{"text_format":"1","workbook":"xlsx","n_sheets":13,"sheets":["Instructions","LookUp","LinkAB","LinkYZMammals","LinkYZFish","LinkYZAmphibian","LinkYZAvian","LinkInVitro","Interpretation","Data","Data summary","Lines of evidence - T","Lines of evidence - EAS"],"not_rendered":{"charts":0,"images":0,"macros":1,"external_links":0,"defined_names":24,"comments":0,"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":183,"n_cols":37,"rows_kept":183,"cut":false,"hidden":false,"merged":[]}
["Compound:"]
["CAS:"]
["Comments:","RMS/Peer review proposal: Skin Sens 1 - H317\nNo harmonised classification by RAC.",null,null,null,null,null,null,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,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"M",89.6,"Oral","Feed","128.5, 387.0, 1327.3",128.5,1327.3,"mg/kg bw/day",90,"Days","Adult","M",1327.3,"In life observation","Body weight",{"$f":"IF(Z12<>0,VLOOKUP(Z12,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Mean bodyweights and bodyweight gains of top dose males were significantly reduced (7% and 12.4% vs control, respectively).",null,"Decrease",129,387,"mg/kg bw/day",{"$f":"IF(Z12<>0,VLOOKUP(Z12,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"F",89.6,"Oral","Feed","157.9, 479.4, 1651.5",157.9,1651.5,"mg/kg bw/day",90,"Days","Adult","F",1651.5,"In life observation","Body weight",{"$f":"IF(Z13<>0,VLOOKUP(Z13,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Not stat. significant decrease on bodyweight and BW gain in females at the highest dose of 1651.5 mg/kg bw/day (4% and 11.2%, respectively).",null,"Decrease",158,479,"mg/kg bw/day",{"$f":"IF(Z13<>0,VLOOKUP(Z13,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"F",89.6,"Oral","Feed","157.9, 479.4, 1651.5",157.9,1651.5,"mg/kg bw/day",90,"Days","Adult","F",null,"Organ Weight","Ovary weight",{"$f":"IF(Z14<>0,VLOOKUP(Z14,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on ovaries weight up to the highest dose of 1651.5 mg/kg bw/day.",null,"No effect",158,479,"mg/kg bw/day",{"$f":"IF(Z14<>0,VLOOKUP(Z14,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"M",89.6,"Oral","Feed","128.5, 387.0, 1327.3",128.5,1327.3,"mg/kg bw/day",90,"Days","Adult","M",null,"Organ Weight","Prostate weight",{"$f":"IF(Z15<>0,VLOOKUP(Z15,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Prostate weight was slightly lower in top dose males (1327.3 mg/kg bw/day), however values did not attain statistical significance.",null,"No effect",129,387,"mg/kg bw/day",{"$f":"IF(Z15<>0,VLOOKUP(Z15,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"M",89.6,"Oral","Feed","128.5, 387.0, 1327.3",128.5,1327.3,"mg/kg bw/day",90,"Days","Adult","M",387,"Organ histopathology","Kidney histopathology",{"$f":"IF(Z16<>0,VLOOKUP(Z16,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increase in the incidence and severity of mineral deposits located free in the renal pelvis or papilla at the top dose of 1327.3 mg/kg bw/day; a slight or minimum hyperplasia of the adjacent transitional epithelium occurred occasionally as a result of the mineral deposition causing a greater incidence of focal urothelial hyperplasia from the dose of 387.0 mg/kg bw/day in males.","basis for NOAEL","Change",129,387,"mg/kg bw/day",{"$f":"IF(Z16<>0,VLOOKUP(Z16,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"M",89.6,"Oral","Feed","128.5, 387.0, 1327.3",128.5,1327.3,"mg/kg bw/day",90,"Days","Adult","M",1327.3,"Organ histopathology","Kidney histopathology",{"$f":"IF(Z17<>0,VLOOKUP(Z17,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increase in the incidence and severity of mineral deposits located free in the renal pelvis or papilla at the top dose of 1327.3 mg/kg bw/day; a slight or minimum hyperplasia of the adjacent transitional epithelium occurred occasionally as a result of the mineral deposition causing a greater incidence of focal urothelial hyperplasia from the dose of 387.0 mg/kg bw/day in males.",null,"Change",129,387,"mg/kg bw/day",{"$f":"IF(Z17<>0,VLOOKUP(Z17,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"F",89.6,"Oral","Feed","157.9, 479.4, 1651.5",157.9,1651.5,"mg/kg bw/day",90,"Days","Adult","F",479,"Organ histopathology","Kidney histopathology",{"$f":"IF(Z18<>0,VLOOKUP(Z18,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increase in the incidence and severity of mineral deposits located free in the renal pelvis or papilla from the dose of 479.4 mg/kg bw/day; a slight or minimum hyperplasia of the adjacent transitional epithelium occurred occasionally as a result of the mineral deposition causing a greater incidence of focal urothelial hyperplasia at the top dose of 1651.5 mg/kg bw/day. In addition to these changes, an increase in the severity and incidence of hydronephrosis was observed from the dose of 479.4 mg/kg bw/day in females. ","basis for NOAEL","Change",158,479,"mg/kg bw/day",{"$f":"IF(Z18<>0,VLOOKUP(Z18,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"F",89.6,"Oral","Feed","157.9, 479.4, 1651.5",157.9,1651.5,"mg/kg bw/day",90,"Days","Adult","F",1651.5,"Organ histopathology","Kidney histopathology",{"$f":"IF(Z19<>0,VLOOKUP(Z19,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increase in the incidence and severity of mineral deposits located free in the renal pelvis or papilla from the dose of 479.4 mg/kg bw/day; a slight or minimum hyperplasia of the adjacent transitional epithelium occurred occasionally as a result of the mineral deposition causing a greater incidence of focal urothelial hyperplasia at the top dose of 1651.5 mg/kg bw/day. In addition to these changes, an increase in the severity and incidence of hydronephrosis was observed from the dose of 479.4 mg/kg bw/day in females. ",null,"Change",158,479,"mg/kg bw/day",{"$f":"IF(Z19<>0,VLOOKUP(Z19,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"M",89.6,"Oral","Feed","128.5, 387.0, 1327.3",128.5,1327.3,"mg/kg bw/day",90,"Days","Adult","M",387,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z20<>0,VLOOKUP(Z20,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Clinical chemistry: Statistically significant changes in: Globulin (↓ 12%), A:G ratio (↑13.3%) in males","basis for NOAEL","Change",129,387,"mg/kg bw/day",{"$f":"IF(Z20<>0,VLOOKUP(Z20,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"F",89.6,"Oral","Feed","157.9, 479.4, 1651.5",157.9,1651.5,"mg/kg bw/day",90,"Days","Adult","F",157.9,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z21<>0,VLOOKUP(Z21,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Clinical chemistry: statistically significant changes on: A:G ratio (↑11.8%), not stati. Sign. Change on Globulin (↓ 8.8%) in females.",null,"Change",158,479,"mg/kg bw/day",{"$f":"IF(Z21<>0,VLOOKUP(Z21,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"M",89.6,"Oral","Feed","128.5, 387.0, 1327.3",128.5,1327.3,"mg/kg bw/day",90,"Days","Adult","M",1327.3,"Organ Weight","Testis weight",{"$f":"IF(Z22<>0,VLOOKUP(Z22,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Mean relative testes weight was significantly higher in top dose males; this value is largely (but not entirely) attributable to one male with an unusually high absolute testes weight (5.65 g). When the outlier was excluded, the percentage fell from 9.6% to 5.5%.",null,"Increase",129,387,"mg/kg bw/day",{"$f":"IF(Z22<>0,VLOOKUP(Z22,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"M",89.6,"Oral","Feed","128.5, 387.0, 1327.3",128.5,1327.3,"mg/kg bw/day",90,"Days","Adult","M",1327.3,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z23<>0,VLOOKUP(Z23,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: statistically significant effects on RBC parameters  consistent with mild macrocytic anaemia: RBC ( ↓ 9.1%), HGB (↓ 7.3%), HCT (↓5.6%), MCV (↑ 4.5%), MCHC (↓ 2.0%). Clinical chemistry: Statistically significant changes in: PTT (↑17%), Protein (↓ 8.7%), Globulin (↓ 17.5%), A:G ratio (↑21%), P (↓ 10.3%) in males.",null,"Change",129,387,"mg/kg bw/day",{"$f":"IF(Z23<>0,VLOOKUP(Z23,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"F",89.6,"Oral","Feed","157.9, 479.4, 1651.5",157.9,1651.5,"mg/kg bw/day",90,"Days","Adult","F",1651.5,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z24<>0,VLOOKUP(Z24,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Haematology: statistically significant effec ts on RBC parameters consistent with mild macrocytic anaemia: RBC ( ↓ 8.2%), HGB (↓ 7.8%), HCT (↓7.0%). Clinical chemistry:  statistically significant changes on: Globulin (↓ 17.3%), A:G ratio (↑20.2%). Not stat. sign. decrease in P (↓ 7.9%) in females.",null,"Change",158,479,"mg/kg bw/day",{"$f":"IF(Z24<>0,VLOOKUP(Z24,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"M",89.6,"Oral","Feed","128.5, 387.0, 1327.3",128.5,1327.3,"mg/kg bw/day",90,"Days","Adult","M",1327.3,"Organ histopathology","Thyroid histopathology",{"$f":"IF(Z25<>0,VLOOKUP(Z25,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Increase in the incidence and severity of thyroid follicular hypertrophy in high dose animals [0, 128.5, 387.0, 1327.3 mg/kg bw/day: 2/10, 1/10, 2/10, 10/10 (slight)]; affected follicles were generally smaller.",null,"Change",129,387,"mg/kg bw/day",{"$f":"IF(Z25<>0,VLOOKUP(Z25,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"F",89.6,"Oral","Feed","157.9, 479.4, 1651.5",157.9,1651.5,"mg/kg bw/day",90,"Days","Adult","F",1651.5,"Organ histopathology","Thyroid histopathology",{"$f":"IF(Z26<>0,VLOOKUP(Z26,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Increase in the incidence and severity of thyroid follicular hypertrophy in high dose animals [0, 157.9, 479.4, 1651.5 mg/kg bw/day: 1/10, -, -, 2/10 (slight) / 6/10 (minimal)]; affected follicles were generally smaller.",null,"Change",158,479,"mg/kg bw/day",{"$f":"IF(Z26<>0,VLOOKUP(Z26,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"M",89.6,"Oral","Feed","128.5, 387.0, 1327.3",128.5,1327.3,"mg/kg bw/day",90,"Days","Adult","M",null,"Organ Weight","Liver weight",{"$f":"IF(Z27<>0,VLOOKUP(Z27,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effect on liver weight in males up to the highest dose of 1327.3 mg/kg bw/day.",null,"No effect",129,387,"mg/kg bw/day",{"$f":"IF(Z27<>0,VLOOKUP(Z27,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"F",89.6,"Oral","Feed","157.9, 479.4, 1651.5",157.9,1651.5,"mg/kg bw/day",90,"Days","Adult","F",null,"Organ Weight","Liver weight",{"$f":"IF(Z28<>0,VLOOKUP(Z28,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effect on liver weight in females up to the highest dose of 1651.5 mg/kg bw/day.",null,"No effect",158,479,"mg/kg bw/day",{"$f":"IF(Z28<>0,VLOOKUP(Z28,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"M",89.6,"Oral","Feed","128.5, 387.0, 1327.3",128.5,1327.3,"mg/kg bw/day",90,"Days","Adult","M",null,"Organ Weight","Thyroid weight",{"$f":"IF(Z29<>0,VLOOKUP(Z29,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on thyroid weight in males up to the highest dose of 1327.3 mg/kg bw/day.",null,"No effect",129,387,"mg/kg bw/day",{"$f":"IF(Z29<>0,VLOOKUP(Z29,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"F",89.6,"Oral","Feed","157.9, 479.4, 1651.5",157.9,1651.5,"mg/kg bw/day",90,"Days","Adult","F",1651.5,"Organ Weight","Thyroid weight",{"$f":"IF(Z30<>0,VLOOKUP(Z30,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Significant increase in the absolute (↑17.6%) and relative-to-body (↑ 22.7%) thyroid weight in females. ",null,"Increase",158,479,"mg/kg bw/day",{"$f":"IF(Z30<>0,VLOOKUP(Z30,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"M",89.6,"Oral","Feed","128.5, 387.0, 1327.3",128.5,1327.3,"mg/kg bw/day",90,"Days","Adult","M",387,"Organ histopathology","Spleen