bw/day","Increase","In the high dose group, the incidences of external, visceral and skeletal malformations were higher than that in the control group. With regard to the heart malformations, 0, 1, 1, and 2 interventricular septal defects were observed in the 0, 125, 250, and 500 mg/kg bw/day dose groups. A similar pattern was seen in the variations observed externally, viscerally and skeletally; in the high dose group, the total number of observed variations was higher than those of the control, low or mid dose groups. The increase in malformations and variations observed in the high dose group occurred in the presence of maternal toxicity (reduced food consumption and body weight gains). Further, this was at a dose (500 mg/kg bw/day) that caused significant toxicity, including mortality, in another rabbit developmental study (study ID 34).\n"]
[46,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rabbit","13 (GD 7-19)","Days","Oral","> 450","mg/kg bw/day","No effect","Increases in fetuses with heart malformations (from 150 mg/kg bw/d) were not considered treatment-related when compared to historic control data of 13 studies performed the same year. Group mean incidences of anomalies and malformations showed no significant differences compared to the control group."]
[47,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rabbit","13 (GD 7-19)","Days","Oral","> 625","mg/kg bw/day","No effect"]
[64,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rat","10 (GD 6-15)","Days","Oral",3500,"mg/kg bw/day","Increase","Skeletal change: The incidence of rib distortion (wavy ribs) was markedly increased at 3500 mg/kg bw/day. The marginally higher incidence at 1000 mg/kg bw/day was of uncertain relationship to treatment.\nNo increase in incidence of malformed foetuses was observed (a total of 1, 2, 1 and 3 foetuses in control to high dose groups, respectively were malformed). Increased incidence of reduced ossification was observed in all treated groups compared to the concurrent control. However, compared to historical control data, the incidence of these skeletal changes at 3500 mg/kg bw/day was only slightly outside the range. Since no clear dosage-response was apparent, reduced ossification was not considered treatment-related.\nThe incidence of foetuses with visceral anomalies was low and did not indicate any adverse treatment-related effects. Moreover, reduced maternal body weight change was observed in the high dose group, which could lead to retarded development of fetuses."]
[65,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rat","10 (GD 6-15)","Days","Oral",1000,"mg/kg bw/day","Increase","The intergroup comparison of litter data regarding \"number of abnormal, dead and live fetuses\" between control group and treatment group has not shown any statistically significant (p=0.5) difference. \nEXTERNAL MALFORMATIONS: No incidence of major external malformations was seen in either of the study groups. VISCERAL MALFORMATION: There was no incidence of major visceral malformations. SKELETAL MALFORMATIONS:  Incidence of minor and major skeletal malformations, did not show any statistically significant intergroup difference. \ndelayed ossification: The incidence of delayed ossification of caudal vertebral arch, forelimb-proximal phalange and hindlimb-distal phalange was significantly higher in the treatment group than in control. The incidence of incomplete to partial ossification of parietal and interparietal of the skull was less in the treatment group."]
[66,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rabbit","22 (GD 6-27)","Days","Oral",">350","mg/kg bw/day","No effect","All fetuses were individually weighed and examined for external malformations and variations, including the palate and eyes. Each fetus was dissected, internally sexed and examined for visceral malformations and variations, including the brain by a mid-coronal slice. There were no statistically significant or biologically meaningful differences in the number of litters with malformations in any of the treatment groups when compared to the control group. Malformations were noted only in the treatment groups, however, this was not considered to be treatment-related as they did not occur in a dose-related pattern, were not similar in nature and the frequency did not exceed that of the historical control."]
[70,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Gross postmortem examinations of the F0, F1 and F2 adults at terminal sacrifice (males and females) did not indicate an adverse effect of treatment."]
[70,"Sensitive to, but not diagnostic of, EATS","Presence of anomalies (external, visceral, skeletal","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Gross postmortem observations of offspring at weaning (F1a, F2a, F3a, F3b) on post-weaning (F1b, F2b) did not reveal an adverse effect of treatment. Likewise, evaluation of dead pups recovered at birth and during the 21-day lactation period did not reveal a treatment-related effect."]
[22,"Sensitive to, but not diagnostic of, EATS","Reproduction","Rat",10,"Weeks","Oral",">15000","ppm","No effect","From the F0 generation, 26/28, 27/28, 27/28 and 26/28 females and from the F1 generation 22/24, 23/24, 24/24 and 23/24 females successfully gave birth at 0, 1500, 5000 and 15000 ppm","No EATS-related adversity on reproduction was observed in rats"]
[25,"Sensitive to, but not diagnostic of, EATS","Reproduction","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect"]
[26,"Sensitive to, but not diagnostic of, EATS","Reproduction","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect","In F1 generation, the pregnancy rate in all groups (including control) was less than expected  (mate 1: 83%, 75%, 58% and 79%, mate 2: 67%, 78%, 67% and 74% at 0, 1000, 3000 and 10000 ppm, no dose relationship)."]
[22,"Sensitive to, but not diagnostic of, EATS","Time to mating","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"No EATS-related adversity on time to mating was observed in rats."]
[23,"Sensitive to, but not diagnostic of, EATS","Time to mating","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[25,"Sensitive to, but not diagnostic of, EATS","Time to mating","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect"]
[26,"Sensitive to, but not diagnostic of, EATS","Time to mating","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[27,"Sensitive to, but not diagnostic of, EATS","Time to mating","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[28,"Sensitive to, but not diagnostic of, EATS","Fetal development","Rat","10 (GD 7-16)","Days","Oral",">1000","mg/kg bw/day","No effect",null,"No EATS-related adversity on fetal development was observed in rats"]
[30,"Sensitive to, but not diagnostic of, EATS","Fetal development","Rabbit","13 (GD 6-18)","Days","Oral",">300","mg/kg bw/day","No effect"]
[31,"Sensitive to, but not diagnostic of, EATS","Fetal development","Rabbit","13 (GD 7-19)","Days","Oral","> 400","mg/kg bw/day","No effect"]
[75,"Sensitive to, but not diagnostic of, EATS","Fetal development","Rat","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Oral",">10","mg/kg bw/day","No effect","Growth rate of pups was not affected."]
[22,"Sensitive to, but not diagnostic of, EATS","Litter size","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"Overall, no effects on litter size were observed in rabbit (4/4 studies) and rat (13/15 studies). \nSlightly reduced litter size (not statistically significant) in F1 pups and F2a pups at 30000 ppm but not in F2b pups (re-mating of F1) was observed in 1/6 two-generation studies. Thus, treatment-relation was considered equivocal within the study. However, since body weights were reduced in parental animals (F0) which might affect the litter size and since no effects were observed in 5/6 two-generation studies (study IDs 22-26) and thus intra-species consistency is lacking, this effect was considered secondary to parental toxicity.\nIn conclusion, no EATS-related adversity on litter size was observed in rats and rabbits.\n"]
[23,"Sensitive to, but not diagnostic of, EATS","Litter size","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"Sensitive to, but not diagnostic of, EATS","Litter size","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[25,"Sensitive to, but not diagnostic of, EATS","Litter size","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect","Mean number of F1 and F2 pups delivered and mean litter sizes in the 100, 1000 and 10000 ppm groups were comparable to the controls."]
[26,"Sensitive to, but not diagnostic of, EATS","Litter size","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect","Reduced at 10000 ppm (consistently but not significant) across all four matings and remained lower at day 4 in 3/4 matings, not conclusively attributable to treatment as the mean litter size at birth whithin each mating was not always the lowest litter size recorded"]
[27,"Sensitive to, but not diagnostic of, EATS","Litter size","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",30000,"ppm","Decrease","Slightly reduced (not statistically significant) in F1 pups and F2a pups at 30000 ppm, not reproduced in F2b pups (re-mating of F1), treatment relation equivocal. Body weights were reduced in parental animals (F0) which might affect the litter size. As findings of litter size in F2a and F2b animals were inconsistent, this effect was considered secondary to parental toxicity. In addition, the reduced litter size was not reproduced in the most recent two-generation studies (study IDs 22, 23) and not toxicologically relevantly affected in older two-generation studies (study IDs 24-26) and thus not consistent."]
[31,"Sensitive to, but not diagnostic of, EATS","Litter size","Rabbit","13 (GD 7-19)","Days","Oral",">400","mg/kg bw/day","No effect"]
[34,"Sensitive to, but not diagnostic of, EATS","Litter size","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect"]
[35,"Sensitive to, but not diagnostic of, EATS","Litter size","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect"]
[47,"Sensitive to, but not diagnostic of, EATS","Litter size","Rabbit","13 (GD 7-19)","Days","Oral","> 625","mg/kg bw/day","No effect"]
[64,"Sensitive to, but not diagnostic of, EATS","Litter size","Rat","10 (GD 6-15)","Days","Oral",">3500","mg/kg bw/day","No effect","A total of 23, 23, 25 and 22 females had live young at Day 20 in control to high dose groups respectively. No treatment related effect on litter size."]
[65,"Sensitive to, but not diagnostic of, EATS","Litter size","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","The intergroup comparison of litter data regarding \"litter size\" between control group and treatment group has not shown any statistically significant (p=0.5) difference."]
[69,"Sensitive to, but not diagnostic of, EATS","Litter size","Rat","5.5 (GD 3 till 21 days post partum)","Weeks","Oral",">30000","ppm","No effect","The implantation rates in all treated groups were higher than the controls. Since pup losses, both pre-birth and from birth to weaning, were generally similar among the groups, litter size of all treated groups was, as a consequence, generally greater than controls throughout weaning. These findings are not, however, considered to be an adverse effect of treatment. "]
[70,"Sensitive to, but not diagnostic of, EATS","Litter size","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","The mean numbers of live, dead and total pups at birth and pup viability at birth for each pregnancy interval were comparable between the control and treated groups for each generation (F0, F1, and F2). Likewise, mean litter size data on day 21 of lactation (weaning) was comparable between the control and treated groups for each litter interval throughout the study for each generation (F0, F1, and F2)."]
[74,"Sensitive to, but not diagnostic of, EATS","Litter size","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effect observed in F1 offspring."]
[74,"Sensitive to, but not diagnostic of, EATS","Litter size","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effect observed in F2 offspring."]
[74,"Sensitive to, but not diagnostic of, EATS","Litter size","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effect observed in F3 offspring."]
[75,"Sensitive to, but not diagnostic of, EATS","Litter size","Rat","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Oral",">10","mg/kg bw/day","No effect"]
[93,"Sensitive to, but not diagnostic of, EATS","Litter size","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Mean litter size (incuding dead and alive pups determined on PND 0, 1, 4, 7, 10, 13, 16, 19, 21, 25) did not differ significantly between groups."]
[95,"Sensitive to, but not diagnostic of, EATS","Litter size","Mouse","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Oral",5000,"mg/L water","No effect","Number of fetuses was not statistically significantly affected."]
[22,"Sensitive to, but not diagnostic of, EATS","Litter viability","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"No EATS-related adversity on litter viability was observed in rats (10/10 studies)."]
[23,"Sensitive to, but not diagnostic of, EATS","Litter viability","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect","Slightly increased in F1 and F2 pups of all treated groups (16/23, 15/22, 19/22 and 18/24 in F0 and 16/22, 17/23, 20/21 and 21/25 in F2 litters with all pups born at 0, 1000, 3000 and 10000 ppm), not treatment-related"]
[24,"Sensitive to, but not diagnostic of, EATS","Litter viability","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect","The viability indices of F1 and F2 pups in the 1200, 6000 and 30000 ppm groups were comparable to the controls."]
[25,"Sensitive to, but not diagnostic of, EATS","Litter viability","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect","The number of live pups on day 1 was reduced in F1 pups at 100 ppm, reduced in F2 pups at 1000 ppm and increased in F2 pups at 10000 ppm, not treatment-related"]
[26,"Sensitive to, but not diagnostic of, EATS","Litter viability","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect","Total litter loss was 2, 3, 1 and 1 at 0, 1000, 3000 and 10000 ppm."]
[27,"Sensitive to, but not diagnostic of, EATS","Litter viability","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[69,"Sensitive to, but not diagnostic of, EATS","Litter viability","Rat","only secondary exposure through milk from PND 0-21","Weeks","Oral",">30000","ppm","No effect","Pup losses, both pre-birth and from birth to weaning, were generally similar among the groups."]
[70,"Sensitive to, but not diagnostic of, EATS","Litter viability","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Mean litter size data on day 21 of lactation (weaning) was comparable between the control and treated groups for each litter interval throughout the study for each generation (F0, F1, and F2).\nThe indices of litters weaned were comparable between the control and treated groups for each lactation interval in the F0, F1, and F2 generation."]
[74,"Sensitive to, but not diagnostic of, EATS","Litter viability","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effect observed in F1 offspring."]
[74,"Sensitive to, but not diagnostic of, EATS","Litter viability","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effect observed in F2 offspring."]
[74,"Sensitive to, but not diagnostic of, EATS","Litter viability","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effect observed in F3 offspring."]
[93,"Sensitive to, but not diagnostic of, EATS","Litter viability","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Live birth index was calculated on PND 0. The mean live birth index was comparable between groups, although the number of dams with stillbirths was higher in the glyphosate (4/8) group compared to control (2/8)."]
[22,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"Litter/pup weight was investigated in 17 rat, one mouse and 9 rabbit studies. Decreased litter/pup weight was observed in 5/17 rat and 2/9 rabbit studies. However, maternal toxicity, manifested in clinical signs and/or decreased body weights, was accompanying the decreased litter/pup weight and thus, the effect was considered secondary to maternal toxicity.\nTherefore, no EATS-related adversity is observed with regard to litter/pup weight."]
[23,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat","10 (pre-mating)","Weeks","Oral",10000,"ppm","Decrease","Decreased in F1 pups of the 10000 ppm group from day 8 to day 29 in males and from day 5 to day 29 in females. Other litter parameters such as litter size and litter viability were not affected by treatment. F2 pup weights were not affected. In addition, this effect was not reproduced in the most recent two-generation study (study ID 22) at a higher dose. Therefore, the observed decrease is considered not consistent and EATS-related."]
[24,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",30000,"ppm","Decrease","F1 pups of both sexes in the 30000 ppm group, showed significantly higher mean body weights on lactation day 0 than the controls. However, mean body weights on days 14 and 21 were significantly decreased when compared controls.\nIn F2 pups in the 30000 ppm group, mean body weights of both sexes on day 21 of lactation were significantly lower than those in the control group.\nParental toxicity was observed at the high dose (> 2000 mg/kg bw/day) as well and consisted of loose stool (F0/F1, m/f), reduced body weight (F0/F1, m) caecum distension (F0/F1, m/f), increased liver and kidney weights (F0/F1, m/f).\nTherefore, decreased pup weight is considered a secondary effect due to systemic toxicity."]
[25,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect","No treatment-related findings (F1 pups: increased litter weight of combined sex and female pups on days 1 and 4, decreased litter weight of combined sex and males at 100 ppm on day 7, increased litter weight of combined sex and males at 10000 ppm on day 7, increased in complete litter and individual sex on day 21 at 1000 ppm, no dose-relation; F2 pups: increased litter weight of combined sex and female pups on days 1 and 4, increased combined sex litter weight at 100 and 1000 ppm and of males and females at 1000 ppm on day 4, decreased in males at 10000 ppm on days 14 and 21, no dose-relation)"]
[26,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect","No treatment-related findings (litter weights were reduced in all treated groups first mating F0 generation from Day 16 post-partum with mean pup weights being lower from Day 8 post-partum, no dose-response, no findings in the 2nd mating of the F0 generation or in both matings of the F1 generation, considered unlikely to be  treatment-related)"]
[27,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",30000,"ppm","Decrease","Reduced (> -10%) by lactation Day 21 at 30000 ppm in F1. In F2 pups the effect appeared to occur earlier (Day 14 of lactctaion), consumption of prepared diet was considered responsible for bw effect. (Not treatment-related: slightly reduced at weaning in the 10000 ppm group, transient, not consistent for both sexes in all generations, toxicological relevance questionable)\nBody weight loss correlated with body weight loss of parental animals at the same dose group. Furthermore, clinical signs were evident in the same animals. Based on this, the effect on litter weight was considered to be secondary to systemic toxicity. "]
[28,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat","10 (GD 7-16)","Days","Oral",">1000","mg/kg bw/day","No effect","Mean litter as well as foetal weight were not affected."]
[29,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect"]
[30,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rabbit","13 (GD 6-18)","Days","Oral",">300","mg/kg bw/day","No effect"]
[31,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rabbit","13 (GD 7-19)","Days","Oral","> 400","mg/kg bw/day","No effect"]
[32,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rabbit","13 (GD 8-20)","Days","Oral",300,"mg/kg bw/day","Decrease","Mean fetal weight was reduced, which was attributed to 2 litters with particularly low fetal weight. Body weights of maternal animals were reduced at the same dose (from 175 mg/kg bw/day) group and below. Futhermore, clinical signs such as diarrhea occurred in maternal animals during the study. Therefore, litter weight decrease was considered to be secondary to systemic toxicity."]
[33,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rabbit","22 (GD 6-27)","Days","Oral","> 350","mg/kg bw/day","No effect","A slight decrease in mean fetal body weight was observed in all treatment groups which was comparable to historical control data."]
[34,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rabbit","13 (GD 6-18)","Days","Oral",20,"mg/kg bw/day","Increase","Litter weight was statistically significant higher in the low and mid dose group, but not in the high dose group. As there was no dose-response and clinical signs occurred in maternal animals, this effect was considered to be secondary to systemic toxicity. In addition, this effect was not reproducible in further pre-natal developmental studies."]
[35,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect","Fetal body weight per litter was not affected."]
[46,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rabbit","13 (GD 7-19)","Days","Oral","> 450","mg/kg bw/day","No effect","Litter weight was similarly reduced at all dose-levels, reflecting the differences in the litter size. However, no change on mean fetal weight was observed."]
[47,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rabbit","13 (GD 7-19)","Days","Oral","> 625","mg/kg bw/day","No effect"]
[64,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat","10 (GD 6-15)","Days","Oral",3500,"mg/kg bw/day","Decrease","At 3500 mg/kg, both litter and mean fetal weights were reduced compared to control (statistically significant for mean fetal weight). Maternal body weight was significantly reduced during the first days of gestation but returned to normal levels thereafter. This might have affected fetal weights and therefore, fetal weight reduction is considered to be secondary to systemic toxicity."]
[65,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","The intergroup comparison of litter data regarding \"mean fetal weight\" (combined sex and sex wise) between control group and treatment group has not shown any statistically significant (p=0.5) difference."]
[66,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rabbit","22 (GD 6-27)","Days","Oral",">350","mg/kg bw/day","No effect","There were no biologically relevant or statistically significant differences in mean fetal body weight in any of the treatment groups when compared to the control group. A slight decrease was noted in mean fetal body weight in all treated groups when compared to the control group, however, the parameter was comparable to the historical control."]
[69,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat","only secondary exposure through milk from PND 0-21","Weeks","Oral",30000,"ppm","Decrease","At birth, (total) litter weight of all treatment groups was increased compared to control - this is due to the increased litter sizes seen in the treatment groups.\nAt 30000 ppm litter weight converged towards control values to Day 8; thereafter litter weight became reduced and by Day 21 (78% of the concurrent control value). Mean pup weight was reduced at birth through to Day 21 (62% of the controls).\nAt 3000 and 10000 ppm litter weight through to weaning was comparable with the controls even though litter size was increased. As a consequence mean pup weight diverged below control values to an extent that on Day 21 post partum mean pup weight at 3000 and 10000 ppm was 91% and 87% lower than the corresponding control value. These differences, however, can probably be attributed to the pivotal association between litter size, litter weight and mean pup weight and, at this stage, no conclusive treatment-related effects can be established.\nIn all dose groups litter sizes were increased and consequently mean pup weight was decreased. In addition, maternal toxicity was observed during gestation manifested in reduced body weights at 30000 ppm. Further, systemic toxicity in maternal animals was observed such as soft stool also at the highest dose group. \nTaken together, the reduced pup weight is considered to be secondary to maternal toxicity and the increased litter size and not directly related to the treatment.\n"]
[70,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Mean pup body weight data during each litter interval for each generation (F1, F2, and F3) were considered comparable between the control and treated groups. No adverse effects of treatment on pup weight data was evident. Accordingly, no treatment-related effect was evident in terminal body weight data for the F3b offspring."]
[74,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effect observed in F1 offspring."]
[74,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effect observed in F2 offspring."]
[74,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effect observed in F3 offspring."]
[75,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Rat","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Oral",">10","mg/kg bw/day","No effect","Group mean pup weight was not affected."]
[95,"Sensitive to, but not diagnostic of, EATS","Litter/pup weight","Mouse","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Oral",5000,"mg/L water","No effect","Group mean body weight of pups by sex showed no statistical differences from control. There was no effect on average birth weight of pups, the slight difference observed in the glyphosate-treated group should be attributed to the slightly larger mean litter size observed (14.4 pups compared to 10.8 in the control group)."]
[22,"Sensitive to, but not diagnostic of, EATS","Number of live births","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"The number of live births was not affected by glyphosate. Consequently, no EATS-related adversity was observed."]
[23,"Sensitive to, but not diagnostic of, EATS","Number of live births","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect","Slightly higher in F1 and F2 pups in the test item treated groups, not treatment-related"]
[24,"Sensitive to, but not diagnostic of, EATS","Number of live births","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[25,"Sensitive to, but not diagnostic of, EATS","Number of live births","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect","Live-birth index increased in F1 pups at 1000 ppm, not treatment-related"]
[26,"Sensitive to, but not diagnostic of, EATS","Number of live births","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[27,"Sensitive to, but not diagnostic of, EATS","Number of live births","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[70,"Sensitive to, but not diagnostic of, EATS","Number of live births","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","The mean numbers of live, dead and toal pups at birth for each pregnancy interval were comparable between the control and treated groups for each generation (F0, F1, and F2)."]
[75,"Sensitive to, but not diagnostic of, EATS","Number of live births","Rat","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Oral",">10","mg/kg bw/day","No effect"]
[22,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"The number of implantations and corpora lutea was not affected by glyphosate. Consequently, no EATS-related adversity was observed."]
[23,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect","Increased in F1 females at 1200 ppm, not treatment-related, no dose relation"]
[25,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect","Decreased no of implantations in F2 dams at 100 and 1000 ppm, considered to be incidental"]
[26,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect","No treatment-related effect was observed on number of corpora lutea."]
[28,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rat","10 (GD 7-16)","Days","Oral",">1000","mg/kg bw/day","No effect","Neither number of implantations nor corpora lutea was affected."]
[29,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect"]
[30,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rabbit","13 (GD 6-18)","Days","Oral",">300","mg/kg bw/day","No effect"]
[31,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rabbit","13 (GD 7-19)","Days","Oral","> 400","mg/kg bw/day","No effect"]
[32,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rabbit","13 (GD 8-20)","Days","Oral",">300","mg/kg bw/day","No effect"]
[33,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rabbit","22 (GD 6-27)","Days","Oral","> 350","mg/kg bw/day","No effect"]
[34,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect"]
[35,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect","No effect on corpora lutea was observed. Low number of viable implants and increase in non-viable implants in high dose group (not statistically significant). "]
[46,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rabbit","13 (GD 7-19)","Days","Oral","> 450","mg/kg bw/day","No effect","No effect on corpora lutea or implantation rate were observed (established parameters prior to treatment). "]
[47,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rabbit","13 (GD 7-19)","Days","Oral","> 625","mg/kg bw/day","No effect","There were no treatment-related effects on corpora lutea count, implantation rate (all established prior to treatment)."]
[64,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rat","10 (GD 6-15)","Days","Oral",">3500","mg/kg bw/day","No effect","No treatment-related effect on pre-treatment events (implantation rate, corpora lutea)."]
[65,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","The number of corpora lutea and implantations were similar in both control and treatment groups."]
[66,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rabbit","22 (GD 6-27)","Days","Oral",">350","mg/kg bw/day","No effect","There were no biologically meaningful or statistically significant differences in the mean numbers of total implantations or corpora lutea in any of the treatment groups when compared to the control group."]
[69,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rat","5.5 (GD 3 till 21 days post partum)","Weeks","Oral",">30000","ppm","No effect","The implantation rates in all treated groups were higher than the controls. Since pup losses, both pre-birth and from birth to weaning, were generally similar among the groups, litter size of all treated groups was, as a consequence, generally greater than controls throughout weaning. These findings are not, however, considered to be an adverse effect of treatment. "]
[75,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rat","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Oral",">10","mg/kg bw/day","No effect","Number of corpora lutea and total implants in females killed at GD 13 were not affected."]
[77,"Sensitive to, but not diagnostic of, EATS","Number of implantations, corpora lutea","Rabbit","22 (GD 6-27)","Days","Oral",">250","mg/kg bw/day","No effect","No significant effect on number of implantations or corpora lutea was obsereved in animals up to 250 mg/kg bw/d. Higher doses cannot be evaluated due to excessive maternal toxicity."]
[22,"Sensitive to, but not diagnostic of, EATS","Pup development","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"No EATS-related adversity was observed on pup development in rat."]
[25,"Sensitive to, but not diagnostic of, EATS","Pup development","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",1000,"ppm","No effect","No treatment and dose related consistent effects on number of pups born (combined and individual sex) and their growth were observed."]
[26,"Sensitive to, but not diagnostic of, EATS","Pup development","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[27,"Sensitive to, but not diagnostic of, EATS","Pup development","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[24,"Sensitive to, but not diagnostic of, EATS","Pup survival index","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect",null,"No EATS-related adversity was observed on pup survival in rat in 7/7 studies."]
[25,"Sensitive to, but not diagnostic of, EATS","Pup survival index","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect","No treatment-related findings (F1 pups: decreased survival at 100 ppm on days 4, 14 and 21, decreased at 1000 ppm on day 4 and increased at 1000 ppm on day 14, increased at 10000 ppm on days 14 and 21; F2 pups: no significant intergroup differences)"]
[26,"Sensitive to, but not diagnostic of, EATS","Pup survival index","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[27,"Sensitive to, but not diagnostic of, EATS","Pup survival index","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[70,"Sensitive to, but not diagnostic of, EATS","Pup survival index","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No treatment-related adverse effect on pup survival index was observed. \n(In the F0 generation, postnatal survival indices for Days 0-4 and 4-21 were comparable between the control and treated groups for the first lactation interval (F1a). For the second litter interval of the F0 (F1b), postnatal survival indices for the Day 0-4 interval were comparable between the control and treated groups. During the day 4-21 interval, survival indices were significantlv lower than control in each treatment group. The increase in pup mortality during this interval (i.e. days 4-21) was attributed to high pup mortality within one or more litters at each treatment level. In the low-dose group the lower pup survival was attributed to one female that experienced complete litter mortality (litter contained 14 live pups at day 4). In the mid-dose group, one female died on Day 7 of lactation and all seven pups in her litter died during the Day 4-7 lactation interval. Additionally, three mid-dose litters lost five or more pups from their litters during Day 4-21 lactation interval. In the high-dose group, one female lost nine of 12 pups during the day 4-21 lactation interval.\nIn the F1, F2, and F3 generations postnatal survival indices for days 0-4 and 4-21 during both litter intervals were considered comparable between the control and treated groups. Some statistically significant differences in these indices were observed between the control and treated groups; however, no trend was evident through successive generations to indicate an adverse effect of treatment.)\n"]
[75,"Sensitive to, but not diagnostic of, EATS","Pup survival index","Rat","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Oral",">10","mg/kg bw/day","No effect"]
[93,"Sensitive to, but not diagnostic of, EATS","Pup survival index","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Survival index was calculated on PND 1, 4, 7, 10, 13, 16, 19, 21, 25."]
[22,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"No EATS-related adversity was observed on sex ratio in prenatal developmental toxicity studies in rabbit (8/8 studies) and rat (5/5 studies) as well as in multi-generation reproductive toxicity studies in rat (6/6 studies)."]
[23,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[26,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[28,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rat","10 (GD 7-16)","Days","Oral",">1000","mg/kg bw/day","No effect"]
[29,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect"]
[30,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rabbit","13 (GD 6-18)","Days","Oral",">300","mg/kg bw/day","No effect"]
[31,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rabbit","13 (GD 7-19)","Days","Oral","> 400","mg/kg bw/day","No effect"]
[32,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rabbit","13 (GD 8-20)","Days","Oral",">300","mg/kg bw/day","No effect","The proportion of male fetuses was increased in the 175 mg/kg bw/day group. This was not considered treatment-related since no dose-response was observed. Moreover, no effect was observed in 6 further prenatal developmental toxicity studies in rabbit at similar or higher doses (study IDs 30, 31, 33, 34, 46, 47, 66)."]
[33,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rabbit","22 (GD 6-27)","Days","Oral","> 350","mg/kg bw/day","No effect"]
[34,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect"]
[46,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rabbit","13 (GD 7-19)","Days","Oral","> 450","mg/kg bw/day","No effect"]
[47,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rabbit","13 (GD 7-19)","Days","Oral","> 625","mg/kg bw/day","No effect"]
[64,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rat","10 (GD 6-15)","Days","Oral",">3500","mg/kg bw/day","No effect","No treatment-related effect on sex ratio."]
[65,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","No statistically significant (p=0.5) effect on sex ration was observed."]
[66,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rabbit","22 (GD 6-27)","Days","Oral",">350","mg/kg bw/day","No effect","There were no biologically meaningful or statistically significant differences in the mean numbers of fetal sex distribution in any of the treatment groups when compared to the control group."]
[69,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rat","only secondary exposure through milk from PND 0-21","Weeks","Oral",">30000","ppm","No effect","Glyphosate did not selectively affect pups of one sex since, in all groups, sex ratios at birth and weaning were similar. "]
[70,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Pup sex distributions ratios at day 0 were generally comparable between the control and treated groups for each litter interval for each generation (F1, F2, and F3). Pup sex distributions at day 21 (weaning) were similar to distributions noted at day 0 in both the control and treated groups for each generation (F1, F2, and F3). No adverse treatment effect on sex distribution data was evident."]
[93,"Sensitive to, but not diagnostic of, EATS","Sex ratio","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Sex ratio was determined on PND 1 and did not differ significantly between groups."]
[22,"Sensitive to, but not diagnostic of, EATS","Functional observation battery","Rat",10,"Weeks","Oral",">15000","ppm","No effect",null,"No EATS-related adversity was observed on functional observation battery in rat in a two-generation study."]

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["Study ID Matrix","Effect classification","Effect target","Species","Duration of exposure","Duration unit","Route of administration","Lowest Effect dose","Dose unit","Effect direction","Observed effect (positive and negative)","Assessment of each line of evidence","Assessment on the integrated line of evidence","Modality"]
[5,"Target organ toxicity","Bone histopathology","Dog",90,"Days","Oral",1000,"mg/kg bw/day","Change","Sternum: increased number of adipocytes in 2/3 males and 3/3 females at 1000 mg/kg bw/day. ","Consistent effects on bone and bone marrow histopathology were not observed in three species up to a chronic exposure period.","Not applicable."]
[14,"Target organ toxicity","Bone histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect","Gross necropsy: no abnormalities observed\nNo relevant treatment-related histopathological changes were observed.\n(non-neoplastic: animals at terminal kill: bone marrow femur: decreased incidences of hematopoesis in males at 3000 ppm: 9/18, 8/20, 10/18 and 6/29 at 0, 3000, 10000 and 30000 ppm; bone marrow sternum: decreased incidences of hematopoesis in males at 3000 ppm: 10/18, 8/20, 10/18 and 6/29 at 0, 3000, 10000 and 30000 ppm; bone marrow vertebra: decreased incidences of hematopoesis in males at 3000 ppm: 9/18, 8/20, 10/18 and 6/29 at 0, 3000, 10000 and 30000 ppm; neoplastic: no treatment-related findings)\n"]
[18,"Target organ toxicity","Bone histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic: no significant lesions; neoplastic: benign osteoma of the cranium in 1/51 males at 15000 ppm which is considered an isolated finding)"]
[19,"Target organ toxicity","Bone histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic findings dead/moribund animals: increased granulopoesis in femur in 5/22, 3/20, 2/22 and 2/27 males and 1/16, 3/16, 0/20 and 4/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related; increased hematopoesis in femur in 1/22, 1/20, 8/22 and 5/27 males and 0/16, 1/16, 2/20 and 3/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related; increased hematopoesis in sternum with marrow in 2/22, 1/20, 5/22 and 6/27 males and 0/16, 1/16, 3/20 and 3/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related; non-neoplastic findings terminal kill animals: increased hematopoesis in sternum with marrow in 5/28 and 2/23 males and 6/34 and 8/30 females at 0 and 10000 ppm, not treatment-related; neoplastic findings: 11 tumors observed, osteomas, no treatment relation)"]
[20,"Target organ toxicity","Bone histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic findings: no treatment-related findings (hyperostosis in 1/51 control females); neoplastic findings: no treatment-related findings (benign osteoma of the sternum in 1/51 control females))"]
[67,"Target organ toxicity","Bone histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"Target organ toxicity","Bone histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[78,"Target organ toxicity","Bone histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[79,"Target organ toxicity","Bone histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect","Femur and epiphysis was examined."]
[18,"Target organ toxicity","Bone marrow histopathology","Rat",2,"Years","Oral",15000,"ppm","Change","Histopathology, non-neoplastic: increased incidence of severe adipose infiltration in males at 15000 ppm at terminal kill, which were attributed to myeloid hyperplasia, no abnormalities in high dose females (not treatment-related: increased incidence of severe adipose infiltration in premature dead animals at 1500 and 5000 ppm)\nhistopathology, neoplastic: myeloid hyperplasia was noted in a few rats of either sex, no dose relation, no treatment relation, no primary neoplastic lesions were seen"]
[20,"Target organ toxicity","Bone marrow histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic findings: no treatment-related findings (adipose infiltration observed in most animals of both sexes, no dose relation on frequency and severity; myeloid hyperplasia in a few mice of either sex, no treatment-related group distribution; fibroplasia, angiectasis and foci/areas of necrosis occasionally observed; neoplastic findings: no treatment-related findings (myeloid leukaemia in 1/51 males at 500 ppm and in 1/51 females at 1500 ppm, lipoma in the marrow cavity of the sternum in 1/51 females at 5000 ppm))"]
[21,"Target organ toxicity","Bone marrow histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic findings: femur: decreased incidences of haematopoesis in females at ≥ 1600 ppm, not treatment-related; sternum and vertebra: decreased incidences of haematopoesis in females at ≥ 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups; neoplastic findings: haematopoetic and lymphatic system, malignant lymphoma in 2/29 terminal kill males at 40000 ppm and in 4/32, 0/36, 5/40 and 3/35 terminal kill females at 0, 1600, 8000 and 40000 ppm, considered to be incidental)"]
[55,"Target organ toxicity","Bone marrow histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","Histopathology was performed for control and high dose group animals including bone and bone marrow."]
[68,"Target organ toxicity","Bone marrow histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect","Bone marrow histopathology was performed of the costochondral junction."]
[70,"Target organ toxicity","Bone marrow histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Bone marrow histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"Target organ toxicity","Bone marrow histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect","No effect on bone and bone marrow was observed."]