histopathology",{"$f":"IF(Z31<>0,VLOOKUP(Z31,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increase in the severity of splenic extramedullary haematopoiesis in males at ≥ 387 mg/kg bw/day. Increase in the severity of haemosiderin deposition in the spleen from the dose of 387 mg/kg bw/day.",null,"Change",129,387,"mg/kg bw/day",{"$f":"IF(Z31<>0,VLOOKUP(Z31,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"F",89.6,"Oral","Feed","157.9, 479.4, 1651.5",157.9,1651.5,"mg/kg bw/day",90,"Days","Adult","F",1651.5,"Organ histopathology","Spleen histopathology",{"$f":"IF(Z32<>0,VLOOKUP(Z32,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increase in the severity of haemosiderin deposition at the top dose of 1651.5 mg/kg bw/day in females.",null,"Change",158,479,"mg/kg bw/day",{"$f":"IF(Z32<>0,VLOOKUP(Z32,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"M",89.6,"Oral","Feed","128.5, 387.0, 1327.3",128.5,1327.3,"mg/kg bw/day",90,"Days","Adult","M",1327.3,"Organ Weight","Spleen weight",{"$f":"IF(Z33<>0,VLOOKUP(Z33,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Significant increase in the absolute (↑14.3%) and relative-to-body (↑ 22.8%) spleen weight in males at the highest dose of 1327.3 mg/kg bw/day. Consistent with haematological findings. ",null,"Increase",129,387,"mg/kg bw/day",{"$f":"IF(Z33<>0,VLOOKUP(Z33,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"F",89.6,"Oral","Feed","157.9, 479.4, 1651.5",157.9,1651.5,"mg/kg bw/day",90,"Days","Adult","F",null,"Organ Weight","Spleen weight",{"$f":"IF(Z34<>0,VLOOKUP(Z34,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effect on spleen weight in females up to the highest dose of 1651.5 mg/kg bw/day.",null,"No effect",158,479,"mg/kg bw/day",{"$f":"IF(Z34<>0,VLOOKUP(Z34,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose 90-day oral toxicity study in rodents",1,null,"OECD TG 408","DAR",null,2000,"Rat","Wistar",10,"F",89.6,"Oral","Feed","157.9, 479.4, 1651.5",157.9,1651.5,"mg/kg bw/day",90,"Days","Adult","F",null,"Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z35<>0,VLOOKUP(Z35,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on uterus weight in females up to the highest dose of 479 mg/kg bw/day.",null,"No effect",158,479,"mg/kg bw/day",{"$f":"IF(Z35<>0,VLOOKUP(Z35,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Subchronic oral toxicity in rodents",2,null,"Not reported","DAR",null,"1989a","Mouse","CD-1",10,"M",88,"Oral","Feed","512, 1673, 5103, 9022",512,9022,"mg/kg bw/day",8,"Weeks","Adult","M",5103,"In life observation","Body weight",{"$f":"IF(Z36<>0,VLOOKUP(Z36,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Body weight was stat. significantly decreased (-8%) and -13% at the highest dose of 9022 mg/kg bw/day",null,"Decrease",1673,5103,"mg/kg bw/day",{"$f":"IF(Z36<>0,VLOOKUP(Z36,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subchronic oral toxicity in rodents",2,null,"Not reported","DAR",null,"1989a","Mouse","CD-1",10,"F",88,"Oral","Feed","675, 2263, 6835, 10828",675,10828,"mg/kg bw/day",8,"Weeks","Adult","F",10828,"In life observation","Body weight",{"$f":"IF(Z37<>0,VLOOKUP(Z37,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Transient weight loss was observed at the top dose",null,"Decrease",6835,10828,"mg/kg bw/day",{"$f":"IF(Z37<>0,VLOOKUP(Z37,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subchronic oral toxicity in rodents",2,null,"Not reported","DAR",null,"1989a","Mouse","CD-1",10,"M",88,"Oral","Feed","512, 1673, 5103, 9022",512,9022,"mg/kg bw/day",8,"Weeks","Adult","M",null,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z38<>0,VLOOKUP(Z38,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Plasma, erythrocyte and cholinesterase activities were comparable in all groups",null,"No effect",1673,5103,"mg/kg bw/day",{"$f":"IF(Z38<>0,VLOOKUP(Z38,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subchronic oral toxicity in rodents",2,null,"Not reported","DAR",null,"1989a","Mouse","CD-1",10,"F",88,"Oral","Feed","675, 2263, 6835, 10828",675,10828,"mg/kg bw/day",8,"Weeks","Adult","F",null,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z39<>0,VLOOKUP(Z39,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Plasma, erythrocyte and cholinesterase activities were comparable in all groups",null,"No effect",6835,10828,"mg/kg bw/day",{"$f":"IF(Z39<>0,VLOOKUP(Z39,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",3,null,null,"DAR",null,1980,"Dog","Beagle",6,"M",99,"Oral","Gavage/Intubation","0, 60, 300, 1500",60,1500,"mg/kg bw/day",26,"Weeks","Adult","M",1500,"Organ Weight","Testis weight",{"$f":"IF(Z40<>0,VLOOKUP(Z40,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Mean absolute testes weight was significantly lower at the top dose of 1500 mg/kg bw/day (25% decrease)",null,"Decrease",60,300,"mg/kg bw/day",{"$f":"IF(Z40<>0,VLOOKUP(Z40,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",3,null,null,"DAR",null,1980,"Dog","Beagle",6,"M",99,"Oral","Gavage/Intubation","0, 60, 300, 1500",60,1500,"mg/kg bw/day",26,"Weeks","Adult","M",1500,"Organ Weight","Kidney weight",{"$f":"IF(Z41<>0,VLOOKUP(Z41,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Relative kidney weight was significantly higher in top dose",null,"Increase",60,300,"mg/kg bw/day",{"$f":"IF(Z41<>0,VLOOKUP(Z41,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",3,null,null,"DAR",null,1980,"Dog","Beagle",6,"M",99,"Oral","Gavage/Intubation","0, 60, 300, 1500",60,1500,"mg/kg bw/day",26,"Weeks","Adult","M",1500,"In life observation","Body weight",{"$f":"IF(Z42<>0,VLOOKUP(Z42,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"10.8% decrease at the top dose (not stat. significant)",null,"Decrease",60,300,"mg/kg bw/day",{"$f":"IF(Z42<>0,VLOOKUP(Z42,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",3,null,null,"DAR",null,1980,"Dog","Beagle",6,"F",99,"Oral","Gavage/Intubation","0, 60, 300, 1500",60,1500,"mg/kg bw/day",26,"Weeks","Adult","F",null,"In life observation","Body weight",{"$f":"IF(Z43<>0,VLOOKUP(Z43,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No effect in BW up to the top dose of 1500 mg/kg bw/day (2.8% decrease)",null,"No effect",60,300,"mg/kg bw/day",{"$f":"IF(Z43<>0,VLOOKUP(Z43,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",3,null,null,"DAR",null,1980,"Dog","Beagle",6,"M",99,"Oral","Gavage/Intubation","0, 60, 300, 1500",60,1500,"mg/kg bw/day",26,"Weeks","Adult","M",1500,"Organ Weight","[Not in list]",{"$f":"IF(Z44<>0,VLOOKUP(Z44,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Absolute (stat. significant) and relative lung weights were lower in top dose males",null,"Decrease",60,300,"mg/kg bw/day",{"$f":"IF(Z44<>0,VLOOKUP(Z44,Interpretation!$C:$E,3,FALSE),\"\")","v":0},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",3,null,null,"DAR",null,1980,"Dog","Beagle",6,"F",99,"Oral","Gavage/Intubation","0, 60, 300, 1500",60,1500,"mg/kg bw/day",26,"Weeks","Adult","F",null,"Organ Weight","[Not in list]",{"$f":"IF(Z45<>0,VLOOKUP(Z45,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"No effect on lung weight up to the top dose of 1500 mg/kg bw/day",null,"No effect",60,300,"mg/kg bw/day",{"$f":"IF(Z45<>0,VLOOKUP(Z45,Interpretation!$C:$E,3,FALSE),\"\")","v":0},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",3,null,null,"DAR",null,1980,"Dog","Beagle",6,"F",99,"Oral","Gavage/Intubation","0, 60, 300, 1500",60,1500,"mg/kg bw/day",26,"Weeks","Adult","F",null,"Organ Weight","Kidney weight",{"$f":"IF(Z46<>0,VLOOKUP(Z46,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effect on kidney weight up to the top dose of 1500 mg/kg bw/day",null,"No effect",60,300,"mg/kg bw/day",{"$f":"IF(Z46<>0,VLOOKUP(Z46,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",3,null,null,"DAR",null,1980,"Dog","Beagle",6,"M",99,"Oral","Gavage/Intubation","0, 60, 300, 1500",60,1500,"mg/kg bw/day",26,"Weeks","Adult","M",300,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z47<>0,VLOOKUP(Z47,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Red blood cell parameters (erythrocyte count, haemoglobin concentration and haematocrit) were stat. significantly depressed in top dose males at Week 26. Dose-related increase in glucose. The total WBC count was significantly lower in treated groups at the majority of time points.",null,"Decrease",60,300,"mg/kg bw/day",{"$f":"IF(Z47<>0,VLOOKUP(Z47,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",3,null,null,"DAR",null,1980,"Dog","Beagle",6,"F",99,"Oral","Gavage/Intubation","0, 60, 300, 1500",60,1500,"mg/kg bw/day",26,"Weeks","Adult","F",300,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z48<>0,VLOOKUP(Z48,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No effect in RBC parameters up to the highest dose tested. The total WBC count was significantly lower in treated groups at the majority of time points.",null,"Change",60,300,"mg/kg bw/day",{"$f":"IF(Z48<>0,VLOOKUP(Z48,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",3,null,null,"DAR",null,1980,"Dog","Beagle",6,"M",99,"Oral","Gavage/Intubation","0, 60, 300, 1500",60,1500,"mg/kg bw/day",26,"Weeks","Adult","M",1500,"Organ Weight","Thyroid weight",{"$f":"IF(Z49<>0,VLOOKUP(Z49,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute and relative thyroid weight was significantly increased at the top dose of 1500 mg/kg bw/day",null,"Increase",60,300,"mg/kg bw/day",{"$f":"IF(Z49<>0,VLOOKUP(Z49,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",3,null,null,"DAR",null,1980,"Dog","Beagle",6,"F",99,"Oral","Gavage/Intubation","0, 60, 300, 1500",60,1500,"mg/kg bw/day",26,"Weeks","Adult","F",300,"Organ Weight","Thyroid weight",{"$f":"IF(Z50<>0,VLOOKUP(Z50,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Absolute and relative thyroid weight was significantly increased at 300 and the top dose of 1500 mg/kg bw/day, respectively. ",null,"Increase",60,300,"mg/kg bw/day",{"$f":"IF(Z50<>0,VLOOKUP(Z50,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",3,null,null,"DAR",null,1980,"Dog","Beagle",6,"M",99,"Oral","Gavage/Intubation","0, 60, 300, 1500",60,1500,"mg/kg bw/day",26,"Weeks","Adult","M",1500,"In life observation","Clinical signs",{"$f":"IF(Z51<>0,VLOOKUP(Z51,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Vomiting immediately following dosing was observed with increased incidence at the top dose",null,"Increase",60,300,"mg/kg bw/day",{"$f":"IF(Z51<>0,VLOOKUP(Z51,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",3,null,null,"DAR",null,1980,"Dog","Beagle",6,"F",99,"Oral","Gavage/Intubation","0, 60, 300, 1500",60,1500,"mg/kg bw/day",26,"Weeks","Adult","F",300,"In life observation","Clinical signs",{"$f":"IF(Z52<>0,VLOOKUP(Z52,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Vomiting immediately following dosing was observed with increased incidence from the dose of 300 mg/kg bw/day",null,"Increase",60,300,"mg/kg bw/day",{"$f":"IF(Z52<>0,VLOOKUP(Z52,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","M",null,"Organ Weight","Heart weight",{"$f":"IF(Z53<>0,VLOOKUP(Z53,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute and relative heart weights were slightly lower in both sexes at the top dose level, however values do not attain statistical significance",null,"No effect",100,300,"mg/kg bw/day",{"$f":"IF(Z53<>0,VLOOKUP(Z53,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","F",null,"Organ Weight","Heart weight",{"$f":"IF(Z54<>0,VLOOKUP(Z54,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Absolute and relative heart weights were slightly lower in both sexes at the top dose level, however values do not attain statistical significance",null,"No effect",100,300,"mg/kg bw/day",{"$f":"IF(Z54<>0,VLOOKUP(Z54,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","M",null,"Organ Weight","Prostate weight",{"$f":"IF(Z55<>0,VLOOKUP(Z55,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Prostate weight (abs & rel) was slightly (but not significantly) lower at the top dose of 600 mg/kg bw/day",null,"No effect",100,300,"mg/kg bw/day",{"$f":"IF(Z55<>0,VLOOKUP(Z55,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","M",null,"In life observation","Body weight",{"$f":"IF(Z56<>0,VLOOKUP(Z56,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No effect in BW and BW gain up to the highest dose of 600 mg/kg bw/day",null,"No effect",100,300,"mg/kg bw/day",{"$f":"IF(Z56<>0,VLOOKUP(Z56,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","F",null,"In life observation","Body weight",{"$f":"IF(Z57<>0,VLOOKUP(Z57,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No effect in BW and BW gain up to the highest dose of 600 mg/kg bw/day",null,"No effect",100,300,"mg/kg bw/day",{"$f":"IF(Z57<>0,VLOOKUP(Z57,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","M",600,"Organ Weight","Testis weight",{"$f":"IF(Z58<>0,VLOOKUP(Z58,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Abs. testes weight were slightly (but not significantly) lower in top dose males (13.2%). ",null,"Decrease",100,300,"mg/kg bw/day",{"$f":"IF(Z58<>0,VLOOKUP(Z58,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","M",300,"Organ histopathology","Thyroid histopathology",{"$f":"IF(Z59<>0,VLOOKUP(Z59,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Thyroid follicular cell hypertrophy was seen in both sexes from the dose of 300 mg/kg bw/d; the incidence and severity of this finding was increased at the top dose level. ",null,"Change",100,300,"mg/kg bw/day",{"$f":"IF(Z59<>0,VLOOKUP(Z59,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","F",300,"Organ histopathology","Thyroid histopathology",{"$f":"IF(Z60<>0,VLOOKUP(Z60,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Thyroid follicular cell hypertrophy was seen in both sexes from the dose of 300 mg/kg bw/d; the incidence and severity of this finding was increased at the top dose level. ",null,"Change",100,300,"mg/kg bw/day",{"$f":"IF(Z60<>0,VLOOKUP(Z60,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","M",null,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z61<>0,VLOOKUP(Z61,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No effect in heamtological and clinical chemistry parameters up to the highest dose of 600 mg/kg bw/day",null,"No effect",100,300,"mg/kg bw/day",{"$f":"IF(Z61<>0,VLOOKUP(Z61,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","M",null,"Organ Weight","Adrenals weight",{"$f":"IF(Z62<>0,VLOOKUP(Z62,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect in adrenal weight up to the highest dose of 600 mg/kg bw/day",null,"No effect",100,300,"mg/kg bw/day",{"$f":"IF(Z62<>0,VLOOKUP(Z62,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","F",600,"Organ Weight","Adrenals weight",{"$f":"IF(Z63<>0,VLOOKUP(Z63,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Increased absolute adrenal weight (26.6%) at the highest dose of 600 mg/kg bw/day",null,"Increase",100,300,"mg/kg bw/day",{"$f":"IF(Z63<>0,VLOOKUP(Z63,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","F",null,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z64<>0,VLOOKUP(Z64,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"No effect in haematological and clinical chemistry parameters up to the highest dose of 600 mg/kg bw/day. Slightly elevated AST, ALP and CK activities however they were sporadic with no dose-response relationship and no stat. significance was reached.",null,"No effect",100,300,"mg/kg bw/day",{"$f":"IF(Z64<>0,VLOOKUP(Z64,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","M",300,"Organ histopathology","Spleen histopathology",{"$f":"IF(Z65<>0,VLOOKUP(Z65,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Gross necropsy revealed increased incidences of ‘small’ spleen at the top dose, corresponding to the organ weight findings. Microscopically, a marginally increased incidence and/or severity of splenic haemosiderosis/sclerosiderosis was seen from the dose of 300 mg/kg bw/d. Findings are not considered to be of clear toxicological significance in the absence of any treatment-related effects on red blood cell parameters.",null,"Change",100,300,"mg/kg bw/day",{"$f":"IF(Z65<>0,VLOOKUP(Z65,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","F",null,"Organ histopathology","Spleen histopathology",{"$f":"IF(Z66<>0,VLOOKUP(Z66,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effect on spleen histopathology up to the highest dose of 600 mg/kg bw/day",null,"No effect",100,300,"mg/kg bw/day",{"$f":"IF(Z66<>0,VLOOKUP(Z66,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","M",300,"Organ Weight","Thyroid weight",{"$f":"IF(Z67<>0,VLOOKUP(Z67,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Mean absolute and relative thyroid weights were higher in all treated groups in a dose-related fashion; values attained statistical significance from the dose of 300 mg/kg bw/d. [300 mg/kg bw/day: 47.9% (abs) 49.8% (rel); 600 mg/kg bw/day: 67.1% (abs) 64.3% (rel)]",null,"Increase",100,300,"mg/kg bw/day",{"$f":"IF(Z67<>0,VLOOKUP(Z67,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","F",600,"Organ Weight","Thyroid weight",{"$f":"IF(Z68<>0,VLOOKUP(Z68,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Mean absolute and relative thyroid weights were higher in all treated groups in a dose-related fashion; values attained statistical significance at the dose of 600 mg/kg bw/d [71.7% (abs), 69.8% (rel)].",null,"Increase",100,300,"mg/kg bw/day",{"$f":"IF(Z68<>0,VLOOKUP(Z68,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","M",300,"In life observation","Clinical signs",{"$f":"IF(Z69<>0,VLOOKUP(Z69,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Salivation and vomiting with increasing incidence and severity. Slight salivation was observed from the dose of 100 mg/kg bw/day but was not considered adverse.",null,"Increase",100,300,"mg/kg bw/day",{"$f":"IF(Z69<>0,VLOOKUP(Z69,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","M",null,"Organ Weight","Spleen weight",{"$f":"IF(Z70<>0,VLOOKUP(Z70,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Spleen weight (abs & rel) was slightly (but not significantly) lower (7%) at the top dose of 600 mg/kg bw/day",null,"No effect",100,300,"mg/kg bw/day",{"$f":"IF(Z70<>0,VLOOKUP(Z70,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","F",null,"Organ Weight","Spleen weight",{"$f":"IF(Z71<>0,VLOOKUP(Z71,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effect in spleen weight up to the highest dose of 600 mg/kg bw/day",null,"No effect",100,300,"mg/kg bw/day",{"$f":"IF(Z71<>0,VLOOKUP(Z71,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Subacute oral in non-rodent ",4,null,"OECD 409 (1981), EPA OPPTS 870.4100 (1998), 96/54/EEC B.32, JMAFF 59 NohSan 4200 (1985)","DAR",null,"2004a","Dog","Beagle",5,"M + F",82.2,"Oral","Gavage/Intubation","0, 100, 300, 600",100,600,"mg/kg bw/day",52,"Weeks","Adult","F",300,"In life observation","Clinical signs",{"$f":"IF(Z72<>0,VLOOKUP(Z72,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Salivation and vomiting with increasing incidence and severity from the dose of 300 mg/kg bw/day.",null,"Increase",100,300,"mg/kg bw/day",{"$f":"IF(Z72<>0,VLOOKUP(Z72,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",5,null,"US FIFRA 82-2","DAR",null,"1989b","Rabbit","New Zealand White",10,"M + F",88,"Dermal","Topical","0, 1000",1000,1000,"mg/kg bw/day",21,"Days","Adult","M + F",null,"No relevant effect observed","No relevant effect observed",{"$f":"IF(Z73<>0,VLOOKUP(Z73,Interpretation!$C:$E,2,FALSE),\"\")","v":"No relevant effect observed"},"No local or systemic effects in males and females",null,"No effect",1000,"<1000","mg/kg bw/day",{"$f":"IF(Z73<>0,VLOOKUP(Z73,Interpretation!$C:$E,3,FALSE),\"\")","v":0},null,"Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",6,null,"US EPA OCSPP 870.3200 (1998)","DAR",null,2015,"Rat","Wistar",10,"M + F","90.01","Dermal","Topical","0, 50, 125, 250",50,250,"mg/kg bw/day",21,"Days","Adult","M + F",null,"Organ histopathology","Thyroid histopathology",{"$f":"IF(Z74<>0,VLOOKUP(Z74,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect in thyroid histopathology in males and females up to the highest dose of 250 mg/kg bw/day",null,"No effect",250,"<250","mg/kg bw/day",{"$f":"IF(Z74<>0,VLOOKUP(Z74,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",6,null,"US EPA OCSPP 870.3200 (1998)","DAR",null,2015,"Rat","Wistar",10,"M + F","90.01","Dermal","Topical","0, 50, 125, 250",50,250,"mg/kg bw/day",21,"Days","Adult","M + F",null,"No relevant effect observed","No relevant effect observed",{"$f":"IF(Z75<>0,VLOOKUP(Z75,Interpretation!$C:$E,2,FALSE),\"\")","v":"No relevant effect observed"},"No local or systemic effects in males and females",null,"No effect",250,"<250","mg/kg bw/day",{"$f":"IF(Z75<>0,VLOOKUP(Z75,Interpretation!$C:$E,3,FALSE),\"\")","v":0},null,"Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",6,null,"US EPA OCSPP 870.3200 (1998)","DAR",null,2015,"Rat","Wistar",10,"M + F","90.01","Dermal","Topical","0, 50, 125, 250",50,250,"mg/kg bw/day",21,"Days","Adult","M + F",null,"Clinical chemistry/hormones","T3 and T4 level",{"$f":"IF(Z76<>0,VLOOKUP(Z76,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"The statistically significant decrease in T3 in males (45.7%) was considered of no toxicological significance in the RAR. T3 was also decreased in females (22%, p>0.05). T3 was decreased in males (15%) and females (22%) but did not achieve toxicological significance.",null,"No effect",250,"<250","mg/kg bw/day",{"$f":"IF(Z76<>0,VLOOKUP(Z76,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",6,null,"US EPA OCSPP 870.3200 (1998)","DAR",null,2015,"Rat","Wistar",10,"M + F","90.01","Dermal","Topical","0, 50, 125, 250",50,250,"mg/kg bw/day",21,"Days","Adult","M + F",null,"Clinical chemistry/hormones","Thyroid-stimulating hormone level (TSH)",{"$f":"IF(Z77<>0,VLOOKUP(Z77,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"TSH changes were inconsistent and without statistical significance (15% increase in males and 53% decrease in females).",null,"No effect",250,"<250","mg/kg bw/day",{"$f":"IF(Z77<>0,VLOOKUP(Z77,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Repeated dose dermal toxicity",6,null,"US EPA OCSPP 870.3200 (1998)","DAR",null,2015,"Rat","Wistar",10,"M + F","90.01","Dermal","Topical","0, 50, 125, 250",50,250,"mg/kg bw/day",21,"Days","Adult","M + F",null,"Organ Weight","Thyroid weight",{"$f":"IF(Z78<>0,VLOOKUP(Z78,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect in thyroid weight in males and females up to the highest dose of 250 mg/kg bw/day; The decrease observed only in mid dose females (percentage not reported) not accompanied by histopathological findings was not considered of toxicological significance",null,"No effect",250,"<250","mg/kg bw/day",{"$f":"IF(Z78<>0,VLOOKUP(Z78,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"F","Not reported","Oral","Feed","47, 243, 1280",47,1280,"mg/kg bw/day",108,"Weeks","Adult","F",null,"Organ Weight","Ovary weight",{"$f":"IF(Z79<>0,VLOOKUP(Z79,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on ovaries weight in females up to the highest dose of 1280 mg/kg bw/day.","NOAEL systemic","No effect",47,243,"mg/kg bw/day",{"$f":"IF(Z79<>0,VLOOKUP(Z79,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"M","Not reported","Oral","Feed","36, 