[78,"Target organ toxicity","Bone marrow histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[79,"Target organ toxicity","Bone marrow histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[13,"Target organ toxicity","Eyes histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Interim kill: no abnormal findings; terminal kill: cateract in 4/44, 4/46, 6/51 and 10/50 and corneal opacity in 4/44, 2/46, 5/51 and 3/50 rats at 0, 100, 1000 and 10000 ppm, not treatment-related)","No effects on the histopathology of eyes were observed in rat and mouse up to a chronic exposure period."]
[18,"Target organ toxicity","Eyes histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic: eyes: no treatment-related effects (retinal atrophy and lenticular degeneration were occasionally observed in rats of either sex, within historical control range; keratitis, corneal vacuolation, focal mineralisation of the cornea, posterior adhesions occasionally observed, spontaneous lesions)/ harderian gland: mononuclear ell foci and/or focal atrophy occasionally observed in both sexes, age-related, glandular epithelial hyperplasia/hypertrophy was frequently observed, spontaneous change, no treatment relation; neoplastic: no treatment-related findings: no abnormalities observed)"]
[20,"Target organ toxicity","Eyes histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic findings: no treatment-related findings (spontaneous lesions such as retinal atrophy, retinal disruption, corneal ulceration, focal mineralisation of cornea/iris, keratitis, thickening of the iris and inflammation of the anterior chamber; lenticular degeneration more frenquently observed, considered as common background change); neoplastic findings: no neoplastic changes observed; Harderian gland: non-neoplastic findings: mononuclear cell foci and foci areas of atrophy, age related; instances of epithelial hyperplasia and generalised distention of the glands, not treatment-related); neoplastic: Harderian gland adenomas in 4/51 males and 4/51 females at 0 and 5000 ppm each; carcinoma in 2/51 control females, not treatment-related; Lacrimal gland:  non-neoplastic: mononuclear cell foci and isolated instances of periductal/interstitial fibrosis, not treatment-related)"]
[21,"Target organ toxicity","Eyes histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Gross pathology: reduced incidence of opacity in females at 8000 and 40000 ppm, not treatment-related; histopathology, non-neoplastic: no treatment-related findings; neoplastic: no treatment-related findings)"]
[49,"Target organ toxicity","Eyes histopathology","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[68,"Target organ toxicity","Eyes histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect","Eyes were examined including the optic nerve and contiguous Harderian glands."]
[70,"Target organ toxicity","Eyes histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Eyes histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[74,"Target organ toxicity","Eyes histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"Target organ toxicity","Eyes histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[78,"Target organ toxicity","Eyes histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[79,"Target organ toxicity","Eyes histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[20,"Target organ toxicity","Aorta histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","Histopathology, non-neoplastic findings: no treatment-related findings (few observations without toxicological significance)\nhistopathology, neoplastic findings: no neoplastic lesions observed","Organ specific toxicity of glyphosate was not observed for aorta and heart in three species up to a chronic exposure period. Weight changes observed in some studies are attributed to effects on body weight. This conclusion is substantiated by the absence of histopathological changes."]
[68,"Target organ toxicity","Aorta histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"Target organ toxicity","Aorta histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study were indicative of common incidental histological findings."]
[74,"Target organ toxicity","Aorta histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"Target organ toxicity","Aorta histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[13,"Target organ toxicity","Heart histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Neoplastic findings, dead/moribund animals: no treatment-related findings (metastatic histiocytic sarcoma in 1/30, 1/32 and 1/21 males at 0, 1000 and 10000 ppm; round cell sarcoma of pericardium in 1/17 females at 1000 ppm); neoplastic findings, surviving animals: no treatment-related findings (metastatic histiocytic sarcoma in 1 of 1/26 and 1 of 1/26 examined female tissues at 100 and 1000 ppm))"]
[14,"Target organ toxicity","Heart histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Gross necropsy: no abnormal findings observed; Histopathology, non-neoplastic: all animals: decreased incidences of myocardial atrophy/fibrosis in females: 22/78, 19/79, 20/78 and 8/78 females at 0, 3000, 10000 and 30000 ppm; interim kill animals week 78: increased incidences of myocardial atrophy/fibrosis in males: 2/6, 5/5, 5/10 and 1/8 at 0, 3000, 10000 and 30000 ppm not treatment-related; animals found dead/killed in extremis: decreased incidences of myocardial atrophy/fibrosis in females: 9/35, 7/31, 6/34 and 3/36 females at 0, 3000, 10000 and 30000 ppm; neoplastic: no treatment-related findings)"]
[18,"Target organ toxicity","Heart histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic: focal myocarditis/fibrosis commonly observed in both sexes bit mainly in males, no dose relation, not treatment-related; focal mineralisation and Schwann cell hyperplasia observed rarely as spontaneous lesion, not treatment-related; neoplastic: no treatment-related findings (malignant Schwannoma in 1/51 males at 1500 ppm and in 2/51 control females))"]
[19,"Target organ toxicity","Heart histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic findings dead/moribund animals: degenerative changes in 11/22, 14/20, 13/22 and 16/27 males and 4/16, 2/16, 4/20 and 1/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related)"]
[20,"Target organ toxicity","Heart histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic: no treatment-related findings (myocarditis/fibrosis and vacuolisation of myocardial fibres commonly observed in males of all groups, no dose-related incidence or serverity; atrial thrombus formation, distention/thinning of the ventricular wall, vasculitis, focal ossification, focal mineralisation, atrial inflammation or fibrosis, atrial distention, pericardial inflammatory or fibrous thickening, focal necrosis/haemorrhage, mononuclear cell foci occasionally observed); neoplastic: no primary neoplastic lesions observed)"]
[49,"Target organ toxicity","Heart histopathology","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[50,"Target organ toxicity","Heart histopathology","Rat",28,"Days","Oral",">2500","mg/kg bw/day","No effect"]
[52,"Target organ toxicity","Heart histopathology","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Target organ toxicity","Heart histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","Heart and aorta were subject to histopathology."]
[55,"Target organ toxicity","Heart histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","Heart and aorta were subject to histopathology."]
[57,"Target organ toxicity","Heart histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","Heart and aorta were subject to histopathology."]
[58,"Target organ toxicity","Heart histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Heart and aorta were subject to histopathology."]
[59,"Target organ toxicity","Heart histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Heart and aorta were subject to histopathology."]
[67,"Target organ toxicity","Heart histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Heart and aorta were subject to histopathology."]
[68,"Target organ toxicity","Heart histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"Target organ toxicity","Heart histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Heart histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[74,"Target organ toxicity","Heart histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"Target organ toxicity","Heart histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[1,"Target organ toxicity","Heart weight","Rat",90,"Days","Oral",20000,"ppm","Decrease","Absolute weight in males was reduced at 20000 ppm which was attributed to reduced body weight (-8%) at this dose."]
[2,"Target organ toxicity","Heart weight","Rat",90,"Days","Oral",50000,"ppm","Change","Absolute weight was reduced in both sexes and relative weight was increased in males at 50000 ppm. This effect was attributed to reduced body weight and thus, not considered toxicologically relevant or organ specific."]
[16,"Target organ toxicity","Heart weight","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect","Absolute weight was increased in terminal kill in females at 300 mg/kg bw/day only without dose-relation."]
[51,"Target organ toxicity","Heart weight","Dog","Study part A: 21\nStudy Part B: 14","Days","Oral",">1000","mg/kg bw/day","No effect","Relative and absolute organ weight were not affected."]
[52,"Target organ toxicity","Heart weight","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[56,"Target organ toxicity","Heart weight","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"Target organ toxicity","Heart weight","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","Relative weight was increased in females at 60 mg/kg bw/day (statist. not signif.), no dose-relation, therefore considered not treatment-related."]
[58,"Target organ toxicity","Heart weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[59,"Target organ toxicity","Heart weight","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[67,"Target organ toxicity","Heart weight","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Absolute organ weight was not affected."]
[68,"Target organ toxicity","Heart weight","Mouse",2,"Years","Oral","> 30000","ppm","No effect","The mean absolute and relative (to body and brain weight) heart weight were not affected."]
[70,"Target organ toxicity","Heart weight","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring."]
[70,"Target organ toxicity","Heart weight","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Mean organ weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females from the F0, F1, and F2 generation."]
[73,"Target organ toxicity","Heart weight","Mouse",90,"Days","Oral",">50000","ppm","No effect","Relative organ weight (relative to body weight) was increased (M 50000 ppm=+16%*) which was attributed to lower terminal body weight (-11%) and thus not of toxicological relevance. No effects on absolute as well as relative (to brain weight) organ weight were observed."]
[78,"Target organ toxicity","Heart weight","Rat",90,"Days","Oral",">50000","ppm","No effect","No treatment-related effects were observed."]
[79,"Target organ toxicity","Heart weight","Mouse",90,"Days","Oral",12500,"ppm","Increase","Relative organ weight was increased in males (M at 12500 ppm; 25000 ppm; 50000 ppm; F no treatment-related effects), which was attributed to decreased body weight."]
[1,"Target organ toxicity","Kidney histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect",null,"Organ specific toxicity of glyphosate was not observed in kidney in four species up to a chronic exposure period. Histopathological changes such as renal necrosis and mineralisation were observed in isolated rat studies. However, these changes were not consistent within rat or in mouse, dog and rabbit."]
[2,"Target organ toxicity","Kidney histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Hydronephrosis in one or both kidneys in 2/10, 1/10 and 1/10 males at 1000, 10000 and 50000 ppm and in 3/10 females at 1000 ppm, not treatment-related)"]
[3,"Target organ toxicity","Kidney histopathology","Rat",90,"Days","Oral",">30000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Polycystic kidney in 1/12 males at 10000 ppm and in 1/12 females at 30000 ppm, not treatment-related)"]
[4,"Target organ toxicity","Kidney histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"Target organ toxicity","Kidney histopathology","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[6,"Target organ toxicity","Kidney histopathology","Dog",90,"Days","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Minimal to mild mineralisation and mild cytoplasmic vacuolisation of the tubular epithelium, not treatment-related)"]
[7,"Target organ toxicity","Kidney histopathology","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"Target organ toxicity","Kidney histopathology","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"Target organ toxicity","Kidney histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"Target organ toxicity","Kidney histopathology","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"Target organ toxicity","Kidney histopathology","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"Target organ toxicity","Kidney histopathology","Rat",1,"Year","Oral",">20000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Chronic progressive glomerulonenephropathy in 23/24 and 22/24 males at 0 and 20000 ppm, intratubular microlithiasis in 22/24 and 18/24 females at 0 and 20000 ppm, no treatment-related)"]
[13,"Target organ toxicity","Kidney histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Interim kill: lymphocytic infiltration, not treatment-related; terminal kill: nephritis-tubulo/tubulo-interstitial/interstitial in 18/56, 14/54, 15/49 and 12/50 dead and moribund rats and 20/44, 2/46, 2/50 and 19/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, attributed to subclinical infections and/or age; neoplastic findings, dead/moribund animals: no treatment-related findings (metastatic cholangio carcinoma in 1/30 males at 100 ppm; metastatic histiosarcoma in 1/32 males at 1000 ppm); neoplastic findings, surviving animals: no treatment-related findings (lymphosarcoma in 1 of 1/26 examined female tissues at 1000 ppm))"]
[14,"Target organ toxicity","Kidney histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Gross necropsy: coarse surface in males found dead/killed in extremis at 30000 ppm, attributed to chronic nephropathy; Histopathology, non-neoplastic: initerim kill animals week 52: decreased incidendes of chronic nephropathy in males at 10000 ppm: 9/10, 9/10, 4/10 and 9/10 at 0, 3000, 10000 and 30000 ppm; animals found dead/killed in extremis: decreased incidence of mineralization in pelvic epithelium in females at 30000 ppm: 6/35, 3/31, 3/34 and 0/36 at 0, 3000, 10000 and 30000 ppm; decreased incidences of pyelitis/pyelonephritis in females at 30000 ppm: 7/35, 3/31, 3/34 and 1/36 at 0, 3000, 10000 and 30000 ppm; neoplastic: increased incidence of adenomas in males found dead/killed in extremis at 30000 ppm (3/23 males), not significant)"]
[15,"Target organ toxicity","Kidney histopathology","Rat",2,"Years","Oral",6000,"ppm","Change","Gross necropsy: Enlarged organ in males at 6000 ppm and 20000 ppm\nHistopathology, non-neoplastic: Papillary necrosis with varying degrees of mineralisation of the papilla and/or transitional cell hyperplasia in both sexes but particularly in males at 20000 ppm, papillary haemorrhage in 2 males and 2 females at 20000 ppm, hydronephrosis in males at ≥ 6000 ppm, within historical control data)\nHistopathology, neoplastic findings: no treatment-related findings"]
[16,"Target organ toxicity","Kidney histopathology","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect","No relevant treatment-related histopathological changes were observed. \n(Decreased incidence of nephropathy in interim kill males at ≥ 100 mg/kg bw/day and reduced severity of nephropathy in terminal kill males at 1000 mg/kg bw/day, toxicologically not relevant (findings of unknown toxicological significance: decreased incidence of urothelial hyperplasia in terminal kill females at ≥ 300 mg/kg bw/day))"]
[17,"Target organ toxicity","Kidney histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"Target organ toxicity","Kidney histopathology","Rat",2,"Years","Oral",15000,"ppm","Change","Histopathology, non-neoplastic: Renal mineralisation, reduced pelvic mineralisation and increased corticomedullary mineralisation in premature death and terminal kill females at 15000 ppm, reduced incidences of hyperplasia in the renal pelvic/papillary epithelium in females at 15000 ppm, reduced pelvic mineralisation in males at 15000 ppm, treatment-related (not treatment-related findings: progressive glomerulonephropathy in rats of both sexes with greater prevalence in males, age-related, pyelitis in males at 5000 ppm, tubular necrosis in premature dead control females, renal tubular hyperplasia in 1/51 females at 1500 ppm and in 1/51 males and 1/51 females at 15000 ppm, occasional findings without dose relation included papillary necrosis, pyeliti, hydronephrosis, cortical cyst formation, tubular dilatation, generalised tubular basophilia, tubular mineralisation, cortical scarring, hypertrophy of the collecting duct epithelium, congestion)\nhistopathology, neoplastic findings: no treatment-related findings (renal tumors (lipoma, tubular carcinoma, clear cell carcinoma) in 1/51 and 1/51 males at 0 and 15000 ppm and in 1/51 females at 5000 ppm)"]
[19,"Target organ toxicity","Kidney histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Gross pathology, terminal kill animals: rough/ uneven surface in 1/28, 2/30, 2/28 and 5/23 males at 0, 100, 1000 and 10000 ppm, considered incidental as histopathological findings were absent; Histopathology, non-neoplastic findings dead/moribund animals: nephropathy in 9/22, 7/20, 10/22 and 12/27 males and 5/16, 1/16, 5/20 and 3/20 females at 0, 100, 1000 and 10000 ppm; amyloidosis in 6/22, 4/20, 10/22 and 9/27 males and 3/16, 2/16, 2/20 and 4/20 females at 0, 100, 1000 and 10000 ppm; histopathology, non-neoplastic findings terminal kill animals: nephropathy in 7/28, 4/30, 3/28 and 6/23 males and 5/34, 2/34, 0/30 and 2/30 females at 0, 100, 1000 and 10000 ppm and amyloidosis in 7/28, 2/30, 2/28 and 8/23 males and 0/34, 1/34, 0/30 and 3/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related)"]
[20,"Target organ toxicity","Kidney histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Histopathology, non-neoplastic: no treatment-related findings (groups of basophilic tubules, mononuclear cell foci, distention of isolated tubules or glomerula spaces frequently observed in both sexes among all groups; chronic nephropathy occasionally observed, tubular vacuolation or dilatation, focal mineralisation, vasculitis, cortical scarring, hydronephrosis, papillary necrosis, focal haemorrhage or necrosis, hyperplasia of the papillary/pelvic epithelium, amyloid deposition and pigment accumulation, no dose relation regarding incidence or severity); neoplastic: no treatment-related findings (haemangiosarcoma in 1/51 females at 1500 ppm))"]
[21,"Target organ toxicity","Kidney histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Gross pathology: reduced incidence of pale color and corse surface in females at 8000 ppm, not treatment-related; Histopathology, non-neoplastic: no treatment-related findings (reduced incidences of cortical cysts in both sexes at 40000 ppm; reduced incidences of glomerula amyoidosis in females at 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups); neoplastic: no treatment-related findings)"]
[22,"Target organ toxicity","Kidney histopathology","Rat",10,"Weeks","Oral",">15000","ppm","No effect","Gross necropsy: No treatment-related findings (pallor in one F0 female found dead at 15000 ppm; dark kidneys in the interim dead control female of the F1 generation; mottled appearance, enlargement and increased renal pelvic cavitation in terminal kill animals of the F0 and F1 generation)"]
[23,"Target organ toxicity","Kidney histopathology","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"Target organ toxicity","Kidney histopathology","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[25,"Target organ toxicity","Kidney histopathology","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect","Gross necropsy: Low incidences of cysts, dilated pelvis in F0 adults and low incidences of hydronephrosis in 2/60 F1 adults, considered to be incidental, not treatment-related"]
[27,"Target organ toxicity","Kidney histopathology","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[44,"Target organ toxicity","Kidney histopathology","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[45,"Target organ toxicity","Kidney histopathology","Rat","31 (PND 23-53)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[49,"Target organ toxicity","Kidney histopathology","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[50,"Target organ toxicity","Kidney histopathology","Rat",28,"Days","Oral",250,"mg/kg bw/day","Change","Nephrocalcinosis (mineral deposition) in 2/5, 2/5 and 4/5 females was observed at 250, 1000 and 2500 mg/kg bw/day."]
[52,"Target organ toxicity","Kidney histopathology","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Target organ toxicity","Kidney histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","Urinary bladder histopathology was performed as well."]
[54,"Target organ toxicity","Kidney histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"Target organ toxicity","Kidney histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"Target organ toxicity","Kidney histopathology","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect","Increased incidence of cortical tubular epithelial hypertrophy in 1/10, 2/10 and 5/10 females and in 2/10, 0/10 and 2/10 males at 0, 200 and 1000 mg/kg bw/day, no findings in the high dose group. Due to lacking dose-response, the effect is not considered treatment-related (probably early stage in the development of nephropathy)."]
[57,"Target organ toxicity","Kidney histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","Urinary bladder was examined as well."]
[58,"Target organ toxicity","Kidney histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Kidney, ureter and urinary bladder were examined."]
[59,"Target organ toxicity","Kidney histopathology","Dog",1,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[60,"Target organ toxicity","Kidney histopathology","Rat",21,"Days","Dermal",1000,"mg/kg bw/day","No effect","No relevant treatment-related histopathological changes were observed. \n(Gross necropsy: unilateral dilatation in 2/5 males at 1000 mg/kg bw/day, common finding in rats of this age, not considered related to treatment; Histopathology: unilateral papillary necrosis in 1/5 males at 1000 mg/kg bw/day, urothelial hyperplasia in 2/5 males at 1000 mg/kg bw/day, pelvic dilatation in 3/5 males at 1000 mg/kg bw/day, common finding in rats of this age, not treatment-related)"]
[61,"Target organ toxicity","Kidney histopathology","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[62,"Target organ toxicity","Kidney histopathology","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[63,"Target organ toxicity","Kidney histopathology","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect"]
[67,"Target organ toxicity","Kidney histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"Target organ toxicity","Kidney histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"Target organ toxicity","Kidney histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Kidney histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[71,"Target organ toxicity","Kidney histopathology","Rat",28,"Days","Oral",">50000","ppm","No effect"]
[73,"Target organ toxicity","Kidney histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect","No treatment-related effect was observed (minimal interstitial inflammation 3/10 M (control), 4/10 M (50000 ppm), 4/10 F (control), 2/10 (50000 ppm)."]
[74,"Target organ toxicity","Kidney histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"Target organ toxicity","Kidney histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[76,"Target organ toxicity","Kidney histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect","Kidney and urinary bladder were examined."]
[1,"Target organ toxicity","Kidney weight","Rat",90,"Days","Oral",20000,"ppm","No effect","Relative weight increased in males at 20000 ppm, not considered treatment related (no histopathological findings)."]
[2,"Target organ toxicity","Kidney weight","Rat",90,"Days","Oral",50000,"ppm","Increase","Relative weight increased in both sexes at 50000 ppm. However, no relevant treatment-related histopathological changes were observed. "]
[3,"Target organ toxicity","Kidney weight","Rat",90,"Days","Oral",30000,"ppm","No effect"]
[4,"Target organ toxicity","Kidney weight","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"Target organ toxicity","Kidney weight","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[6,"Target organ toxicity","Kidney weight","Dog",90,"Days","Oral",">10000","ppm","No effect"]
[7,"Target organ toxicity","Kidney weight","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"Target organ toxicity","Kidney weight","Dog",90,"Days","Oral",10000,"ppm","Increase","Absolute and relative weight were increased in males at ≥ 10000 ppm. This increased organ weight is considered not toxicologically relevant due to the absence of histopathological findings."]
[9,"Target organ toxicity","Kidney weight","Dog",1,"Years","Oral",">500","mg/kg bw/day","No effect"]
[10,"Target organ toxicity","Kidney weight","Dog",1,"Years","Oral",">50000","ppm","No effect"]
[11,"Target organ toxicity","Kidney weight","Dog",1,"Years","Oral",">30000","ppm","No effect"]
[12,"Target organ toxicity","Kidney weight","Rat",1,"Years","Oral",">20000","ppm","No effect","Absolute weight was reduced in females at 8000 ppm. Since no dose-response was observed, the effect is considered not treatment-related."]
[13,"Target organ toxicity","Kidney weight","Rat",24,"Months","Oral",">10000","ppm","No effect"]
[14,"Target organ toxicity","Kidney weight","Rat",24,"Months","Oral",">30000","ppm","No effect","Increased in females at 30000 ppm in week 26, considered secondary to body weight changes or incidental."]
[15,"Target organ toxicity","Kidney weight","Rat",2,"Years","Oral",">20000","ppm","No effect","Absolute and relative weight were increased (+10%) in males at 6000 ppm, which is not treatment-related since no dose-response was observed."]
[16,"Target organ toxicity","Kidney weight","Rat",2,"Years","Oral",100,"mg/kg bw/day","No effect","Absolute and relative weight decreased in terminal kill males at 100 and 1000 mg/kg bw/day, which was reported as not treatment-related."]
[17,"Target organ toxicity","Kidney weight","Rat",24,"Months","Oral",20000,"ppm","No effect"]
[18,"Target organ toxicity","Kidney weight","Rat",2,"Years","Oral",">15000","ppm","No effect"]
[19,"Target organ toxicity","Kidney weight","Mouse",18,"Months","Oral",">10000","ppm","No effect"]
[20,"Target organ toxicity","Kidney weight","Mouse",18,"Months","Oral",">5000","ppm","No effect"]
[21,"Target organ toxicity","Kidney weight","Mouse",18,"Months","Oral",40000,"ppm","Increase","Relative weight was statistically significantly increased in females at 40000 ppm. However, no relevant treatment-related histopathological changes were observed. And body weight reductions were also observed at this dose level."]
[22,"Target organ toxicity","Kidney weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect","Abs.+rel. weight increased in F0 females at 15000 ppm, abs. weight increased in F1 females at 5000 ppm, no histopathological findings, considered to be adaptive in nature and non-adverse, no effect in males"]
[23,"Target organ toxicity","Kidney weight","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect","Rel. weight increased in F0 males at 10000 ppm, abs. values comparable to control group,  considered to be incidental"]
[24,"Target organ toxicity","Kidney weight","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",30000,"ppm","Increase","Relative organ weight was increased in F0+F1 males and females at 30000 ppm, where also reductions in body weight were observed for males."]
[44,"Target organ toxicity","Kidney weight","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[45,"Target organ toxicity","Kidney weight","Rat","31 (PND 23-53)","Days","Oral",300,"mg/kg bw/day","No effect"]
[49,"Target organ toxicity","Kidney weight","Rat",28,"Days","Oral",">20000","ppm","No effect","No effect on absolute and relative organ weight was observed."]
[50,"Target organ toxicity","Kidney weight","Rat",28,"Days","Oral",">2500","mg/kg bw/day","No effect"]
[51,"Target organ toxicity","Kidney weight","Dog","Study part A: 21\nStudy Part B: 14","Days","Oral",">1000","mg/kg bw/day","No effect","No effect on absolute and relative organ weight was observed."]
[52,"Target organ toxicity","Kidney weight","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Target organ toxicity","Kidney weight","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[54,"Target organ toxicity","Kidney weight","Rat",90,"Days","Oral",">20000","ppm","No effect","No effect on absolute and relative organ weight was observed."]
[55,"Target organ toxicity","Kidney weight","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"Target organ toxicity","Kidney weight","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"Target organ toxicity","Kidney weight","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","No effect on absolute and relative organ weight was observed."]
[58,"Target organ toxicity","Kidney weight","Dog",12,"Months","Oral",">500","mg/kg bw/day","No effect","No effect on absolute and relative organ weight was observed."]
[59,"Target organ toxicity","Kidney weight","Dog",1,"Years","Oral",">1000","mg/kg bw/day","No effect","No effect on absolute and relative organ weight was observed."]
[60,"Target organ toxicity","Kidney weight","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[61,"Target organ toxicity","Kidney weight","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[62,"Target organ toxicity","Kidney weight","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","Increase","A significant increase in mean relative organ weight was observed in females of the 5000 mg/kg bw/d group which was not considered toxicologically relevant since no histopathological effects were observed."]
[63,"Target organ toxicity","Kidney weight","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect","Absolute and organ weight relative to brain weight was assessed."]
[67,"Target organ toxicity","Kidney weight","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Absolute organ weight was not affected."]
[68,"Target organ toxicity","Kidney weight","Mouse",2,"Years","Oral","> 30000","ppm","No effect","The mean absolute and relative (to body and brain weight) kidneys weight were not affected."]
[70,"Target organ toxicity","Kidney weight","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring."]
[70,"Target organ toxicity","Kidney weight","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Mean organ weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females from the F0, F1, and F2 generation."]
[73,"Target organ toxicity","Kidney weight","Mouse",90,"Days","Oral",">50000","ppm","Increase","Relative organ weight (relative to body weight) was increased (M 50000 ppm =+18.5%*) which was attributed to lower terminal body weight and thus not of toxicological relevance. No effects on absolute as well as relative (to brain weight) organ weight were observed.\n"]
[76,"Target organ toxicity","Kidney weight","Rat","90-92","Days","Oral",2000,"ppm","Decrease","Absolute: F 7500 ppm=-8%*; F 5000 ppm=-11%*; F 2000 ppm=-13%*\nRelative: M 2000 ppm=+12%* ; F 2000 ppm=-9%* (not dose-dependent)"]
[78,"Target organ toxicity","Kidney weight","Rat",90,"Days","Oral",50000,"ppm","Increase","Relative weight was increased in males at 25000 ppm and 50000 ppm, which is attributed to lower body weight at these doses."]
[79,"Target organ toxicity","Kidney weight","Mouse",90,"Days","Oral",6250,"ppm","Increase","Relative weight was increased in males at 6250 ppm, 12500 ppm, 25000 ppm, and 50000 ppm which is in line with reduced body weight from 25000 ppm. "]
[4,"Target organ toxicity","Urinary bladder histopathology","Mouse",90,"Days","Oral",50000,"ppm","Change","Cystitis of the urinary bladder was observed in 4/12 males only at 50000 ppm (0/12 in the control group), which is a very high dose (> 6000 mg/kg bw/day), where also reduced body weight as well as pH reduction of urine were observed.","One study in mice showed cystitis developed in the urinary bladder. This effect was not reproduced in a second mouse study at the same dose level and expsoure duration. Specific effects on the urinary bladder were thus not observed in dog, mouse, and rat."]
[11,"Target organ toxicity","Urinary bladder histopathology","Dog",1,"Years","Oral",">30000","ppm","No effect","Areas or diffuse reddening in 1/4, 2/4 and 2/4 females at 3000, 15000 and 30000 ppm, no dose-relation, in the absence of a similar effect in males the findings were considered not treatment-related"]
[13,"Target organ toxicity","Urinary bladder histopathology","Rat",24,"Months","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Neoplastic findings, dead/moribund animals: no treatment-related findings (transitional cell carcinoma in 1/28 females at 10000 ppm))"]
[18,"Target organ toxicity","Urinary bladder histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Urinary bladder: non-neoplastic: no treatment-related findings (epithelial/subepithelial or peripheral inflammatory cell infiltrates, epithelial erosion, subepithelial haemorrhage, epithelial hyperplasia and focal mineralisation were occasionally observed); neoplastic: no treatment-related findings (benign transitional cell papilloma in 1/51 males at 1500 ppm); Urether: distention in 1/51 females at 5000 ppm, not treatment-related)"]
[20,"Target organ toxicity","Urinary bladder histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic: no treatment-related findings (epithelial/subepithelial or peripheral inflammatory cell infiltrates, epithelial ulceration, subepithelial haemorrhage, acute inflammatory cells in the lumen and amorphous contents occasionally observed); neoplastic: no neoplasms observed)"]
[55,"Target organ toxicity","Urinary bladder histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[59,"Target organ toxicity","Urinary bladder histopathology","Dog",1,"Years","Oral",">1000","mg/kg bw/day","No effect","No relevant treatment-related histopathological changes were observed. \n(Thickened wall in 1/4 males at 1000 mg/kg bw/day and in 1/4 females at 30 mg/kg bw/day, microscopically verified as muscular hypertrophy and in 2/4 females at 30 mg/kg bw/day, microscopically verified as lymphocyte infiltration, not treatment-related)"]
[67,"Target organ toxicity","Urinary bladder histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"Target organ toxicity","Urinary bladder histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(A slight-to-mild epithelial hyperplasia of the urinary bladder in males. The incidence was 6%, 6%, 20% and 16% controls through high-dose, respectively. Even though the increase at the mid- and high-dose was present, no test substance relationship was derived based on the missing dose-relationship.)"]
[70,"Target organ toxicity","Urinary bladder histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No relevant treatment-related histopathological changes were observed. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Urinary bladder histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No relevant treatment-related histopathological changes were observed. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"Target organ toxicity","Urinary bladder histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[74,"Target organ toxicity","Urinary bladder histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"Target organ toxicity","Urinary bladder histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[20,"Target organ toxicity","Gall bladder histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic: no treatment-related findings (focal epithelial cell hyperplasia, amorphous bodies in the lumen, vasculitis, cystic distention, focal necrosis, thickening of the wall and epithelial ulceration occasionally observed); neoplastic: no neoplasms observed)","No histopathological effects on the gall bladder were observed in mouse and rabbit."]
[67,"Target organ toxicity","Gall bladder histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"Target organ toxicity","Gall bladder histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[73,"Target organ toxicity","Gall bladder histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[77,"Target organ toxicity","Gall bladder histopathology","Rabbit","22 (GD 6-27)","Days","Oral",">2500","mg/kg bw/day","No effect"]
[79,"Target organ toxicity","Gall bladder histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[1,"Target organ toxicity","Liver histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect",null,"Few studies report changes (increases and decreases) of liver weights (absolute and relative) in rat, dog and mouse within which no relevant histopathological changes were observed. One isolated published study (study ID 95) describes a disturbance of lipid metabolism. Specific effects on the liver were thus not observed in dog, mouse, and rat."]
[2,"Target organ toxicity","Liver histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[3,"Target organ toxicity","Liver histopathology","Rat",90,"Days","Oral",">30000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Bile duct proliferation and cholangiectatis in 1/12 males at 10000 ppm and in 1/12 females at 30000 ppm, not treatment-related)"]
[4,"Target organ toxicity","Liver histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"Target organ toxicity","Liver histopathology","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[6,"Target organ toxicity","Liver histopathology","Dog",90,"Days","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Minimal to mild leucocyte infiltration in 3/4 and 3/4 males and in 4/4 and 4/4 females at 0 and 10000 ppm, not treatment-related)"]
[7,"Target organ toxicity","Liver histopathology","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"Target organ toxicity","Liver histopathology","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"Target organ toxicity","Liver histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"Target organ toxicity","Liver histopathology","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"Target organ toxicity","Liver histopathology","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"Target organ toxicity","Liver histopathology","Rat",1,"Year","Oral",">20000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Minor degree of proliferative cholangitis in 12/24 and 11/24 males and 10/24 and 19/24 females at 0 and 20000 ppm, within historical control data, not treatment-related)"]
[13,"Target organ toxicity","Liver histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed (neoplastic and non-neoplastic). \n"]
[14,"Target organ toxicity","Liver histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Gross necropsy: no abnormalities observed; Histopathology, non-neoplastic: reduced incidence of focal hepatocellular fatty change in females of the interim kill at week 26: 4/10, 0/10, 2/10 and 0/10 at 0, 3000, 10000 and 30000 ppm, reduced incidence of micro granuloma in females of the interim kill at week 78: 5/8, 0/9, 3/8 and 1/8 at 0, 3000, 10000 and 30000 ppm and in females of the terminal kill: 4/15, 0/19, 3/16 and 0/14 at 0, 3000, 10000 and 30000 ppm, reduced incidences of spongiosis hepatitis in males of the terminal kill: 7/18, 6/20, 2/18 and 3/29 at 0, 3000, 10000 and 30000 ppm, peliosis hepatis in 6/30 males at 3000 ppm found dead/killed in extremis when compared to control (1/32); neoplastic: no treatment-related findings)\n"]
[15,"Target organ toxicity","Liver histopathology","Rat",2,"Years","Oral",6000,"ppm","Change","Gross necropsy: increased masses in males at 20000 and/or 6000 ppm, treatment-related\nHistopathology, non-neoplastic findings: proliferative cholangitis and hepatitis in males at 20000 ppm at interim and terminal kill, treatment-related (not treatment-related: fatty vacuolisation in males at ≥ 6000 ppm, below historical control levels)\nHistopathology, neoplastic findings: no treatment-related findings (hepatocellular adenoma in males at 20000 ppm, not statistically significant with Fisher'S Exact test but with Peto test, as no preneoplastic foci or adenocarcinomas were found and a dose-response was absent, findings were considered to be unrelated to treatment)"]
[16,"Target organ toxicity","Liver histopathology","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[17,"Target organ toxicity","Liver histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"Target organ toxicity","Liver histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic: no treatment-related findings (mononuclear cell foci frequently observed in both sexes but with a higher incidence in males at 1500 and 5000 ppm, highly variable finding in aging rats; lipid vacuolation, focal, diffuse or zonal distribution was frequently observed in either sex, no treatment relation/dose relation, statistically significant excess pigment in high dose females at terminal kill, considered not treatment-related due to low incidence and secondary nature of the condition; occasionally observed hepatic necrosis, focal/centrilobular distribution, subcaspular congestion/telangiecatsis, focal haemorrhage, cyst formation, congestion, bile duct proliferation, hyperplasia, dilatation or thickening, focal myelopoesis, malformation, thrombus formation, inflammatory cell infiltration, dilatation of sinusoids, basophilia or enlargement, periportal fibrosis, not treatment-related, foci/areas of altered hepatocytes as precursors of hepatic neoplasia in 0/51, 2/51, 6/51 and 2/51 males and in 32/51, 37/51, 33/51 and 36/51 females at 0, 1500, 5000 and 15000 ppm); neoplastic: no treatment-related findings (hepatocellular adenoma/carcinoma, cholangiocarcinoma in 1/51, 2/51, 1/51 and 1/51 males and 2/51, 0/51, 2/51 and 1/51 females at 0, 1500, 5000 and 15000 ppm))"]
[19,"Target organ toxicity","Liver histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Gross pathology, dead/moribund animals: enlarged in 3/22, 1/20, 3/22 and 1/27 males and 3/16, 4/16, 2/20 and 2/20 females at 0, 100, 1000 and 10000 ppm, no dose depedency but associated with histopathological findings; terminal kill animals: masses in 4/28, 4/30, 2/28 and 2/23 males and 1/34, 1/34, 2/30 and 2/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related; Histopathology, non-neoplastic findings dead/moribund animals: amyloidosis in 10/22, 9/20, 10/22 and 11/27 males and 5/16, 1/16, 4/20 and 5/20 females at 0, 100, 1000 and 10000 ppm, no dose dependency, not treatment-related; non-neoplastic findings terminal kill animals: necrobiotic foci in 2/28, 0/30, 0/28 and 1/23 males and 4/34, 1/34, 0/30 and 7/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related; extramedullary hematopoesis in 5/28, 0/30, 2/28 and 5/23 males and 2/34, 2/34, 0/30 and 6/30 females at 0, 100, 1000 and 10000 ppm; amyloidosis in 9/28, 1/30, 3/28 and 8/23 males and 2/34, 2/34, 0/30 and 5/30 females at 0, 100, 1000 and 10000 ppm; neoplastic findings: 26 tumors observed, mostly hepatocellular adenomas, no treatment relation)"]
[20,"Target organ toxicity","Liver histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic findings: no treatment-related findings (centrilobular hepatocyte vacuolation, periportal hepatocyte vacuolation, focal or centrilobular hepatocyte necrosis, areas or nodules of necrosis, lobular necrosis, thrombus formation, non-neoplastic cyst formation, granulocytic or myelopoietic foci, scattered lipid vacuolation of hepatocytes, higher grades of severity of pigment accumulation, focal hepatocyte hypertrophy, and proliferation of sinusoid lining cells occasionally observed; foci of altered hepatocytes in 4/51, 2/51, 2/51 and 1/51 males at 0, 500, 1500 and 5000 ppm and in 1/51 females at 5000 ppm); neoplastic: no treatment-related findings (total hepatocellular tumours in 7/51, 12/51, 11/51 and 6/51 males at 0, 500, 1500 and 5000 ppm and in 1/51 females at 500 ppm; adenoma in 2/12 interim dead males at 1500 ppm, carcinoma in 1/16 interim dead males at 5000 ppm; adenoma in 1/39, 1/41, 2/39 and 2/35 terminal kill males at 0, 500, 1500 and 5000 ppm, carcinoma in 6/39, 11/41, 7/39 and 3/35 terminal kill males at 0, 500, 1500 and 5000 ppm and in 1/38 terminal kill females at 500 ppm))"]
[21,"Target organ toxicity","Liver histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic: no treatment-related findings (decreased incidences of microgranuloma in females of groups found dead/killed in extremis and at terminal kill at 40000 ppm and decreased incidences of amyloid deposition in males at 40000 ppm and in females at ≥ 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups); neoplastic findings: no treatment-related findings)"]
[22,"Target organ toxicity","Liver histopathology","Rat",10,"Weeks","Oral",">15000","ppm","No effect","Gross necropsy: no treatment-related findings (pallor in the dead F0 female at 15000 ppm, mottled appearence in the interim dead F1 control female)"]
[23,"Target organ toxicity","Liver histopathology","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"Target organ toxicity","Liver histopathology","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[25,"Target organ toxicity","Liver histopathology","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect"]
[26,"Target organ toxicity","Liver histopathology","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[49,"Target organ toxicity","Liver histopathology","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[50,"Target organ toxicity","Liver histopathology","Rat",28,"Days","Oral",">2500","mg/kg bw/day","No effect"]
[52,"Target organ toxicity","Liver histopathology","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Target organ toxicity","Liver histopathology","Rat",90,"Weeks","Oral",">20000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Minimal focal subacute inflammation in both sexes of all groups, common finding among laboratory rats, not attributed to treatment)"]
[54,"Target organ toxicity","Liver histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(A few gross lesions were observed at comparable incidences among all groups, no dose- or treatment-relation; focal chronic hepatitis in 1/10 males at 20000ppm, considered to be incidental)"]
[55,"Target organ toxicity","Liver histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"Target organ toxicity","Liver histopathology","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"Target organ toxicity","Liver histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"Target organ toxicity","Liver histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"Target organ toxicity","Liver histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Prominent lobulation and pale patches at necropsy in animals of all groups, not treatment-related"]
[60,"Target organ toxicity","Liver histopathology","Rat",21,"Days","Dermal",1000,"mg/kg bw/day","No effect"]
[61,"Target organ toxicity","Liver histopathology","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[62,"Target organ toxicity","Liver histopathology","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[63,"Target organ toxicity","Liver histopathology","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect"]
[65,"Target organ toxicity","Liver histopathology","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","Histopathology was not performed. During macroscopic examination (necropsy) no treatment-related findings were observed. "]
[67,"Target organ toxicity","Liver histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"Target organ toxicity","Liver histopathology","Mouse",2,"Years","Oral","> 30000","ppm","Change","Centrilobular hepatocyte hypertrophy: 6%, 10%, 18% and 34% in control to high dose groups, respectively (no further neoplasms). This change may represent an adaptation to hepatocellular metabolism."]
[70,"Target organ toxicity","Liver histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No relevant treatment-related histopathological changes were observed. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Liver histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No relevant treatment-related histopathological changes were observed. No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[71,"Target organ toxicity","Liver histopathology","Rat",28,"Days","Oral",">50000","ppm","No effect"]
[73,"Target organ toxicity","Liver histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Small focal accumulations of inflammatory cells in control and treated animals at 50000 ppm)"]
[74,"Target organ toxicity","Liver histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"Target organ toxicity","Liver histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[76,"Target organ toxicity","Liver histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[95,"Target organ toxicity","Liver histopathology","Mouse","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Oral",5000,"mg/L water","Change","Hepatic steatosis with excessive lipid droplet formation was observed."]
[95,"Target organ toxicity","Liver (fat metabolism)","Mouse","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Oral",5000,"mg/L","Change","There were significant differences in the expression levels of the genes SREBP1C, SREBP2, Fasn, Hmgcr, Hmgcs and PPARa.\nThe relative expression levels of the genes SREBP1C, SREBP2, Fasn, Acc, Scd, Hmgcr, Hmgcs1 and Hmgcs2 showed a significant increase in GD19 fetuses and PND7 and PND21 offspring. These genes are closely related to hepatic lipid production, so their elevation contributes to increased fat storage. However, this kind of increase does not match well to the trend in serum lipid content alteration. The levels of PPARa in PND7 males and PND21 females increased remarkably, which is likely due to the growing demand for lipid catabolism caused by the increased lipid content.\n(The expression levels of the genes SREBP1C (Sterol Regulatory Element Binding Protein 1C), SREBP2 (Sterol Regulatory Element Binding Protein 2), Fasn (Fatty acid synthase, which catalyzes fatty acid synthesis), Scd (Stearoyl-CoA Desaturase 1), Acc (Acetyl-CoACarboxylase), Hmgcr (3-hydroxy-3-methyl-glutaryl-CoA reductase), Hmgcs1 (3-hydroxy-3-methylglutaryl-CoA synthase 1), Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthase 2) and PPARa (Peroxisome proliferator-activated receptor alpha) were determined. The relative expression levels of the above genes were normalized to b-actin expression.)"]
[1,"Target organ toxicity","Liver weight","Rat",90,"Days","Oral",10000,"ppm","Decrease","Absolute organ weight was reduced in males only at 1000 and 20000 ppm, no consistent trend, changes at 20000 ppm attributed to reduced body weight observed at this dose level."]
[2,"Target organ toxicity","Liver weight","Rat",90,"Days","Oral",50000,"ppm","Increase","Relative organ weight was increased in both sexes at 50000 ppm. However, histopathological changes were not observed."]
[3,"Target organ toxicity","Liver weight","Rat",90,"Days","Oral",">30000","ppm","No effect","Relative organ weight was increased in females only at 30000 ppm, which is not treatment-related but attributed to the genetic disorder of one animal"]
[4,"Target organ toxicity","Liver weight","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"Target organ toxicity","Liver weight","Dog",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[6,"Target organ toxicity","Liver weight","Dog",90,"Days","Oral",">10000","ppm","No effect"]
[7,"Target organ toxicity","Liver weight","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"Target organ toxicity","Liver weight","Dog",90,"Days","Oral",10000,"ppm","Increase","Absolute and relative organ weight was increased in males at ≥ 10000 ppm, but considered toxicologically not relevant due to the absence of histopathological findings"]
[9,"Target organ toxicity","Liver weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"Target organ toxicity","Liver weight","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"Target organ toxicity","Liver weight","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"Target organ toxicity","Liver weight","Rat",1,"Year","Oral",">20000","ppm","No effect","Absolute weight was reduced in females only at 8000 ppm, not dose-related and thus considered not treatment-related."]
[13,"Target organ toxicity","Liver weight","Rat",2,"Years","Oral",">10000","ppm","No effect","Interim kill: no change\nTerminal kill: weighing not performed as too many tumors were present"]
[14,"Target organ toxicity","Liver weight","Rat",2,"Years","Oral",">30000","ppm","No effect","Increased relative weight in males at 30000 ppm in week 26. Since this was observed in week 26 only it is considered incidental."]
[15,"Target organ toxicity","Liver weight","Rat",2,"Years","Oral",20000,"ppm","Decrease","Absolute and relative organ weight decreased (-7%) in interim killed males at 20000 ppm."]
[16,"Target organ toxicity","Liver weight","Rat",2,"Years","Oral",100,"mg/kg bw/day","Decrease","Relative organ weight reduced in interim kill in females at ≥ 100 mg/kg bw/day but no histopathological changes were observed. Absolute organ weight was reduced in interim kill females at 100 and 1000 mg/kg bw/day)"]
[17,"Target organ toxicity","Liver weight","Rat",2,"Years","Oral",20000,"ppm","Increase","Relative organ weight increased at interim kill, absolute and relative (to brain weight) weight increased at terminal kill in males at 20000 ppm."]
[18,"Target organ toxicity","Liver weight","Rat",2,"Years","Oral",">15000","ppm","No effect"]
[19,"Target organ toxicity","Liver weight","Mouse",18,"Months","Oral",">10000","ppm","No effect"]
[20,"Target organ toxicity","Liver weight","Mouse",18,"Months","Oral",">5000","ppm","No effect"]
[21,"Target organ toxicity","Liver weight","Mouse",18,"Months","Oral",">40000","ppm","No effect"]
[22,"Target organ toxicity","Liver weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect","Absolute and relative weight increased in F0 and F1 females only at 15000 ppm without any histopathological findings. Therefore, increased organ weight is considered to be adaptive and non-adverse."]
[23,"Target organ toxicity","Liver weight","Rat","10 (pre-mating)","Weeks","Oral",10000,"ppm","Increase","Relative organ weight increased in F0 males at 10000 ppm, absolute values comparable to control group,  considered to be incidental"]
[24,"Target organ toxicity","Liver weight","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",30000,"ppm","Increase","Relative organ weight increased in F0+F1 males and females at 30000 ppm without any histopathological changes. "]
[26,"Target organ toxicity","Liver weight","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[44,"Target organ toxicity","Liver weight","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[45,"Target organ toxicity","Liver weight","Rat","31 (PND 23-53)","Days","Oral",300,"mg/kg bw/day","Decrease","Statictically significantly lower mean absolute liver weight (15.1% and 9.8% for 1000 and 300 mg/kg bw/day dose group, respectively) was observed. The effect was considered secondary to the decreased body weight changes."]
[49,"Target organ toxicity","Liver weight","Rat",28,"Days","Oral",">20000","ppm","No effect","Neither absolute nor relative organ weight was affected."]
[50,"Target organ toxicity","Liver weight","Rat",28,"Days","Oral",">2500","mg/kg bw/day","No effect"]
[51,"Target organ toxicity","Liver weight","Dog","Study part A: 21\nStudy Part B: 14","Days","Oral",">1000","mg/kg bw/day","No effect"]
[52,"Target organ toxicity","Liver weight","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Target organ toxicity","Liver weight","Rat",90,"Days","Oral",6000,"ppm","Decrease","Decreased absolute and relative organ weight at 20000 ppm in males only, statistically not significant, and decreased relative weight at 6000 ppm in males. However, no histopathological changes were obserevd."]
[54,"Target organ toxicity","Liver weight","Rat",90,"Days","Oral",">20000","ppm","No effect","No effect on absolute and relative organ weight was observed."]
[55,"Target organ toxicity","Liver weight","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"Target organ toxicity","Liver weight","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect","Liver was weighed together with gall bladder."]
[57,"Target organ toxicity","Liver weight","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","No effect on relative and absolute organ weight was observed."]
[58,"Target organ toxicity","Liver weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[59,"Target organ toxicity","Liver weight","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Liver and drained gall bladder were weighed. Absolute and relative organ weights were not affected."]
[60,"Target organ toxicity","Liver weight","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[61,"Target organ toxicity","Liver weight","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[62,"Target organ toxicity","Liver weight","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[63,"Target organ toxicity","Liver weight","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect","Absolute and organ weight relative to brain weight was assessed."]
[67,"Target organ toxicity","Liver weight","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Liver with gall bladder was weighed. Absolute organ weight was not affected."]
[68,"Target organ toxicity","Liver weight","Mouse",2,"Years","Oral","> 30000","ppm","No effect","The mean absolute and relative (to body and brain weight) liver weight were not affected."]
[70,"Target organ toxicity","Liver weight","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring."]
[70,"Target organ toxicity","Liver weight","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Mean liver weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females from the F0, F1, and F2 generation. In the F2 female group, mean liver/body weight ratios were significantly lower than control in each of the treated groups; however, no clear dose-relationship was apparent. Mean liver/brain weight ratios for the treated F2 females were lower than control; however, these differences from control values were not statistically significant."]
[73,"Target organ toxicity","Liver weight","Mouse",90,"Days","Oral",">50000","ppm","No effect","Relative organ weight (relative to body weight) was increased ( M 10000 ppm=+9%*; M 50000 ppm=+12%* ) which was attributed to lower terminal body weight and thus not of toxicological relevance. No effects on absolute as well as relative (to brain weight) organ weight were observed."]
[76,"Target organ toxicity","Liver weight","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[78,"Target organ toxicity","Liver weight","Rat",90,"Days","Oral",50000,"ppm","Increase","Increase in relative organ weight observed in males only (at 6250 ppm; 12500 ppm; 25000 ppm and 50000 ppm)."]
[79,"Target organ toxicity","Liver weight","Mouse",90,"Days","Oral",6250,"ppm","Increase","Increase in relative organ weight observed in males only (at 6250 ppm; 12500 ppm; 25000 ppm; 50000 ppm)."]
[8,"Target organ toxicity","Lung histopathology","Dog",90,"Days","Oral",">50000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Minor granulomatous/inflammatory lesions were occasionally observed, no dose-relation, incidental, not treatment-related)","Organ specific toxicity of glyphosate was not observed in lung in three species up to a chronic exposure period. "]
[10,"Target organ toxicity","Lung histopathology","Dog",1,"Year","Oral",">50000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Slight focal pneumonia / focal granulumatous pneumonia in 1/4, 1/4, 1/4 and 4/4 females at 0, 1600, 8000 and 50000 ppm, common finding in untreated rats, statistically not significant, not related to treatment)"]
[13,"Target organ toxicity","Lung histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Interim kill: no treatment-related findings (petechiae/ecchymoses, collapse, consolidation, emphysema at gross necropsy, congestion, atelectatis, perivascular lymphocytic aggregations at histopathology, findings were explained by subclinical infections or age-related),\nterminal kill: no treatment related findings (suppurative pneumonia/ bronchopneumonia in 26/56, 21/54, 20/49 and 21/50 dead and moribund rats and chronic inflammation in 7/44, 6/46, 5/50 and 8/50 surviving rats of the 0, 100, 1000 and 10000 ppm group at histopathology; consolidation/ focal consolidation in 19/56, 13/54, 12/49 and 18/50 rats at gross necropsy in the 0, 100, 1000 and 10000 ppm group); neoplastic, dead/moribund rats: no treatment-related findings (adenoma in 1/24 females at 100 ppm; metastatic histiocytic sarcoma in 1/30, 1/31 and 1/21 males at 0, 1000 and 10000 ppm and in 1/26 females at 0 ppm; metaastatic cholangiosarcoma in 1/30 males at 100 ppm; metastatic hepatocellular carcinoma in 1/30 and 1/21 males at 100 and 10000 ppm; bronchio alveolar adenoma in 1/17 females at 1000 ppm; metastatic squamous cell carcinoma in 1/30 males at 0 ppm; giant cell tumor in 1/21 males at 10000 ppm; fibroma in 1/24 females at 100 ppm; metastatic round cell sarcoma in 1/17 females at 1000 ppm); neoplastic, surviving rats: no treatment-related findings (bronchio-alveolar adenocarcinoma in 1/3 males at 1000 ppm; metastatic hepatocellular carcinoma in 1/3 males at 1000 ppm; bronchio-alveolar adenoma in 1/24 females at 0 ppm; histiocytic sarcoma in 1/5 females at 1000 ppm)"]
[14,"Target organ toxicity","Lung histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Gross necropsy: no abnormalities observed; Histopathology, non-neoplastic: animals at terminal kill: decreased incidences of foam cell aggregation in males at 30000 ppm: 6/18, 6/20, 2/18 and 2/29 at 0, 3000, 10000 and 30000 ppm; neoplastic: no treatment-related findings)"]
[15,"Target organ toxicity","Lung histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Gross necropsy: increased incidences of mottled lungs in males at 20000 ppm, not treatment-related; Histopathology, non-neoplastic and neoplastic: no treatment-related findings)"]
[18,"Target organ toxicity","Lung histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Histopathology, non-neoplastic: no treatment-related findings (accumulations of perivascular/peribroncheolar lymphocytes among all groups, statistically significantly increased in females at 15000 ppm, considered to be without toxicological significance as the difference was numerically small; lower incidence and severity of accumulations of alveolar macrophages in females at 15000 ppm, non-adverse; focal pneumonitis, cuboidal cell metaplasia, thickening of alveolar walls, thrombus formation, granulomas reaction, diffuse mononuclear cell infiltrates, abscess formation and pleural thickening occasionally observed among all groups, not treatment-related); neoplastic: no pulmonary neoplastic findings)"]
[19,"Target organ toxicity","Lung histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Histopathology, neoplastic findings: 11 tumors observed, mostly bronchioalveolar adenomas, no treatment relation)"]
[20,"Target organ toxicity","Lung histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic: no treatment-related findings (accumulation of perivascular/peribronchiolar lymphocytes, accumulation of alveolar macrophages, associated with pulmonary neoplasia, focal pneumonitis, focal fibrosis, hyperplasia of the bronchioloar epithelium, focal pleural thickening, foci/area of haemorrhage, granulomatous foci, thrombus formation, perivascular acute inflammatory cells occasionally observed; cuboidal cell metaplasia of the alveolar in few animals, pre-neoplastic change); neoplastic: no treatment-related findings (adenoma in 2/12 interim dead males at 1500 ppm, in 9/39, 7/41, 7/39 and 4/35 terminal kill males  and 2/37, 4/38, 2/38 and 2/40 terminal kill females at 0, 500, 1500 and 5000 ppm; adenocarcinoma in 2/12, 1/10, 2/12 and 2/16 interim dead males and in 3/39, 4/41, 5/39 and 9/35 terminal kill males and in 5/37, 2/38, 2/38 and 3/40 terminal kill females at 0, 500, 1500 and 5000 ppm)"]
[21,"Target organ toxicity","Lung histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Gross pathology: masses in 9/50, 14/50, 17/50 and 15/50 males and in 10/50, 8/50, 20/50 and 11/50 females at 0, 1600, 8000 and 40000 ppm, findings predominantly observed at terminal kill, no dose relation; histopathology, non-neoplastic: no treatment-related findings (increased alveolar epithelial cell hyperplasia in males at 1600 ppm, no dose-response relationship); neoplastic: no treatment-related findings)"]
[25,"Target organ toxicity","Lung histopathology","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect","Gross pathology: Low incidences of consolidation, ecchymoses, collapse and/or emphysema in F0 and F1 adults, not dose- or treatment-related, 1/30 F0 females at 100 ppm died because of suppurative pneumonia."]
[49,"Target organ toxicity","Lung histopathology","Rat",28,"Days","Oral",20000,"ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Gross necropsy: Petechiae in 1/5 males and 2/5 recovery males at 20000 ppm, ecchymosis in 1/5 males at 20000 ppm, focal congestion in 1/5 males and 1/5 females at 20000 ppm; all findings were considered to be incidental; Histopathology: Lymphoid hyperplasia in 1/5 and 5/5 males and in 2/5 and 1/5 females at 0 and 20000 ppm, considered to be incidental as the severity was not increased in the high dose group; increased incidences of congestion, atelectasis, interstitial pneumonia, perivascular leucocytic infiltration and perivascular lymphocytic aggregation were comparable between treated and control animals)"]
[52,"Target organ toxicity","Lung histopathology","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Target organ toxicity","Lung histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Focal mineralisation of the vascular intima was commonly observed in both sexes of all groups, general finding among laboratory rats, not regarded as treatment-related. Trachea was analysed as well and no changes were observed.)"]
[54,"Target organ toxicity","Lung histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","No relevant treatment-related histopathological changes were observed. "]
[55,"Target organ toxicity","Lung histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"Target organ toxicity","Lung histopathology","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"Target organ toxicity","Lung histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"Target organ toxicity","Lung histopathology","Dog",12,"Months","Oral",">500","mg/kg bw/day","No effect","Lung and trachea were examined."]
[59,"Target organ toxicity","Lung histopathology","Dog",1,"Years","Oral",">1000","mg/kg bw/day","No effect","No relevant treatment-related histopathological changes were observed. \n(Gross necropsy: Pale or dark patches were commonly observed among all groups, not treatment-related; Histopathology: Performed for trachea and lung. Localised inflammatory lesions including small granulomas correlating with macroscopical findings in lung in 1/4, 3/4, 1/4 and 3/4 males and in 1/4, 1/4, 0/4 and 0/4 females at 0, 30, 300 and 1000 mg/kg bw/day, not treatment-related)"]
[65,"Target organ toxicity","Lung histopathology","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","Histopathology was not performed. During macroscopic examination (necropsy) no treatment-related findings were observed. "]
[67,"Target organ toxicity","Lung histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","flocoumafen\n(Gross pathology: Incidence of lung masses was slightly higher in the male high dose group (18/50) compared to control (10/50). No effect in females was observed. Moreover, there was little difference between the groups in the numbers of tumours after histological evaluation. Therefore, the necropsy finding is considered incidental.)"]
[67,"Target organ toxicity","Lung histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"Target organ toxicity","Lung histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"Target organ toxicity","Lung histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Lung histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"Target organ toxicity","Lung histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect","No relevant treatment-related histopathological changes were observed.  \n(Pneumonitis 1/10 M (control), 2/10 M (50000ppm), 1/10 F (control), 2/10 F (50000ppm); peribronchial lymphoid hyperplasia 4/10 M (control), 5/10 M (50000ppm), 1/10 F (control), 2/10 F (50000ppm); perivascullar lymphoid hyperplasia 2/10 M (control), 2/10 F (control), 1/10 F (50000 ppm))."]
[74,"Target organ toxicity","Lung histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"Target organ toxicity","Lung histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[76,"Target organ toxicity","Lung histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[56,"Target organ toxicity","Lung weight","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect","Lung weight was not affected."]
["59a","Target organ toxicity","Lung weight","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Absolute and relative lung weight was not affected."]
[67,"Target organ toxicity","Lung weight","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","No effect on absolute lung weight was observed. "]
[78,"Target organ toxicity","Lung weight","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[79,"Target organ toxicity","Lung weight","Mouse",90,"Days","Oral",6250,"ppm","Increase","Relative lung weight was increased in males (M at 6250 ppm; 12500 ppm; 25000 ppm; 50000 ppm; F no treatment-related effects)."]
[13,"Target organ toxicity","Trachea histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed.  \n(Suppurative inflammation in 4/56, 10/54, 1/49 and 6/50 dead and moribund rats and chronic inflammation in 6/44, 0/46, 0/50 and 8/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, not treatment-related; Neoplastic findings, surviving animals: no treatment-related findings (metastatic histiocytic sarcoma in 1/1 females at 100 ppm)\n"]
[18,"Target organ toxicity","Trachea histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed.  \n(Non-neoplastic: no treatment-related findings (dilatation of subepithelial glands noted in a few control and treated rats of either sex; isolated instances of inflammation and excess mineralisation of cartilage; neoplastic: no neoplasms observed)"]
[55,"Target organ toxicity","Trachea histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[67,"Target organ toxicity","Trachea histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"Target organ toxicity","Trachea histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"Target organ toxicity","Trachea histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Trachea histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[76,"Target organ toxicity","Trachea histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[8,"Target organ toxicity","Lymph nodes histopathology","Dog",90,"Days","Oral",">50000","ppm","No effect","No relevant treatment-related histopathological changes were observed.  \n(Minor granulomatous/inflammatory lesions were occasionally observed, no dose-relation, incidental, not treatment-related)","Organ specific toxicity of glyphosate was not observed in lymph nodes in three species up to a chronic exposure period. "]
[13,"Target organ toxicity","Lymph nodes histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed.  \n(Interim kill: no findings; terminal kill: lymphoid hyperplasia of the mandibular lymph node in 11/56, 30/54, 15/49 and 23/50 dead and moribund rats and 24/44, 14/46, 10/50 and 35/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, no dose-relation (not treatment-related: lymphoid hyperplasia of the mediastinal lymph nodes at 100 ppm in dead/moribund rats); neoplastic findings, dead/moribund rats: no treatment-related findings in mediastinal lymph nodes (metastatic histiocytic sarcoma in 1/28 and 1/30 males at 0 and 1000 ppm and in 1/26 females at 0 ppm; metastatic cholangiocarcinoma in 1/28 males at 100 ppm and in 1/26 females at 0 ppm; metastatic hepatocellular carcinoma in 1/28 males at 100 ppm; giant cell tumor and histiocytic sarcoma in 1/20 males at 10000 ppm); neoplastic findings, surviving rats: no treatment-related findings (histiocytic sarcoma of mesenteric lymph nodes in 1/20 males at 0 ppm; histiocytic sarcoma of mediastinal lymph nodes in 1 of 1/26 examined female tissues at 100 ppm; lymphoma of mandibular lymph nodes in 2/29 males at 10000 ppm))"]
[14,"Target organ toxicity","Lymph nodes histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect","No relevant treatment-related histopathological changes were observed.  \n(Gross necropsy: no abnormalities observed; Histopathology, non-neoplastic: animals found dead/killed in extremis: decreased incidences of plasma cell hyperplasia in females at 30000 ppm: 5/35, 2/31, 2/34 and 0/36 at 0, 3000, 10000 and 30000 ppm; neoplastic: no treatment-related findings)\n"]
[15,"Target organ toxicity","Lymph nodes histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect","No relevant treatment-related histopathological changes were observed.  \n(Gross necropsy: increased incidences of cystic changes at cervical lymph node in males at 20000 ppm, enlarged redded thymic lymph nodes in females at ≥ 6000 ppm, not treatment-related; histopathology, non-neoplastic and neoplastic findings: no treatment-related findings)"]
[18,"Target organ toxicity","Lymph nodes histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed.  \n(Non-neoplastic: no treatment-related findings (cysts, cystic distentiion of sinusoids, lymphoid atrophy, accumulations histiocytes, focal endothelial hyperplasia and haemorrhage were occasionally observed, common findings in aging rats); neoplastic: no treatment-related findings (angioma, angiosarcoma in 11/51, 4/51, 3/51 and 6/51 males and in 3/51, 1/51, 0/51 and 1/51 females at 0, 1500, 5000 and 15000 ppm))"]
[19,"Target organ toxicity","Lymph nodes histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed.  \n(Non-neoplastic findings dead/moribund animals: mandibular lymph node hyperplasia in 6/22, 5/20, 3/22 and 7/27 males and 3/16, 3/16, 2/20 and 6/20 females at 0, 100, 1000 and 10000 ppm; extramedullary hematopoesis in 3/22, 2/20, 5/22 and 3/27 males and 1/16, 1/16, 1/20 and 2/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related; non-neoplastic findings terminal kill animals: mesenteric lymph nodes hyperplasia in 12/28, 12/30, 17/28 and 9/23 males and 13/34, 20/34, 16/30 and 11/30 females at 0, 100, 1000 and 10000 ppm; meseneteric extramedullary hematopoesis in 8/28, 10/30, 9/28 and 6/23 males and 6/34, 9/34, 4/30 and 8/30 females at 0, 100, 1000 and 10000 ppm; mandibular lymph node hyperplasia in 13/28, 24/30, 24/28 and 14/23 males and 21/34, 24/34, 23/30 and 11/30 females at 0, 100, 1000 and 10000 ppm; mandibular extramedullary hematopoesis in 5/28, 7/30, 9/28 and 9/23 males and 3/34, 9/34, 7/30 and 4/30 females at 0, 100, 1000 and 10000 ppm, considered to be incidental; hyperplasia in superficial ing lymph nodes in 3/28, 0/30, 0/28 and 6/23 males and 6/34, 2/34, 0/30 and 6/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related)\nhistopathology, neoplastic findings: mesenteric lymph nodes: 9 tumours observed among all groups (1/16 and 2/20 dead/moribund females at 0 and 10000 ppm, 1/16 dead/moribund males at 100 ppm and 1/28, 1/27 and 1/23 terminal kill males at 0, 1000 and 10000 ppm and in 2/30 terminal kill females at 10000 ppm), mostly hemangiomas (7/9), no treatment relation"]
[20,"Target organ toxicity","Lymph nodes histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed.  \n(Non-neoplastic findings: no treatment-related findings (myelopoiesis, lymphoid hyperplasia, histiocytosis and angiectasis occasionally observed, age-related); neoplastic findings: no treatment-related findings (malignant lymphoma in 0/51, 1/51, 2/51 and 5/51 males and 11/51, 8/51, 10/51 and 11/51 females at 0, 500, 1500 and 5000 ppm; histiocystic sarcoma in a few females observed))"]
[21,"Target organ toxicity","Lymph nodes histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect","No relevant treatment-related histopathological changes were observed.  \n(Gross pathology: swelling of cervical lymph nodes, reduced incidence in females at 8000 ppm, increased incidence swelling of mesenteric lymph nodes in males at  40000ppm (0/50 in control, 6/50 at 40000 ppm with 5/6 in animals found dead/killed in extrmis), increased incidence of swollen lymph nodes in females found dead/killed in extremis at ≥ 8000 ppm; histopathology, non-neoplastic findings: no treatment-related findings (decreased incidence of plasma cell hyperplasia in females at ≥ 8000 ppm, attributed to decreased occurence of skin lesions in the treated groups; decreased incidences of myeloid cell aggregation in males at 1600 ppm); neoplastic findings: haematopoetic and lymphatic system, malignant lymphoma in 2/29 terminal kill males at 40000 ppm and in 4/32, 0/36, 5/40 and 3/35 terminal kill females at 0, 1600, 8000 and 40000 ppm, considered to be incidental)"]
[49,"Target organ toxicity","Lymph nodes histopathology","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[52,"Target organ toxicity","Lymph nodes histopathology","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect","Mesenteric lymph nodes"]
[53,"Target organ toxicity","Lymph nodes histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"Target organ toxicity","Lymph nodes histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","Histopathology was performed for control and high dose group animals only for mesenteric, submandibular lymph nodes."]
[57,"Target organ toxicity","Lymph nodes histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"Target organ toxicity","Lymph nodes histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Mesenteric lymph nodes were examined."]
[59,"Target organ toxicity","Lymph nodes histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Submandibular and mesenteric lymph nodes were examined."]
[67,"Target organ toxicity","Lymph nodes histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Mesentric lymph nodes were investigated."]
[68,"Target organ toxicity","Lymph nodes histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect","Mediastinal, mesenteric and regional lymph nodes were examined."]
[70,"Target organ toxicity","Lymph nodes histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Mesenteric, mandibular, and cervical lymph nodes: No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Lymph nodes histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","Mesenteric and cervical lymph nodes: No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"Target organ toxicity","Lymph nodes histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect","No effect on mesenteric lymph nodes was observed."]
[76,"Target organ toxicity","Lymph nodes histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[13,"Target organ toxicity","Pancreas histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed. (Neoplastic findings, dead/moribund animals: no treatment-related findings: islet adenoma in 1/28 males of the 0 ppm group; metastatic cholangio-carcinoma in 1/30 males at 100 ppm and 1/26 females at 0 ppm; undifferentiated metastatic sarcoma in 1/32 males at 1000 ppm and metastatic histiocytic sarcoma in 1/26 females at 0 ppm, considered to be incidental; neoplastic findings, surviving animals: no treatment-related findings: islet cell adenoma in 1/20 and 1/29 males at 0 and 10000 ppm and in 1/21 females at 10000 ppm; metastatic lymphosarcoma in 1/20 males at 0 ppm)","Organ specific toxicity of glyphosate was not observed in pancreas in three species up to a chronic exposure period. "]
[14,"Target organ toxicity","Pancreas histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect","No relevant treatment-related histopathological changes were observed. (Gross necropsy: no abnormalities observed; histopathology, non-neoplastic: animals at terminal kill: acinar cell atrophy in males at 3000 ppm: 3/18, 10/20, 7/18 and 10/29 and arteritis in males at 3000 ppm: 0/18, 5/20, 1/18, 3/29 at 0, 3000, 10000 and 30000 ppm; histopathology, neoplastic: no treatment-related findings)"]
[15,"Target organ toxicity","Pancreas histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect","Slight exocrine hyperplasia was observed in males at 20000 ppm but incidences were within historical control data and considered not treatment-related."]