180, 953",36,953,"mg/kg bw/day",108,"Weeks","Adult","M",null,"Organ Weight","Prostate weight",{"$f":"IF(Z80<>0,VLOOKUP(Z80,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on prostate weight in males up to the highest dose of 953 mg/kg bw/day.","NOAEL systemic","No effect",36,180,"mg/kg bw/day",{"$f":"IF(Z80<>0,VLOOKUP(Z80,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"M","Not reported","Oral","Feed","36, 180, 953",36,953,"mg/kg bw/day",108,"Weeks","Adult","M",953,"In life observation","Body weight",{"$f":"IF(Z81<>0,VLOOKUP(Z81,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased bodyweight (↓ 4.2%) and bodyweight gain (↓ 10.4% for 0-52 weeks. Data not given for 0-108 weeks).","NOAEL systemic","Decrease",36,180,"mg/kg bw/day",{"$f":"IF(Z81<>0,VLOOKUP(Z81,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"F","Not reported","Oral","Feed","47, 243, 1280",47,1280,"mg/kg bw/day",108,"Weeks","Adult","F",243,"In life observation","Body weight",{"$f":"IF(Z82<>0,VLOOKUP(Z82,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased bodyweight gain (↓ 10.4% for 0-52 weeks. Data not given for 0-108 weeks). At the top dose of 1280 mg/kg bw/day: Decreased bodyweight (↓ 5.0%) and bodyweight gain (↓ 15.1% for 0-52 weeks. Data not given for 0-108 weeks).","NOAEL systemic","Decrease",47,243,"mg/kg bw/day",{"$f":"IF(Z82<>0,VLOOKUP(Z82,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"M","Not reported","Oral","Feed","36, 180, 953",36,953,"mg/kg bw/day",108,"Weeks","Adult","M",953,"Organ histopathology","Liver histopathology",{"$f":"IF(Z83<>0,VLOOKUP(Z83,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Bile duct hyperplasia (17/50 males vs 10/50 in controls). ","NOAEL systemic","Change",36,180,"mg/kg bw/day",{"$f":"IF(Z83<>0,VLOOKUP(Z83,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"M","Not reported","Oral","Feed","36, 180, 953",36,953,"mg/kg bw/day",108,"Weeks","Adult","M",null,"Organ Weight","Testis weight",{"$f":"IF(Z84<>0,VLOOKUP(Z84,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on testes weight in males up to the highest dose of 953 mg/kg bw/day.","NOAEL systemic","No effect",36,180,"mg/kg bw/day",{"$f":"IF(Z84<>0,VLOOKUP(Z84,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"M","Not reported","Oral","Feed","36, 180, 953",36,953,"mg/kg bw/day",108,"Weeks","Adult","M",953,"Organ histopathology","Adrenals histopathology",{"$f":"IF(Z85<>0,VLOOKUP(Z85,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Adrenals medullary hyperplasia (17/50 males vs 8/50 in controls). ","NOAEL systemic","Change",36,180,"mg/kg bw/day",{"$f":"IF(Z85<>0,VLOOKUP(Z85,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"F","Not reported","Oral","Feed","47, 243, 1280",47,1280,"mg/kg bw/day",108,"Weeks","Adult","F",null,"Organ histopathology","Adrenals histopathology",{"$f":"IF(Z86<>0,VLOOKUP(Z86,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect on adrenals histopathology at the top dose of 1280 mg/kg bw/day in females.","NOAEL systemic","No effect",47,243,"mg/kg bw/day",{"$f":"IF(Z86<>0,VLOOKUP(Z86,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"F","Not reported","Oral","Feed","47, 243, 1280",47,1280,"mg/kg bw/day",108,"Weeks","Adult","F",1280,"Organ histopathology","Liver histopathology",{"$f":"IF(Z87<>0,VLOOKUP(Z87,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Bile duct hyperplasia (13/50 females vs 6/50 in controls). ","NOAEL systemic","Change",47,243,"mg/kg bw/day",{"$f":"IF(Z87<>0,VLOOKUP(Z87,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"M","Not reported","Oral","Feed","36, 180, 953",36,953,"mg/kg bw/day",108,"Weeks","Adult","M",953,"Organ histopathology","Thyroid histopathology",{"$f":"IF(Z88<>0,VLOOKUP(Z88,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Thyroid hyperplasia (11/50 males vs 0/50 in controls) and thyroid epithelial whorls (5/50 males vs 1/50 in controls). Enlarged thyroid (11/50 males vs 1/50 in controls). According to the RMS, the thyroid effects reported were consistent, however, within the historical control range and therefore not considered teatment-related.","NOAEL systemic","Change",36,180,"mg/kg bw/day",{"$f":"IF(Z88<>0,VLOOKUP(Z88,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Thyroid weight not measured in the study.","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"F","Not reported","Oral","Feed","47, 243, 1280",47,1280,"mg/kg bw/day",108,"Weeks","Adult","F",1280,"Organ histopathology","Thyroid histopathology",{"$f":"IF(Z89<>0,VLOOKUP(Z89,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Thyroid hyperplasia (3/50 females vs 0/50 in controls) and thyroid epithelial whorls (4/50 females vs 2/50 in controls). Enlarged thyroid (11/50 females vs 4/50 in controls). According to the RMS, the thyroid effects reported were consistent, however, within the historical control range and therefore not considered teatment-related.","NOAEL systemic","Change",47,243,"mg/kg bw/day",{"$f":"IF(Z89<>0,VLOOKUP(Z89,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Thyroid weight not measured in the study.","Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"M","Not reported","Oral","Feed","36, 180, 953",36,953,"mg/kg bw/day",108,"Weeks","Adult","M",null,"Organ Weight","Liver weight",{"$f":"IF(Z90<>0,VLOOKUP(Z90,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"No effect on liver weight in males up to the highest dose of 953 mg/kg bw/day.","NOAEL systemic","No effect",36,180,"mg/kg bw/day",{"$f":"IF(Z90<>0,VLOOKUP(Z90,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"F","Not reported","Oral","Feed","47, 243, 1280",47,1280,"mg/kg bw/day",108,"Weeks","Adult","F",1280,"Organ Weight","Liver weight",{"$f":"IF(Z91<>0,VLOOKUP(Z91,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increase in the absolute (↑10.3%) and relative-to-body (↑ 6.6%) liver weight in females. ","NOAEL systemic","Increase",47,243,"mg/kg bw/day",{"$f":"IF(Z91<>0,VLOOKUP(Z91,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"M","Not reported","Oral","Feed","36, 180, 953",36,953,"mg/kg bw/day",108,"Weeks","Adult","M",null,"No relevant effect observed","No relevant effect observed",{"$f":"IF(Z92<>0,VLOOKUP(Z92,Interpretation!$C:$E,2,FALSE),\"\")","v":"No relevant effect observed"},"No evidence of treatment-related tumours in males up to the highest dose of 953 mg/kg bw/day. There is insufficient evidence that substance causes phaechromocytomas in male rats; data in the context of historical control range.","NOAEL carcinogenic","No effect",953,">953","mg/kg bw/day",{"$f":"IF(Z92<>0,VLOOKUP(Z92,Interpretation!$C:$E,3,FALSE),\"\")","v":0},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"F","Not reported","Oral","Feed","47, 243, 1280",47,1280,"mg/kg bw/day",108,"Weeks","Adult","F",null,"No relevant effect observed","No relevant effect observed",{"$f":"IF(Z93<>0,VLOOKUP(Z93,Interpretation!$C:$E,2,FALSE),\"\")","v":"No relevant effect observed"},"No evidence of treatment-related tumours in females up to the highest dose of 1280 mg/kg bw/day.","NOAEL carcinogenic","No effect",1280,">1280","mg/kg bw/day",{"$f":"IF(Z93<>0,VLOOKUP(Z93,Interpretation!$C:$E,3,FALSE),\"\")","v":0},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"M","Not reported","Oral","Feed","36, 180, 953",36,953,"mg/kg bw/day",108,"Weeks","Adult","M",null,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z94<>0,VLOOKUP(Z94,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Not consistent haematology changes in males up to the highest dose of 953 mg/kg bw/day. Significantly increased clotting times were noted in top dose males at Weeks 12, 14 and 24; as a result the diet was supplemented with Vit. K and similar effects were not apparent.","NOAEL systemic","No effect",36,180,"mg/kg bw/day",{"$f":"IF(Z94<>0,VLOOKUP(Z94,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"F","Not reported","Oral","Feed","47, 243, 1280",47,1280,"mg/kg bw/day",108,"Weeks","Adult","F",null,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z95<>0,VLOOKUP(Z95,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Not consistent haematology changes in males up to the highest dose of 1280 mg/kg bw/day.","NOAEL systemic","No effect",47,243,"mg/kg bw/day",{"$f":"IF(Z95<>0,VLOOKUP(Z95,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"M","Not reported","Oral","Feed","36, 180, 953",36,953,"mg/kg bw/day",108,"Weeks","Adult","M",953,"Organ histopathology","Spleen histopathology",{"$f":"IF(Z96<>0,VLOOKUP(Z96,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Prominent siderocytes (7/50 males vs 1/50 in controls). ","NOAEL systemic","Change",36,180,"mg/kg bw/day",{"$f":"IF(Z96<>0,VLOOKUP(Z96,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"F","Not reported","Oral","Feed","47, 243, 1280",47,1280,"mg/kg bw/day",108,"Weeks","Adult","F",243,"Organ histopathology","Spleen histopathology",{"$f":"IF(Z97<>0,VLOOKUP(Z97,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Prominent siderocytes (6/50 females vs 2/50 in controls) at 243 mg/kg bw/day. Same incidence at top dose of 1280 mg/kg bw/day.","NOAEL systemic","Change",47,243,"mg/kg bw/day",{"$f":"IF(Z97<>0,VLOOKUP(Z97,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"F","Not reported","Oral","Feed","47, 243, 1280",47,1280,"mg/kg bw/day",108,"Weeks","Adult","F",1280,"Organ histopathology","Spleen histopathology",{"$f":"IF(Z98<>0,VLOOKUP(Z98,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Prominent siderocytes (6/50 females vs 2/50 in controls) at top dose of 1280 mg/kg bw/day.","NOAEL systemic","Change",47,243,"mg/kg bw/day",{"$f":"IF(Z98<>0,VLOOKUP(Z98,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"M","Not reported","Oral","Feed","36, 180, 953",36,953,"mg/kg bw/day",108,"Weeks","Adult","M",953,"Organ histopathology","Pituitary histopathology",{"$f":"IF(Z99<>0,VLOOKUP(Z99,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Pituitary hyperplasia (13/50 males vs 6/50 in controls). ","NOAEL systemic","Change",36,180,"mg/kg bw/day",{"$f":"IF(Z99<>0,VLOOKUP(Z99,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"F","Not reported","Oral","Feed","47, 243, 1280",47,1280,"mg/kg bw/day",108,"Weeks","Adult","F",null,"Organ histopathology","Pituitary histopathology",{"$f":"IF(Z100<>0,VLOOKUP(Z100,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect on pituitary histopathology at the top dose of 1280 mg/kg bw/day in females.","NOAEL systemic","No effect",47,243,"mg/kg bw/day",{"$f":"IF(Z100<>0,VLOOKUP(Z100,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Combined chronic toxicity/carcinogenicity studies",7,null,"None stated","DAR",null,1980,"Rat","Sprague-Dawley",50,"F","Not reported","Oral","Feed","47, 243, 1280",47,1280,"mg/kg bw/day",108,"Weeks","Adult","F",null,"Organ Weight","Uterus weight (with cervix)",{"$f":"IF(Z101<>0,VLOOKUP(Z101,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on uterus weight in females up to the highest dose of 1280 mg/kg bw/day.","NOAEL systemic","No effect",47,243,"mg/kg bw/day",{"$f":"IF(Z101<>0,VLOOKUP(Z101,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},null,"Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"M",88,"Oral","Feed","74, 730, 8040",74,8040,"mg/kg bw/day",24,"Months","Adult","M",null,"Organ histopathology","Thyroid histopathology",{"$f":"IF(Z102<>0,VLOOKUP(Z102,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on thyroid histopathology up to the highest dose of 8040 mg/kg bw/day in males",null,"No effect",74,730,"mg/kg bw/day",{"$f":"IF(Z102<>0,VLOOKUP(Z102,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"F",88,"Oral","Feed","95, 938, 10353",95,10353,"mg/kg bw/day",24,"Months","Adult","F",null,"Organ histopathology","Thyroid histopathology",{"$f":"IF(Z103<>0,VLOOKUP(Z103,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on thyroid histopathology up to the highest dose of 10353 mg/kg bw/day in females",null,"No effect",95,938,"mg/kg bw/day",{"$f":"IF(Z103<>0,VLOOKUP(Z103,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"M",88,"Oral","Feed","74, 730, 8040",74,8040,"mg/kg bw/day",24,"Months","Adult","M",null,"Organ histopathology","Testis histopathology",{"$f":"IF(Z104<>0,VLOOKUP(Z104,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Incidence of testes mineralisation: 7, 7, 10, 12 males at 74, 730, 8040 mg/kg bw/day, respectively. In RAR, not considered treatment-related adverse effect.","NOAEL systemic","No effect",74,730,"mg/kg bw/day",{"$f":"IF(Z104<>0,VLOOKUP(Z104,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"F",88,"Oral","Feed","95, 938, 10353",95,10353,"mg/kg bw/day",24,"Months","Adult","F",10353,"Organ histopathology","Kidney histopathology",{"$f":"IF(Z105<>0,VLOOKUP(Z105,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Brown granular pigment deposition (6/21 females vs 5/30 controls)","NOAEL systemic","Increase",95,938,"mg/kg bw/day",{"$f":"IF(Z105<>0,VLOOKUP(Z105,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",10,"M",88,"Oral","Feed","74, 730, 8040",74,8040,"mg/kg bw/day",12,"Months","Adult","M",8040,"Organ histopathology","Kidney histopathology",{"$f":"IF(Z106<>0,VLOOKUP(Z106,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Brown granular pigment deposition (3/10 males vs 0/10 controls)",null,"Change",74,730,"mg/kg bw/day",{"$f":"IF(Z106<>0,VLOOKUP(Z106,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",10,"F",88,"Oral","Feed","95, 938, 10353",95,10353,"mg/kg bw/day",12,"Months","Adult","F",10353,"Organ histopathology","Kidney histopathology",{"$f":"IF(Z107<>0,VLOOKUP(Z107,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Brown granular pigment deposition (4/10 males vs 0/10 controls)",null,"Change",95,938,"mg/kg bw/day",{"$f":"IF(Z107<>0,VLOOKUP(Z107,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"M",88,"Oral","Feed","74, 730, 8040",74,8040,"mg/kg bw/day",24,"Months","Adult","M",8040,"In life observation","Body weight",{"$f":"IF(Z108<>0,VLOOKUP(Z108,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Bodyweights were significantly lower (↓ 5.1%).","NOAEL systemic","Decrease",74,730,"mg/kg bw/day",{"$f":"IF(Z108<>0,VLOOKUP(Z108,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"F",88,"Oral","Feed","95, 938, 10353",95,10353,"mg/kg bw/day",24,"Months","Adult","F",10353,"In life observation","Body weight",{"$f":"IF(Z109<>0,VLOOKUP(Z109,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Bodyweights were significantly lower (↓ 6.1%).","NOAEL systemic","Decrease",95,938,"mg/kg bw/day",{"$f":"IF(Z109<>0,VLOOKUP(Z109,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"M",88,"Oral","Feed","74, 730, 8040",74,8040,"mg/kg bw/day",24,"Months","Adult","M",null,"Organ Weight","Testis weight",{"$f":"IF(Z110<>0,VLOOKUP(Z110,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on testes weight in males up to the highest dose of 8040 mg/kg bw/day.","NOAEL systemic","No effect",74,730,"mg/kg bw/day",{"$f":"IF(Z110<>0,VLOOKUP(Z110,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",10,"M",88,"Oral","Feed","74, 730, 8040",74,8040,"mg/kg bw/day",12,"Months","Adult","M",8040,"In life observation","Body weight",{"$f":"IF(Z111<>0,VLOOKUP(Z111,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Bodyweights were significantly lower (↓7.3%).",null,"Decrease",74,730,"mg/kg bw/day",{"$f":"IF(Z111<>0,VLOOKUP(Z111,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",10,"F",88,"Oral","Feed","95, 938, 10353",95,10353,"mg/kg bw/day",12,"Months","Adult","F",null,"In life observation","Body weight",{"$f":"IF(Z112<>0,VLOOKUP(Z112,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Bodyweights not affected in females after 12 month treatment with the top dose of 10353 mg/kg bw/day.",null,"No effect",95,938,"mg/kg bw/day",{"$f":"IF(Z112<>0,VLOOKUP(Z112,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"M",88,"Oral","Feed","74, 730, 8040",74,8040,"mg/kg bw/day",24,"Months","Adult","M",8040,"Organ histopathology","Liver histopathology",{"$f":"IF(Z113<>0,VLOOKUP(Z113,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Brown granular pigment deposition (2/28 males vs 0/28 controls)","NOAEL systemic","Increase",74,730,"mg/kg bw/day",{"$f":"IF(Z113<>0,VLOOKUP(Z113,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"F",88,"Oral","Feed","95, 938, 10353",95,10353,"mg/kg bw/day",24,"Months","Adult","F",10353,"Organ histopathology","Liver histopathology",{"$f":"IF(Z114<>0,VLOOKUP(Z114,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Brown granular pigment deposition (3/21 females vs 0/30 controls)","NOAEL systemic","Increase",95,938,"mg/kg bw/day",{"$f":"IF(Z114<>0,VLOOKUP(Z114,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",10,"M",88,"Oral","Feed","74, 730, 8040",74,8040,"mg/kg bw/day",12,"Months","Adult","M",8040,"Organ histopathology","Liver histopathology",{"$f":"IF(Z115<>0,VLOOKUP(Z115,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Brown granular pigment deposition (8/10 males vs 0/10 controls)",null,"Change",74,730,"mg/kg bw/day",{"$f":"IF(Z115<>0,VLOOKUP(Z115,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",10,"F",88,"Oral","Feed","95, 938, 10353",95,10353,"mg/kg bw/day",12,"Months","Adult","F",10353,"Organ histopathology","Liver histopathology",{"$f":"IF(Z116<>0,VLOOKUP(Z116,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Brown granular pigment deposition (2/10 males vs 0/10 controls)",null,"Change",95,938,"mg/kg bw/day",{"$f":"IF(Z116<>0,VLOOKUP(Z116,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"M",88,"Oral","Feed","74, 730, 8040",74,8040,"mg/kg bw/day",24,"Months","Adult","M",8040,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z117<>0,VLOOKUP(Z117,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Effects in haematological parameters indicative of mild anaemia: RBC (↓11%), HCT (↓8.6%), MCH (↑ 19.2%), MCHC (↑16.3%).","NOAEL systemic","Change",74,730,"mg/kg bw/day",{"$f":"IF(Z117<>0,VLOOKUP(Z117,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"F",88,"Oral","Feed","95, 938, 10353",95,10353,"mg/kg bw/day",24,"Months","Adult","F",10353,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z118<>0,VLOOKUP(Z118,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Effects in haematological parameters indicative of mild anaemia: RBC (↓15.3%), HCT (↓7.9%), MCH (↑ 17.6%), MCHC (↑6.6%).","NOAEL systemic","Change",95,938,"mg/kg bw/day",{"$f":"IF(Z118<>0,VLOOKUP(Z118,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",10,"M",88,"Oral","Feed","74, 730, 8040",74,8040,"mg/kg bw/day",12,"Months","Adult","M",8040,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z119<>0,VLOOKUP(Z119,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Effects in haematological parameters indicative of mild anaemia: RBC (↓11.4%), HCT (↓12.4%), MCH (↑ 14.7%), MCHC (↑16.3%).",null,"Change",74,730,"mg/kg bw/day",{"$f":"IF(Z119<>0,VLOOKUP(Z119,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"M",88,"Oral","Feed","74, 730, 8040",74,8040,"mg/kg bw/day",24,"Months","Adult","M",null,"No relevant effect observed","No relevant effect observed",{"$f":"IF(Z120<>0,VLOOKUP(Z120,Interpretation!$C:$E,2,FALSE),\"\")","v":"No relevant effect observed"},"There were no treatment-related tumours.","NOAEL carcinogenic","No effect",8040,">8040","mg/kg bw/day",{"$f":"IF(Z120<>0,VLOOKUP(Z120,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"F",88,"Oral","Feed","95, 938, 10353",95,10353,"mg/kg bw/day",24,"Months","Adult","F",null,"No relevant effect observed","No relevant effect observed",{"$f":"IF(Z121<>0,VLOOKUP(Z121,Interpretation!$C:$E,2,FALSE),\"\")","v":"No relevant effect observed"},"There were no treatment-related tumours.","NOAEL carcinogenic","No effect",10353,">10353","mg/kg bw/day",{"$f":"IF(Z121<>0,VLOOKUP(Z121,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",10,"F",88,"Oral","Feed","95, 938, 10353",95,10353,"mg/kg bw/day",12,"Months","Adult","F",10353,"In life observation","Clinical chemistry and haematology",{"$f":"IF(Z122<>0,VLOOKUP(Z122,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Effects in haematological parameters indicative of mild anaemia: RBC (↓7.0%), HCT (↓8.8%), MCH (↑ 7.8%), MCHC (↑9.5%).",null,"Change",95,938,"mg/kg bw/day",{"$f":"IF(Z122<>0,VLOOKUP(Z122,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"M",88,"Oral","Feed","74, 730, 8040",74,8040,"mg/kg bw/day",24,"Months","Adult","M",730,"Organ Weight","Spleen weight",{"$f":"IF(Z123<>0,VLOOKUP(Z123,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increase in the absolute (↑69.2%) and relative-to-body (↑ 78.2%) spleen weight in males. ","NOAEL systemic","Increase",74,730,"mg/kg bw/day",{"$f":"IF(Z123<>0,VLOOKUP(Z123,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"F",88,"Oral","Feed","95, 938, 10353",95,10353,"mg/kg bw/day",24,"Months","Adult","F",938,"Organ Weight","Spleen weight",{"$f":"IF(Z124<>0,VLOOKUP(Z124,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increase in the absolute (↑42.9%) and relative-to-body (↑ 37.5%) spleen weight in females. ","NOAEL systemic","Increase",95,938,"mg/kg bw/day",{"$f":"IF(Z124<>0,VLOOKUP(Z124,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",10,"M",88,"Oral","Feed","74, 730, 8040",74,8040,"mg/kg bw/day",12,"Months","Adult","M",8040,"Organ Weight","Spleen weight",{"$f":"IF(Z125<>0,VLOOKUP(Z125,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increase in the absolute (↑42.9%) and relative-to-body (↑ 53.7%) spleen weight in males. ",null,"Increase",74,730,"mg/kg bw/day",{"$f":"IF(Z125<>0,VLOOKUP(Z125,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"M",88,"Oral","Feed","74, 730, 8040",74,8040,"mg/kg bw/day",24,"Months","Adult","M",null,"Organ histopathology","Pituitary histopathology",{"$f":"IF(Z126<>0,VLOOKUP(Z126,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No increased incidence in pituitary adenomas up to the highest dose of 8040 mg/kg bw/day in males.","NOAEL systemic","No effect",74,730,"mg/kg bw/day",{"$f":"IF(Z126<>0,VLOOKUP(Z126,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"F",88,"Oral","Feed","95, 938, 10353",95,10353,"mg/kg bw/day",24,"Months","Adult","F",null,"Organ histopathology","Pituitary histopathology",{"$f":"IF(Z127<>0,VLOOKUP(Z127,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No increased incidence in pituitary adenomas up to the highest dose of 8040 mg/kg bw/day in females.","NOAEL systemic","No effect",95,938,"mg/kg bw/day",{"$f":"IF(Z127<>0,VLOOKUP(Z127,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"M",88,"Oral","Feed","74, 730, 8040",74,8040,"mg/kg bw/day",24,"Months","Adult","M",8040,"In life observation","Food consumption",{"$f":"IF(Z128<>0,VLOOKUP(Z128,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption was consistently higher; findings likely due to the inclusion of the test material at a high level (5%) in the diet.","NOAEL systemic","Change",74,730,"mg/kg bw/day",{"$f":"IF(Z128<>0,VLOOKUP(Z128,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",10,"F",88,"Oral","Feed","95, 938, 10353",95,10353,"mg/kg bw/day",12,"Months","Adult","F",10353,"Organ Weight","Spleen weight",{"$f":"IF(Z129<>0,VLOOKUP(Z129,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Increase in the absolute (↑114.3%) and relative-to-body (↑ 117.3%) spleen weight in females. ",null,"Increase",95,938,"mg/kg