[17,"Target organ toxicity","Pancreas histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect","No relevant treatment-related histopathological changes were observed. (Pancreas islet cell adenomas in males at 2000 ppm, not dose-related (2/58, 8/57, 5/60 and 7/59 males and 5/60, 1/60, 4/60 and 0/59 females at 0, 2000, 8000 and 20000 ppm), not attributed to treatment; no further corresponding effects of hyperplasia or carcinoma)"]
[18,"Target organ toxicity","Pancreas histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed. (Non-neoplastic: no treatment-related findings (islet cell hyperplasia frequently noted in males and occasionally in females, no dose relation; lower incidence of exocrine atrophy in males at 15000 ppm; occasional observations of exocrine hypertrophy, inflammatory lesions, cystic distention, dilatation or epithelial hyperplasia of ducts, peripheral abscess formation; neoplastic: no treatment-related findings (islet cell adenoma/carcinoma in 4/51, 1/51, 2/51 and 1/51 males and in 0/51, 0/51, 1/51 and 0/51 females at 0, 1500, 5000 and 15000 ppm))"]
[19,"Target organ toxicity","Pancreas histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic findings dead/moribund animals: amyloidosis in 1/22, 6/20, 4/22 and 4/27 males at 0, 100, 1000 and 10000 ppm and in 1/16 control females, not treatment-related)"]
[20,"Target organ toxicity","Pancreas histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic findings: no treatment-related findings (exocrine atrophy, exocrine cell hyperplasia, areas of necrosis, interstitial fibrosis, prominent lymphoid foci occasionally seen; islet cell hyperplasia occasionally; neoplastic findings: no treatment-related findings (islet cell adenocarcinoma in 1/51 control females))"]
[22,"Target organ toxicity","Pancreas histopathology","Rat",10,"Weeks","Oral",">15000","ppm","No effect","Gross necropsy: no treatment-related findings (enlarged and fluid-filled in the dead control female of the F1 generation)"]
[26,"Target organ toxicity","Pancreas histopathology","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect","Gross necropsy: Pale and oedematous pancreas in 1/28 F0 males at 10000 ppm which died during the course of the study, not treatment-related"]
[49,"Target organ toxicity","Pancreas histopathology","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[52,"Target organ toxicity","Pancreas histopathology","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Target organ toxicity","Pancreas histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[54,"Target organ toxicity","Pancreas histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"Target organ toxicity","Pancreas histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(3/12 males at 20000 ppm had chronic or active inflammation of the pancreatic islets which extended into the acinar parenchyma in 2/3 animals, common finding in rats of this strain, thus considered to be incidental.)"]
[57,"Target organ toxicity","Pancreas histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"Target organ toxicity","Pancreas histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"Target organ toxicity","Pancreas histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[67,"Target organ toxicity","Pancreas histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"Target organ toxicity","Pancreas histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"Target organ toxicity","Pancreas histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Pancreas histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"Target organ toxicity","Pancreas histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[74,"Target organ toxicity","Pancreas histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"Target organ toxicity","Pancreas histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[76,"Target organ toxicity","Pancreas histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[59,"Target organ toxicity","Pancreas weight","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Relative and absolute pancreas weight was not affected."]
[14,"Target organ toxicity","Peripheral nerve histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Gross necropsy: no abnormalities observed; Histopathology, non-neoplastic: terminal kill animals: decreased incidences of sciatic nerve fibre degerenation in females at 3000 ppm: 5/15, 1/19, 3/16 and 1/14 at 0, 3000, 10000 and 30000 ppm; neoplastic: no treatment-related findings)\n","Organ specific toxicity of glyphosate was not observed in peripheral nerves in three species up to a chronic exposure period. "]
[18,"Target organ toxicity","Peripheral nerve histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed. \n(Non-neoplastic: no treatment-related findings (fibre degeneration/necrosis in a few treated and control animals, isolated instances of mononuclear cell infiltration and nuclear pyknosis); neoplastic: no neoplasms observed)"]
[20,"Target organ toxicity","Peripheral nerve histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic findings: no treatment-related findings (fibre degeneration in several control and treated females; isolated instances of focal mineralisation and neuritis); neoplastic findings: no neoplasms observed)"]
[55,"Target organ toxicity","Peripheral nerve histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","The sciatic nerve was examined."]
[58,"Target organ toxicity","Peripheral nerve histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","The sciatic nerve was examined."]
[57,"Sensitive to, but not diagnostic of, EATS","Pituitary histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","The sciatic nerve was examined."]
[59,"Target organ toxicity","Peripheral nerve histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","The sciatic nerve was examined."]
[67,"Target organ toxicity","Peripheral nerve histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","The sciatic nerve was examined."]
[68,"Target organ toxicity","Peripheral nerve histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect","The sciatic nerve was examined."]
[70,"Target organ toxicity","Peripheral nerve histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Sciatic nerve: No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Peripheral nerve histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","Sciatic nerve: No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[12,"Target organ toxicity","Salivary glands histopathology","Rat",1,"Year","Oral",8000,"ppm","Change","Mild focal basophilia of the acinar cells of the parotid salivary glands in both sexes at ≥ 8000 ppm, treatment-related but not toxicologically significant (2/24, 0/24, 3/24 and 13/24 males and 2/24, 0/24, 6/24 and 15/24 females at 0, 2000, 8000 and 20000 ppm)","In some oral rat studies and in one mouse study, cellular alterations in salivary glands were observed upon histopathological examination. The glyphosate taskforce believes these salivary gland findings are a non-adverse adaptive response to treatment with a low pH diet (See CA 5.10)."]
[16,"Target organ toxicity","Salivary glands histopathology","Rat",2,"Years","Oral",100,"mg/kg bw/day","Change","Interim kill: mild cellular alterations of submaxillary salivary glands at ≥ 300 mg/kg bw/day in males and at 1000 mg/kg bw/day in females; mild to severe cellular alterations of the parotid salivary gland in males at ≥ 100 mg/kg bw/day  and in females at ≥ 300 mg/kg bw/day, \nterminal kill:  cellular alterations of submaxillary salivary glands at ≥ 100 mg/kg bw/day in males and at 1000 mg/kg bw/day in females; cellular alterations of the parotid salivary gland in both sexes at ≥ 100 mg/kg bw/day"]
[18,"Target organ toxicity","Salivary glands histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","Histopathology, non-neoplastic: no treatment-related findings (isolated instances of secretory depletion, focal hyperplasia and focal hypertrophy of the mucous acini in the submandibulary gland)\nhistopathology, neoplastic: no treatment-related findings (acinar adenoma in the paratoid gland of 1/51 males at 15000 ppm, considered to be spontaneous)"]
[20,"Target organ toxicity","Salivary glands histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","Histopathology, non-neoplastic findings: no treatment-related findings (secretory depletion of the submandibular gland was frequently observed and more prevalent in females, no treatment related distribution; isolated instances if lymphocyte infiltration, distention of ducts, atrophy, abscess formation, hypertrophy of mucous acini and peripheral inflammation)\nhistopathology, neoplastic findings: no neoplastic lesions"]
[26,"Target organ toxicity","Salivary glands histopathology","Rat","10 prior to mating, continued until termination","Weeks","Oral",3000,"ppm","Change","Hypertrophy of acinar cells with prominent granular cytoplasms in the parotid salivary gland in F0 and F1 males and females at ≥ 3000 ppm and in the submaxillary salivary gland in F0 females at ≥ 3000 ppm, (parotid: 2/27, 2/28, 3/28 and 12/26 F0 males and 1/24, 0/24, 4/23 and 10/23 F1 males and in 0/28, 2/27, 5/28 and 17/28 F0 females and 0/24, 0/23, 4/24 and 9/23 F1 females at 0, 1000, 3000 and 10000 ppm; submaxillary: 0/28, 1/27, 4/28 and 14/28 F0 females and 0/24, 0/23, 0/28 and 3/23 F1 females at 0, 1000, 3000 and 10000 ppm)\nhypertrophy of acinar cells with prominent granular cytoplasms in the submaxillary salivary gland in females at ≥ 3000 ppm (0/28, 1/27, 4/28 and 14/28 F0 females and in 0/24, 0/23, 0/24 and 3/23 F1 females at 0, 1000, 3000 and 10000 ppm)"]
[52,"Target organ toxicity","Salivary glands histopathology","Rat",90,"Days","Oral",30,"mg/kg bw/day","Change","Increased incidence of cellular alteration in the parotid salivary glands in both sexes at 30, 300 and 1000 mg/kg bw/day and increased severity of cellular alteration in the parotid salivary glands in both sexes at 1000 mg/kg bw/day and in males at 300 mg/kg bw/day"]
[57,"Target organ toxicity","Salivary glands histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","Mandibular salivary glands were investigated."]
[58,"Target organ toxicity","Salivary glands histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Mandibular salivary glands were investigated."]
[59,"Target organ toxicity","Salivary glands histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Submaxillary, sublingual, parotid salivary glands were examined."]
[67,"Target organ toxicity","Salivary glands histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Parotid, sublingual and submaxilliar salivary glands were investigated. Histopathological examination was performed for control and high dose group."]
[68,"Target organ toxicity","Salivary glands histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect","Mandibular salivary glands were investigated."]
[69,"Target organ toxicity","Salivary glands histopathology","Rat","5.5 (GD 3 till 21 days post partum)","Weeks","Oral",3000,"ppm","Change","F0: Macroscopic changes to the salivary glands (enlarged/firm/congested/swollen) were observed in 0, 2, 6 and 8 animals respectively in Groups 1 to 4 of F0 generation.\nDose-related incidence and degree of granular basophilic cytoplasm of acinar cells was seen with 0, 2, 0 and 0 animals showing minimal effects, 0, 0, 2 and 0 animals showing moderate effects and 0, 0, 8 and 9 animals showing marked effects in Groups 1 to 4, respectively. This change was associated with hypertrophy of acinar cells with 0, 2, 2 and 0 animals with minimal hypertrophy and 0, 0, 8 and 9 animals in Groups 1 to 4 respectively with moderate hypertrophy of the acinar cells. Prominent mitoses were also seen in 2 animals at 30000 ppm, but not in lower treatment levels or the controls.\nF1: Post mortem examination of F1 generation at PND 42 revealed swollen/enlarged parotid salivary glands in 5/10 males and 2/10 females at 30000 ppm, and in 1/10 males at 3000 ppm. No histopathological examinations were performed."]
[69,"Target organ toxicity","Salivary glands histopathology","Rat","only secondary exposure through milk from PND 0-21","Weeks","Oral",3000,"ppm","Change","Post mortem examination of weanlings at PND 21 revealed four pups with congested salivary glands at 10000 ppm and one pup with congested salivary glands at 3000 ppm. Since no similar findings were seen at 30000 ppm the significance of these incidences is unclear. No histopathological examinations were performed."]
[70,"Target organ toxicity","Salivary glands histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Salivary glands histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[74,"Target organ toxicity","Salivary glands histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"Target organ toxicity","Salivary glands histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[76,"Target organ toxicity","Salivary glands histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[78,"Target organ toxicity","Salivary glands histopathology","Rat",90,"Days","Oral",3125,"ppm","Change","Parotid and submandibular salivary glands in M and F: Cytoplasmic alterations (basophilic change and hypertrophy of acinar cells) in M and F at 3125 ppm; 6250 ppm; 12500 ppm; 25000 ppm; 50000 ppm"]
[79,"Target organ toxicity","Salivary glands histopathology","Mouse",90,"Days","Oral",6250,"ppm","Change","Parotid salivary gland: Increase of basophilia in acinar cells (Cytoplasmic alteration) in M and F at 6250 ppm; 12500 ppm; 25000 ppm; 50000 ppm"]
[16,"[Not in list]","Salivary glands weight","Rat",2,"Years","Oral",100,"mg/kg bw/day","Increase","Paratoid salivary glands: Absolute and relative weight increased in interim kill males at ≥ 100 mg/kg bw/day\nSublingual and submaxillary salivary glands: Absolute and relative weight increased in interim kill animals of both sexes at 1000 mg/kg bw/day, increased abs+rel weight in terminal kill females at 300 mg/kg bw/day"]
[52,"[Not in list]","Salivary glands weight","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect","Salivary gland weights were weighed."]
[67,"[Not in list]","Salivary glands weight","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Salivary glands (paratoid, sublingual and submaxillary): Absolute organ weight was not affected."]
[18,"Target organ toxicity","Skeletal muscle histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic: no treatment-related findings (isolated instances of mononuclear cell foci, fibre atrophy and fibre degeneration/necrosis among all groups, age-related); neoplastic: no neoplasms observed)","No effects on the histopathology of skeletal muscels were observed in rats and mice including different life stages. "]
[20,"Target organ toxicity","Skeletal muscle histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Histopathology, non-neoplastic findings: no treatment-related findings (isolated instances of mononuclear cell foci, vasculitis and focal mineralisation, spontaneous changes); neoplastic findings: no neoplastic changes)"]
[67,"Target organ toxicity","Skeletal muscle histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Thigh was investigated. "]
[68,"Target organ toxicity","Skeletal muscle histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect","The biceps femoris was examined."]
[70,"Target organ toxicity","Skeletal muscle histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Skeletal muscle histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"Target organ toxicity","Skeletal muscle histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[7,"Target organ toxicity","Skin histopathology","Dog",90,"Days","Oral",">40000","ppm","No effect","Cutaneous histiocytoma in 1/4 females at 40000, not treatment-related","No specific effects on the histopathology of skin were observed in dogs, rats and mice. Hair loss was observed in some studies in rodents."]
[14,"Target organ toxicity","Skin histopathology","Rat",2,"Years","Oral",10000,"ppm","Change","No relevant treatment-related histopathological changes were observed.\n(Gross necropsy: all animals: hair loss in at 30000 ppm (treatment relation unclear); Histopathology, non-neoplastic: terminal kill animals: decreased incidences of plantar granuloma in males at 30000 ppm (12/18, 11/20, 11/18 and 8/29) and increased incidences in females at 10000 ppm (6/15, 8/19, 13/16 and 7/14) at 0, 3000, 10000 and 30000 ppm, animals found dead/killed in extremis: follicular hyperkeratosis in males at 30000 ppm (3/32, 2/30, 1/32 and 10/21) and plantar granuloma in females at 30000 ppm (3/35, 6/31, 7/34 and 10/36) at 0, 3000, 10000 and 30000 ppm; neoplastic: no treatment-related findings)"]
[18,"Target organ toxicity","Skin histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic: no treatment-related findings but several spontaneous lesions observed (dilatation of hair folicles, subepithelial inflammatory cell infiltrates, abscess formation, epidermal ulceration, cystic cutaneous lymph node, nodule fat necrosis, cystic hair follicles, keratin cyst formation, focal acanthosis, subcutaneous fibrosis and dermal thickening occasionally observed among all groups; areas of necrosis/giant cell reaction to keratin in males with statistically increased significance at 15000 ppm, secondary lesion associated with development of keratoacanthoma); histopathology, neoplastic: no treatment-related findings (8 types of cutaneous tumors with benign keratoacanthoma as most pervalent in male rats of all groups, 6 types of subcutaneous tumors among all groups, none of them with special prevalence; most of the tumor types diagnosed occured in males of all groups, 7 of them were fibrosarcoma))"]
[19,"Target organ toxicity","Skin histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Gross pathology, dead/moribund animals: alopecia/patchy alopecia in 2/22, 1/20, 0/22 and 3/27 males and 1/16, 0/16, 2/20 and 0/20 females at 0, 100, 1000 and 10000 ppm, not dose- or treatment-related; histopathology, non-neoplastic findings dead/moribund animals: epidermal hyperplasia in 10/22, 13/20, 7/22 and 10/27 males and 6/16, 5/16, 6/20 and 6/20 females at 0, 100, 1000 and 10000 ppm; suppurative necrotising dermatitis/healing in 5/22, 6/20, 2/22 and 5/27 males and 3/16, 1/16, 4/20 and 1/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related)"]
[20,"Target organ toxicity","Skin histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic: no treatment-related findings (several spontaneous lesions: epidermal ulceration, scab formation, inflammatory lesions, abscess formation, focal acanthosis, focal mineralisation, focal dermal thickening, focal necrosis occasionally observed; few instances of ectasia, atrophy or inflammation of unidentified subcutaneous glandular tissue); neoplastic: no treatment-related findings (dermal/subcutaneous fibrosarcoma in 6 males among all treatment-groups; haemangiosarcoma in 1/51 females at 500 ppm))"]
[21,"Target organ toxicity","Skin histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Gross pathology: no treatment-related findings (loss of hair increased in males at 8000 ppm and decreased in females at 40000 ppm, reduced incidences of wounds in males at 40000 ppm and reduced incidences of ulcer/erosion in females at ≥ 8000 ppm, reduced incidences of swelling in males at 1600 and 40000 ppm, no dose relation); Histopathology, non-neoplastic: no treatment-related findings;neoplastic: no treatment-related findings)"]
[29,"Target organ toxicity","Skin histopathology","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","Hair loss in 1/10 control females, not treatment-related"]
[60,"Target organ toxicity","Skin histopathology","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[62,"Target organ toxicity","Skin histopathology","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect","No treatment-related findings. Findings of inflammation evident as mild dermal inflammatory cell infiltrate was comparable for treated and untreated skin among all groups in both sexes. (Inflammation of treated skin in 3/5, 4/5, 3/5 and 3/5 males and of untreated skin in 5/5, 4/5, 4/5 and 3/5 males; inflammation of treated skin in 4/5, 4/5, 5/5 and 5/5 females and of untreated skin in 4/5, 5/5, 4/5 and 5/5 females))"]
[70,"Target organ toxicity","Skin histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Skin histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[6,"Target organ toxicity","Oesophagus histopathology","Dog",90,"Days","Oral",">10000","ppm","No effect","Minimal to mild lymphocytic infiltration was observed which was considered not treatment-related.","No specific effects on the GI tract including oesophagus, stomach and small intestines were observed in dog, mouse, rabbit, an rat. Distention of the caecum was observed in rat and mouse which is in line with the observation of increased absolute and relative weight of the caecum. "]
[20,"Target organ toxicity","Oesophagus histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","Histopathology, non-neoplastic: No treatment-related findings (background inflammatory lesions in a few animals)"]
[59,"Target organ toxicity","Oesophagus histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[67,"Target organ toxicity","Oesophagus histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"Target organ toxicity","Oesophagus histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"Target organ toxicity","Oesophagus histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Oesophagus histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[74,"Target organ toxicity","Oesophagus histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"Target organ toxicity","Oesophagus histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[78,"Target organ toxicity","Oesophagus histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[79,"Target organ toxicity","Oesophagus histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[17,"Target organ toxicity","Stomach histopathology","Rat",2,"Years","Oral",">20000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Histopathology: inflammation of gastric squamous mucosa in females at 8000 ppm (0/59, 3/60, 9/60 and 6/59 at 0, 2000, 8000 and 20000 ppm), findings predominantly observed in decedent animals, inflammation in surviving animals restricted to each one surviving male and female at 20000 ppm, no dose relation, considered not treatment-related)"]
[18,"Target organ toxicity","Stomach histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic: no treatment-related findings (acanthosis/hyperkeratosis in both sexes among all groups, no treatment relation; occasional observations included dilatation of gastric glands, subepithelial inflammatory cell infiltrates, acanthosis, hyperkeratosis, subepithelial oedema, ulceration of the forestomach or mucosa, mucosal erosion, focal mineralisation and mucosal atropy); neoplastic: no treatment-related findings (squamous papilloma in the forestomach of 1/51, 0/51, 2/51 and 1/51 males and 0/51, 1/51, 0/51 and 0/51 females at 0, 1500, 5000 and 15000 ppm)"]
[19,"Target organ toxicity","Stomach histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic findings dead/moribund animals: cystic glands in 8/22, 8/20, 9/22 and 16/27 males and 1/16, 4/16, 5/20 and 6/20 females at 0, 100, 1000 and 10000 ppm, within historical control range, considered to be incidental; non-neoplastic findings terminal kill animals: cystic glands in 9/28, 19/30, 22/28 and 17/23 males and 22/34, -/34, -/30 and 19/30 females at 0, 100, 1000 and 10000 ppm, no dose-dependent increase in severity)"]
[20,"Target organ toxicity","Stomach histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic findings: no treatment-related findings (mucosal hyperplasia commonly observed, age-related; acanthosis and hypokeratosis of the forestomach frequently observed in both sexes, no toxicological significance, subepithelial and mucosal inflammation, epithelial ulceration, mineralisation of the muscularis, diverticulum formation and focal mucosal necrosis occasionally observed); neoplastic findings: no gastric neoplasia observed)"]
[26,"Target organ toxicity","Stomach histopathology","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect","Gross necropsy: Thickened forestomach, invaginated stomach and abnormal contents in the gastrointestinal tract in one F0 female at 1000 ppm which was sacrificed on Day 2 post-partum, not treatment-related"]
[31,"Target organ toxicity","Stomach histopathology","Rabbit","13 (GD 7-19)","Days","Oral",400,"mg/kg bw/day","Change","Macroscopic findings in 2/4 females at 400 mg/kg bw/day that died/were killed in extremis, treatment-related (fluid-filled large intestines, haemorrhage, ulceration and sloughing of the stomach, duodenum, congestion and colon, rectum and appendix gas distended; the animal killed in extremis had blood and dead fetuses in the uterus, which was attributed to the general poor state of the animals)"]
[55,"Target organ toxicity","Stomach histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[57,"Target organ toxicity","Stomach histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","Stomach and oesophagus were histopathologically examined."]
[58,"Target organ toxicity","Stomach histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"Target organ toxicity","Stomach histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[67,"Target organ toxicity","Stomach histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Histopathological examination was performed of the glandular and non-glandular stomach."]
[68,"Target organ toxicity","Stomach histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[69,"Target organ toxicity","Stomach histopathology","Rat","5.5 (GD 3 till 21 days post partum)","Weeks","Oral",3000,"ppm","Change","Gross necropsy: Distended and/or congested stomach was seen in 0, 2, 5 and 4 animals in Groups 1 to 4 respectively. These findings generally followed the trend noted in the clinical signs observed. No histopathology performed."]
[70,"Target organ toxicity","Stomach histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Stomach histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"Target organ toxicity","Stomach histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect","No effect on gastro-intestinal tract was observed."]
[74,"Target organ toxicity","Stomach histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effect on gastro-intestinal tract was observed."]
[74,"Target organ toxicity","Stomach histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","F2: No effect on gastro-intestinal tract was observed."]
[76,"Target organ toxicity","Stomach histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect","No effect on gastro-intestinal tract was observed."]
[77,"Target organ toxicity","Stomach histopathology","Rabbit","22 (GD 6-27)","Days","Oral",">2500","mg/kg bw/day","No effect"]
[2,"Target organ toxicity","Small and large intestines histopathology","Rat",90,"Days","Oral",1000,"ppm","Change","Macroscopical findings: Caecum enlarged/distended and fluid-filled in 10/10 males and 10/10 females at 50000 ppm; microscopical findings: atrophy in 5/10 males and 5/10 females at 50000 ppm and for 1/10 males and 2/10 females at 10000 ppm, probably attributed to caecal distention "]
[3,"Target organ toxicity","Small and large intestines histopathology","Rat",90,"Days","Oral",10000,"ppm","Change","Macroscopic finding: Caecum distention in 9/12 males and 7/12 females at 30000 ppm and in 3/12 males and 0/12 females at 10000 ppm"]
[4,"Target organ toxicity","Small and large intestines histopathology","Mouse",90,"Days","Oral",50000,"ppm","Change","Macroscopic finding: Caecum distention in 12/12 males and 10/12 females at 50000 ppm and in 1/12 females at 10000 ppm at necropsy, no histopathological findings"]
[8,"Target organ toxicity","Small and large intestines histopathology","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[13,"Target organ toxicity","Small and large intestines histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Colon: no treatment-related findings (not treatment-related: colon lymphoid hyperplasia at histopathology in 4/56, 3/54, 8/49 and 3/50 dead and moribund rats and 8/44, 0/46, 0/50 and 12/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, considered age-related); Caecum: Neoplastic findings, surviving animals: no treatment-related findings (histiocytic sarcoma in 1 of 1/20 examined male tissues at 100 ppm))"]
[14,"Target organ toxicity","Small and large intestines histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Large intestine: Gross necropsy: no abnormalities observed; Histopathology, non-neoplastic: all animals: reduced incidences of granuloma in males at 10000 ppm (5/76, 3/75, 0/80 and 2/78 at 0, 3000, 10000 and 30000 ppm); neoplastic: no treatment-related findings)\n"]
[14,"Target organ toxicity","Small and large intestines histopathology","Rat",2,"Years","Oral",30000,"ppm","Change","Macroscopical finding: Significantly increased incidence of caecum distention  (m: 32/78; f: 18/78)  in both sexes at 30000 ppm , treatment-related but without histopathological abnormalities.\n"]
[18,"Target organ toxicity","Small and large intestines histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic: isolated instances of mucosal ulceration and diverticulum formation, not treatment-related; neoplastic: no treatment-related findings (leiomyoma in the rectum of 1/51 males at 5000 ppm and leiomyosarcoma in 1/51 females at 15000 ppm))"]
[19,"Target organ toxicity","Small and large intestines histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Rectum: non-neoplastic findings terminal kill animals: lymphoid hyperplasia in 2/28 and 0/23 males at 0 and 10000 ppm and in 0/34, 1/34, 1/30 and 4/30 females at 0, 100, 1000 and 10000 ppm, lower than histoircal control data, considered to be incidental)"]
[20,"Target organ toxicity","Small and large intestines histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Intestinal tract: non-neoplastic: no treatment-related findings (isolated instances of mucosal hypertrophy, mucosal hyperplasia, focal mucosal ulceration, submucosal oedema and inflammatory cell infiltration at various levels); neoplastic: no treatment-related findings (benign adenoma in 1/51 control females)"]
[21,"Target organ toxicity","Small and large intestines histopathology","Mouse",18,"Months","Oral",40000,"ppm","Change","Macroscopical finding: Caecum distention in males (28%) and females (36%) at 40000 ppm (14/50 males and 18/50 females at 40000 ppm, findings predominantly observed in terminal kill animals (11/29 males, 16/35 females); anal prolaps in the anus of 5/50 males at 40000 ppm, no findings in any other group, related to findings of loose stool\nHistopathology, non-neoplastic: no treatment-related findings; neoplastic: no treatment-related findings"]
[24,"Target organ toxicity","Small and large intestines histopathology","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",30000,"ppm","Change","Macroscopical finding: Distention of the caecum in F0 and F1 males and females at 30000 ppm was observed."]
[49,"Target organ toxicity","Small and large intestines histopathology","Rat",28,"Days","Oral",20000,"ppm","No effect","Histopathology colon: Lymphoid hyperplasia in 1/5 and 2/5 females at 0 and 20000 ppm, considered to be incidental as the severitiy was not increased in the high dose group"]
[53,"Target organ toxicity","Small and large intestines histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","Oesophagus and stomach were also analysed."]
[54,"Target organ toxicity","Small and large intestines histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Intestine: hyperplasia of lymphoid nodules in the submucosa of the duodenum, ileum and colon with varying frequencies and severity were considered as spontaneous lesions; No effect was observed on stomach.)"]
[55,"Target organ toxicity","Small and large intestines histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[57,"Target organ toxicity","Small and large intestines histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"Target organ toxicity","Small and large intestines histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"Target organ toxicity","Small and large intestines histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[67,"Target organ toxicity","Small and large intestines histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"Target organ toxicity","Small and large intestines histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[69,"Target organ toxicity","Small and large intestines histopathology","Rat","5.5 (GD 3 till 21 days post partum)","Weeks","Oral",3000,"ppm","Change","Gross pathology: Distended caecum was seen in 0, 0, 0 and 4 animals in Groups 1 to 4 respectively.Watery and/or dark contents in the gastro-intestinal tract were observed in 0, 2, 7 and 8 animals in Groups 1 to 4 respectively. These findings generally followed the trend noted in the clinical signs observed. No histopathology performed."]
[69,"Target organ toxicity","Small and large intestines histopathology","Rat","only secondary exposure through milk from PND 0-21","Weeks","Oral",">30000","ppm","No effect","No effect observed at necropsy."]
[69,"Target organ toxicity","Small and large intestines histopathology","Rat","3 (PND 21-42)","Weeks","Oral",30000,"ppm","Change","Gross pathology: Soft gastro-intestinal contents were noted in 7/10 males and 9/10 females at 30000 ppm; grey/blue contents of the jejunum were noted in 2/10 females at this dosage. No histopathological examinations were performed."]
[70,"Target organ toxicity","Small and large intestines histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","Duodenum, Ileum, Colon: No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Small and large intestines histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","Duodenum, Ileum, Colon: No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[3,"Target organ toxicity","Small and large intestines weight","Rat",90,"Days","Oral",30000,"ppm","Increase","Caecum: Absolute and relative weight statistically significantly increased in both sexes, which is in line with the observed distention."]
[4,"Target organ toxicity","Small and large intestines weight","Mouse",90,"Days","Oral",10000,"ppm","Increase","Caecum:  Absolute and relative weight increased (m: +15%/+11%; f: +22%/+17%) in both sexes at ≥ 10000 ppm (stat. significant at 50000 ppm), which is in line with the observed distention."]
[14,"Target organ toxicity","Small and large intestines weight","Rat",2,"Years","Oral",10000,"ppm","Increase","Caecum: Absolute and relative weight increased (>20%) in both sexes at 10000 ppm (occasional stat. significance), at 30000 ppm stat. significant over the entire study period, which is in line with the observed distention."]
[21,"Target organ toxicity","Small and large intestines weight","Mouse",18,"Months","Oral",40000,"ppm","Increase","Caecum: Absolute and relative weight stat. significantly increased in both sexes at 40000 ppm, which is in line with the observed distention."]
[18,"Target organ toxicity","Spinal cord histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic: isolated necrotic, degenerative or inflammatory lesions occasionally observed, no toxicological significance; neoplastic: no treatment-related findings (ependymoma in 1/51 females of the control group))","No effects on the histopathology of the spinal cord was observed in dog, mouse, and rat."]
[26,"Target organ toxicity","Spinal cord histopathology","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect"]
[55,"Target organ toxicity","Spinal cord histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect","Cervical, thoracic and lumbar sections of spinal cord were examined."]
[58,"Target organ toxicity","Spinal cord histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Cervical, midthoracic and lumbar sections of spinal cord were examined."]
[67,"Target organ toxicity","Spinal cord histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Cervical, thoracic and lumbar sections of spinal cord were examined."]
[68,"Target organ toxicity","Spinal cord histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"Target organ toxicity","Spinal cord histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Spinal cord histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"Target organ toxicity","Spinal cord histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[2,"Target organ toxicity","Spleen histopathology","Rat",90,"Days","Oral",">50000","ppm","No effect",null,"No specific effects on spleen were observed in dog, mouse, and rat."]
[13,"Target organ toxicity","Spleen histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Lymphoid hyperplasia in 2/56, 8/54, 2/49 and 4/50 dead and moribund rats and 7/44, 0/46, 3/50 and 2/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, not treatment-related; neoplastic findings, dead/moribund animals: no treatment-related findings (metastatic cholangiocarcinoma in 1/30 males at 100 ppm)"]
[14,"Target organ toxicity","Spleen histopathology","Rat",2,"Years","Oral",">30000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Gross necropsy: no abnormalities observed; histopathology, non-neoplastic: all animals: increased extramedullary hematopoesis in males at 10000 ppm (11/76, 18/75, 23/80 and 18/78 in males and 22/78, 28/79, 23/78 and 26/78 in females at 0, 3000, 10000 and 30000 ppm)\nterminal kill animals: increased extramedullary hematopoesis in males at 10000 ppm (1/18, 5/20, 8/18 and 6/29 in males and 10/15, 10/19, 11/16 and 9/14 females at 0, 3000, 10000 and 30000 ppm); neoplastic: no treatment-related findings)\n"]
[18,"Target organ toxicity","Spleen histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic: no treatment-related findings (extramedullary hematopoesis in the majority of rats among both sexes and all groups, within historical control data; atrophy of lymphoid tissue, atrophy of the red pulp, mononuclear cell proliferation, areas of necrosis and hyperaemia were occasionally observed); neoplastic: no treatment-related findings (angioma in 1/51 males at 15000 ppm and angiosarcoma in 1/51 control males))"]
[19,"Target organ toxicity","Spleen histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Gross pathology, dead/moribund animals: enlarged in 8/22, 8/20, 11/22 and 13/27 males and 10/16, 11/16, 12/20 and 7/20 females at 0, 100, 1000 and 10000 ppm, no dose depedency but associated with histopathological findings; terminal kill animals: enlarged in 8/28, 11/30, 11/28 and 10/23 males and 9/34, 15/34, 6/30 and 14/30 females at 0, 100, 1000 and 10000 ppm, not treatment-related, associated with neoplasia of the hemolymphoreticular system, amyloidosis and increased extramedullary hematopoesis; histopathology, non-neoplastic findings dead/moribund animals: increased extramedullary hematopoesis in 3/22, 7/20, 1/22 and 3/27 males and 5/16, 5/16, 3/20 and 6/20 females at 0, 100, 1000 and 10000 ppm; amyloidosis in 12/22, 8/20, 10/22 and 12/27 males and 5/16, 1/16, 4/20 and 4/20 females at 0, 100, 1000 and 10000 ppm, not treatment-related; non-neoplastic findings terminal kill animals: increased extramedullary hematopoesis in 10/28, 13/30, 11/28 and 5/23 males and 9/34, 18/34, 10/30 and 10/30 females at 0, 100, 1000 and 10000 ppm; amyloidosis in 10/28, 9/30, 9/28 and 8/23 males and 2/34, 5/34, 3/30 and 5/30 females at 0, 100, 1000 and 10000 ppm, no dose relation, considered to be incidental)"]
[20,"Target organ toxicity","Spleen histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic: no treatment-related findings (higher grades of severity of extramedullary haematopoesis frequently observed in mice of either sex; lymphoid hyperplsaia, atrophy of lymphoid tissue and of the red pulp, background changes); neoplastic: no treatment-related findings (haemangioma in 1/51 control males, haemangiosarcoma in 1/51 and 1/51 females at 0 and 5000 ppm))"]
[21,"Target organ toxicity","Spleen histopathology","Mouse",18,"Months","Oral",">40000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Gross pathology: reduced incidence in swelling of spleen in males at 1600 ppm and in females at 1600 and 8000 ppm, no dose relation; histopathology, non-neoplastic: no treatment-related findings (decreased incidences of extramedullary haematopoesis in  both sexes at 8000 ppm; amyloid deposition in females at ≥ 1600 ppm, attributed to decreased occurence of skin lesions in the treated groups); neoplastic: no treatment-related findings)"]
[22,"Target organ toxicity","Spleen histopathology","Rat",10,"Weeks","Oral",">15000","ppm","No effect","Gross necropsy: No treatment-related findings. "]
[29,"Target organ toxicity","Spleen histopathology","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect"]
[49,"Target organ toxicity","Spleen histopathology","Rat",28,"Days","Oral",">20000","ppm","No effect","Gross necropsy: thickening of capsule in 1/5 females at 20000 ppm in the recovery group, considered to be incidental as histopathological findings were absent"]
[50,"Target organ toxicity","Spleen histopathology","Rat",28,"Days","Oral",">2500","mg/kg bw/day","No effect"]
[52,"Target organ toxicity","Spleen histopathology","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Target organ toxicity","Spleen histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[54,"Target organ toxicity","Spleen histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"Target organ toxicity","Spleen histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[57,"Target organ toxicity","Spleen histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"Target organ toxicity","Spleen histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"Target organ toxicity","Spleen histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[67,"Target organ toxicity","Spleen histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"Target organ toxicity","Spleen histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"Target organ toxicity","Spleen histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Spleen histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[73,"Target organ toxicity","Spleen histopathology","Mouse",90,"Days","Oral",">50000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic: extramedullary hematopoesis 8/10 M (control), 9/10 M (50000 ppm), 10/10 F (control), 10/10 F (50000 ppm); pigment 7/10 M (control), 6/10 F (50000ppm), 10/10 F (control), 10/10 F (50000ppm))"]
[74,"Target organ toxicity","Spleen histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F1 observed."]