bw/day",{"$f":"IF(Z129<>0,VLOOKUP(Z129,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"F",88,"Oral","Feed","95, 938, 10353",95,10353,"mg/kg bw/day",24,"Months","Adult","F",10353,"In life observation","Food consumption",{"$f":"IF(Z130<>0,VLOOKUP(Z130,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Food consumption was consistently higher; findings likely due to the inclusion of the test material at a high level (5%) in the diet.","NOAEL systemic","Increase",95,938,"mg/kg bw/day",{"$f":"IF(Z130<>0,VLOOKUP(Z130,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Carcinogenicity",8,null,"EPA 83-2","DAR",null,"1992a","Mouse","CD-1",75,"F",88,"Oral","Feed","95, 938, 10353",95,10353,"mg/kg bw/day",24,"Months","Adult","F",null,"Organ histopathology","Uterus histopathology (with cervix)",{"$f":"IF(Z131<>0,VLOOKUP(Z131,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Incidence of uterine corpus cystic endometrial hyperplasia: 23, 30, 40, 36 females at 74, 730, 8040 mg/kg bw/day, respectively. In RAR, not considered treatment-related adverse effect.","NOAEL systemic","No effect",95,938,"mg/kg bw/day",{"$f":"IF(Z131<>0,VLOOKUP(Z131,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Thyroid weight not measured in the study. ","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F0)","M",1136,"In life observation","Body weight",{"$f":"IF(Z132<>0,VLOOKUP(Z132,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased body weight (8%) and body weight gain (10%) in F0 males at the end of the study, p>0.05","NOAEL parental","Decrease",224,1136,"mg/kg bw/day",{"$f":"IF(Z132<>0,VLOOKUP(Z132,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",21,"F",99,"Oral","Feed","0, 58, 278, 1456",58,1456,"mg/kg bw/day",29,"Weeks","Adult (F1)","F",1456,"In life observation","Body weight",{"$f":"IF(Z133<>0,VLOOKUP(Z133,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased body weight (9.4%) and body weight gain (14.5%, p>0.05) in F1 females during pre-mating period ","NOAEL parental","Decrease",278,1456,"mg/kg bw/day",{"$f":"IF(Z133<>0,VLOOKUP(Z133,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",21,"F",99,"Oral","Feed","0, 58, 278, 1456",58,1456,"mg/kg bw/day",29,"Weeks","Adult (F1)","F",1456,"Organ Weight","Liver weight",{"$f":"IF(Z134<>0,VLOOKUP(Z134,Interpretation!$C:$E,2,FALSE),\"\")","v":"Target organ toxicity"},"Decreased absolute (15.6%) and relative (8.5%) liver weight in F1 females","NOAEL parental","Decrease",278,1456,"mg/kg bw/day",{"$f":"IF(Z134<>0,VLOOKUP(Z134,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F1)","M",1136,"Organ Weight","Thyroid weight",{"$f":"IF(Z135<>0,VLOOKUP(Z135,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"Increased absolute (25%) and relative (19.6%)thyroid weight in F1 males","NOAEL parental","Increase",224,1136,"mg/kg bw/day",{"$f":"IF(Z135<>0,VLOOKUP(Z135,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F0+F1)","M + F",null,"Organ Weight","Adrenals weight",{"$f":"IF(Z136<>0,VLOOKUP(Z136,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect on adrenals weight up to the highest dose of 1136 (males) and 1456 (females) mg/kg bw/day.","NOAEL parental","No effect",224,1136,"mg/kg bw/day",{"$f":"IF(Z136<>0,VLOOKUP(Z136,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F0+F1)","M",null,"Organ Weight","Testis weight",{"$f":"IF(Z137<>0,VLOOKUP(Z137,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on testicular weight up to the highest dose of 1136 mg/kg bw/day","NOAEL parental","No effect",224,1136,"mg/kg bw/day",{"$f":"IF(Z137<>0,VLOOKUP(Z137,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F0+F1)","M",null,"Organ Weight","Prostate weight",{"$f":"IF(Z138<>0,VLOOKUP(Z138,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on prostate weight up to the highest dose of 1136 mg/kg bw/day","NOAEL parental","No effect",224,1136,"mg/kg bw/day",{"$f":"IF(Z138<>0,VLOOKUP(Z138,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F0+F1)","F",null,"Organ Weight","Ovary weight",{"$f":"IF(Z139<>0,VLOOKUP(Z139,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on ovarian weight up to the highest dose of 1456 mg/kg bw/day","NOAEL parental","No effect",278,1136,"mg/kg bw/day",{"$f":"IF(Z139<>0,VLOOKUP(Z139,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F0+F1)","M",null,"Organ histopathology","Thyroid histopathology",{"$f":"IF(Z140<>0,VLOOKUP(Z140,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on thyroid histopathology up to the highest dose of 1136 mg/kg bw/day","NOAEL parental","No effect",224,1136,"mg/kg bw/day",{"$f":"IF(Z140<>0,VLOOKUP(Z140,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F0+F1)","F",null,"Organ histopathology","Thyroid histopathology",{"$f":"IF(Z141<>0,VLOOKUP(Z141,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on thyroid histopathology up to the highest dose of 1456 mg/kg bw/day","NOAEL parental","No effect",278,1136,"mg/kg bw/day",{"$f":"IF(Z141<>0,VLOOKUP(Z141,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F0+F1)","M",null,"Organ histopathology","Pituitary histopathology",{"$f":"IF(Z142<>0,VLOOKUP(Z142,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect on pituitary histopathology up to the highest dose of 1136 mg/kg bw/day","NOAEL parental","No effect",224,1136,"mg/kg bw/day",{"$f":"IF(Z142<>0,VLOOKUP(Z142,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F0+F1)","F",null,"Organ histopathology","Pituitary histopathology",{"$f":"IF(Z143<>0,VLOOKUP(Z143,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"No effect on pituitary histopathology up to the highest dose of 1456 mg/kg bw/day","NOAEL parental","No effect",278,1136,"mg/kg bw/day",{"$f":"IF(Z143<>0,VLOOKUP(Z143,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F0+F1)","M",null,"Organ histopathology","Prostate histopathology (with seminal vesicles and coagulating glands)",{"$f":"IF(Z144<>0,VLOOKUP(Z144,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on prostate and seminal vesicles histopathology up to the highest dose of 1136 mg/kg bw/day. No information on coagulating gland histology.","NOAEL parental","No effect",224,1136,"mg/kg bw/day",{"$f":"IF(Z144<>0,VLOOKUP(Z144,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F0+F1)","M",null,"Organ histopathology","Seminal vesicles histopathology",{"$f":"IF(Z145<>0,VLOOKUP(Z145,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on seminal vesicles histopathology up to the highest dose of 1136 mg/kg bw/day. ","NOAEL parental","No effect",224,1136,"mg/kg bw/day",{"$f":"IF(Z145<>0,VLOOKUP(Z145,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F0+F1)","M",null,"Organ histopathology","Epididymis histopathology",{"$f":"IF(Z146<>0,VLOOKUP(Z146,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on epididymides histopathology up to the highest dose of 1136 mg/kg bw/day. ","NOAEL parental","No effect",224,1136,"mg/kg bw/day",{"$f":"IF(Z146<>0,VLOOKUP(Z146,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F0+F1)","M",null,"Organ histopathology","Testis histopathology",{"$f":"IF(Z147<>0,VLOOKUP(Z147,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on testes histopathology up to the highest dose of 1136 mg/kg bw/day. ","NOAEL parental","No effect",224,1136,"mg/kg bw/day",{"$f":"IF(Z147<>0,VLOOKUP(Z147,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F0+F1)","F",null,"Organ histopathology","Ovary histopathology",{"$f":"IF(Z148<>0,VLOOKUP(Z148,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on ovary histopathology up to the highest dose of 1456 mg/kg bw/day","NOAEL parental","No effect",278,1136,"mg/kg bw/day",{"$f":"IF(Z148<>0,VLOOKUP(Z148,Interpretation!$C:$E,3,FALSE),\"\")","v":"E, A, S"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F0+F1)","F",null,"Organ histopathology","Uterus histopathology (UT assay)",{"$f":"IF(Z149<>0,VLOOKUP(Z149,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"No effect on uterus histopathology up to the highest dose of 1456 mg/kg bw/day","NOAEL parental","No effect",278,1136,"mg/kg bw/day",{"$f":"IF(Z149<>0,VLOOKUP(Z149,Interpretation!$C:$E,3,FALSE),\"\")","v":"E"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Adult (F1)","M",224,"Reproductive","Litter size",{"$f":"IF(Z150<>0,VLOOKUP(Z150,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Decreased litter size (9.1 vs 11.2 in control) in F1. Also in F2 (7.2 vs 9.3 in control, however p>0.05 and no dose response, not considered in the basis for LOAEL setting)","NOAEL reproductive","Decrease",46,224,"mg/kg bw/day",{"$f":"IF(Z150<>0,VLOOKUP(Z150,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",21,"F",99,"Oral","Feed","0, 58, 278, 1456",58,1456,"mg/kg bw/day",29,"Weeks","Adult (F1)","F",278,"Reproductive","Litter size",{"$f":"IF(Z151<>0,VLOOKUP(Z151,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Decreased litter size (9.1 vs 11.2 in control) in F1. Also in F2 (7.2 vs 9.3 in control, however p>0.05 and no dose response, not considered in the basis for LOAEL setting)","NOAEL reproductive","Decrease",58,278,"mg/kg bw/day",{"$f":"IF(Z151<>0,VLOOKUP(Z151,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Two-generation reproduction toxicity test",9,null,"Not fully in compliance with OECD 416","DAR",null,"1981a","Rat","CD",12,"M",99,"Oral","Feed","0, 46, 224, 1136",46,1136,"mg/kg bw/day",29,"Weeks","Offspring (F1+F2)","M + F",null,"No relevant effect observed","No relevant effect observed",{"$f":"IF(Z152<>0,VLOOKUP(Z152,Interpretation!$C:$E,2,FALSE),\"\")","v":"No relevant effect observed"},"No effects in the offspring up to the highest dose of 1136 mg/kg bw/day; however animals not exposed to test material for 30 days prior to necropsy","NOAEL offpring","No effect",1136,null,"mg/kg bw/day",{"$f":"IF(Z152<>0,VLOOKUP(Z152,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",10,null,"No guideline specified","DAR",null,1982,"Rat","CD",20,"F","98.4-98.5","Oral","Gavage/Intubation","0, 500, 1000, 2000",500,2000,"mg/kg bw/day","Not specified",null,"Adult","F",null,"No relevant effect observed","No relevant effect observed",{"$f":"IF(Z153<>0,VLOOKUP(Z153,Interpretation!$C:$E,2,FALSE),\"\")","v":"No relevant effect observed"},"No maternal effects","NOAEL maternal","No effect",2000,null,"mg/kg bw/day",{"$f":"IF(Z153<>0,VLOOKUP(Z153,Interpretation!$C:$E,3,FALSE),\"\")","v":0},null,"Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",10,null,"No guideline specified","DAR",null,1982,"Rat","CD",20,"F","98.4-98.5","Oral","Gavage/Intubation","0, 500, 1000, 2000",500,2000,"mg/kg bw/day","Not specified",null,"Fetus","M + F",2000,"Abnormalities","Presence of anomalies (external, visceral, skeletal",{"$f":"IF(Z154<>0,VLOOKUP(Z154,Interpretation!$C:$E,2,FALSE),\"\")","v":"Sensitive to, but not diagnostic of, EATS"},"Decreased ossification of the cranium (0.5% foetal incidence, 5% litter incidence vs 0 in control), short/absent 13th rib (4.1% foetal incidence, 15% litter incidence vs 1.1% and 10% in control), fused cervical arches (0.5% foetal incidence, 5% litter incidence vs 0 in control) and decreased ossification of the caudal vertebrae (2.5% foetal incidence, 5% litter incidence vs 1.1% and 5% in control)","NAOEL developmental","Increase",2000,null,"mg/kg bw/day",{"$f":"IF(Z154<>0,VLOOKUP(Z154,Interpretation!$C:$E,3,FALSE),\"\")","v":"N"},null,"Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",11,null,"No guideline specified","DAR",null,"1981a","Rabbit","New Zealand White",15,"F",98,"Oral","Gavage/Intubation","0, 150, 300, 750, 1500",150,1500,"mg/kg bw/day",16,"Days","Adult","F",750,"In life observation","Body weight",{"$f":"IF(Z155<>0,VLOOKUP(Z155,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased body weight and body weight gain at the end of the study","NOAEL maternal","Decrease",2000,null,"mg/kg bw/day",{"$f":"IF(Z155<>0,VLOOKUP(Z155,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"High mortality, however the number of animals surviving to produce a litter exceeded the minimum specified in OECD TG 414","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",11,null,"No guideline specified","DAR",null,"1981a","Rabbit","New Zealand White",15,"F",98,"Oral","Gavage/Intubation","0, 150, 300, 750, 1500",150,1500,"mg/kg bw/day",16,"Days","Adult","F",750,"In life observation","Food consumption",{"$f":"IF(Z156<>0,VLOOKUP(Z156,Interpretation!$C:$E,2,FALSE),\"\")","v":"Systemic toxicity"},"Decreased food consumption","NOAEL maternal","Decrease",2000,null,"mg/kg bw/day",{"$f":"IF(Z156<>0,VLOOKUP(Z156,Interpretation!$C:$E,3,FALSE),\"\")","v":"_"},"High mortality, however the number of animals surviving to produce a litter exceeded the minimum specified in OECD TG 414","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",11,null,"No guideline specified","DAR",null,"1981a","Rabbit","New Zealand White",15,"F",98,"Oral","Gavage/Intubation","0, 150, 300, 750, 1500",150,1500,"mg/kg bw/day",16,"Days","Fetus","M + F",null,"No relevant effect observed","No relevant effect observed",{"$f":"IF(Z157<>0,VLOOKUP(Z157,Interpretation!$C:$E,2,FALSE),\"\")","v":"No relevant effect observed"},"No developmental effects","NAOEL developmental","No effect",750,null,"mg/kg bw/day",{"$f":"IF(Z157<>0,VLOOKUP(Z157,Interpretation!$C:$E,3,FALSE),\"\")","v":0},"High mortality, however the number of animals surviving to produce a litter exceeded the minimum specified in OECD TG 414","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",12,null,"Adapted from OECD 414 & 421","DAR",null,2016,"Rat","Wistar","25 (gestation phase)","F",98,"Oral","Gavage/Intubation","0, 30, 45, 67.5",30,"67.5","mg/kg bw/day","14 (GD6 to GD19)","Days","Adult","F",null,"Organ histopathology","Thyroid histopathology",{"$f":"IF(Z158<>0,VLOOKUP(Z158,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on thyroid histopathology up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation",null,"No effect","67.5",null,"mg/kg bw/day",{"$f":"IF(Z158<>0,VLOOKUP(Z158,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",12,null,"Adapted from OECD 414 & 421","DAR",null,2016,"Rat","Wistar","30 (lactation phase)","F",98,"Oral","Gavage/Intubation","0, 30, 45, 67.5",30,"67.5","mg/kg bw/day","37 (GD6 to LD21)","Days","Adult","F",null,"Organ histopathology","Thyroid histopathology",{"$f":"IF(Z159<>0,VLOOKUP(Z159,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on thyroid histopathology up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation and lactation",null,"No effect","67.5",null,"mg/kg bw/day",{"$f":"IF(Z159<>0,VLOOKUP(Z159,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",12,null,"Adapted from OECD 414 & 421","DAR",null,2016,"Rat","Wistar","not reported","M + F",98,"Oral","Gavage/Intubation","0, 30, 45, 67.5",30,"67.5","mg/kg bw/day","14 (GD6 to GD19)","Days","Fetus","M + F",null,"Organ histopathology","Thyroid histopathology",{"$f":"IF(Z160<>0,VLOOKUP(Z160,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on thyroid histopathology in fetuses at GD20 up to the highest dose of 67.5 mg/kg bw/day ",null,"No effect","67.5",null,"mg/kg bw/day",{"$f":"IF(Z160<>0,VLOOKUP(Z160,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",12,null,"Adapted from OECD 414 & 421","DAR",null,2016,"Rat","Wistar","not reported","M + F",98,"Oral","Gavage/Intubation","0, 30, 45, 67.5",30,"67.5","mg/kg bw/day","35 (GD8 to LD21)","Days","Offspring (F1)","M + F",null,"Organ histopathology","Thyroid histopathology",{"$f":"IF(Z161<>0,VLOOKUP(Z161,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on thyroid histopathology in pups on PND4 and PND22 up to the highest dose of 67.5 mg/kg bw/day ",null,"No effect","67.5",null,"mg/kg bw/day",{"$f":"IF(Z161<>0,VLOOKUP(Z161,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",12,null,"Adapted from OECD 414 & 421","DAR",null,2016,"Rat","Wistar","25 (gestation phase)","F",98,"Oral","Gavage/Intubation","0, 30, 45, 67.5",30,"67.5","mg/kg bw/day","14 (GD6 to GD19)","Days","Adult","F",null,"Organ Weight","Thyroid weight",{"$f":"IF(Z162<>0,VLOOKUP(Z162,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on thyroid weight up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation",null,"No effect","67.5",null,"mg/kg bw/day",{"$f":"IF(Z162<>0,VLOOKUP(Z162,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",12,null,"Adapted from OECD 414 & 421","DAR",null,2016,"Rat","Wistar","30 (lactation phase)","F",98,"Oral","Gavage/Intubation","0, 30, 45, 67.5",30,"67.5","mg/kg bw/day","37 (GD6 to LD21)","Days","Adult","F",null,"Organ Weight","Thyroid weight",{"$f":"IF(Z163<>0,VLOOKUP(Z163,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on thyroid weight up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation and lactation",null,"No effect","67.5",null,"mg/kg bw/day",{"$f":"IF(Z163<>0,VLOOKUP(Z163,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",12,null,"Adapted from OECD 414 & 421","DAR",null,2016,"Rat","Wistar","not reported","M + F",98,"Oral","Gavage/Intubation","0, 30, 45, 67.5",30,"67.5","mg/kg bw/day","35 (GD8 to LD21)","Days","Offspring (F1)","M + F",null,"Organ Weight","Thyroid weight",{"$f":"IF(Z164<>0,VLOOKUP(Z164,Interpretation!$C:$E,2,FALSE),\"\")","v":"EATS-mediated"},"No effect on thyroid weight in pups on PND4 and PND22 up to the highest dose of 67.5 mg/kg bw/day ",null,"No effect","67.5",null,"mg/kg bw/day",{"$f":"IF(Z164<>0,VLOOKUP(Z164,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",12,null,"Adapted from OECD 414 & 421","DAR",null,2016,"Rat","Wistar","25 (gestation phase)","F",98,"Oral","Gavage/Intubation","0, 30, 45, 67.5",30,"67.5","mg/kg bw/day","14 (GD6 to GD19)","Days","Adult","F",null,"Clinical chemistry/hormones","T3 and T4 level",{"$f":"IF(Z165<>0,VLOOKUP(Z165,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"No effect on T3 and T4 up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation",null,"No effect","67.5",null,"mg/kg bw/day",{"$f":"IF(Z165<>0,VLOOKUP(Z165,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",12,null,"Adapted from OECD 414 & 421","DAR",null,2016,"Rat","Wistar","30 (lactation phase)","F",98,"Oral","Gavage/Intubation","0, 30, 45, 67.5",30,"67.5","mg/kg bw/day","37 (GD6 to LD21)","Days","Adult","F",null,"Clinical chemistry/hormones","T3 and T4 level",{"$f":"IF(Z166<>0,VLOOKUP(Z166,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"No effect on T3 and T4 up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation and lactation",null,"No effect","67.5",null,"mg/kg bw/day",{"$f":"IF(Z166<>0,VLOOKUP(Z166,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",12,null,"Adapted from OECD 414 & 421","DAR",null,2016,"Rat","Wistar","25 (gestation phase)","F",98,"Oral","Gavage/Intubation","0, 30, 45, 67.5",30,"67.5","mg/kg bw/day","14 (GD6 to GD19)","Days","Adult","F",null,"Clinical chemistry/hormones","Thyroid-stimulating hormone level (TSH)",{"$f":"IF(Z167<>0,VLOOKUP(Z167,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"No effect on TSH up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation",null,"No effect","67.5",null,"mg/kg bw/day",{"$f":"IF(Z167<>0,VLOOKUP(Z167,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",12,null,"Adapted from OECD 414 & 421","DAR",null,2016,"Rat","Wistar","30 (lactation phase)","F",98,"Oral","Gavage/Intubation","0, 30, 45, 67.5",30,"67.5","mg/kg bw/day","37 (GD6 to LD21)","Days","Adult","F",null,"Clinical chemistry/hormones","Thyroid-stimulating hormone level (TSH)",{"$f":"IF(Z168<>0,VLOOKUP(Z168,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"No effect on TSH up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation and lactation",null,"No effect","67.5",null,"mg/kg bw/day",{"$f":"IF(Z168<>0,VLOOKUP(Z168,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",12,null,"Adapted from OECD 414 & 421","DAR",null,2016,"Rat","Wistar","not reported","M + F",98,"Oral","Gavage/Intubation","0, 30, 45, 67.5",30,"67.5","mg/kg bw/day","14 (GD6 to GD19)","Days","Fetus","M + F",null,"Clinical chemistry/hormones","T3 and T4 level",{"$f":"IF(Z169<>0,VLOOKUP(Z169,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"No effect on T3 and T4 in fetuses at GD20 up to the highest dose of 67.5 mg/kg bw/day ",null,"No effect","67.5",null,"mg/kg bw/day",{"$f":"IF(Z169<>0,VLOOKUP(Z169,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",12,null,"Adapted from OECD 414 & 421","DAR",null,2016,"Rat","Wistar","not reported","M + F",98,"Oral","Gavage/Intubation","0, 30, 45, 67.5",30,"67.5","mg/kg bw/day","14 (GD6 to GD19)","Days","Fetus","M + F",null,"Clinical chemistry/hormones","Thyroid-stimulating hormone level (TSH)",{"$f":"IF(Z170<>0,VLOOKUP(Z170,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"No effect on TSH in fetuses at GD20 up to the highest dose of 67.5 mg/kg bw/day ",null,"No effect","67.5",null,"mg/kg bw/day",{"$f":"IF(Z170<>0,VLOOKUP(Z170,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",12,null,"Adapted from OECD 414 & 421","DAR",null,2016,"Rat","Wistar","not reported","M + F",98,"Oral","Gavage/Intubation","0, 30, 45, 67.5",30,"67.5","mg/kg bw/day","35 (GD8 to LD21)","Days","Offspring (F1)","M + F",null,"Clinical chemistry/hormones","T3 and T4 level",{"$f":"IF(Z171<>0,VLOOKUP(Z171,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"No effect on T3 and T4 in pups on PND4 and PND22 up to the highest dose of 67.5 mg/kg bw/day ",null,"No effect","67.5",null,"mg/kg bw/day",{"$f":"IF(Z171<>0,VLOOKUP(Z171,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes"]
["Mammals","Prenatal developmental toxicity study",12,null,"Adapted from OECD 414 & 421","DAR",null,2016,"Rat","Wistar","not reported","M + F",98,"Oral","Gavage/Intubation","0, 30, 45, 67.5",30,"67.5","mg/kg bw/day","35 (GD8 to LD21)","Days","Offspring (F1)","M + F",null,"Clinical chemistry/hormones","Thyroid-stimulating hormone level (TSH)",{"$f":"IF(Z172<>0,VLOOKUP(Z172,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vivo mechanistic"},"No effect on TSH in pups on PND4 and PND22 up to the highest dose of 67.5 mg/kg bw/day ",null,"No effect","67.5",null,"mg/kg bw/day",{"$f":"IF(Z172<>0,VLOOKUP(Z172,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes"]
["InVitroToxCast Estrogen","ToxCast ER prediction model",13,null,null,"US-EPA",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,0,"Receptor (trans)activation","Estrogen receptor",{"$f":"IF(Z173<>0,VLOOKUP(Z173,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Negative","No ER mediated agonistic effects","No effect",null,null,null,{"$f":"IF(Z173<>0,VLOOKUP(Z173,Interpretation!$C:$E,3,FALSE),\"\")","v":"E"},null,"Yes","Yes"]
["InVitroToxCast Estrogen","ToxCast ER prediction model",14,null,null,"US-EPA",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,0,"Receptor (trans)activation","Estrogen receptor",{"$f":"IF(Z174<>0,VLOOKUP(Z174,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Negative","No ER mediated antagonistic effects","No effect",null,null,null,{"$f":"IF(Z174<>0,VLOOKUP(Z174,Interpretation!$C:$E,3,FALSE),\"\")","v":"E"},null,"Yes","Yes"]
["InVitroToxCast Androgen","ToxCast AR prediction model",15,null,null,"US-EPA",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,0,"Receptor (trans)activation","Androgen receptor",{"$f":"IF(Z175<>0,VLOOKUP(Z175,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Negative","No AR mediated agonistic effects","No effect",null,null,null,{"$f":"IF(Z175<>0,VLOOKUP(Z175,Interpretation!$C:$E,3,FALSE),\"\")","v":"A"},null,"Yes","Yes"]