[74,"Target organ toxicity","Spleen histopathology","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","No effects in F2 observed."]
[76,"Target organ toxicity","Spleen histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[2,"Target organ toxicity","Spleen weight","Rat",90,"Days","Oral",50000,"ppm","Decrease","Absolute weight reduced in both sexes at 50000 ppm which was attributed to reduced body weight. Since no histopathological changes were observed, a specific toxicological effect on spleen is not deduced."]
[5,"Target organ toxicity","Spleen weight","Dog",90,"Days","Oral",">1000","mg/kg bw/day","Decrease","Absolute and relative weight (not significantly) decreased in males only at 30 mg/kg bw/day (-16 and -7%), at 300 mg/kg bw/day (-25 and -19) and at 1000 mg/kg bw/day (-35 and -10%). In addition, no histopathological changes observed, therefore toxicological significance is doubtful."]
[22,"Target organ toxicity","Spleen weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect","Absolute weight reduced in F1 males at 15000 ppm, considered to be incidental"]
[22,"Target organ toxicity","Spleen weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"Target organ toxicity","Spleen weight","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[23,"Target organ toxicity","Spleen weight","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[36,"Target organ toxicity","Spleen weight","Mouse",28,"Days","Oral","> 5000","ppm","No effect"]
[51,"Target organ toxicity","Spleen weight","Dog","Study part A: 21\nStudy Part B: 14","Days","Oral",100,"mg/kg bw/day","Decrease","Study part A (21 days of treatment): Absolute and relative spleen weight were considered reduced in the female animal.\nStudy part B (14 days of treatment): no abnormalities observed"]
[52,"Target organ toxicity","Spleen weight","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Target organ toxicity","Spleen weight","Rat",90,"Days","Oral",20000,"ppm","Increase","Absolute weight increased in females only in all treatment groups (reaching statistical significance in high dose group only), relative weight statistically signif. increased for the high dose group only; relative weight (relative to brain weight) not statistically significantly increased. However, no effect was observed during macroscopic and microscopic examination. "]
[56,"Target organ toxicity","Spleen weight","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[59,"Target organ toxicity","Spleen weight","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[67,"Target organ toxicity","Spleen weight","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Absolute organ weight was not affected."]
[68,"Target organ toxicity","Spleen weight","Mouse",2,"Years","Oral","> 30000","ppm","No effect","The mean absolute and relative (to body and brain weight) spleen weight were not affected."]
[70,"Target organ toxicity","Spleen weight","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","Mean organ weight data (absolute and relative to body weights or brain weights) were comparable between the control and treated groups for both males and females.\nNo treatment-related effect was evident in organ weight data for the F3b offspring."]
[70,"Target organ toxicity","Spleen weight","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","In general, mean spleen weight data (absolute and relative to body weights or brain weights) were considered comparable between the control and treated groups for both males and females from the F0, F1, and F2 generation. Some statistically significant differences were noted between control and treated groups (mid dose) both in absolute and relative organ weight; however, no trends were evident within dose levels or through the generations. In the F2 female group, mean spleen weights (absolute and relative to brain and body weights) were significantly higher than the control value in the F2 mid-dose female group; however, mean spleen weight data for the low- and high-dose F2 females were comparable to control values. In the absence of an effect on spleen weight in the high-dose F2 female group, the change seen in spleen weight data for the mid-dose females was considered spontaneous and not biologically relevant."]
[73,"Target organ toxicity","Spleen weight","Mouse",90,"Days","Oral",">50000","ppm","No effect","Absolute and relative (to body and brain weight) organ weight was not affected."]
[13,"Target organ toxicity","Thymus histopathology","Rat",2,"Years","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Neoplastic findings, surviving animals: no treatment-related findings; macroscopic: involution in 25/56, 35/54, 40/49 and 32/50 dead and moribund rats and 25/44, 0/46, 0/50 and 34/50 surviving rats of the 0, 100, 1000 and 10000 ppm group, age-related)","No histopathologic changes of the thymus were observed in dog, rat and mouse. An inconsistent change of relative thymus weights was observed in male rats and mice at very high doses (>1000 mg/kg bw/day). Overall, no specific effects on thymus were induced by glyphosate."]
[18,"Target organ toxicity","Thymus histopathology","Rat",2,"Years","Oral",">15000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic: no treatment-related findings (moderate to severe lymphoid atrophy in rats of both sexes among all groups, no effect on thymic atrophy); neoplastic: no treatment-related findings (lymphocytic thymoma, carcinoma in 0/51, 1/51, 1/51 and 2/51 males and 7/51, 2/51, 4/51 and 4/51 females at 0, 1500, 5000 and 15000 ppm))"]
[19,"Target organ toxicity","Thymus histopathology","Mouse",18,"Months","Oral",">10000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Gross pathology, dead/moribund animals: enlarged in 0/22, 1/20, 0/22 and 3/27 males and 0/16, 3/16, 1/20 and 2/20 females at 0, 100, 1000 and 10000 ppm, associated with neoplasms of the hemolymphoreticular system, no dose relation; histopathology, non-neoplastic findings terminal kill animals: involution in 13/28 and 6/23 males and in 6/34 and 7/30 females at 0 and 10000 ppm, no involution in 9/28 and 9/23 males and in 20/34 and 14/30 females at 0 and 10000 ppm, not treatment-related)"]
[20,"Target organ toxicity","Thymus histopathology","Mouse",18,"Months","Oral",">5000","ppm","No effect","No relevant treatment-related histopathological changes were observed.\n(Non-neoplastic: no treatment-related findings (lymphoid hyperplasia, atrophy and peripheral inflammatory cells occasionally observed upon all groups, more prevalent in females, age-related; one incidence of histiocytic sarcoma in 1/7 examined females at 1500 ppm at terminal kill)"]
[22,"Target organ toxicity","Thymus histopathology","Rat",10,"Weeks","Oral",">15000","ppm","No effect","Gross necropsy: no treatment-related findings (low incidence of small thymus in terminal kill animals of the F0 generation)"]
[52,"Target organ toxicity","Thymus histopathology","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Target organ toxicity","Thymus histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[54,"Target organ toxicity","Thymus histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"Target organ toxicity","Thymus histopathology","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"Target organ toxicity","Thymus histopathology","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"Target organ toxicity","Thymus histopathology","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"Target organ toxicity","Thymus histopathology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"Target organ toxicity","Thymus histopathology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[67,"Target organ toxicity","Thymus histopathology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect"]
[68,"Target organ toxicity","Thymus histopathology","Mouse",2,"Years","Oral","> 30000","ppm","No effect"]
[70,"Target organ toxicity","Thymus histopathology","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"Target organ toxicity","Thymus histopathology","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","No microscopic findings were considered compound related. The overall microscopic tissue alterations were indicative of common incidental histological findings."]
[76,"Target organ toxicity","Thymus histopathology","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[22,"Target organ toxicity","Thymus weight","Rat",10,"Weeks","Oral",">15000","ppm","No effect","Absolute weight reduced in F2 males at 15000 ppm, considered to be without toxicological significance"]
[23,"Target organ toxicity","Thymus weight","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[36,"Target organ toxicity","Thymus weight","Mouse",28,"Days","Oral","> 5000","ppm","No effect"]
[52,"Target organ toxicity","Thymus weight","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[56,"Target organ toxicity","Thymus weight","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect","Statistically signif. increased absolute relative weight in males only at the mid dose group (1000 mg/kg bw/day) was considered to be incidental, since no dose-response was observed."]
[59,"Target organ toxicity","Thymus weight","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Absolute and relative organ weights were not affected."]
[67,"Target organ toxicity","Thymus weight","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","Increase","Males: Absolute thymus weight was increased in the intermediate and high dose groups (P<0.01 and P<0.05 respectively) compared to control. Thymus weight was also increased in the intermediate and high dose groups after covariance analysis. The increase in high dose males was due to one animal which had an enlarged thymus infiltrated with lymphoma cells. Moreover, since no effect was observed at necropsy or histopathological examination, the increased thymus weight is considered not toxicologically relevant. \nFemales: No effect on organ weight was observed."]
[78,"Target organ toxicity","Thymus weight","Rat",90,"Days","Oral",50000,"ppm","Decrease","Relative organ weight was decreased in males only (50000 ppm= -13%*), where also decreased body weight gain and signs of general systemic toxicity were observed."]
[79,"Target organ toxicity","Thymus weight","Mouse",90,"Days","Oral",50000,"ppm","Increase","Relative organ weight was increased in males only, where also decreased body weight gain and signs of general systemic toxicity were observed."]
[18,"[Not in list]","Further examined organs","Rat",2,"Years","Oral",">15000","ppm","No effect","Nasal cavities: histopathology, (non-)neoplastic: no treatment-related findings (dilatation of subepithelial glands in rats of either sex, spontaneous change, statistically significantly decreased in males at 15000 ppm, incidental; chronic inflammatory lesions adjacent to the palate, associated with plant material/ hair fragments, reaction to foreign material impacted ti gland ducts; inflammatory/non-inflammatory exudate overlying the endothelium, focal epithelial ulceration, thrombus formation, fungal growth and dental hyperplasia occasionally observed); histopathology, neoplastic: no treatment-related findings (polypoid adenoma in 2/51, 1/51, 0/51 and 0/51 males at 0, 1500, 5000 and 15000 ppm)\nPharynx: histopathology, non-neoplastic: no treatment-related findings (inflammatory cell lesions, inflammatory exudate and mucous cell hyperplasia/hypertrophy in a few animals)\nhistopathology, neoplastic: squamous cell papilloma in 1/51 females at 15000 ppm\nLarynx: histopathology, (non-)neoplastic: no treatment-related findings (distention of glands commonly observed among all control and treated rats of either sex; focal ulceration and debris in the ventral pouch, considered incidental)\nTongue: histopathology, (non-)neoplastic: no treatment-related findings (isolated instances of mononuclear cell infiltrates and mucous cysts in the epithelium in males, without toxicological significance); histopathology, neoplastic: no treatment-related findings (benign granular cell tumor in 1/51 females at 15000 ppm)","Specific effects on further examined orans or treatment-related neoplasia were not observed."]
[20,"[Not in list]","Further examined organs","Mouse",18,"Months","Oral",">5000","ppm","No effect","Nasal cavities: no treatment-related findings \n(focal epithelial hyperplasia in both sexes frequently observed, epithelial inflammation, exudate overlaying the epithelium, dilatation of subepithelial glands, focal epithelial ulceration, prominent fibroplasia and resorption of bone occasionally observed; dental dysplasia and dental erosion/abscess formation in a few control and treated males)\nPharynx: no treatment-related findings (mononuclear cell infiltrates, exudate overlaying the epithelium, focal epithelial hyperplasia in a few animals, extensive inflammation and abscess formation in the supra-pharyngeal tissues in one control mouse)\nLarynx: no treatment-related findings (dilatation of subepithelial glands and epithelial/subepithelial inflammatory cell infiltrates, incidental)\nTrachea: no treatment-related findings (dilatation of subepithelial glands frequently observed in both sexes, isolated instances of inflammation)\nTongue: no treatment-related findings (focal inflammation, fibrosis, ulceration, vasculitis and abscess formation occasionally observed)"]
[67,"[Not in list]","Neoplastic findingd","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","There were no statistically significant increases in incidence of any tumour. The number of animals with tumours, both benign and malignant, was similar between the control and high dose groups (m+f).\n(Animals with multiple tumour types was slightly increased in the high dose group of both sexes (males: 16/50 and females: 11/50) compared to control (males: 11/50 and females: 6/50) causing a slight increase in the total number of tumours in the high dose group of both sexes (males: 60 and females: 43) compared to control (males: 49 and females: 36); Haemangiosarcoma was evident in 4/50 high dose males, 2/50 low dose females and 1/50 high dose females (not significant) compared to the respective controls (m+f: 0/50). Histiocytic sarcoma in the lymphoreticular/haemopoietic tissue was evident in 2 low and 2/50 high dose males and 3 low, 3 intermediate and 1/50 high dose females (not significant) compared to the respective controls (m+f: 0/50). The incidences of haemangiosarcoma and histiocytic sarcoma were higher in all groups of both sexes exposed to the test substance. Similar incidences of haemangiosarcoma and histiocytic sarcoma have been seen in other studies using mice of a similar age and strain (historic control data). Due to the lack of a dose relationship, statistical significance and the incidences in this study falling within the historic control ranges, these changes are not considered to be due to test substance treatment.)\n"]
[68,"[Not in list]","Neoplastic findingd","Mouse",2,"Years","Oral","> 30000","ppm","No effect","There were no statistically significant increases in incidence of any tumour.\n(Neoplastic findings were those commonly encountered in mice: Bronchiolaralveolar tumors of the lungs, hepatocellular neoplasms, and tumors of the lymphoreticular system accounted for the majority encountered. There were no suspected test substance-associated trends in the incidence of these tumors or in any of the other spontaneously occurring neoplasms. Lymphoreticular tumors tended to be more frequent in treated animals, particularly the females. The numbers were relatively small and differences from the control failed to provide supportive evidence that the neoplasms had a test substance relationship. The other neoplasms that occurred with any frequency in treated mice only were renal tubule adenomas (males: 3 present at the high-dose; 1 at the mid-dose level). However, the distribution of this benign tumor was considered spurious and unrelated to treatment. Renal tubule adenomas (males only; 3 in high-dose and 1 in the mid-dose) -> spurious and unrelated to treatment due to the absence of other renal lesions.)"]
[70,"[Not in list]","Overall microscopic evaluation","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","The overall microscopic tissue alterations found throughout the study for each generation (F0, F1, and F2) were indicative of common incidental histological findings."]
[70,"[Not in list]","Overall microscopic evaluation","Rat","21 (PND0-21, exposure through milk)","Days","Oral",">30","mg/kg bw/day","No effect","F3: The overall microscopic tissue alterations were indicative of common incidental histological findings."]

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["Study ID Matrix","Effect classification","Effect target","Species","Duration of exposure","Duration unit","Route of administration","Lowest Effect dose","Dose unit","Effect direction","Observed effect (positive and negative)","Assessment of each line of evidence","Assessment on the integrated line of evidence","Modality"]
[1,"Systemic toxicity","Body weight","Rat",90,"Days","Oral",20000,"ppm","Decrease","Decreased in males at 20000 ppm over the whole study period, -8% in final bw (no effect in females).","Body weight (gain) decreases were observed frequently at high doses in dog, mouse, rabbit, and rat after oral exposure. ","Not applicable."]
[2,"Systemic toxicity","Body weight","Rat",90,"Days","Oral",50000,"ppm","Decrease","Reduced body weight gain in males and females at 50000 ppm during the fist 4 weeks, effects partially reversible in males and fully reversible in females."]
[3,"Systemic toxicity","Body weight","Rat",90,"Days","Oral",30000,"ppm","Decrease","Decreased bw (5--10% ) in both sexes at 30000 ppm."]
[4,"Systemic toxicity","Body weight","Mouse",90,"Days","Oral",50000,"ppm","Decrease","Decreased body weight (-9% at week 13) in males at 50000 ppm, occasionally statistically significant."]
[5,"Systemic toxicity","Body weight","Dog",90,"Days","Oral",1000,"mg/kg bw/day","Decrease","Reduced mean body weight (-28%) and lower weight gain in males (+4% vs +31% in controls) and body weight loss in females (-7% vs. +14% in controls) at 1000 mg/kg bw/day (males: study week 4-11, females: study week 1-11."]
[6,"Systemic toxicity","Body weight","Dog",90,"Days","Oral",">10000","ppm","No effect"]
[7,"Systemic toxicity","Body weight","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"Systemic toxicity","Body weight","Dog",90,"Days","Oral",50000,"ppm","Decrease","Depressed in males (not statistically significant) and females (occasionally statistically significant) at 50000 ppm."]
[9,"Systemic toxicity","Body weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Decreased body weight in males at 500 mg/kg bw/day, within historical control data, sporadic body weight changes in single dogs among all dose groups, not treatment-related"]
[10,"Systemic toxicity","Body weight","Dog",1,"Year","Oral",50000,"ppm","Decrease","Retarded body weight gain in both sexes at 50000 ppm (terminated bw were -6% in males, -11% in females when compared to controls, not statistically significant)."]
[11,"Systemic toxicity","Body weight","Dog",1,"Year","Oral",30000,"ppm","Decrease","Reduced body weight (-11%) in females at 30000 ppm during the second half of the study, reflects a palatability effect"]
[12,"Systemic toxicity","Body weight","Rat",1,"Year","Oral",8000,"ppm","Decrease","Reduced body weight at ≥ 8000 ppm in both sexes."]
[13,"Systemic toxicity","Body weight","Rat",2,"Years","Oral",">10000","ppm","No effect","No treatment-related effect (reduced body weight in males during the first 4 weeks in all treatment groups, statistically not significant; significant increase in females at 1000 ppm at 12 month was considered incidental)"]
[14,"Systemic toxicity","Body weight","Rat",2,"Years","Oral",10000,"ppm","Decrease","Decreased body weight gain in males at ≥ 10000 ppm and in females at 30000 ppm (terminal bw: 93-95% of control) during the treatment period, which is in line with reduced food consumption and low food efficiency."]
[15,"Systemic toxicity","Body weight","Rat",2,"Years","Oral",20000,"ppm","Decrease","Decreased in males (-5%) and females (-8%) at 20000 ppm throughout the study."]
[16,"Systemic toxicity","Body weight","Rat",2,"Years","Oral",1000,"mg/kg bw/day","Decrease","Reduced body weight gain in both sexes at 1000 mg/kg bw/day in week 52 and 104 (m: -14-32%; f: -11-17%)  (not treatment-related findings: reduced at interim kill at 100 and 300 mg/kg bw/day, not reproduced at terminal kill, occasional fluctuations among all groups, no dose-relation)."]
[17,"Systemic toxicity","Body weight","Rat",2,"Years","Oral",20000,"ppm","Decrease","Statistically significantly decreased in females only at 20000 ppm from study Day 51 until month 20 (bw 86% of control after 20 month, -23% bw gain after 20 month)."]
[18,"Systemic toxicity","Body weight","Rat",2,"Years","Oral",">15000","ppm","No effect","Overall body weight gain was comparable for all treatment groups (91% for males and 97% for females at 15000 ppm when compared to controls)"]
[19,"Systemic toxicity","Body weight","Mouse",18,"Months","Oral",">10000","ppm","No effect","Occasional fluctuations of body weight in males at 100 and 1000 ppm, no dose response, not treatment-related"]
[20,"Systemic toxicity","Body weight","Mouse",18,"Months","Oral",">5000","ppm","No effect"]
[21,"Systemic toxicity","Body weight","Mouse",18,"Months","Oral",8000,"ppm","Decrease","Occasional decreases among groups at 8000 and 40000 ppm throughout the treatment in both sexes, reduction in females at 8000 during weeks 6, 9 and 24 were considered to be treatment-related, body weight gain was comparable to those of controls at study termination"]
[22,"Systemic toxicity","Body weight","Rat",10,"Weeks","Oral",15000,"ppm","Decrease","No adverse effect of bodyweight change was evident for treated animals in comparison to controls throughout the treatment period for both the F0 and F1 generations except for post-partum females treated with 15000 ppm. During the final week of lactation, both the F0 and F1 generations showed statistically significant less bodyweight loss in comparison to controls."]
[23,"Systemic toxicity","Body weight","Rat","10 (pre-mating)","Weeks","Oral",10000,"ppm","Decrease","Decreased body weight in F1 males at 10000 ppm during week 1, decreased body weight gain in F1 males at 10000 ppm from weeks 2 to 8, (there were no effects in females during maturation, gestation and lactation)"]
[24,"Systemic toxicity","Body weight","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",30000,"ppm","Decrease","Decreased in F0 and F1 males at 30000 ppm from treatment week 1 until necropsy (non treatment-related findings in females, increased mean body weight in F1 females at 30000 ppm on lactation day 0)"]
[25,"Systemic toxicity","Body weight","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect","No treatment-related findings \n(Initial bw of F0 males in treatment groups was higher than in control group, the trend continued during the entire treatment period but terminal body weight gain was comparable for all groups; increased bw in F1 males at 1000 ppm prior to and during treatment; decreased bw in F1 males at 10000 ppm at week 2 and 3; increased in females of all F1 treatment groups at selection and at 1000 and 10000 ppm up to week 10; increased in F1 females at 1000 ppm on Days 1 and 4 and in F1 females at 10000 ppm during the whole lactation period; reduced in F1 females at 1000 ppm during the lactation period)"]
[26,"Systemic toxicity","Body weight","Rat","10 prior to mating, continued until termination","Weeks","Oral",10000,"ppm","Decrease","Absolute weight reduced in F1 males at 10000 ppm apparent at selection, overall weight gain was comparable to control, (no clear adverse effects on bw gain during pregnancy and lactation, during the first mate of each generation bw gains during the initial stages of pregnancy were slightly lower than control at all dosage groups, no consistent dose-response)"]
[27,"Systemic toxicity","Body weight","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",30000,"ppm","Decrease","Reduced in both sexes (F0+F1) at 30000 ppm throughout the study, (F0: -8% and F1 -10% during pre-mating) (Not treatment-related findings: during gestation and lactation maternal bw at 30000 ppm tended to be lower than controls although bw gain was comparable to those of controls)"]
[28,"Systemic toxicity","Body weight","Rat","10 (GD 7-16)","Days","Oral",">1000","mg/kg bw/day","No effect"]
[29,"Systemic toxicity","Body weight","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect"]
[30,"Systemic toxicity","Body weight","Rabbit","13 (GD 6-18)","Days","Oral",300,"mg/kg bw/day","Decrease","Decreased bw at 300 mg/kg bw/day on gestation days 16-24, not statistically significant; decreased bw gain at 300 mg/kg bw/day during gestation days 0-16 and 0-24"]
[31,"Systemic toxicity","Body weight","Rabbit","13 (GD 7-19)","Days","Oral",200,"mg/kg bw/day","Decrease","Reduced bw gain at ≥ 200 mg/kg bw/day from days 9-29 of gestation. Statistical significance was observed for body weight gain in the high dose group only from Days 13-29 post coitum."]
[32,"Systemic toxicity","Body weight","Rabbit","13 (GD 8-20)","Days","Oral",175,"mg/kg bw/day","Decrease","Body weight decrease statistically significant; all animals except one showed recovery in the post dosing period"]
[33,"Systemic toxicity","Body weight","Rabbit","22 (GD 6-27)","Days","Oral","> 350","mg/kg bw/day","No effect","Mean maternal body weight gain was not affected."]
[34,"Systemic toxicity","Body weight","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect","Lower body weight was observed at different stages of the study, but due to lower initial body weight the effect is not considered treatment-related; body weight gain is unaffected"]
[35,"Systemic toxicity","Body weight","Rabbit","13 (GD 6-18)","Days","Oral",500,"mg/kg bw/day","Decrease","Reduced body weight was observed in the high dose group."]
[36,"Systemic toxicity","Body weight","Mouse",28,"Days","Oral","> 5000","ppm","No effect"]
[42,"Systemic toxicity","Body weight","Rat",3,"Days","Oral","> 1000","mg/kg bw/day","No effect","Mean body weights and body weight gains were not affected."]
[43,"Systemic toxicity","Body weight","Rat",10,"Days","Oral","> 1000","mg/kg bw/day","No effect"]
[44,"Systemic toxicity","Body weight","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[45,"Systemic toxicity","Body weight","Rat","31 (PND 23-53)","Days","Oral",300,"mg/kg bw/day","Decrease","Mean body weight gains for the 300 and 1000 mg/kg/day groups were decreased (7.5% and 12.4%, respectively) when the overall treatment period (PND 23-53) was evaluated, reaching statistical significance for the high dose group. Mean body weights for the 300 mg/kg/day group were 5.07% - 8.08% lower than the control group towards the end of the treatment period (PND 44-53), whereas mean body weights for the 1000 mg/kg/day group were 5.09% - 11.06% lower generally throughout the entire treatment period (PND 24-53). Final body weight was statistically significantly decreased by 12.4% and 7.5% for high and mid dose, respectively. "]
[46,"Systemic toxicity","Body weight","Rabbit","13 (GD 7-19)","Days","Oral",150,"mg/kg bw/day","Decrease","Body weight gain was slightly reduced from 150 mg/kg bw (GD11-19)"]
[47,"Systemic toxicity","Body weight","Rabbit","13 (GD 7-19)","Days","Oral",100,"mg/kg bw/day","Decrease","Transient body weight gain reductions were observed in the low and mid dose group and throughout the treatment period for the high dose group. "]
[48,"Systemic toxicity","Body weight","Rabbit"," 7 (high dose) -13 (mid and low dose)","Days","Oral",750,"mg/kg bw/day","Decrease","Marked weight loss was observed from 750 mg/kg bw/day."]
[49,"Systemic toxicity","Body weight","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[50,"Systemic toxicity","Body weight","Rat",28,"Days","Oral",2500,"mg/kg bw/day","No effect","Reduced total body weight gain at 2500 mg/kg bw/day in males (-9%) and females (-11%) throughout the dosing period, statistically not significant, not considered treatment-related"]
[51,"Systemic toxicity","Body weight","Dog","Study part A: 21\nStudy Part B: 14","Days","Oral",">1000","mg/kg bw/day","No effect"]
[52,"Systemic toxicity","Body weight","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Systemic toxicity","Body weight","Rat",90,"Days","Oral",">20000","ppm","No effect","The total mean body weight gain was similar for all groups. \nStatistically sign. increased mean body weight gains in males on Day 43 at 6000 and 20000 ppm were attributed to decreased weight gain in the control group. Statistically signif. decreased body weight  at 20000 ppm in both sexes on Day 50 and in males on Day 85. "]
[54,"Systemic toxicity","Body weight","Rat",90,"Days","Oral",20000,"ppm","Decrease","Reduced body weight gain in females at 20000 ppm during study weeks 3-6 and thereafter, statistically signif. reduced body weight throughout the treatment period. Findings were restricted to females and were not evident in the high dose recovery group during the exposure period."]
[55,"Systemic toxicity","Body weight","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"Systemic toxicity","Body weight","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"Systemic toxicity","Body weight","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect","Beginning midway through the study, the body weights (also final body weights) of males in the high-dose group were slightly decreased (-4-6%) beginning from the mid of the study (not statistically significant). Body weight of females was not affected."]
[58,"Systemic toxicity","Body weight","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"Systemic toxicity","Body weight","Dog",1,"Year","Oral",30,"mg/kg bw/day","Decrease","Reduced mean body weight gain in males at 30 (-17%), 300 (-25%) and 1000 mg/kg bw/day (-25%) and in females at 1000 mg/kg bw/day (-19%), statistically not significant"]
[60,"Systemic toxicity","Body weight","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect","Reduced body weight gain in males (-17%, statistically not significant) and statistically signifcant increased body weight gain in females (58%), due to the lack opf statistical significance, the wide variation between the sexes and the lack of similar observations in previous studies the changes were not attributed to treatment ."]
[61,"Systemic toxicity","Body weight","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[62,"Systemic toxicity","Body weight","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[63,"Systemic toxicity","Body weight","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect"]
[64,"Systemic toxicity","Body weight","Rat","10 (GD 6-15)","Days","Oral",3500,"mg/kg bw/day","Decrease","At 3500 mg/kg/day, the rate of body weight gain was markedly reduced during the first two days of treatment when compared to the concurrent control values. Thereafter, apart from a slight reduction in the rate of body weight gain during Days 12 to 14 of pregnancy, the rate of body weight gain was comparable with the controls, although absolute parity with the control group was not attained by Day 20.\nAt 1000 mg/kg/day, there was a marginal reduction in the rate of body weight gain during the first two days of treatment when compared with the concurrent control group. Thereafter, the pattern of bodyweight change was similar to the controls."]
[65,"Systemic toxicity","Body weight","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","There were no significant intergroup differences in body weight at GD0; GD6; GD15; and GD20. The mean body weight gain during pre-treatment, treatment, post-treatment or overall gestation period did not show any statistical difference between the control and treatment groups. Similarly absolute body weight at the end of pregnancy had significantly (p=0.01) increased in both the study groups (control group and treatment group) as compared to GD0 weights."]
[66,"Systemic toxicity","Body weight","Rabbit","22 (GD 6-27)","Days","Oral",">350","mg/kg bw/day","No effect","There were no relevant differences in mean maternal body weight gain in any of the treatment groups when compared to the control group throughout the entire gestation period."]
[67,"Systemic toxicity","Body weight","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Treatment groups showed a comparable weight gain compared to controls.\nA slight decrease in absolute body weight at Week 40 was evident in all groups of both sexes except control and intermediate dose females. This transient effect is not considered to be attributable to the test substance."]
[68,"Systemic toxicity","Body weight","Mouse",2,"Years","Oral",30000,"ppm","Decrease","Mean body weights for the high-dose males were generally lower than control (-11% at Week 102) and were (mostly) statistically significant. Mean body weights for the high-dose females and the males and females at the low- and mid-dose levels were not affected. Mean fasted body weight at termination of the study was statistically significantly reduced for male high dose animals. Moreover, no effect on body weight gain was observed for all dose groups."]
[69,"Systemic toxicity","Body weight","Rat","5.5 (GD 3 till 21 days post partum)","Weeks","Oral",30000,"ppm","Decrease","At 30000 ppm, the rate of bodyweight gain following the initiation of treatment was reduced to Day 14 of pregnancy: thereafter, the rate of bodyweight gain to Day 20 of pregnancy was similar to controls, however, absolute parity with controls at Day 20 was not achieved.\nAt both 3000 and 10000 ppm the pattern of bodyweight gain during pregnancy was essentially similar to controls throughout, although by Day 14 of pregnancy, bodyweights were slightly lower than controls.\nDuring the first week of lactation the pattern of bodyweight change in all groups was comparable. Thereafter, slight differences in the pattern of change were apparent to weaning at 10000 and 30000 ppm in so much as more weight loss occurred than in the control group. There were no further effects at 3000 ppm."]
[69,"Systemic toxicity","Body weight","Rat","3 (PND 21-42)","Weeks","Oral",30000,"ppm","Decrease","From weaning to termination (PND 21 - 42), males at 30000 ppm had a reduced rate of weight change. At lower dosages, and at all dosages among females, the rate of weight change was comparable with controls, however, differences inherent at weaning were still present by Week 6."]
[70,"Systemic toxicity","Body weight","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","F0, F1, and F2: Mean body weight data during the growth and rest periods were comparable between the control and treated groups for each generation, throughout the study. Likewise, mean weight gain during the growth periods were comparable between these same groups for both sexes throughout all generations. No treatment effect on body weight data during the growth and rest periods was evident.\nMean body weight data during the gestation and lactation intervals and mean weight change during these same periods were considered comparable between the control and treated group for each pregnancy interval from each generation throughout the study.\nNo treatment effect was indicated in gestation - lactation body weight data throughout the study.\nAlso mean terminal body weight data were comparable between the control and treated groups for both males and females throughout the study."]
[71,"Systemic toxicity","Body weight","Rat",28,"Days","Oral",30000,"ppm","Decrease","Cumulative body weight change treated vs. control: M 40000= -53%* (day 1 - 8); M 40000=-40%* (day 1-16); M 50000=-100%* (day 1-8); M 50000=-50%* (day 1-16); M 50000=-44%* (day 1-23); M50000=-44%* (day 1-28); F 50000=-64%* (day 1-8); F 50000=-46%* (day 1-16); F 50000=-47%* (day 1-23); F 50000=-46%* (day 1-28); F 30000= -38%* (day 1-23); F 50000=-33%* (day 1-28)\nBody weight reduction are considered secondary to gastrointestinal effects."]
[72,"Systemic toxicity","Body weight","Mouse",28,"Days","Oral",">1000","mg/kg bw/day","No effect","Slightly lower mean body weights, compared to control, were noted for males receiving 300 and 1000 mg/kg/day through week two. However, these a differences were not considered treatment-related but attributed to slightly lower pretest body weights."]
[73,"Systemic toxicity","Body weight","Mouse",90,"Days","Oral",50000,"ppm","Decrease","Statistically significant decrease of body weights in males and females at 50000 ppm throughout the study period leading to final body weight reduction of -11%* in M at 50000 ppm and -8%* in F at 50000 ppm (compared to control). Incidences of statistically significant lower body weights were observed in males at 10000 ppm and females at 5000 and 10000 ppm."]
[74,"Systemic toxicity","Body weight","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","Body weight was not affected in F0 adults."]
[74,"Systemic toxicity","Body weight","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","Body weight was not affected in F1 adults."]
[74,"Systemic toxicity","Body weight","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","Body weight was not affected in F2 adults."]
[75,"Systemic toxicity","Body weight","Rat","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Oral",">10","mg/kg bw/day","No effect"]
[76,"Systemic toxicity","Body weight","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[77,"Systemic toxicity","Body weight","Rabbit","22 (GD 6-27)","Days","Oral",500,"mg/kg bw/day","Decrease","Severe body weight loss at 500 mg/kg bw ( -9%* on GD 24 compared to GD 0) was observed."]
[78,"Systemic toxicity","Body weight","Rat",90,"Days","Oral",25000,"ppm","Decrease","Reduced weight gain in M at 25000 and 50000 ppm. Terminal body weight M 50000 ppm= -18% (in comparison to control)\nTerminal body weight F 50000 ppm= -5% (in comparison to control)"]
[79,"Systemic toxicity","Body weight","Mouse",90,"Days","Oral",25000,"ppm","Decrease","Decreased body weight gains in M and F at 25000 ppm and 50000 ppm"]
[80,"Systemic toxicity","Body weight","Rat",5,"Weeks","Oral",50,"mg/kg bw/day","Decrease","Although not statistically significant there was a dose-dependent decrease in daily weight gain. Mean terminal body weight was not statistically significantly changed. However, there was a ~10% reduction of mean body weights at 50 and 500 mg/kg bw groups providing an indication that the MTD was reached or exceeded."]
[92,"Systemic toxicity","Body weight","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Body weight and body weight gain of the dams during gestation and lactation were not statistically different among groups."]
[92,"Systemic toxicity","Body weight","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Post-weaning body weight of female and male offspring was homogeneous and no statistically significant differences in body weight gain were observed among groups. "]
[95,"Mouse","Body weight","Mouse","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Oral",5000,"mg/L water","No effect","Body weight gain of pregnant mice was not statistically significantly affected."]
[1,"Systemic toxicity","Clinical chemistry and haematology","Rat",90,"Days","Oral",20000,"ppm","Change","Haematology: reduced platelet count in both sexes at ≥ 5000 ppm, marginal increase in prothrombin time in males at all doses, both considered to be not tox. relevant\nClinical chemistry: ALT↑ and ALP ↑in both sexes at 20000 ppm throughout the study  (non-treatment related findings: AST ↑ in females at 20000 ppm at week 4, ALT in males+females ocassionally increased at 5000 ppm, ALP in males at 1000 and 5000 ppm marginally increased, ALP↑ in each one females at control group and 1000 ppm in week 13, no dose-response relationship; ↓plasma urea (both sexes), plasma glucose (males) and triglyceride levels (males) at 20000 ppm)\nUrinalysis: lower pH in both sexes at 20000 ppm and higher values at 1000 and 5000 ppm for females, marginal changes within historical control data","Changes in clinical chemistry parameters were observed and included: \nIn rats: Increased ALT ( 2500 ppm in females  and 8000 ppm in males or 250 mg/kg bw/day in males) and ALP (250 mg/kg bw/day in males, 100 mg/kg bw/day in females or 2000 ppm in females and 8000 ppm in males). These changes were observed in the long-time studies and are indicative for liver damage. Other changes included but were not limited to decreased creatinine, proteine, albumine and calcium. These changes were however rare or not consistently observed among the studies.\nIn dog: Increased ALT, ALP and GGT were observed in males and females from 1000 mg/kg bw/day or 10000 ppm. \nIn mouse: Increased calcium and decreased albumin were observed at 50000 ppm in females which is consistent with the findings in dogs, this change might be a consequence of effects on the kidney, however no correlating histopathological changes were observed.\nNo effects on clinical chemistry were observed in rabbits. \nHematology paramteres were not affected in rats. Dogs and mice however showed the same effects: Decreased hematocrit, hemoglobin and red blood cells."]
[2,"Systemic toxicity","Clinical chemistry and haematology","Rat",90,"Days","Oral",10000,"ppm","Change","Haematology: MCHC ↑ in females at 50000 ppm within historical control data, Neutrophils ↑ in males at 1000 and 50000 ppm, no dose-relation, findings incidental\nClinical chemistry: Ca ↓ and ALP ↑ in both sexes at ≥ 10000 ppm, P↑ and Creat↓ in both sexes at 50000 ppm, total plama protein and albumin ↓ in females at 50000 ppm, treatment-related (non-treatment-related findings: plasma urea↓ and Na ↓ in both sexes at 50000, within historical control data) \nUrinalysis: haemoglobin in urine ↑ in both sexes at 50000 ppm, particulate matter in sediment in males at 50000 ppm, findings may be attributed to faecal contamination"]
[3,"Systemic toxicity","Clinical chemistry and haematology","Rat",90,"Days","Oral",30000,"ppm","Change","Haematology: no abnormalities observed\nClinical chemistry:  ALP ↑ in females at 30000 ppm, treatment-related (findings without toxicological relevance: Alb ↓ in females at 30000 ppm)\nUrinalysis: lower pH in males at ≥ 10000 ppm and in females at 30000 ppm, attributed to the acidic nature of the test substance (findings without toxicological significante: decreased urine protein in males at ≥ 10000 ppm and in females at 30000 ppm, not treatment-related findings: increased urine volume in females at 30000 ppm)"]
[4,"Systemic toxicity","Clinical chemistry and haematology","Mouse",90,"Days","Oral",50000,"ppm","Change","Haematology: ↓ Ht, ↓ Hb and ↓ RBC and anemia in females at 50000 ppm, treatment-related; no changes in males\nClinical chemistry:  ↑ALP in both sexes at 50000 ppm, ↑ P in females at 50000 ppm, treatment-related (not treatment-related findings: ↓GPT in females at 50000 ppm, ↑ Creat.phosphokinase in females at 5000 and 50000 ppm, ↑BUN in females at 10000 ppm)\nUrinalysis: reduced pH in males of all treatment-groups, attributed to the acidic nature of the test substance"]
[5,"Systemic toxicity","Clinical chemistry and haematology","Dog",90,"Days","Oral",1000,"mg/kg bw/day","Change","Haematology: no treatment-related findings (occassional changes in Hb, Ht in females at 1000 mg/kg bw/day, reduced RBC in males at 30 and 300 mg/kg bw/day and reduced leucocytes in females at 30 mg/kg bw/day were without dose relation)\nClinical chemistry: ALT ↑ in 2/3 males and 1/3 females at 1000 mg/kg bw, ALP↓ in 3/3 females at 1000 mg/kg bw/day, T.Prot and Alb ↓ in 3/3 females at 1000 mg/kg bw/day, treatment-related (not treatment-related findings: ocassionally Na↓, Creat↓ and urea ↓ in males at 1000 mg/kg bw, P↑ in females at 30 mg/kg bw/day, Gluc↓ in both sexes at 1000 mg/kg bw/day, findings not consistent throughout the study or not dose-related)\nUrinalysis: ↓ mean specific gravity in 1/3 males and 3/3 females at 1000 mg/kg bw/day, ↑ mean urinary volume and less marked colour in 3/3 females at 1000 mg/kg bw/day, treatment-related"]
[6,"Systemic toxicity","Clinical chemistry and haematology","Dog",90,"Days","Oral",">10000","ppm","Change","Haematology: after 45 days of treatment: dose-related increase in clotting time in both sexes at all dose, treatment-related but fully reversible (non-treatment-related findings: MCH  ↑ in females at 10000 ppm, but within normal range); after 90 days of treatment: Neutrophils↓ in males at 2000 ppm, WBC↑ in females at 200 ppm, and Hct, MCV and MCH↑in females at 10000 ppm, within HCD); all effects were considered non-adverse\nClinical chemistry:  after 45 days of treatment: ALP↑ and GGT ↑ in males at 10000 ppm, GGT ↑ in females at 10000 ppm (non-treatment-related findings: T.Bilirubin ↑ in females at ≥ 2000 ppm and Ca ↑ in females at 10000 ppm, but within normal range); after 90 days of treatment: T.Bilirubin ↑ in both sexes at 10000 ppm, treatment- and dose-related; all effects were considered non-adverse\nUrinalysis: no adverse effects observed"]
[7,"Systemic toxicity","Clinical chemistry and haematology","Dog",90,"Days","Oral",">40000","ppm","No effect","Haematology: no treatment-related findings (statistically significant changes: RBC ↑ in males at 1600 and 8000 ppm, MCV ↓in males at 1600 ppm, MCHC ↓ in females at 40000 ppm, considered incidental as no other findings were observed)\nClinical chemistry: no treatment-related findings (statistically significant changes: Cl ↑ in males at 2000 and 40000 ppm (minimal magnitude, no dose-relation), Alb ↑ in females at 2000 ppm, no dose relation)\nUrinalysis: decreased pH in 3/4 females at 40000 ppm, statistically not significant, attributed to the acidic nature of the test item"]
[8,"Systemic toxicity","Clinical chemistry and haematology","Dog",90,"Days","Oral",50000,"ppm","Change","Haematology: no treatment-related findings\nClinical chemistry: at 50000 ppm Alb ↓, Ca ↓and T.Protein ↓ in males , treatment-related, and ALP ↑ in females\nUrinalysis: no treatment-related findings"]
[9,"Systemic toxicity","Clinical chemistry and haematology","Dog",52,"Weeks","Oral",">500","mg/kg bw/day","No effect","Haematology: no treatment-related findings (not treatment-related findings: APTT↓, MCHC↓, Eosinophils↓, all slight and/or not dose-related)\nClinical chemistry: no treatment-related findings (not treatment-related findings: Pi↓, Ca↓, T.Protein↓, Gluc↑, A/G ratio↑, ALP↑, all slight and/or not dose-related or within historical controls)\nUrinalysis: no treatment-related findings"]
[10,"Systemic toxicity","Clinical chemistry and haematology","Dog",1,"Year","Oral",50000,"ppm","Change","Haematology: Ht↓, Hb↓and RBC↓ in females at 50000 ppm, anemic condition may be caused by malnutrition, treatment-related (no abnormalities in males)\nClinical chemistry: Cl↑ (week 26), Alb↓ and Pi↓ (both week 52) in females at 50000 ppm, treatment-related (not treatment-related: Ca↓ in females at 1600 and 50000 ppm at week 52, CPK↓ in males at 8000 ppm in week 52, no dose-relation)\nUrinalysis: reduced pH in both sexes at 50000 ppm, attributed to the acidic nature of the test item"]
[11,"Systemic toxicity","Clinical chemistry and haematology","Dog",1,"Year","Oral",">30000","ppm","No effect","Haematology: no treatment-related findings \nClinical chemistry: no toxicologically relevant findings (not treatment-related findings:  T.Chol.↑ was increased in both sexes at 3000 and 30000 ppm in weeks 26+52, no dose-relation; P↓ in males in week 52, due to higher control levels; Na↓, in males at 30000 ppm due to one male of this group; ALT, AST, Creat. kinase occasionally increaased, no dose-relation)\nUrinalysis: no treatment-related findings "]
[12,"Systemic toxicity","Clinical chemistry and haematology","Rat",1,"Year","Oral",2000,"ppm","Change","Haematology: no treatment-related findings (changes on several parameters were found but there was no dose-relation and differences were small + inconsistent)\nClinical chemistry: ALP↑ in females at ≥ 2000 and in males at ≥ 8000 ppm, treatment-related but toxicologically not significant as no pathological change was found; Creat↓ in males at ≥ 2000 ppm, no dose-relation; T.Chol↓ and TG↓ in males at ≥ 8000 ppm at weeks 14+27; ALT↑ in both sexes at ≥8000 ppm; Creat. Kinase↑ in both sexes at 20000 ppm, treatment-related \nUrinalysis: reduced volume in males at ≥ 8000 ppm in week 13+26 and in 2000 ppm at week 26, treatment-related"]
[13,"Systemic toxicity","Clinical chemistry and haematology","Rat",2,"Years","Oral",10000,"ppm","Change","Haematology: no treatment-related findings (not treatment-related findings: surviving rats: occasional fluctuations of several parameters were all witihn historical control data, no dose-relation; Ht↑ (after 6 months) and Eosinophils↑ (after 18 months) in females at 10000 ppm were slightly outside historical control data, not consistent/ moribund rats: lymphocyte count↓ and neutrophil count↑ in both sexes among all treatment and control groups)\nClinical chemistry: Alb↓  and ALP↑ in females at 10000 after 6 months, treatment-related, GGT↓ in males at 10000 ppm after 12 months, treatment-related (not treatment-related findings, occasional fluctuations were all within historical control range, not consistent or without dose relation)\nUrinalysis: Protein↑ in females at 10000 ppm, treatment-related (non treatment-related findings: occasional fluctuations  of other parameters were not consistent throughout the study and/or not dose-related)"]
[14,"Systemic toxicity","Clinical chemistry and haematology","Rat",2,"Years","Oral",10000,"ppm","Change","Haematology: Ht↑ and PT↓ in males at 30000 ppm in week 104, attributed to altered values of the control animals which had callosities in the hind paw and anemia due to haemorrhage from the ulcered surfaces of the callosities\nClinical chemistry: Gluc↓ and Glob↓ in females at 30000 ppm, considered secondary to the decreased body weight gain , Creat↓ (week 26) in females at ≥ 10000 ppm, GPT↓ in males (week 52) at 30000 ppm, treatment-related but considered not to be of toxicological significance, ALP↑(week 52) in females at 30000 ppm, treatment-relation unclear  (not treatment-related findings: ALP↑ in males at 3000 ppm in week 78, Alb↓ in females at 3000 ppm in week 26, A/G↓ in females at 3000 ppm in week 26 and in males at 30000 ppm in week 104, attributed to the presence of callosities in control animals, T.Bil↓ in females at 3000 ppm in week 26, Cl↓ in males at 3000 and 10000 ppm in week 104, no dose-relation) \nUrinalysis: low pH in both sexes at ≥ 10000 ppm throughout the treatment period, attributed to the metabolic features of the test item; reduced protein in males at 30000 ppm at study week 26, treatment-related but toxicologically not significant as no blood chemistry or histopathological findings were noted (not treatment-related findings: dark coloured urine in females at ≥ 3000 ppm at study week 104, increased volume in males at 3000 ppm at week 104, no dose-relation)"]
[15,"Systemic toxicity","Clinical chemistry and haematology","Rat",2,"Years","Oral",20000,"ppm","Change","Haematology: no treatment-related findings (Hb↑ and PT↓ in all females at the interim kill, no dose-relation)\nClinical chemistry: ALP↑ (weeks 1-79) in both sexes at 20000 ppm, ALT↑ in males (weeks 1-79) and occasionally in females at 20000 ppm, T.Bil↑ (throughout the study) and AST↑ (at interim kill) in males at 20000 ppm, findings in males in line with increased liver weight, hepatitis and proliferative cholangitis, treatment-related (not treatment-related/ no tox. relevance: occasionally reduced TG and Chol. in males at 20000 ppm, ALP↑ during the first study year and variations in ALT at 6000 ppm, considered to be without toxicological significance as no histopathological abnormalities were found, Creat↓ in females at 6000 ppm in week 27 and at 20000 ppm in week 14 )\nUrinalysis: pH↓ in males at 20000 ppm, attributed to the acidic nature of the test material; blood/RBC↑  in both sexes at 20000 ppm, treatment-related"]
[16,"Systemic toxicity","Clinical chemistry and haematology","Rat",2,"Years","Oral",100,"mg/kg bw/day","Change","Haematology: Ht and MCH were occasionally increased at 100 and 1000 mg/kg bw/day in males, Hb occasionally increased in males at ≥ 100 mg/kg bw/day and in females at 1000 mg/kg bw/day, MCH occasionally increased in females at 1000 mg/kg bw/day, not treatment-related as changes were of small magnitude and inconsistent during the study, Eosinophils↓, Lymphocytes↓ and WBC↓ in females, effect not dose-related and not consistent throughout the study, high degree of individual variation, not reproducible\nClinical chemistry: ALP↑ in males at 1000 mg/kg bw/day and in females at 100 mg/kg bw/day, treatment-related but without histopathological abnormalities (not treatment-related findings: T.Bil↑ in females, effect not consistent, high degree of individual variation, not reproducible, T.Chol↓ in males at 100 and 1000 mg/kg bw/day, no dose relationship, reproducibility questionable, occasional variations in BUN, Glc and Ca, ALT and AST, Alb, T.Chol in males, no dose-relation, incidental, occasional variations of Creat and P in females, no dose-relation and/or inconsistent effect)\nUrinalysis: pH↓ in males at 1000 mg/kg bw/day, toxicological significance unknown"]
[17,"Systemic toxicity","Clinical chemistry and haematology","Rat",2,"Years","Oral",">20000","ppm","No effect","Haematology: occasional fluctuations without toxicological significance (data within historical control range, of small magnitude and/or not dose-related)\nClinical chemistry: occasional fluctuations without toxicological significance (data within historical control range, of small magnitude and/or not dose-related; ALP↑ in females at 20000 ppm was attributed to a single animal)\nUrinalysis: increased specific gravity (month 6) and decreased pH (months 6, 18 and 24) in males at 20000 ppm, treatment-related, considered toxicologically not significant as histopathological findings were absent"]
[18,"Systemic toxicity","Clinical chemistry and haematology","Rat",2,"Years","Oral",15000,"ppm","Change","Haematology: no treatment-related findings (not treatment-related findings: APTT↑ in males at ≥ 1500 ppm at 6 months, APTT↑ and leucocytes↓ in females at ≥ 1500 ppm at 18 months, PT↑ in females at 15000 ppm after 6 months, neutrophils↑ in males at 15000 ppm and in females at 5000 ppm after 18 months, Hb↓ in females at ≥ 5000 ppm after 12 months, Hb↑ and Ht↑ in males at 1500 ppm after 6 months, lymphocytes↓ in females at 15000 ppm after 18 months, monocytes↑ in females at 1500 ppm after 24 months, MCHC↓ in males at ≥ 5000 ppm at 6 months)\nClinical chemistry:  ALP↑ in males at 15000 ppm 6, 12 and 18 months, marginal, considered to be a minor adaptive change to test substance intake; increase in plasma electrolytes in both sexes at 15000 ppm, treatment-related, considered minor and adaptive responses (further findings without toxicological relevance: changes in plasma electrocytes in all groups (Na↑ and Cl↑ in both sexes and K↑ in males at ≥ 1500 ppm and Ca↓ in females at 15000 ppm after 18 months, Na↓ in satellite females at 15000 ppm after 12 months, P↓ in both sexes at 1500 ppm after 18 months and P↑ in males at 15000 ppm after 24 months) no dose relation, toxicological significance unclear; TBil↑ in males at ≥ 1500 ppm after 18 months, A/G ratio↓ in females at ≥ 1500 ppm after 24 months, ALT↑ in satellite males at 150000 ppm after 6 months, in females after 12 months and in males after 18 months, TG↑ in females at 150000 ppm after 12 months, ALP↑ in satellite males at 5000 ppm after 12 months, urea↑ in females at 1500 ppm after 6 months, all findings without dose-relation and/or inconsistency throughout the study)\nUrinalysis: no treatment-related findings"]
[19,"Systemic toxicity","Clinical chemistry and haematology","Mouse",18,"Months","Oral",">10000","ppm","No effect","Haematology: only differential leukocyte count was analysed, data appeared to be within the range of biological variation\nClinical chemistry: not performed\nUrinalysis: not performed"]
[20,"Systemic toxicity","Clinical chemistry and haematology","Mouse",18,"Months","Oral",">5000","ppm","No effect","Haematology (differential white blood cell count performed only ): no treatment-related findings\nClinical chemistry: not performed\nUrinalysis: not performed"]
[21,"Systemic toxicity","Clinical chemistry and haematology","Mouse",18,"Months","Oral",8000,"ppm","Change","Haematology (differential white blood cell count only): no treatment-related findings (increased lymphocytes in males and decreased neutrophils in males killed in extremis at 40000 ppm and increased lymphocytes in females at week 78, findings were attributed to skin lesions of high grade in moribund animals of the control group, which had high values of leukocytes and reduced values of lymphocytes, considered to be of sporadic nature)\nClinical Chemistry: not performed\nUrinalysis: decreased pH in males at ≥ 8000 ppm, treatment-related, no histopathological correlates"]
[44,"Systemic toxicity","Clinical chemistry and haematology","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect","Lower AST in all three dose groups, lower potassium in the 100 and 300 mg/kg/day groups, higher chloride and ALP in the 1000 mg/kg/day group, and lower phosphorus in the 100 mg/kg/day group.  Since no histopathological changes were observed, the changes in clinical chemistry parameters were considered not toxicologically relevant."]
[45,"Systemic toxicity","Clinical chemistry and haematology","Rat","31 (PND 23-53)","Days","Oral","> 1000","mg/kg bw/day","No effect","Higher mean alanine aminotransferase (ALT) and sodium levels were noted in the 300 and 1000 mg/kg/day groups, respectively; higher mean albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), chloride, phosphorus, and total protein levels and a lower urea nitrogen level were noted in the 1000 mg/kg/day group compared to the control group. These effects are reported as toxicologically not significant."]
[49,"Systemic toxicity","Clinical chemistry and haematology","Rat",28,"Days","Oral",20000,"ppm","Change","Haematology: No treatment-related findings. (Statistically significant decrease in haemoglobin in the high dose recovery animals; as the animals of the main group were not affected the effect was considered to be incidental.)\nClinical chemistry: Statistically significant increase in GPT and BUN at 20000 ppm in both sexes, which is reversible after 14 days of recovery (Non-treatment-related findings: statistically significant increase in BUN at 200 ppm, considered to be incidental due to the lack of a dose-relationship NOEAL for changes in BUN and GPT is 2000 mg/kg bw/d equivalent to 100 mg/kg bw; incidental decrease in Ca2+ at 200 ppm, increase in Ca2+ in 20000 ppm recovery group but not in the main group)"]
[50,"Systemic toxicity","Clinical chemistry and haematology","Rat",28,"Days","Oral",250,"mg/kg bw/day","Change","Haematology: No treatment-related findings (statistically significantly decreased MCHC (-2%) in males at 50 mg/kg bw/day was considered to be incidental)\nClinical chemistry: statistically significantly increased ALT in males at ≥ 250 mg/kg bw/day and in females at 2500 mg/kg bw/day, increased ALP in males at ≥ 250 mg/kg bw/day (statistically significant at 250 and 2500 mg/kg bw/day) and in females at ≥ 1000 mg/kg bw/day (not significant) and bilirubin were regarded as normal responses to increased liver activity; increased phosphate levels in males at ≥ 1000 mg/kg bw/day, treatment-related (slightly increased Na in females at 50, 1000 and 2500 mg/kg bw/day and slighly decreased Cl in females at 50 mg/kg bw/day were considered to be incidental)"]
[51,"Systemic toxicity","Clinical chemistry and haematology","Dog","Study part A: 21\nStudy Part B: 14","Days","Oral",1000,"mg/kg bw/day","Change","Haematology: \nStudy part A (21 days treatment): the male dog showed a reduced Hb and a mild increase in reticulocytes on Day 22 (treatment period 1000 mg/kg bw/day), not treatment-related, attributed to repeated blood sampling\nStudy part B (14 days treatment): no treatment-related findings\nClinical chemistry: \nStudy part A (21 days treatment): mild increase in ALT in the male dog and reduced cholesterol in the male and the female dog over the whole treatment period, considered to be not treatment-related\nStudy part B (14 days treatment): mild increase in ALT in the male dog, considered to be not treatment-related\nUrinalysis (available for study part B only, 14 days treatment): no adverse effects observed\nFaecal occult blood: no adverse effects observed"]
[52,"Systemic toxicity","Clinical chemistry and haematology","Rat",90,"Days","Oral",1000,"mg/kg bw/day","Change","Haematology: statistically significant increase in eosinophils in males at 300 mg/kg bw/day, no dose relation, considered to be incidental\nClinical chemistry: statistically significantly increased glucose (11%), total protein (9%), albumin (9%) and creatinine (8%) in females at 1000 mg/kg bw/day, treatment-related (statistically significantly increased ALP in males (28%) at 300 mg/kg bw/day was considered to be incidental as it was not observed at the higher dose)\nUrinalysis: reduced pH in males at 1000 mg/kg bw/day, treatment-related"]
[53,"Systemic toxicity","Clinical chemistry and haematology","Rat",90,"Days","Oral",6000,"ppm","Change","Haematology: No changes in haematological parameters observed.\nClinical chemistry: No treatment-related effects observed. (K was statistically signif. reduced in males at 2000 ppm, which was considered to be incidental because a dose-response relationship was lacking. Reduced ALT and increased bilirubin in males at 20000 ppm were considered to be without toxicological significance)\nUrinalysis: Treatment-related increase in RBC and detection of blood in females at ≥ 6000 ppm and in all treatment groups in males. Findings in males were not unequivocally attributed to treatment, as a mild elevation of RBC is commonly observed in male rats"]
[54,"Systemic toxicity","Clinical chemistry and haematology","Rat",90,"Days","Oral",200,"ppm","Change","Haematology: No treatment-related findings (decreased RBC and HCT in males at 200 ppm and reduced RBC in males at 2000 ppm with concomitant increase in MCH and MCHC in the respective groups were not dose-related and considered to be incidental; decrease in eosinophils in males at 20000 ppm was not consistent with findings in high dose recovery group, increased MCH and MCHC in high dose recovery males were considered to be incidental)\nClinical chemistry: statistically signif. increase in ALP in males at 20000 ppm which remained high (not statistically signif.) at the end of the recovery period; decreased creatinine and Ca2+ levels in females in all dose groups (not reversible after recovery) and increased glucose levels in females at 20000 ppm (reversible after recovery), treatment-related\nUrinalysis: not performed in the study"]
[55,"Systemic toxicity","Clinical chemistry and haematology","Rat",90,"Days","Oral",">5000","ppm","Change","Haematology: No adverse effects observed.\nClinical chemistry: No treatment-related findings. \n(Statistically significant increases in lymphocytes in males at 1000 and 5000 ppm and increased WBC in males at 5000 ppm were not dose-related and therefore not attributed to treatment; statistically signif. increased P and K in both sexes in all test item-treated groups and statistically signif. increased glucose levels in males at 5000 and 20000 ppm showed no dose-relation and/or where within or close to the upper levels of normal values and therefore considered to be without toxicological significance; increased BUN and AP (not siginificant) was attributed to extreme values of one rat)\nUrinalysis: Statistically signif. changes in specific gravity and pH at 5000 ppm in males were not considered to be related to treatment"]
[56,"Systemic toxicity","Clinical chemistry and haematology","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect","Haematology: No toxicologically relevant finding was observed. (Prothrombin time statist. signif. increased in females at 200 mg/kg bw/day, no dose-relation, considered to be incidental)\nClinical chemistry:  No toxicologically relevant finding was observed. (Dose-related increase in glucose levels in males over all test item treated groups, statistically not signifant; increase in  plasma cholinesterase and AP and decrease of K in males over all dose groups, not dose-related, toxicological significance of this finding is unclear; slightly increased glucose and AP levels in females in all test item treated groups, statistically not significant, no dose-response relationship)\nUrinalysis: Not performed"]
[57,"Systemic toxicity","Clinical chemistry and haematology","Dog",6,"Months","Oral",300,"mg/kg bw/day","Change","Haematology: Statistically significantly increased MCHC in both sexes at different sampling time points, no dose-relation, within normal range, not related to treatment\nClinical chemistry: A dose-related increase in alkaline phosphatase activity was observed in males and females at all doses (statistically significant in high-dose males (month 5) only) and total lactic dehydrogenase levels statist. signif. decreased in males at 60 and 300 mg/kg bw/day after 4 months of treatment until study termination. As no gross or microscopic liver lesions were observed, biological relevance equivocal\nUrinalysis: No treatment-related effects observed."]
[58,"Systemic toxicity","Clinical chemistry and haematology","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Haematology: No treatment related findings (mild elevations in RBC, HGB and HCT in females at 20 mg/kg bw/day, not dose-related and within normal range; mild changes in MCHC in males at 100 mg/kg bw/day after 12 months and in females at 10 and 100 mg/kg bw/day after 3 and 12 month, not dose-related).\nClinical chemistry: No treatment-related findings (statistically significant decrease in P and changes in SGPT, Na, K, Ca, Gluc and Alb were transient and within normal ranges and therefore not related to treatment).\nUrinalysis: No adverse effects observed."]
[59,"Systemic toxicity","Clinical chemistry and haematology","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect","Haematology: No treatment-related findings\nClinical chemistry: No treatment-related findings\nUrinalysis: No treatment-related findings\nFaeces: Occult blood determinations performed in faecal samples were negative for all animals throughout the study.\nBrain cholinesterase: No effect was observed."]
[60,"Systemic toxicity","Clinical chemistry and haematology","Rat",21,"Days","Dermal",1000,"mg/kg bw/day","Change","Haematology: statistically significant increase in MCH (4%) and MCV (4%) in females, reduced number of neutrophils (31%) in females. There was a decrease in monocytes (44%, P<0.05) and large unstained cells (62%, P<0.05) in the high dose males compared to\ncontrols. These findings have not been seen in previous studies and the decrease in monocytes may partly be due to higher values in concurrent control animals.\nClinical chemistry: no adverse effects observed\nUrinalysis: not performed"]
[61,"Systemic toxicity","Clinical chemistry and haematology","Rat",21,"Days","Dermal",1000,"mg/kg bw/day","Change","Haematology: statistically significant increase in Hb in females at 1000 mg/kg bw/day, treatment-related; statist. signif. decrease in RBC in females at 250 and 1000 mg/kg bw/day, considered not to be of tox. significance since no effect on the red cell parameters were observed\nClinical chemistry: statistically significant increase in plasma urea but not urea levels in females at 1000 mg/kg bw/day, considered to be not of tox significance; stat. signif. decrease in triglycerides in males at 500 mg/kg bw/day, no dose relation, considered to be not treatment-related\nUrinalysis: not performed"]
[62,"Systemic toxicity","Clinical chemistry and haematology","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect","Haematology: No treatment-related findings (statist. signif. increase in Hb and Hct in males at 100 mg/kg bw/day, no dose-relation)\nClinical chemistry: No treatment-related findings (statist. siginif. increase in Na in males at 5000 mg/kg bw/day, statist. signif. increase in glucose in females at 100 and 5000 mg/kg bw/day, statist. signif. decreased LDH in females at 5000 mg/kg bw/day were considered to be without biological significance)\nUrinalysis: not performed"]
[63,"Systemic toxicity","Clinical chemistry and haematology","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect","Haematology: no treatment-related findings. Mean corpuscular volume of platelets and variation of platelet volume were statist. signif. decreased in females at 1000 and 2000 mg/kg bw/day were within normal limits and therefore not attributed to treatment.\nClinical chemistry: no treatment-related findings. Statist. signif. increased urea values in males at 2000 mg/kg bw/day were within normal limits and therefore not attributed to treatment.\nUrinalysis: not performed"]
[67,"Systemic toxicity","Clinical chemistry and haematology","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","Haematology: No effect on differential blood count was observed (weeks 52, 77, 102)."]
[68,"Systemic toxicity","Clinical chemistry and haematology","Mouse",2,"Years","Oral","> 30000","ppm","No effect","Haematology (12, 18, 24 months): Differences observed (after 12 month) were not attributed to treatment. Moreover, morphologic evaluation of leukocytes and erytrocytes showed no effect."]
[76,"Systemic toxicity","Clinical chemistry and haematology","Rat","90-92","Days","Oral",2000,"ppm","Change","Hematology: RBC in F 2000 ppm=+13.6%* and M 7500 ppm=-1.4%* (males within normal range of historical controls); HCT in F 2000 ppm=+13.2%* and M 7500 ppm=-1.4%*; All values were close to the historical controls. \nSlight change in monocytes in males and females at 2000 ppm however not considered treatment-related\nClincal chemistry: Ca in M 5000 ppm increase; Na in M changed ; Cl in M 7500 ppm increase (none of the clinical chemistry parameters is considered treatment-related)"]
[78,"Systemic toxicity","Clinical chemistry and haematology","Rat",90,"Days","Oral",12500,"ppm","Change","Hematology: mild increase in hct and RBC in M at 12500 ppm; 25000 ppm; 50000 ppm; mild increase in hgb in M at 25000 ppm; 50000 ppm; mild increase in plts in M at 50000 ppm\nminimal but significant increase in lymphocyte and plts counts, WBC, MCH, MCV in F\nClinical chemistry: Changes in: ALP in M and F at all time points (except 90 days), total bile acids in M (days 23 and 90) and F (day 23), total protein in F at all time points; sporadic increases in urea nitrogen and albumin"]
[1,"Systemic toxicity","Clinical signs","Rat",90,"Days","Oral",">20000","ppm","No effect","Low incidence of diarrhoea and pale faeces in both sexes at 20000 ppm in week 2, reversible\nophthalmoscopy: incidences of abnormal findings occasionally observed in control and 20000 ppm rats, not treatment-related","The most common finding were related to distrubances of the gastrointestinal tract such as soft/loose feces, diarrhea or reduced fecal output.\nIn some studies rales were observed in rat and rabbit.\nNo effects were observed in mice."]
[2,"Systemic toxicity","Clinical signs","Rat",90,"Days","Oral",50000,"ppm","Increase","Soft faeces and diarrhea in 10/10 males and 10/10 females at 50000 ppm from Day 4 until termination."]
[3,"Systemic toxicity","Clinical signs","Rat",13,"Weeks","Oral",">30000","ppm","No effect","Poor general condition in 1/12 females (emaciation, decreased spontaneous motor activity), not treatment-related"]
[4,"Systemic toxicity","Clinical signs","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"Systemic toxicity","Clinical signs","Dog",90,"Days","Oral",1000,"mg/kg bw/day","Increase","At 1000 mg/kg bw/day: liquid/soft feces in 3/3 males and 3/3 females, vomiting in 2/3 females, thin appearance in 1/3 males and 3/3 females, dehydration in 1/3 males and 2/3 females, pallor of ears and mouth in 1/3 females."]
[6,"Systemic toxicity","Clinical signs","Dog",90,"Days","Oral",">10000","ppm","No effect"]
[7,"Systemic toxicity","Clinical signs","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"Systemic toxicity","Clinical signs","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"Systemic toxicity","Clinical signs","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Vomiting, soft feces, thin appearance, hyperactivity, ptyalism, cutaneous signs and nodules on the ears were occasionally observed among all dose groups, not treatment-related"]
[10,"Systemic toxicity","Clinical signs","Dog",1,"Year","Oral",50000,"ppm","Increase","Loose stool in 3/4 males and 4/4 females at 50000 ppm"]
[11,"Systemic toxicity","Clinical signs","Dog",1,"Year","Oral",">30000","ppm","No effect","Salivation in both sexes among all doses with increased incidences in 2/4 males and 1/4 females the high dose group, attributed to anticipation of feeding, not related to treatment; low incidence of scrotal skin redddening in 2/4 males at 15000 ppm and in 1/4 males at 30000 ppm, not treatment-related; incidences of fluid feces, vomiting, blood or mucus in feces were noted but not related to treatment\nophthalmology: low incidence of corneal or lentiocular opacities among treatment and control animals, not treatment-related"]
[12,"Systemic toxicity","Clinical signs","Rat",1,"Year","Oral",20000,"ppm","Increase","Slight increase in urinary staining (wet and dry) at 20000 ppm in both sexes "]
[13,"Systemic toxicity","Clinical signs","Rat",2,"Years","Oral",">10000","ppm","No effect","No treatment-related findings (weakness, loss of body weight, nasal discharge and snuffling were common toxic signs among both sexes of all treatment and control groups, soft stool/diarrhoea and alopecia were found in males of all groups, no dose-relation)"]
[14,"Systemic toxicity","Clinical signs","Rat",2,"Years","Oral",30000,"ppm","Increase","Loose stool and soiled and/or wetted fur in perianal/genital region in both sexes at 30000 ppm, bradypnea and integument mass (tail) in males at 30000 ppm (non treatment-related findings: decreased spontaneous motor activity and bradypnea in males at 3000 ppm, ptosis in females at 3000 ppm, reduced tactile hairloss in males at ≥ 3000 ppm and in females at 3000 and 10000 ppm, reduced integument wounds and hairloss in males at 30000 ppm)"]
[15,"Systemic toxicity","Clinical signs","Rat",2,"Years","Oral",20000,"ppm","Increase","Clinical signs: red-brown staining of tray papers, particularly in males at 20000 ppm (not treatment-related findings: red/brown colored urine in 3/52 males and 1/52 females at 20000 ppm)\nFunctional observational battery: decreased landing foot splay in females at 20000 ppm, not treatment-related"]
[16,"Systemic toxicity","Clinical signs","Rat",2,"Years","Oral",300,"mg/kg bw/day","Increase","Pale faeces in males and females at ≥ 300 mg/kg bw/day from weeks 16-104, treatment-related, considered to be not toxicologically significant"]
[17,"Systemic toxicity","Clinical signs","Rat",2,"Years","Oral",20000,"ppm","Increase","No signs of clinical toxicity\nOphthalmology (examined by 3 independent experts): increased incidences of degenerative lens changes in males at 20000 ppm, within historical control range, treatment-related as histopathological abnormalities were exacerbated by treatment"]
[18,"Systemic toxicity","Clinical signs","Rat",2,"Years","Oral",">15000","ppm","No effect","Clinical signs: No treatment-related findings\nFunctional observation: No treatment-related findings"]
[19,"Systemic toxicity","Clinical signs","Mouse",18,"Months","Oral",">10000","ppm","No effect","Clinical signs: no treatment-related findings (incidences of alopecia and skin injuries among all test groups, common finding in this species)\nOpthalmology: no treatment-related findings (cataract in 1/50 females at 100 ppm, corneal opacity in 1/50, 1/50 and 2/50 at 0, 100 and 1000 ppm. considered incidental)"]
[20,"Systemic toxicity","Clinical signs","Mouse",18,"Months","Oral",">5000","ppm","No effect","No treatment-related findings. Wounds, scab formation, loss of whiskers, fur loss and limb swelling occasionally observed, consequence of intra-cage aggression"]
[21,"Systemic toxicity","Clinical signs","Mouse",18,"Months","Oral",">40000","ppm","No effect","No treatment-related findings (increased loss of tactile hair loss in males at 40000 ppm and in females at 1600 ppm, masses in the anus (associated with neoplastic changes) and pale coloured skin in males at 40000 ppm, hairloss in males at 8000 ppm, loose stool in both sexes from week 20/21 onwards at 40000 ppm)"]
[22,"Systemic toxicity","Clinical signs","Rat",10,"Weeks","Oral",">15000","ppm","No effect","No treatment-related findings (findings considered unrelated to treatment: incidences of red/brown staining of the external body surface, generalised fur loss, scab formation and red/brown staining on cage tray-liners in treated and control F0 + F1 animals, abrasion to the dorsal/cranial regions in males at 0 and 15000 ppm, physical injury to the tail apex in 1/28 females at 1500 ppm, red swollen ears in 1/28 and 1/28 females at 5000 and 15000 ppm; red stained urine, exophthalmia and piloerection each in one high dose group male or female, considered to be incidental; presence of mass in single animals, age-related; blood around the vagina in 1/28 females each at 0 and 5000 ppm; one control female showed lethargy, piloerection, hunched posture and staining around ano-genital region and was killed in extremis, incidence of protruding sternums in F1 females of control and treaetment groups, related to lactation phase)"]
[22,"Systemic toxicity","Clinical signs","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"Systemic toxicity","Clinical signs","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect","No treatment-related findings. Annular constrictions in tails of the F0 and F1 males and females during pre-mating, almost all males and half of the females affected in all groups, considered to be incidental"]
[23,"Systemic toxicity","Clinical signs","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect"]
[24,"Systemic toxicity","Clinical signs","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",30000,"ppm","Increase","Loose stool in F1 males during pre-mating and in F0 + F1 females during pre-mating and lactation at 30000 ppm, treatment-related (not treatment-related findings: hairloss in F0 males at ≥ 1200 ppm, considered to be incidental, malocclusion of the incisors, respiratory wheezing and red sebum in 1/24 F0 control males, 1/24 F0 control females and 1/24 F0 males at 6000 ppm and in 1/24 F1 males at 1200 ppm; distention of the abdomen in 1/24 F0 males at 6000 ppm)"]
[24,"Systemic toxicity","Clinical signs","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect","No effects in offspring observed"]
[25,"Systemic toxicity","Clinical signs","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect","No treatment-related findings (nasal discharge and snuffling in both sexes of all treatment and control groups; rare instances of soft stool, biting injuries, urine incontinence and alopecia in single F0 and/or F1 animals; circling disease in 2/30 F1 females at 10000 ppm)"]
[25,"Systemic toxicity","Clinical signs","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect"]
[26,"Systemic toxicity","Clinical signs","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect","No treatment-related findings (occasional observations of skin ulceration, hair loss/scabbing, brown staining of the coat, red/brown eye discharge, dental abnormalities and soft faeces in F0 and F1 rats, no treatment relation)"]
[27,"Systemic toxicity","Clinical signs","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",30000,"ppm","Increase","Soft stool at 30000 ppm in F0 and F1 animals of both sexes, treatment-related (not treatment-related findings: red ocular discharge, result of overgrown / maloccluded teeth in both sexes, no dose-relation)"]
[27,"Systemic toxicity","Clinical signs","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[28,"Systemic toxicity","Clinical signs","Rat","10 (GD 7-16)","Days","Oral",">1000","mg/kg bw/day","No effect"]
[29,"Systemic toxicity","Clinical signs","Rat","10 (GD 6-15)","Days","Oral",1000,"mg/kg bw/day","Increase","Loose stool in 20/22 pregnant females at 1000 mg/kg bw/day during the dosing period and in 9/20 females one day after treatment (gestation day 16) (not treatment-related findings: hair loss or scabs in maternal rats at 30 and 300 mg/kg bw/day during the dosing period, within historical control data, hairloss in 1-2 maternal rats per group in each treated group)"]
[30,"Systemic toxicity","Clinical signs","Rabbit","13 (GD 6-18)","Days","Oral",300,"mg/kg bw/day","Increase","Loose stool in 4/17 females during the dosing period at 300 mg/kg bw/day  and soiled fur in the perianal region in 2 of them, loose stool remained in 2/4 affected females of this group after dosing, one of the affected does aborted on gestation day 26 and the other one prematurely delivered on gestation day 27, treatment-related (not treatment-related findings: hair loss in 1/17 and 1/16 females at 10 and 100 mg/kg bw/day during dosing and in  1/17 and 1/16 females at 10 and 100 mg/kg bw/day post-dosing, loose stool and red material on the tray in 2/18 control females after dosing, loose stool in 1/17 females at 10 mg/kg bw/day post-dosing)"]
[31,"Systemic toxicity","Clinical signs","Rabbit","13 (GD 7-19)","Days","Oral",400,"mg/kg bw/day","Increase","Scours (16/18 does), reduced faecal output (6/18 does) and diarrhoea (10/18 does) at 400 mg/kg bw/day, treatment-related (lethargy, ptosis, hunched posture, hypothermia and blood on tray in 1/18 females at 400 mg/kg bw/day killed in extremis) (not treatment-related: vaginal bleeding in 1/18 females at 200 mg/kg bw/day, no dose-relation, not evaluated as toxicological effect, scours in 5/18, 10/18 and 7/18 females at 0, 50 and 200 mg/kg bw/day)"]
[32,"Systemic toxicity","Clinical signs","Rabbit","13 (GD 8-20)","Days","Oral",175,"mg/kg bw/day","Increase","Sings of diarrhoea; reduction in faecal output; staining in the genital area (300 mg/kg bw/day group); not significant for all groups"]
[33,"Systemic toxicity","Clinical signs","Rabbit","22 (GD 6-27)","Days","Oral",175,"mg/kg bw/day","Increase","Increase in soft stool and diarrhea (from 175 mg/kg bw/d); nasal discharge (350 mg/kg bw/day group only)"]
[34,"Systemic toxicity","Clinical signs","Rabbit","13 (GD 6-18)","Days","Oral",500,"mg/kg bw/day","Increase","Toxic symptoms of the respiratory and the gastrointestinal tract (rales, dyspnoea, diarrhea/soft stool and weakness)"]
[35,"Systemic toxicity","Clinical signs","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect"]
[36,"Systemic toxicity","Clinical signs","Mouse",28,"Days","Oral","> 5000","ppm","No effect"]
[42,"Systemic toxicity","Clinical signs","Rat",3,"Days","Oral","> 1000","mg/kg bw/day","No effect"]
[43,"Systemic toxicity","Clinical signs","Rat",10,"Days","Oral","> 1000","mg/kg bw/day","No effect"]
[44,"Systemic toxicity","Clinical signs","Rat","21 (PND 22-42)","Days","Oral",300,"mg/kg bw/day","Increase","Dose dependent rales were noted in 4/15 animals in the 300 mg/kg bw/day group and 13/15 animals in the 1000 mg/kg bw/day group."]
[45,"Systemic toxicity","Clinical signs","Rat","31 (PND 23-53)","Days","Oral",300,"mg/kg bw/day","Increase","Rales were noted in 9/15 animals in the 300 mg/kg bw/day group and 14/14 animals in the 1000 mg/kg bw/day group throughout the treatment period approximately 4 hours following dose administration."]
[46,"Systemic toxicity","Clinical signs","Rabbit","13 (GD 7-19)","Days","Oral",50,"mg/kg bw/day","Increase","Light increase in females with gastro-intestinal disturbances (from 50 mg/kg bw/day), dose-related increase in the incidence of females showing soft/liquid faeces; sings of inappetence (150 mg/kg bw/day group and higher dose groups)"]
[47,"Systemic toxicity","Clinical signs","Rabbit","13 (GD 7-19)","Days","Oral",100,"mg/kg bw/day","Increase","Signs of gastro-intestinal disturbances and inappetence were observed in all dose groups."]
[48,"Systemic toxicity","Clinical signs","Rabbit"," 7 (high dose) -13 (mid and low dose)","Days","Oral",500,"mg/kg bw/day","Increase","Soft feces (from 500 mg/kg bw/day); gastro-intestinal disturbances (from 750 mg/kg bw/day); haemorrhagic depressions of the stomach and damp/stained fur of the tail (1000 mg/kg bw/day)."]
[49,"Systemic toxicity","Clinical signs","Rat",28,"Days","Oral",">20000","ppm","No effect","No treatment-related findings. (A few incidences of urine incontinence were observed at 2000 ppm (2/5 males) and 20000 ppm (2/5 females), but not in 20000 ppm recovery animals, therefore the findings wer considered to be incidental)"]
[50,"Systemic toxicity","Clinical signs","Rat",28,"Days","Oral",2500,"mg/kg bw/day","Increase","Soft faeces in 3/5 males at 2500 mg/kg bw/day during weeks 3 and 4."]
[51,"Systemic toxicity","Clinical signs","Dog","Study part A: 21\nStudy Part B: 14","Days","Oral",">1000","mg/kg bw/day","No effect","Study part A (21 days of treatment): No abnormal findings were observed.\nStudy part B (14 days of treatment): The female dog showed loose faeces during the course of the treatment period, findings were not attributed to treatment"]
[52,"Systemic toxicity","Clinical signs","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Systemic toxicity","Clinical signs","Rat",90,"Days","Oral",20000,"ppm","Increase","Diarrhea in 10/10 males and 9/10 females at 20000 ppm\nOphthalmic examinations: persistent pupillary membrane in the right eye of 1/10 control males and numerous corneal deposits in the right eye of 1/10 males at 20000 ppm, not treatment-related"]
[54,"Systemic toxicity","Clinical signs","Rat",90,"Days","Oral",200,"ppm","Increase","Higher incidences of respiratory affections (nasal discharge, snuffling) in both sexes in all test item treated groups, persistent in males after recovery period."]
[55,"Systemic toxicity","Clinical signs","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"Systemic toxicity","Clinical signs","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"Systemic toxicity","Clinical signs","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"Systemic toxicity","Clinical signs","Dog",1,"Year","Oral",20,"mg/kg bw/day","Increase","Increased incidences of abnormal excrement (bloody stool, yellow mucoid stool, diarrhea, emesis) were observed in a few females at 20 and 500 mg/kg bw/day; most observations were attributed to 1 female of each group (1/6), no findings at 100 mg/kg bw/day females or in males (all dose groups), considered to be not dose-related and of questionable biological significance; skin redness with slight alopecia in 1/6 females at 100 and in 1/6 females at 500 mg/kg bw/day.\nOphthalmoscopy: no treatment-related findings"]
[59,"Systemic toxicity","Clinical signs","Dog",1,"Year","Oral",1000,"mg/kg bw/day","Increase","Increased incidences of changes in faecal consistency (soft, loose, liquid) were recorded more frequently at 1000 mg/kg bw/day, treatment-related (not treatment-related observations: vomiting, salivation, minor wound bites and conjunctivitis were infrequently observed, no dose or treatment relation)\nOphthalmoscopy: no treatment-related findings"]
[60,"Systemic toxicity","Clinical signs","Rat",21,"Days","Dermal",1000,"mg/kg bw/day","Increase","Clinical signs of systemic toxicity: no adverse effects observed\nLocal skin reactions: 2/5 males and 3/5 females showed very slight erythema during Week 2, which remained apparent in 1/5 females in Week 3 at 1000 mg/kg bw/day, moderate to severe desquamation in 3/5 males and mild to severe desquamation in 5/5 females at 1000 mg/kg bw/day during Week 2 and in 1/5 males and 1/5 females at 1000 mg/kg bw/day in Week 3."]
[61,"Systemic toxicity","Clinical signs","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect","No treatment-related signs of systemic toxicity or local skin reactions observed. 1/5 females at 500 mg/kg bw/day had desquamation during the latter part of the study, no dose-relation, toxicologically not significant"]
[62,"Systemic toxicity","Clinical signs","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect","Clinical signs of systemic toxicity: soft stool, diarrhea and mucoid diarrhea and ocular and nasal discharge were observed in a few animals of both sexes among all groups, not treatment-related\nLocal skin reactions: doubtful or barely perceptible to very slight erythema at 5000 mg/kg bw/day in 3/5 males and 3/5 females with abraded skin and in 3/5 males and 2/5 females with intact skin, doubtful to barely perceptable edema at 5000 mg/kg bw/day in 2/5 males and 2/5 females with abraded skin and in 2/5 males and 2/5 females with intact skin, not considered biologically significant"]
[63,"Systemic toxicity","Clinical signs","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect","Clinical signs of systemic toxicity: no adverse effects observed\nLocal skin reactions: very slight erythema in males at 2000 mg/kg bw/day through Days 7-20 and in females at 500 mg/kg bw/day lasting for 5 days were not attributed to treatment. No edema was observed."]
[64,"Systemic toxicity","Clinical signs","Rat","10 (GD 6-15)","Days","Oral",1000,"mg/kg bw/day","Change","3500 mg/kg: respiratory distress (noisy respiration/gasping (15/25)), post-dose salivation (22/22), wet coats (13/22), loose faeces from GD7-GD16 (22/22). 1000 mg/kg: noisy respiration on one occasion (2/25). Hair loss/scabbing in occasional animals, including controls, not treatment related."]
[65,"Systemic toxicity","Clinical signs","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","No treatment-related clinical signs were observed."]
[66,"Systemic toxicity","Clinical signs","Rabbit","22 (GD 6-27)","Days","Oral",175,"mg/kg bw/day","Change","Soft stool and diarrhea were noted in all groups during the treatment period. A slight increase was noted, however, in the 175 mg/kg/day dosage group when compared to the control group and either soft stool, diarrhea or both were noted in each animal at least once during the treatment period in the 350 mg/kg/day dosage group. A definite increase in nasal discharge was also noted in the 350 mg/kg/day dosage group when compared to the control group."]
[67,"Systemic toxicity","Clinical signs","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","There were no notable intergroup differences in either sex. There were no notable intergroup differences in the incidences of externally palpable masses."]
[68,"Systemic toxicity","Clinical signs","Mouse",2,"Years","Oral","> 30000","ppm","No effect","No treatment-related clinical signs were observed."]
[69,"Systemic toxicity","Clinical signs","Rat","5.5 (GD 3 till 21 days post partum)","Weeks","Oral",10000,"ppm","Change","Clinical signs  included soft faeces and yellow stained sawdust (considered to be caused by the urine) in both cages of animals at 10000 and 30000 ppm. Onset of these signs was earlier at 30000 ppm than at 10000 ppm (soft faeces occurred immediately dietary administration commenced at 30000 ppm but not until the third week post partum at 10000 ppm; yellow staining of the sawdust occurred on Day 26 post coitum at 30000 ppm but not until Day 28 post coitum at 10000 ppm), with signs still apparent in both groups at termination. There were no clinical signs at 3000 ppm considered to be attributable to treatment."]
[69,"Systemic toxicity","Clinical signs","Rat","3 (PND 21-42)","Weeks","Oral",30000,"ppm","Change","Soft faeces were observed for all animals at 30000 ppm from Week 4 through to sacrifice at Week 6. No other clinical signs were observed at this or lower dosages."]
[70,"Systemic toxicity","Clinical signs","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","In-life physical observation data were considered comparable between the control and treated groups for each generation interval throughout the study. No adverse treatment-related effects were reported for adult F0, F1, and F2 animals."]
[71,"Systemic toxicity","Clinical signs","Rat",28,"Days","Oral",30000,"ppm","Increase","Significant incidences of soft stools and/or diarrhea were noted for both sexes at all three exposure levels with the highest dose group most affected (M/F 30000= Soft stool, diarrhea; M/F 40000= soft  stool/diarrhea; M/F 50000=marked diarrhea)."]
[72,"Systemic toxicity","Clinical signs","Mouse",28,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[73,"Systemic toxicity","Clinical signs","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[74,"Systemic toxicity","Clinical signs","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","Signs of systemic toxicity were not observed in F0 generation."]
[74,"Systemic toxicity","Clinical signs","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","Signs of systemic toxicity were not observed in F1 generation."]
[74,"Systemic toxicity","Clinical signs","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","Signs of systemic toxicity were not observed in F0 generation."]
[76,"Systemic toxicity","Clinical signs","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[77,"Systemic toxicity","Clinical signs","Rabbit","22 (GD 6-27)","Days","Oral",">2500","mg/kg bw/day","No effect","The single surviving female of the 500 mg/kg bw group aborted on GD 26."]
[78,"Systemic toxicity","Clinical signs","Rat",90,"Days","Oral",50000,"ppm","Increase","F and M at 50000 ppm = diarrhea during first 50 days was observed (normal thereafter)."]
[92,"Sensitive to, but not diagnostic of, EATS","Clinical signs","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","There was no clinical evidence of alterations in activity or behavior, reflexes, eyes or skin, respiratory, gastrointestinal, genito-urinary and cardiovascular systems."]
[1,"Systemic toxicity","Food consumption","Rat",90,"Days","Oral",20000,"ppm","Decrease","Food consumption: reduced in males at 20000 ppm from week 5, not significant, treatment-related\nfood efficiency: reduced in males at 20000 ppm throughout the study, treatment-related","Food consumption was decreased in most studies at high doses. In rats: From 1000 ppm in males and 7500 ppm in females or 1000 mg/kg bw/day in females. In dogs: From 1000 mg/kg bw/day or 10000 ppm in males and females.\nIn rabbits: From 100 mg/kg bw/day in females. In mice: From 40000 ppm in males and females. There was one study in mice with increased food consumption in males and females from 5000 ppm although incidents of body weight loss were observed in this dose group."]
[2,"Systemic toxicity","Food consumption","Rat",90,"Days","Oral",50000,"ppm","Decrease","Food consumption/efficiency: reduced in males and females at 50000 ppm during the first 4 weeks, effects partially reversible in males and fully reversible in females, effects in line with reduced bw development, treatment-related"]
[3,"Systemic toxicity","Food consumption","Rat",90,"Days","Oral",30000,"ppm","Decrease","Food consumption: statistically significantly decreased in both sexes at 30000 ppm during the first week, in line with reduced body weight, treatment-related (not treatment-related findings: decreased  food consumption in both sexes at 3000 ppm)\nfood efficiency: statistically significantly decreased (-5-6 %) in both sexes at 30000 ppm during the first week, in line with reduced body weight, treatment-related "]
[4,"Systemic toxicity","Food consumption","Mouse",90,"Days","Oral",50000,"ppm","Decrease","Food consumption: decreased (-6%) in males at 50000 ppm during the treatment period, treatment-related \nfood efficiency: decreased (m:-21%; f: -12%  ) in both sexes at 50000 ppm during the treatment period, treatment-related "]
[5,"Systemic toxicity","Food consumption","Dog",90,"Days","Oral",1000,"mg/kg bw/day","Decrease","Food consumption: reduced food consumption, varying from 25-75% of the amount given, was observed on many occasions in both sexes at 1000 mg/kg bw (males: study week 4-11, females: study week 1-11), treatment-related"]
[6,"Systemic toxicity","Food consumption","Dog",90,"Days","Oral",10000,"ppm","Decrease","Food consumption: decreased in both sexes at 10000 ppm during study week 2, fully reversible\nfood efficiency: no adverse effects observed"]
[7,"Systemic toxicity","Food consumption","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"Systemic toxicity","Food consumption","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"Systemic toxicity","Food consumption","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect","Occasional fluctuations (25-75% of amount given) in control and treated animals, not test item-related"]
[10,"Systemic toxicity","Food consumption","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"Systemic toxicity","Food consumption","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"Systemic toxicity","Food consumption","Rat",1,"Year","Oral",8000,"ppm","Decrease","Food consumption: reduced in both sexes at ≥ 8000 ppm, treatment-related (20000 ppm: reduced during the first 12 weeks of the study, 8000 ppm: occasionally reduced at the end of the study)\nfood efficiency: reduced in both sexes at 20000 ppm, treatment-related  (reduced during the first 4 weeks of the study)"]
[13,"Systemic toxicity","Food consumption","Rat",2,"Years","Oral",">10000","ppm","No effect","Food consumption: no treatment-related findings (occasional fluctuations in males of all groups; reduced in females in all treatment groups during months 8-13 and 18-22, statistically not significant)\nfood efficiency: no treatment-related findings"]
[14,"Systemic toxicity","Food consumption","Rat",2,"Years","Oral",30000,"ppm","Decrease","Food consumption: decreased in males at 30000 ppm during the first weeks of treatment, treatment-related (not treatment-related findings: increased in females at 3000 ppm during study week 48)\nfood efficiency: decreased in both sexes at 30000 ppm during the first 13 weeks of treatment (not treatment-related findings: reduced in males at 10000 ppm during the first 6 weeks)"]
[15,"Systemic toxicity","Food consumption","Rat",2,"Years","Oral",20000,"ppm","Decrease","Food consumption: statistically significantly reduced in males (-6%) and females (-5%) at 20000 ppm during the first study year, treatment-related\nfood efficiency: statistically significantly reduced in both sexes at 20000 ppm during study weeks 1-4, reduced in males at 20000 ppm in weeks 1-12, treatment-related (not treatment-related: slightly increased in females at 20000 ppm during weels 9-12)"]
[16,"Systemic toxicity","Food consumption","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[17,"Systemic toxicity","Food consumption","Rat",2,"Years","Oral",">20000","ppm","No effect","Food consumption: occasionally increased in males at 2000 and 20000 ppm, considered toxicologically not significant\nFood efficiency: no abnormalities observed"]
[18,"Systemic toxicity","Food consumption","Rat",2,"Years","Oral",">15000","ppm","No effect","Food consumption: occasional fluctuations, not treatment-related\nFood efficiency: occasional fluctuations, not treatment-related"]
[19,"Systemic toxicity","Food consumption","Mouse",18,"Months","Oral",">10000","ppm","No effect","Food consumption: occasionally altered in both sexes among all groups throughout the study, no dose relation, of minor degree and/or not consistent, considered to be incidental\nFood efficiency: no treatment-related findings"]
[20,"Systemic toxicity","Food consumption","Mouse",18,"Months","Oral",">5000","ppm","No effect","Food consumption: no treatment-related findings\nFood efficiency: reduced in females of all dose levels in weeks 1 and 2, reduced in males at 5000 ppm in week 4 to 5, considered as an isolated event and not treatment-related"]
[21,"Systemic toxicity","Food consumption","Mouse",18,"Months","Oral",8000,"ppm","Decrease","Food consumption: statistically significantly depressed (-6% overall) in males at 40000 ppm at weeks 1 and 68 and in females (-7% overall) at 40000 ppm at weeks 1, 4, 8, 12, 20, 28, 40, 48 and 68, treatment-related\nFood efficiency: decreased in both sexes at 40000 ppm (-9% and -24% in males and femeles, respectively) and in females at 8000 ppm  throughout the study period (-16% overall), treatment-related"]
[22,"Systemic toxicity","Food consumption","Rat",10,"Weeks","Oral",">15000","ppm","No effect"]
[23,"Systemic toxicity","Food consumption","Rat","10 (pre-mating)","Weeks","Oral",10000,"ppm","Decrease","Food consumption: decreased in F1 males at 10000 ppm during pre-mating, treatment-related \nFood efficiency: increased in F1 males at 10000 ppm during weeks 5-8, treatment-related"]
[24,"Systemic toxicity","Food consumption","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect","No treatment-related findings (increased in F0 males at 1200 ppm in week 13; reduced in F1 males at 30000 ppm in week 4; increased in F0 females at 30000 ppm in weeks 2-4 and reduced in the same group on lactation days 7-14, no clear treatment-relation; increased in F1 females at 1200 and 6000 ppm on laction days 14-21, no dose relation, considered to be incidental)"]
[25,"Systemic toxicity","Food consumption","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",10000,"ppm","Change","Decreased in F1 males at ≥ 1000 ppm during weeks 0-2; increased in F1 females at 10000 ppm during gestation (not treatment-related findings: decreased in F0 females at 100 and 1000 ppm and in F1 females at 100 ppm during lactation; increased in F0 females at 10000 ppm during lactation)"]
[26,"Systemic toxicity","Food consumption","Rat","10 prior to mating, continued until termination","Weeks","Oral",10000,"ppm","Increase","Food consumption: slightly increased in F1 females at 10000 ppm during the latter stage of the first pre-mating period, not statistically significant\nFood efficiency: no clear consistent adverse effects observed across both generations\nWater consumption: slightly increased in F1 females at 10000 ppm with statistical significance in week 16"]
[27,"Systemic toxicity","Food consumption","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",30000,"ppm","No effect","Food consumption: slightly decreased at 30000 ppm in F0 and F1 males and females during the first week of treatment and in F0 dams at 30000 ppm during the last week of lactation. However, in general food intake was not substantially affected during the study period."]
[28,"Systemic toxicity","Food consumption","Rat","10 (GD 7-16)","Days","Oral",">1000","mg/kg bw/day","No effect","Food consumption: marginally reduced at 1000 mg/kg bw/day during dosing period, differences were not statistically significant"]
[29,"Systemic toxicity","Food consumption","Rat","10 (GD 6-15)","Days","Oral",1000,"mg/kg bw/day","Decrease","Decreased at 1000 mg/kg bw/day on gestation days 6-9, treatment-related (increase at 1000 mg/kg bw/day on gestation days 15-20 was considered to be due to the rebound effect against the reduced food consumption during the dosing period)"]
[30,"Systemic toxicity","Food consumption","Rabbit","13 (GD 6-18)","Days","Oral",">300","mg/kg bw/day","No effect"]
[31,"Systemic toxicity","Food consumption","Rabbit","13 (GD 7-19)","Days","Oral",400,"mg/kg bw/day","Decrease","Food consumption: Reduced at 400 mg/kg bw/day during the dosing period, treatment-related"]
[32,"Systemic toxicity","Food consumption","Rabbit","13 (GD 8-20)","Days","Oral",175,"mg/kg bw/day","Decrease","Food consumption was statistically significantly decreased."]
[34,"Systemic toxicity","Food consumption","Rabbit","13 (GD 6-18)","Days","Oral","> 500","mg/kg bw/day","No effect","Feed intake was only decreased in the pre-dosing period"]
[35,"Systemic toxicity","Food consumption","Rabbit","13 (GD 6-18)","Days","Oral",500,"mg/kg bw/day","Decrease"]
[36,"Systemic toxicity","Food consumption","Mouse",28,"Days","Oral","> 5000","ppm","No effect"]
[46,"Systemic toxicity","Food consumption","Rabbit","13 (GD 7-19)","Days","Oral",150,"mg/kg bw/day","Decrease","Food consumption was decreased throughout the treatment period."]
[47,"Systemic toxicity","Food consumption","Rabbit","13 (GD 7-19)","Days","Oral",100,"mg/kg bw/day","Decrease","A marked reduction was observed in the high dose group and slight or transient reductions in the low and mid-dose group."]
[48,"Systemic toxicity","Food consumption","Rabbit"," 7 (high dose) -13 (mid and low dose)","Days","Oral",1000,"mg/kg bw/day","Decrease"]
[49,"Systemic toxicity","Food consumption","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[50,"Systemic toxicity","Food consumption","Rat",28,"Days","Oral",">2500","mg/kg bw/day","No effect","Neither food nor water consumption were affected."]
[51,"Systemic toxicity","Food consumption","Dog","Study part A: 21\nStudy Part B: 14","Days","Oral",">1000","mg/kg bw/day","No effect"]
[52,"Systemic toxicity","Food consumption","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Systemic toxicity","Food consumption","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[54,"Systemic toxicity","Food consumption","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"Systemic toxicity","Food consumption","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"Systemic toxicity","Food consumption","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect","Neither food nor water consumption were affected."]
[57,"Systemic toxicity","Food consumption","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"Systemic toxicity","Food consumption","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"Systemic toxicity","Food consumption","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[60,"Systemic toxicity","Food consumption","Rat",21,"Days","Dermal",1000,"mg/kg bw/day","No effect","Increased food consumption in females at 1000 mg/kg bw/day (14%), as findings in males and in previous studies were lacking the effect was considered to be by chance and not of toxicological importance"]
[61,"Systemic toxicity","Food consumption","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[62,"Systemic toxicity","Food consumption","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[63,"Systemic toxicity","Food consumption","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect"]
[64,"Systemic toxicity","Food consumption","Rat","10 (GD 6-15)","Days","Oral",3500,"mg/kg bw/day","Change","Food: 3500 mg/kg: Food consumption was decreased throughout the treatment period, thereafter, food intake was comparable with controls to termination. At lower dosages, food consumption was comparable with controls throughout.\nWater: 3500 mg/kg: Water consumption was increased following the start of treatment and continued to increase throughout the remainder of the treatment period. Thereafter, intake decreased, but was still slightly greater than controls at termination. At lower dosages, the pattern of water consumption did not indicate any clear effects, although at 1000 mg/kg/day, there was a suggestion of increased intake from Days 14 - 15 to termination, although at this stage no clear association with treatment can be made.\n"]
[65,"Systemic toxicity","Food consumption","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","There was no intergroup differnce in feed intake between treatment and control group. "]
[67,"Systemic toxicity","Food consumption","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","No effect on food and water (visual assessment) consumption was observed."]
[68,"Systemic toxicity","Food consumption","Mouse",2,"Years","Oral","> 30000","ppm","No effect","No consistent effect on feed and water consumption was observed."]
[69,"Systemic toxicity","Food consumption","Rat","5.5 (GD 3 till 21 days post partum)","Weeks","Oral",">30000","ppm","No effect","WATER: At 30000 ppm, slight increases in water intake during gestation were apparent towards the end of pregnancy when compared with concurrent control values. At 3000 and 10000 ppm, no adverse effects on water consumption were observed.\nFOOD: Apart from a slight reduction in food intake during the first three days of treatment at 30000 ppm, food intake of all the treated groups was comparable with concurrent controls throughout pregnancy."]
[69,"Systemic toxicity","Food consumption","Rat","3 (PND 21-42)","Weeks","Oral",30000,"ppm","Decrease","Food consumption at 30000 ppm was lower than controls during Weeks 5 and 6 (males only). There were no other effects considered attributable to treatment for males or females at any dosage.\nThe food conversion ratio for males at 30000 ppm was slightly greater when compared to controls (Week 6 only), indicating a slightly lower efficiency of food utilisatian into bodyweight gain.\nThere were no other effects on food conversion ratios."]
[70,"Systemic toxicity","Food consumption","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","F0, F1, and F2: Mean food consumption data were considered comparable between the control and treated groups (both sexes) during the growth and rest periods for each generation, throughout the study. No adverse effect of treatment on food consumption data was evident throughout the study."]
[71,"Systemic toxicity","Food consumption","Rat",28,"Days","Oral",">50000","ppm","No effect"]
[72,"Systemic toxicity","Food consumption","Mouse",28,"Days","Oral",">1000","mg/kg bw/day","No effect","Incidences of changes in food consumption not treatment-related"]
[73,"Systemic toxicity","Food consumption","Mouse",90,"Days","Oral",">50000","ppm","Increase","Incidents of statistically significant increased food consumption in M at 5000; 10000; 50000 ppm and in F at 5000; 50000 ppm."]
[74,"Systemic toxicity","Food consumption","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","Food consumption of F0 adults was not affected."]
[74,"Systemic toxicity","Food consumption","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","Food consumption of F1 adults was not affected."]
[74,"Systemic toxicity","Food consumption","Rat","F0 (M 20; F 20); F1 (M 20; F 27); F2 (M 20; F 27)","Weeks","Oral",">300","ppm","No effect","Food consumption of F2 adults was not affected."]
[75,"Systemic toxicity","Food consumption","Rat","Males: 60 days prior to mating; females: 14 days prior to mating until end of lactation (PND 21) or until sacrifice GD 13","Days","Oral",">10","mg/kg bw/day","No effect"]
[76,"Systemic toxicity","Food consumption","Rat","90-92","Days","Oral",7500,"ppm","Decrease","Indication for slight decrease in males and females at 7500 ppm"]
[78,"Systemic toxicity","Food consumption","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[79,"Systemic toxicity","Food consumption","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[80,"Systemic toxicity","Food consumption","Rat",5,"Weeks",null,">500","mg/kg bw/day","No effect","Average daily feed intake was significantly decreased at 50 mg/kg bw but not at 500 mg/kg bw. It is therefore suggested that the decrease of average daily feed intake is independent of glyphosate treatment. "]
[92,"Systemic toxicity","Food consumption","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Water and feed consumption during gestation and lactation were not different across groups (dams)."]
[92,"Systemic toxicity","Food consumption","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","Post weaning water and feed consumption were not affected by treatment (pups)."]
[95,"Systemic toxicity","Food consumption","Mouse","Dams were exposed during gestation. Offspring samples were collected on GD 19, PND 7, and PND 21 ","Days","Oral",5000,"mg/L water","No effect","Water consumption of dams was statistically significantly reduced. Feed intake was reduced (not statistically significant)."]
[1,"Systemic toxicity","Mortality","Rat",90,"Days","Oral",">20000","ppm","No effect",null,"Mortalities were observed in some studies in rat and rabbit at high doses."]
[2,"Systemic toxicity","Mortality","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[3,"Systemic toxicity","Mortality","Rat",90,"Days","Oral",">30000","ppm","No effect"]
[4,"Systemic toxicity","Mortality","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[5,"Systemic toxicity","Mortality","Dog",90,"Days","Oral",1000,"mg/kg bw/day","Change","Each 1/4 males and 1/4 females were sacrificed for human reasons on Days 61 and 72, associated with clinical signs and histopathological findings."]
[6,"Systemic toxicity","Mortality","Dog",90,"Days","Oral",">10000","ppm","No effect"]
[7,"Systemic toxicity","Mortality","Dog",90,"Days","Oral",">40000","ppm","No effect"]
[8,"Systemic toxicity","Mortality","Dog",90,"Days","Oral",">50000","ppm","No effect"]
[9,"Systemic toxicity","Mortality","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[10,"Systemic toxicity","Mortality","Dog",1,"Year","Oral",">50000","ppm","No effect"]
[11,"Systemic toxicity","Mortality","Dog",1,"Year","Oral",">30000","ppm","No effect"]
[12,"Systemic toxicity","Mortality","Rat",1,"Year","Oral",">20000","ppm","No effect"]
[13,"Systemic toxicity","Mortality","Rat",2,"Years","Oral",">10000","ppm","No effect","No treatment-related findings (no mortality before interim kill, after 24 month pre-terminal deaths were 23/50, 21/50, 23/50 and 16/50 in males and 16/50, 11/50, 10/50 and 18/50 in females; higher survival in pre-terminally dead females at 10000 ppm was considered incidental)"]
[14,"Systemic toxicity","Mortality","Rat",2,"Years","Oral",">30000","ppm","No effect","Decreased in males at 30000 ppm (42%) when compared to control (64%) during the last study year, not treatment-related (temporal findings: increased in males at 10000 ppm during the first study year, decreased in males at 3000 ppm during the last study year, final mortality rate comparable to those of controls), no effect in females"]
[15,"Systemic toxicity","Mortality","Rat",2,"Years","Oral",20000,"ppm","Increase","Statistically increased in males at 20000 ppm, attributed to the overall decreased severity of glomerula nephropathy occuring as a consequence of lower food consumption and body weight gain in this group; no effect in females"]
[16,"Systemic toxicity","Mortality","Rat",2,"Years","Oral",">1000","mg/kg bw/day","No effect"]
[17,"Systemic toxicity","Mortality","Rat",2,"Years","Oral",">20000","ppm","No effect"]
[18,"Systemic toxicity","Mortality","Rat",2,"Years","Oral",">15000","ppm","No effect","No treatment-related mortality. There were no deaths within the satellite/interim kill groups."]
[19,"Systemic toxicity","Mortality","Mouse",18,"Months","Oral",10000,"ppm","Increase","Increased mortality at 10000 ppm (survival was 56, 60, 56 and 46% in males and 62, 64, 58 and 53% in females at 0, 100, 1000 and 10000 ppm); mortality rates at study termination were 44, 40, 44 and 54% at 0, 100, 1000 and 10000 ppm, life expectancy was not affected in any treated group"]
[20,"Systemic toxicity","Mortality","Mouse",18,"Months","Oral",">5000","ppm","No effect","No treatment-related findings, mortality rate was highest in males at 5000 ppm and lowest in females at 5000 ppm (survival up to terminal kill: 39/51, 41/51, 39/51 and 35/51 males and 37/51, 38/51, 38/51 and 40/51 females at 0, 500, 1500 and 5000 ppm)"]
[21,"Systemic toxicity","Mortality","Mouse",18,"Months","Oral",">40000","ppm","No effect","No significant differences between groups. Cumulative mortality was 24/50, 16/50, 23/50 and 21/50 in males and 18/50, 14/50, 10/50 and 15/50 in females at 0, 1600, 8000 and 40000 ppm"]
[22,"Systemic toxicity","Mortality","Rat",10,"Weeks","Oral",">15000","ppm","No effect","No treatment-related deaths; 1/28 P0 males at 1500 ppm was killed for humane reasons, 1/28 P0 females at 15000 ppm was found dead, 1/28 P0 females at 5000 ppm was killed in extremis; 1/24 control F1 females was killed for humane reasons"]
[23,"Systemic toxicity","Mortality","Rat","10 (pre-mating)","Weeks","Oral",">10000","ppm","No effect","No treatment-related findings "]
[24,"Systemic toxicity","Mortality","Rat","10 for pre-mating rearing\n8 for subsequent breeding","Weeks","Oral",">30000","ppm","No effect"]
[25,"Systemic toxicity","Mortality","Rat","10 for pre-mating in F0, commencing at age of 8 weeks in F0 and continued for 2 successive generations up to weaning of F2","Weeks","Oral",">10000","ppm","No effect","No treatment-related deaths; 2/30 F0 females at 100 pppm (one distocia and one suppurative pneumonia), 1/30 F0 females at 10000 ppm (death not ascertained) and 1/30 F1 females at 100 ppm died"]
[26,"Systemic toxicity","Mortality","Rat","10 prior to mating, continued until termination","Weeks","Oral",">10000","ppm","No effect","No treatment-related findings (mortalities observed: 1/28 F0 males at 0 ppm sacrificed, 1/28 F0 females at 1000 ppm sacrificed, 2/28 F0 males at 10000 ppm found dead/sacrificed, 1/24 F1 females at 1000 ppm sacrificed, 1/24 F1 males at 3000 ppm found dead, 1/24 F1 females at 10000 ppm found dead and 1/24 F1 males at 10000 ppm sacrificed)"]
[27,"Systemic toxicity","Mortality","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect","No treatment-related findings (one F0 female died before treatment, 2 F1a males and one F1a female died, one F1a female was sacrificed in extremis, causes of death were not due to toxicity of the test item)"]
[27,"Systemic toxicity","Mortality","Rat","11 prior to mating for F0, further generations for approx. 14 weeks until termination","Weeks","Oral",">30000","ppm","No effect"]
[28,"Systemic toxicity","Mortality","Rat","10 (GD 7-16)","Days","Oral",">1000","mg/kg bw/day","No effect","One control animal was killed on Day 7 as a result of being misdosed, not treatment-related"]
[29,"Systemic toxicity","Mortality","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect"]
[30,"Systemic toxicity","Mortality","Rabbit","13 (GD 6-18)","Days","Oral",300,"mg/kg bw/day","Increase","1/18 females died at 300 mg/kg bw/day, histopathology revealed pale color in the liver and ascites in the abdomnial cavity, treatment relation could not be entirely denied (not treatment-related findings: 1/18 females at 10 mg/kg bw/day died, necropsy revealed no abnormalities)"]
[31,"Systemic toxicity","Mortality","Rabbit","13 (GD 7-19)","Days","Oral",400,"mg/kg bw/day","Increase","Intercurrent deaths in 2/18 females at 400 mg/kg bw/day (one died on gestation day 19, one was sacrificed in extremis on day 20, histopathological findings of the stomach and intestine in the animal found dead, treatment-related (further mortalities, not treatment-related: each 1/18 females at 0 and 200 mg/kg bw/day, mal-dosing)"]
[32,"Systemic toxicity","Mortality","Rabbit","13 (GD 8-20)","Days","Oral","> 300","mg/kg bw/day","No effect","1/20; 2/20; 2/20; 2/20 in the control, 100, 175 and 300 mg/kg bw/day group, respectively. The mortality was not considered to be treatment-related."]
[33,"Systemic toxicity","Mortality","Rabbit","22 (GD 6-27)","Days","Oral",350,"mg/kg bw/day","Increase","11/16 animals died in the high dose group; 2/16, 1/16 and 3/16 animals died in the control, 75 and 175 mg/kg bw/day group, respectively. Reasons for mortality were: pneumonia, gastroenteritis, enteritis, respiratory disease, gastroenteritis and caecal ulcerations"]
[34,"Systemic toxicity","Mortality","Rabbit","13 (GD 6-18)","Days","Oral",500,"mg/kg bw/day","Increase","4/16 and 8/15 animals died in the 100 and 500 mg/kg bw/day group, respectively."]
[36,"Systemic toxicity","Mortality","Mouse",28,"Days","Oral","> 5000","ppm","No effect"]
[42,"Systemic toxicity","Mortality","Rat",3,"Days","Oral","> 1000","mg/kg bw/day","No effect"]
[43,"Systemic toxicity","Mortality","Rat",10,"Days","Oral","> 1000","mg/kg bw/day","No effect"]
[44,"Systemic toxicity","Mortality","Rat","21 (PND 22-42)","Days","Oral","> 1000","mg/kg bw/day","No effect"]
[45,"Systemic toxicity","Mortality","Rat","31 (PND 23-53)","Days","Oral",1000,"mg/kg bw/day","Increase","One male in the 1000 mg/kg/day group was found dead prior to dose administration on PND 24."]
[46,"Systemic toxicity","Mortality","Rabbit","13 (GD 7-19)","Days","Oral",450,"mg/kg bw/day","Increase","1/20 animals of the high dose group died after abortion: gastro-intestinal disturbances; heart and kidneys pale; a few haemorrhagic depressions in the stomach (concurrent severe reduction in food intake; body weight loss)"]
[47,"Systemic toxicity","Mortality","Rabbit","13 (GD 7-19)","Days","Oral",625,"mg/kg bw/day","Increase","2/6 animals died in the high dose group (following marked body weight loss, inappetence, complete litter loss)."]
[49,"Systemic toxicity","Mortality","Rat",28,"Days","Oral",">20000","ppm","No effect"]
[50,"Systemic toxicity","Mortality","Rat",28,"Days","Oral",">2500","mg/kg bw/day","No effect"]
[51,"Systemic toxicity","Mortality","Dog","Study part A: 21\nStudy Part B: 14","Days","Oral",">1000","mg/kg bw/day","No effect"]
[52,"Systemic toxicity","Mortality","Rat",90,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[53,"Systemic toxicity","Mortality","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[54,"Systemic toxicity","Mortality","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[55,"Systemic toxicity","Mortality","Rat",90,"Days","Oral",">20000","ppm","No effect"]
[56,"Systemic toxicity","Mortality","Mouse",90,"Days","Oral",">4500","mg/kg bw/day","No effect"]
[57,"Systemic toxicity","Mortality","Dog",6,"Months","Oral",">300","mg/kg bw/day","No effect"]
[58,"Systemic toxicity","Mortality","Dog",1,"Year","Oral",">500","mg/kg bw/day","No effect"]
[59,"Systemic toxicity","Mortality","Dog",1,"Year","Oral",">1000","mg/kg bw/day","No effect"]
[60,"Systemic toxicity","Mortality","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[61,"Systemic toxicity","Mortality","Rat",21,"Days","Dermal",">1000","mg/kg bw/day","No effect"]
[62,"Systemic toxicity","Mortality","Rabbit",21,"Days","Dermal",">5000","mg/kg bw/day","No effect"]
[63,"Systemic toxicity","Mortality","Rabbit",28,"Days","Dermal",">2000","mg/kg bw/day","No effect"]
[64,"Systemic toxicity","Mortality","Rat","10 (GD 6-15)","Days","Oral",3500,"mg/kg bw/day","Increase","One female was sacrificed on GD10 immediately after dosing following a probable intubation error (white fluid was found in the thoracic cavity). A further two females were sacrificed on GD7 and GD13 respectively following signs of respiratory distress (noisy respiration/gasping). Post mortem observation did not reveal the cause of distress but the marked signs were a continuation of the signs representative for this group and these two deaths are considered to be related to treatment. There were no further deaths."]
[65,"Systemic toxicity","Mortality","Rat","10 (GD 6-15)","Days","Oral",">1000","mg/kg bw/day","No effect","No mortality was observed."]
[66,"Systemic toxicity","Mortality","Rabbit","22 (GD 6-27)","Days","Oral",350,"mg/kg bw/day","Increase","Two rabbits in the control group aborted and were sacrificed (GD 22). One rabbit in the 75 mg/kg/day dosage group died on gestation day 26. In the 175 mg/kg/day dosage group, one rabbit aborted and was sacrificed on gestation day 27 and two rabbits died, one each on gestation days 22 and 25. One rabbit in the 350 mg/kg/day dosage group aborted and was sacrificed on gestation day 23 and 10 died by gestation day 21. One rabbit in this group died on gestation day 3. On the same day, a replacement female was selected and artificially inseminated."]
[67,"Systemic toxicity","Mortality","Mouse",2,"Years","Oral","> 1000","mg/kg bw/day","No effect","There were 208 pre-terminal deaths throughout the study. There was no evidence to suggest that any of these deaths were treatment-related. "]
[68,"Systemic toxicity","Mortality","Mouse",2,"Years","Oral","> 30000","ppm","No effect","The incidence of mortality was considered to demonstrate no dose- or test substance-related adverse effect."]
[69,"Systemic toxicity","Mortality","Rat","5.5 (GD 3 till 21 days post partum)","Weeks","Oral",">30000","ppm","No effect","There were two mortalities. One at 3000 ppm was sacrificed Day 22 of pregnancy due to poor condition. Post mortem examination did not reveal any reason for the apparent dystocia. Since no similar mortalities were seen at higher levels, this death is not considered to be attributed to treatment.\nA second animal at 30000 ppm was found dead Day 21 post partum (Day 43 of study). Post mortem examination or signs prior to sacrifice did not reveal the cause of death; it is difficult to relate this death to treatment or not."]
[69,"Systemic toxicity","Mortality","Rat","3 (PND 21-42)","Weeks","Oral",">30000","ppm","No effect","There were no mortalities."]
[70,"Systemic toxicity","Mortality","Rat","life-time, all three generations","Weeks","Oral",">30","mg/kg bw/day","No effect","In the F0 generation, no unscheduled mortality occurred in the control, low- or high-dose groups. In the mid-dose group, one female died on day 20 of lactation, during the first litter interval (F1a). A second mid-dose female died on day 7 during the lactation period of the second litter interval (F1b). None of the mid-dose males died during this interval of study.\nIn the F1 generation, no unscheduled mortality occurred in the control or low-dose groups. In the mid-dose group one female was killed in a moribund condition during the post-mating period for the second litters (F2b). This female had mated during the first mating interval but did not deliver a litter; this female had not mated during the second mating period. No other mortality occurred in the mid-dose group. In the high-dose group, one female died during the first week of the growth period; this animal was caught in the feeder jar and death was considered accidental. A second high-dose female died during the gestation period for the second (F2b) litters. This female died on Day 21 of gestation and the uterus contained 15 term fetuses. No other mortality  ccurred in the high-dose group.\nIn the F2 generation, no mortality occurred in the control or high-dose groups. In the low-dose group one female died during the F3a lactation period. This female delivered a litter containing only  dead pups (13 pups) and died the day after parturition. No other mortality occurred in the low-dose group. In the mid-dose group, one male was killed in a moribund condition during the period between mating of the first and second litters. This male had mated and impregnated both females during the first mating period. No other mortality occurred in the mid-dose group."]
[71,"Systemic toxicity","Mortality","Rat",28,"Days","Oral",">50000","ppm","No effect"]
[72,"Systemic toxicity","Mortality","Mouse",28,"Days","Oral",">1000","mg/kg bw/day","No effect"]
[73,"Systemic toxicity","Mortality","Mouse",90,"Days","Oral",">50000","ppm","No effect","No treatment-related deaths were observed (1 male (control) and 1 female (10000 ppm) died spontaneously)."]
[76,"Systemic toxicity","Mortality","Rat","90-92","Days","Oral",">7500","ppm","No effect"]
[77,"Systemic toxicity","Mortality","Rabbit","22 (GD 6-27)","Days","Oral",500,"mg/kg bw/day","Increase","4/5 at 500 mg/kg bw died between GD 15 and 22; 5/5 at 1250 mg/kg bw died on GD 10 and 11; 5/5 at 2500 mg/kg bw die on GD 9 and 10"]
[78,"Systemic toxicity","Mortality","Rat",90,"Days","Oral",">50000","ppm","No effect"]
[79,"Systemic toxicity","Mortality","Mouse",90,"Days","Oral",">50000","ppm","No effect"]
[92,"Sensitive to, but not diagnostic of, EATS","Mortality","Rat","F0 from GD 6 and offspring up to PND 73±2 and PND 125±2 for the 6 and 13 weeks cohorts, respectively","Weeks","Oral",">1.75","mg/kg bw/day","No effect","All 24 dams and 108 rats from the 6-week and 13-week cohorts survived until sacrifice."]

{"sheet":"Study overview","index":16,"n_rows":97,"n_cols":7,"rows_kept":97,"cut":false,"hidden":false,"merged":[[46,6,48,6]]}
["Study ID Matrix","Study type","Species","Study Guideline","Author, Year","Study Reference (Report No.)","KCA No."]
[1,"Repeated dose 90-day oral toxicity study in rodents","Rat","equivalent to OECD 408 (2018)","XXXXX, 1996",null,"KCA 5.3.2/001-002"]
[2,"Repeated dose 90-day oral toxicity study in rodents","Rat","JMAFF (1985), similar to OECD 408 (2018)","XXXXX, 1996","434/016","KCA 5.3.2/003"]
[3,"Repeated dose 90-day oral toxicity study in rodents","Rat","JMAFF (1985), similar to OECD 408 (2018)","XXXXX, 1995",null,"KCA 5.3.2/004"]
[4,"Repeated dose 90-day oral toxicity study in rodents","Mouse","OECD 408 (1981), JMAFF (1985) ","XXXXX, 1995",null,"KCA 5.3.2/017"]
[5,"Repeated dose 90-day oral toxicity study in dogs","Dog","OECD 409 (1998), JMAFF (2000)","XXXXX, 2007",null,"KCA 5.3.2/020"]
[6,"Repeated dose 90-day oral toxicity study in dogs","Dog","OECD 409 (1981)","XXXXX, 1999",1816,"KCA 5.3.2/021-024"]
[7,"Repeated dose 90-day oral toxicity study in dogs","Dog","OECD 409 (1981), JMAFF (1985), US EPA OPPTS (1984)","XXXXX, 1996",null,"KCA 5.3.2/027"]
[8,"Repeated dose 90-day oral toxicity study in dogs","Dog","OECD 409 (1981), US EPA 82-1","XXXXX, 1996",null,"KCA 5.3.2/025-026"]
[9,"Repeated dose 1-year oral toxicity study in dogs","Dog","OECD 452 (1981), JMAFF (2000)","XXXXX, 2008",null,"KCA 5.3.2/031"]
[10,"Repeated dose 1-year oral toxicity study in dogs","Dog","OECD 409 (1981), JMAFF (1985), US EPA OPPTS (1984)","XXXXX, 1997",null,"KCA 5.3.2/032"]
[11,"Repeated dose 1-year oral toxicity study in dogs","Dog","OECD 452 (1981), EEC Directive 67/548 (1987), US EPA 83-1(b)","XXXXX, 1996",null,"KCA 5.3.2/033-034"]
[12,"Chronic toxicity 1-year oral toxicity study in rats","Rat","OECD 452 (1981), US EPA 83-1","XXXXX, 1996",null,"KCA 5.5-006_XXXXX_1996_XXXXX-P-5143_SYN"]
[13,"Chronic toxicity 2-year oral toxicity study in rats","Rat","OECD 453 (1981)","XXXXX, 1996","886CCR","KCA 5.5-005_XXXXX_1996_886.C.C-R_ADM"]
[14,"Chronic toxicity 2-year oral toxicity study in rats","Rat","OECD 453 (1981), JMAFF (1985), US EPA 83-5 (1984)","XXXXX, 1997",null,"KCA 5.5-004_XXXXX_1997_XXXXX 94-0150_ALS"]
[15,"Chronic toxicity 2-year oral toxicity study in rats","Rat","OECD 453 (1981), EEC Directive 87/302 (1988), US EPA OPPTS 870.4300 (1998)","XXXXX, 2001",null,"KCA 5.5-002_XXXXX_2001_XXXXX-PR1111_SYN"]
[16,"Chronic toxicity 2-year oral toxicity study in rats","Rat","US EPA 83-5 (1984)","XXXXX, 1993",7867,"KCA 5.5-007_XXXXX_1993_7867_Vol 1_CHE\nKCA 5.5-008_XXXXX_1993_7867_Vol 2_CHE\nKCA 5.5-009_XXXXX_1993_7867_Vol 3_CHE"]
[17,"Chronic toxicity 2-year oral toxicity study in rats","Rat","US EPA 83-5 (1984)","XXXXX, 1990",null,"KCA 5.5-010_XXXXX_1990_XXXXX-10495_MON"]
[18,"Chronic toxicity 2-year oral toxicity study in rats","Rat","OECD 453, JMAFF (2005), US EPA OPPTS 870.4300 (1996)","XXXXX, 2009a",null,"KCA 5.5-001_XXXXX_2009_XXXXX2060-0012_NUF"]
[19,"Chronic toxicity 18 months oral toxicity study in mice","Mouse","OECD 451 (1981)","XXXXX, 2001","1559.CARCI-M","KCA 5.5-016_XXXXX_2001_1559.CARCI-M_ADM\nKCA 5.5-017_XXXXX_2001_1559.CARCI-M_Statistics_ADM"]
[20,"Chronic toxicity 18 months oral toxicity study in mice","Mouse","OECD 416 (2001), US EPA OPPTS 870.3800 (1998), JMAFF 12 Nohsan No 8147 (2005)","XXXXX, 2009b",null,"KCA 5.5-012_XXXXX_2009_XXXXX 2060-0011_NUF\nKCA 5.5-013_XXXXX_2010_XXXXX2015-2531_GRG\nKCA 5.5-014_XXXXX_2011_2060-0011_Amendment_NUF\nKCA 5.5-015_XXXXX_2011_2060-0011_Assessment_NUF"]
[21,"Chronic toxicity 18 months oral toxicity study in mice","Mouse","US EPA 82-1 (1984)","XXXXX, 1997",null,"KCA 5.5-018_XXXXX_1997_IET 940151_UPL\nKCA 5.5-019_XXXXX_2013_13-C015_HCD_UPL"]
[22,"Two-generation oral toxicity study in rats","Rat","OECD 416 (2001), JMAFF 2-1-17 (2000), US EPA OPPTS 870.3800 (1998)","XXXXX, 2007","2060-0013","KCA 5.6.1-001_XXXXX_2007_2060-0013_NUF\nKCA 5.6.1-002_XXXXX_2007_2060-0013_Amend1_NUF\nKCA 5.6.1-003_XXXXX_2007_2060-0013_Amend2_NUF"]
[23,"Two-generation oral toxicity study in rats","Rat","OECD 416 (1983), US EPA OPPTS 870.3800, EEC Directive 67/548 (1988)","XXXXX, 2000",null,"KCA 5.6.1-004_XXXXX_1996_XXXXX-P-5009_SYN"]
[24,"Two-generation oral toxicity study in rats","Rat","OECD 416 (1983), JMAFF (1985), US EPA 83-4 (1984)","XXXXX, 1997",null,"KCA 5.6.1-05_XXXXX_1997_XXXXX 96-0031_UPL"]
[25,"Two-generation oral toxicity study in rats","Rat","OECD 416 (1983)","XXXXX, 1993a","885-RP-G2","KCA 5.6.1-06_XXXXX_1993_885-RP-G2_ADM"]
[26,"Two-generation oral toxicity study in rats","Rat","OECD 416 (1983), US EPA 83-4 (1982)","XXXXX, 1992",null,"KCA 5.6.1-007_XXXXX_1992_XXXXX 47_911129_Vol 1_BCS\nKCA 5.6.1-008_XXXXX_1992_XXXXX 47_911129_Vol 2_BCS"]
[27,"Two-generation oral toxicity study in rats","Rat","similar to OECD 416","XXXXX, 1990",null,"KCA 5.6.1-010_XXXXX 1990_XXXXX-10387_BCS"]
[28,"Prenatal developmental toxicity study in rats","Rat","similar to OECD 414","XXXXX, 1996",null,"KCA 5.6.2-001_XXXXX_1996_XXXXX4819_SYN"]
[29,"Prenatal developmental toxicity study in rats","Rat","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","XXXXX, 1995",null,"KCA 5.6.2-002_XXXXX_1995_XXXXX 94-0152_UPL"]
[30,"Prenatal developmental toxicity study in rabbits","Rabbit","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","XXXXX, 1995",null,"KCA 5.6.2-011_XXXXX_1995_XXXXX 94-0153_UPL"]
[31,"Prenatal developmental toxicity study in rabbits","Rabbit","OECD 414 (1981), US EPA 83-3, JMAFF (1985)","XXXXX, 1996","434/020","KCA 5.6.2-010_XXXXX_1996_434-020_NUF"]
[32,"Prenatal developmental toxicity study in rabbits","Rabbit","OECD 414","XXXXX, 1996",null,"KCA 5.6.2-009_XXXXX_1996_XXXXX-P-5009_SYN"]
[33,"Prenatal developmental toxicity study in rabbits","Rabbit","pre-Guideline; in general compliance with OECD 414 or US EPA 83-3","XXXXX, 1980",null,"KCA 5.6.2-019_XXXXX_1980_XXXXX-79-018_BCS"]
[34,"Prenatal developmental toxicity study in rabbits","Rabbit","OECD 414 (1981)","XXXXX, 1993","884-TER-RB","KCA 5.6.2-012_XXXXX_1993_884-TER-RB_ADM\nKCA 5.6.2-013_XXXXX_1993_884-TER-RB_Amend1_ADM"]
[35,"Prenatal developmental toxicity study in rabbits","Rabbit","OECD 414 (1981)","XXXXX, 1989",1086,"KCA 5.6.2-016_XXXXX_1989_1086_EXC"]
[36,"Repeated dose 28-day oral toxicity study in rodents","Rat","OPPTS 870.7800","XXXXX, 2012",null,"KCA 5.8.2-001_XXXXX_2012_XXXXX-50393_GRG"]
[37,"ER Binding Assay","Rat, Sprague-Dawley, cytosol from uterus","OPPTS 890.1250 (2009)","XXXXX, 2012","6500V-100334ERB","KCA 5.8.3-003_XXXXX_2012_XXXXX-11-029_GRG"]
[38,"Stably Transfected Human ERα Transcriptional Activation Assay (ER STTA)","Human cell line (HeLa-9903)","OECD 455 (2009)","XXXXX, 2012","6500V-100334ERTA","KCA 5.8.3-002_XXXXX_2012_XXXXX-11-028_GRG"]
[39,"AR Binding Assay","Rat, Sprague-Dawley, cytosol from prostate","OPPTS 890.1150 (2009)","XXXXX, 2012","6500V-100334ARB","KCA 5.8.3-001_XXXXX_2012_XXXXX-11-026_GRG"]
[40,"Aromatase Assay","Human (CYP19 (aromatase) and P450 reductase Supersomes TM)","OPPTS 890.1200","XXXXX, 2012","6500V-100334AROM","KCA 5.8.3-004_XXXXX_2012_XXXXX-11-027_GRG"]
[41,"H295R steroidogenesis assay","Human cell line (H295R)","OECD 456","Hecker et al., The OECD validation program of the H295R steroidogenesis assay: Phase 3. Final inter-laboratory validation study. Environ Sci Pollut Res (2011) 18:503–515","DOI 10.1007/s11356-010-0396-x","KCA 5.8.3-009_Hecker et al._2011_LIT"]
[42,"Uterotrophic assay","Rat","OECD 440","XXXXX, 2012",null,"KCA 5.8.3-005_XXXXX_2012_XXXXX-843002_GRG"]
[43,"Hershberger Assay","Rat","OECD 441","XXXXX, 2012",null,"KCA 5.8.3-006_XXXXX_2012_XXXXX-843003_GRG"]
[44,"Female pubertal assay (PP Male Assay)","Rat","OPPTS 890.1450","XXXXX, 2012",null,"KCA 5.8.3-008_XXXXX_2012_XXXXX-843007_GRG"]
[45,"Male pubertal assay (PP Male Assay)","Rat","OPPTS 890.1500","XXXXX, 2012",null,"KCA 5.8.3-007_XXXXX_2012_XXXXX-843005_GRG"]
[46,"Prenatal developmental toxicity study in rabbits","Rabbit","OECD 414","XXXXX, 1991",null,"KCA 5.6.2-014_XXXXX_1991_XXXXX 45_39_40-901303_FMC\nKCA 5.6.2-015_XXXXX_1991_XXXXX 45_39_40-901303_HCD_FMC"]
[47,"Prenatal developmental toxicity study in rabbits","Rabbit","OECD 414","XXXXX, 1991"]
[48,"Prenatal developmental toxicity study in rabbits","Rabbit","DRF","XXXXX, 1991"]
[49,"Subacute oral toxicity in rats (28 days)","Rat","OECD 407 (1981)","XXXXX, 1991",null,"KCA 5.3.1/001-003"]
[50,"Subacute oral toxicity in rats (28 days)","Rat","OECD 407 (1981)","XXXXX, 1989",5626,"KCA 5.3.1/004"]
[51,"Subacute oral toxicity in dogs ","Dog","DRF","XXXXX, 1989",5660,"KCA 5.3.1/007"]
[52,"Repeated dose 90-day oral toxicity study in rodents","Rat","OECD 408","XXXXX, 1991",7136,"KCA 5.3.2/011"]
[53,"Repeated dose 90-day oral toxicity study in rodents","Rat","US EPA 82-1, OECD 408 (1981)","XXXXX, 1993","011-0001","KCA 5.3.2/005-007"]
[54,"Repeated dose 90-day oral toxicity study in rodents","Rat","OECD 408 (1981)","XXXXX, 1992",null,"KCA 5.3.2/008-010"]
[55,"Repeated dose 90-day oral toxicity study in rodents","Rat","similar to OECD 408","XXXXX, 1987",null,"KCA 5.3.2/014"]
[56,"Repeated dose 90-day oral toxicity study in rodents","Mouse","OECD 408 (1981), FIFRA 82-1","XXXXX, 1991",7024,"KCA 5.3.2/018"]
[57,"Repeated dose 6-month oral toxicity study in dogs","Dog","similar to OECD 409","XXXXX, 1983",null,"KCA 5.3.2/029"]
[58,"Repeated dose 1-year oral toxicity study in dogs","Dog","similar to OECD 452 (1981)","XXXXX, 1985",null,"KCA 5.3.2/036"]
[59,"Repeated dose 1-year oral toxicity study in dogs","Dog","similar to OECD 452 (1981)","XXXXX, 1990",7502,"KCA 5.3.2/035"]
[60,"Repeated dose dermal toxicity in rats","Rat","equivalent to OECD 410","XXXXX, 1993",7839,"KCA 5.3.3/003"]
[61,"Repeated dose dermal toxicity in rats","Rat","OECD 410","XXXXX, 1996",null,"KCA 5.3.3/001-002"]
[62,"Repeated dose dermal toxicity in rabbits","Rabbit","OECD 410","XXXXX, 1982",null,"KCA 5.3.3/008"]
[63,"Repeated dose dermal toxicity in rabbits","Rabbit","OECD 410","XXXXX, 1994",null,"KCA 5.3.3/004-006"]
[64,"Prenatal developmental toxicity study","Rat","OECD 414, US EPA 83-3 (1982)","XXXXX, 1991","43-90716","KCA 5.6.2-003_XXXXX_1991_XXXXX 43 u 41-90716_CHE"]
[65,"Prenatal developmental toxicity study","Rat","OECD 414 (1981)","XXXXX, 1991",null,"KCA 5.6.2-004_XXXXX_1991_883-1991_ADM\nKCA 5.6.2-005_XXXXX_1991_883-1991_Amend1_ADM"]
[66,"Prenatal developmental toxicity study","Rabbit","similar to OECD 414 (\"Teratology study in rabbits\")","XXXXX, 1980",null,"KCA 5.6.2-019_XXXXX_1980_IR-79-018_BCS"]
[67,"Carcinogenicity study","Mouse","similar to OECD 451","XXXXX, 1989",7793,"KCA 5.5-020_XXXXX_1989_7793_CHE\nKCA 5.5-021_XXXXX_2016_438618_HCD_CHE"]
[68,"Carcinogenicity study","Mouse","no guideline specified; in general compliance with OECD 451","XXXXX, 1983",null,"KCA 5.5-023_XXXXX_77-2061_BCS"]
[69,"One-generation reproduction toxicity study - DRF","Rat","EPA FIFRA Guideline 83-4 (dose-range finder for multigeneration study)","XXXXX, 1991","42-90619","KCA 5.6.1-009_XXXXX_1991_XXXXX 42-90619_RF_CHE"]
[70,"Multigenerational reproductive toxicity","Rat","Three generation reproduction study","XXXXX, 1981","77-2063","KCA 5.6.1-014_XXXXX_1981_77-2063_MON"]
[71,"Repeated dose 28 days","Rat","Range finding study, similar to OECD 407","XXXXX, 1989",null,"KCA 5.3.1/005"]
[72,"Repeated dose 28 days","Mouse","Range finding study, similar to OECD 408","XXXXX, 1978","77-2110","KCA 5.3.1/006"]
[73,"Repeates dose 90 days","Mouse","None, similar to OECD 407","XXXXX, 1979","77-2111","KCA 5.3.2/019"]
[74,"Multigeneration reproductive toxicity","Rat","None","XXXXX, 1988","Not provided","KCA 5.6.1-012_XXXXX_1988_TOX9551965_EXC"]
[75,"One-generation reproductive toxicity","Rat","None","XXXXX, 1988","Not provided","KCA 5.6.1-011_XXXXX_1988_TOX9551832_EXC"]
[76,"Repeated dose 90 days","Rat","OECD 408","XXXXX, 1990",null,"KCA 5.3.2/012"]
[77,"Prenatal developmental toxicity","Rabbit","None","XXXXX, 1979",null,"KCA 5.6.2-018_XXXXX_1979_XXXXX-79-017_RF_BCS"]
[78,"Repeated dose 13 weeks","Rats","None, similar to OECD 408","XXXXX, 1992","92-3135 (NIH publication)","NIH publication"]
[79,"Repeated dose 13 weeks","Mouse","None, similar to OECD 408","XXXXX, 1992","92-3135 (NIH publication)","NIH publication"]
[80,"Repeated dose 5 weeks","Rats","None, published study","Dai et al., 2016","None, published study","KCA 5.6.1/023"]
[81,"Other Steroidogenesis in vitro assay in murine Leydig cells","Mouse in vitro","None, published study","Forgacs et al., 2012","None, published study","KCA 5.6.1/024"]
[82,"Other Steroidogenesis in vitro assay in swine granulosa cells","Swine in vitro","None, published study","Gigante et al., 2018","None, published study","KCA 5.8.3/012"]
[83,"In vitro method (general) (Sertoli cell permeability)","Rat in vitro","None, published study","Gorga et al., 2020","None, published study","KCA 5.6.1/015"]
[84,"ER Binding Assay","Human in vitro","None, published study","Mesnage et al., 2017","None, published study","KCA 5.8.3/014"]
[85,"Other ER in vitro assay","Human in vitro","None, published study","Thongprakaisang et al., 2013","None, published study","KCA 5.8.3/015"]
[86,"In vitro method (general, immature sertoli cell line)","Mouse in vitro","None, published study","Vanlaeys et al., 2018","None, published study","KCA 5.8.3/013"]
[87,"In vitro method (general)","Mouse in vitro","None, published study","Zhang et al., 2019","None, published study","KCA 5.6.1/019"]
[88,"Other Steroidogenesis in vitro assay ","Cow in vitro","None, published study","Perego et al., 2017","None, published study","KCA 5.6.1/022"]
[89,"In vitro estrogen (Estrogen Receptor Transactivation Assay with a variant of a human breast cancer (MCF7) cell line)","Human in vitro","None, published study","Brennan et al., 2016; Corrigendum 2017","None, published study","KCA 5.8.3/016 (initial article) KCA 5.8.3/017 (corrigendum, 2017)"]
[90,"Aromatase Assay","Human in vitro","None, published study","Defarge et al., 2016","None, published study","KCA 5.8.3/018"]
[91,"Subacute oral in rodent ","Rat","None, published study","Johansson et al., 2018","None, published study","KCA 5.6.1/020"]
[92,"Pilot study for EOGRTS (description of study design)","Rat","None, published study (one generation, dose range-finder OECD 443)","Panzacchi et al., 2018","None, published study","KCA 5.6.1/021"]
[93,"Pilot study for EOGRTS (description of ED-relevant parameters)","Rat","None, published study (one generation, dose range-finder OECD 443)","Manservisi, 2019","None, published study","KCA 5.6.1/016"]
[94,"Subchronic oral toxicity in rodents","Mouse","None, published study","Pham et al., 2019","None, published study","KCA 5.6.1/017"]
[95,"Subacute oral in rodent ","Mouse","None, published study","Ren et al., 2019","None, published study","KCA 5.6.1/018"]
[96,"Repeated dose 90 days","rat","OECD 408","XXXXX, 1989",null,"KCA 5.3.2/013"]