["InVitroToxCast Androgen","ToxCast AR prediction model",16,null,null,"US-EPA",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,0,"Receptor (trans)activation","Androgen receptor",{"$f":"IF(Z176<>0,VLOOKUP(Z176,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"Negative","No AR mediated antagonistic effects","No effect",null,null,null,{"$f":"IF(Z176<>0,VLOOKUP(Z176,Interpretation!$C:$E,3,FALSE),\"\")","v":"A"},null,"Yes","Yes"]
["InVitroToxCast Thyroid","ATG_THRa1_TRANS_up",17,null,null,"US-EPA",null,null,"Human ","Liver HepG2 cells",null,null,null,"Uptake from the medium (in vitro)",null,null,null,null,"µM",24,"Hours",null,null,"-","Receptor (trans)activation","Thyroid receptor",{"$f":"IF(Z177<>0,VLOOKUP(Z177,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"No TRα transactivation",null,"No effect",null,null,null,{"$f":"IF(Z177<>0,VLOOKUP(Z177,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Biological Process Target: regulation of transcription factor activity","Yes","Yes"]
["InVitroToxCast Thyroid","Tox21_TR_LUC_GH3_Agonist",18,null,null,"US-EPA",null,null,"Rat","Pituitary gland GH3 cells ",null,null,null,"Uptake from the medium (in vitro)",null,null,null,null,"µM",28,"Hours",null,null,"-","Receptor (trans)activation","Thyroid receptor",{"$f":"IF(Z178<>0,VLOOKUP(Z178,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"No TR mediated agonistic effects",null,"No effect",null,null,null,{"$f":"IF(Z178<>0,VLOOKUP(Z178,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Biological Process Target: regulation of transcription factor activity","Yes","Yes"]
["InVitroToxCast Thyroid","Tox21_TR_LUC_GH3_Antagonist",19,null,null,"US-EPA",null,null,"Rat","Pituitary gland GH3 cells ",null,null,null,"Uptake from the medium (in vitro)",null,null,null,null,"µM",28,"Hours",null,null,"-","Receptor (trans)activation","Thyroid receptor",{"$f":"IF(Z179<>0,VLOOKUP(Z179,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"No TR mediated antagonistic effects; No effect on cell viability",null,"No effect",null,null,null,{"$f":"IF(Z179<>0,VLOOKUP(Z179,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"},"Biological Process Target: regulation of transcription factor activity","Yes","Yes"]
["InVitroToxCast Steroidogenesis","TOX21_Aromatase_Inhibition",20,null,null,"US-EPA",null,null,"Human","Breast cancer MCF-7 cells ",null,null,null,"Uptake from the medium (in vitro)",null,null,null,null,"µM",24,"Hours",null,null,"-","Steroidogenesis","CYP19",{"$f":"IF(Z180<>0,VLOOKUP(Z180,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"No effect on aromatase activity (and cell viability)",null,"No effect",null,null,null,{"$f":"IF(Z180<>0,VLOOKUP(Z180,Interpretation!$C:$E,3,FALSE),\"\")","v":"S"},"Biological Process Target: regulation of transcription factor activity","Yes","Yes"]
["InVitroThyroid","Other TR in vitro assay",22,null,null,"ToxCast",null,null,"Rat (cell free)",null,null,null,null,"Uptake from the medium (in vitro)",null,null,null,null,"µM",0.5,"Hours",null,null,21.14,"Enzyme inhibition/induction","Thyroperoxidase activity (TPO) (in vitro)",{"$f":"IF(Z181<>0,VLOOKUP(Z181,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"TPO inhibition",null,"Increase",null,null,null,{"$f":"IF(Z181<>0,VLOOKUP(Z181,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"}]
["InVitroThyroid","Other TR in vitro assay",23,null,null,"ToxCast",null,null,"Porcine thyroid gland",null,null,null,null,"Uptake from the medium (in vitro)",null,null,null,null,"µM",0.5,"Hours",null,null,149.33000000000001,"Enzyme inhibition/induction","Thyroperoxidase activity (TPO) (in vitro)",{"$f":"IF(Z182<>0,VLOOKUP(Z182,Interpretation!$C:$E,2,FALSE),\"\")","v":"In vitro mechanistic"},"TPO inhibition",null,"Increase",null,null,null,{"$f":"IF(Z182<>0,VLOOKUP(Z182,Interpretation!$C:$E,3,FALSE),\"\")","v":"T"}]
["InVitroThyroid","Other TR in vitro assay",24,null,null,"ToxCast",null,null,"E. Coli (cell free)",null,null,null,null,"Uptake from the medium (in vitro)",null,null,null,null,"µM",0.5,"Hours",null,null,0.14000000000000001,"Enzyme inhibition/induction","[Not in list]",{"$f":"IF(Z183<>0,VLOOKUP(Z183,Interpretation!$C:$E,2,FALSE),\"\")","v":"[Not in list]"},"Monooxygenase activity",null,"Increase",null,null,null,{"$f":"IF(Z183<>0,VLOOKUP(Z183,Interpretation!$C:$E,3,FALSE),\"\")","v":0}]

{"sheet":"Data summary","index":10,"n_rows":50,"n_cols":53,"rows_kept":50,"cut":false,"hidden":false,"merged":[[3,15,3,52],[47,0,47,14],[48,0,48,14],[49,0,49,14]]}
[]
[]
[]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Insert a sorting number (1 .. n) on targets loading as lines of evidence"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,1]
[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 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","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","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","CYP19","Estrogen receptor","Thyroid receptor","Thyroperoxidase activity (TPO) (in vitro)","T3 and T4 level","Thyroid-stimulating hormone level (TSH)","Uterus histopathology (UT assay)","Epididymis histopathology","Ovary histopathology","Ovary weight","Prostate histopathology (with seminal vesicles and coagulating glands)","Prostate weight","Seminal vesicles histopathology","Testis histopathology","Testis weight","Thyroid histopathology","Thyroid weight","Uterus histopathology (with cervix)","Uterus weight (with cervix)","Adrenals histopathology","Adrenals weight","Litter size","Pituitary histopathology","Presence of anomalies (external, visceral, skeletal","Heart weight","Kidney histopathology","Kidney weight","Liver histopathology","Liver weight","Spleen histopathology","Spleen weight","Body weight","Clinical chemistry and haematology","Clinical signs","Food consumption","[Not in list]","No relevant effect observed"]
[3,"DAR",1980,"Mammals","Subacute oral in non-rodent ","Dog","0, 60, 300, 1500","mg/kg bw/day","Oral",26,"Weeks","Adult",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 1500 (Mean absolute testes weight was significantly lower at the top dose of 1500 mg/kg bw/day (25% decrease))",null,"Increase 300 (Absolute and relative thyroid weight was significantly increased at 300 and the top dose of 1500 mg/kg bw/day, respectively. )",null,null,null,null,null,null,null,null,null,"No effect (No effect on kidney weight up to the top dose of 1500 mg/kg bw/day)",null,null,null,null,"No effect (No effect in BW up to the top dose of 1500 mg/kg bw/day (2.8% decrease))","Change 300 (No effect in RBC parameters up to the highest dose tested. The total WBC count was significantly lower in treated groups at the majority of time points.)","Increase 300 (Vomiting immediately following dosing was observed with increased incidence from the dose of 300 mg/kg bw/day)",null,"No effect (No effect on lung weight up to the top dose of 1500 mg/kg bw/day)"]
[4,"DAR","2004a","Mammals","Subacute oral in non-rodent ","Dog","0, 100, 300, 600","mg/kg bw/day","Oral",52,"Weeks","Adult",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,"No effect (Prostate weight (abs & rel) was slightly (but not significantly) lower at the top dose of 600 mg/kg bw/day)",null,null,"Decrease 600 (Abs. testes weight were slightly (but not significantly) lower in top dose males (13.2%). )","Change 300 (Thyroid follicular cell hypertrophy was seen in both sexes from the dose of 300 mg/kg bw/d; the incidence and severity of this finding was increased at the top dose level. )","Increase 600 (Mean absolute and relative thyroid weights were higher in all treated groups in a dose-related fashion; values attained statistical significance at the dose of 600 mg/kg bw/d [71.7% (abs), 69.8% (rel)].)",null,null,null,"Increase 600 (Increased absolute adrenal weight (26.6%) at the highest dose of 600 mg/kg bw/day)",null,null,null,"No effect (Absolute and relative heart weights were slightly lower in both sexes at the top dose level, however values do not attain statistical significance)",null,null,null,null,"No effect (No effect on spleen histopathology up to the highest dose of 600 mg/kg bw/day)","No effect (No effect in spleen weight up to the highest dose of 600 mg/kg bw/day)","No effect (No effect in BW and BW gain up to the highest dose of 600 mg/kg bw/day)","No effect (No effect in haematological and clinical chemistry parameters up to the highest dose of 600 mg/kg bw/day. Slightly elevated AST, ALP and CK activities however they were sporadic with no dose-response relationship and no stat. significance was reached.)","Increase 300 (Salivation and vomiting with increasing incidence and severity from the dose of 300 mg/kg bw/day.)"]
[2,"DAR","1989a","Mammals","Subchronic oral toxicity in rodents","Mouse","512, 1673, 5103, 9022","mg/kg bw/day","Oral",8,"Weeks","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,"Decrease 5103 (Body weight was stat. significantly decreased (-8%) and -13% at the highest dose of 9022 mg/kg bw/day)","No effect (Plasma, erythrocyte and cholinesterase activities were comparable in all groups)"]
[2,"DAR","1989a","Mammals","Subchronic oral toxicity in rodents","Mouse","675, 2263, 6835, 10828","mg/kg bw/day","Oral",8,"Weeks","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,"Decrease 10828 (Transient weight loss was observed at the top dose)","No effect (Plasma, erythrocyte and cholinesterase activities were comparable in all groups)"]
[8,"DAR","1992a","Mammals","Carcinogenicity","Mouse","74, 730, 8040","mg/kg bw/day","Oral",24,"Months","Adult","Thyroid weight not measured in the study. ","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect (Incidence of testes mineralisation: 7, 7, 10, 12 males at 74, 730, 8040 mg/kg bw/day, respectively. In RAR, not considered treatment-related adverse effect., NOAEL systemic)","No effect (No effect on testes weight in males up to the highest dose of 8040 mg/kg bw/day., NOAEL systemic)","No effect (No effect on thyroid histopathology up to the highest dose of 8040 mg/kg bw/day in males)",null,null,null,null,null,null,"No effect (No increased incidence in pituitary adenomas up to the highest dose of 8040 mg/kg bw/day in males., NOAEL systemic)",null,null,null,null,"Increase 8040 (Brown granular pigment deposition (2/28 males vs 0/28 controls), NOAEL systemic)",null,null,"Increase 730 (Increase in the absolute (↑69.2%) and relative-to-body (↑ 78.2%) spleen weight in males. , NOAEL systemic)","Decrease 8040 (Bodyweights were significantly lower (↓ 5.1%)., NOAEL systemic)","Change 8040 (Effects in haematological parameters indicative of mild anaemia: RBC (↓11%), HCT (↓8.6%), MCH (↑ 19.2%), MCHC (↑16.3%)., NOAEL systemic)",null,"Change 8040 (Food consumption was consistently higher; findings likely due to the inclusion of the test material at a high level (5%) in the diet., NOAEL systemic)",null,"No effect (There were no treatment-related tumours., NOAEL carcinogenic)"]
[8,"DAR","1992a","Mammals","Carcinogenicity","Mouse","95, 938, 10353","mg/kg bw/day","Oral",24,"Months","Adult","Thyroid weight not measured in the study. ","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect (No effect on thyroid histopathology up to the highest dose of 10353 mg/kg bw/day in females)",null,"No effect (Incidence of uterine corpus cystic endometrial hyperplasia: 23, 30, 40, 36 females at 74, 730, 8040 mg/kg bw/day, respectively. In RAR, not considered treatment-related adverse effect., NOAEL systemic)",null,null,null,null,"No effect (No increased incidence in pituitary adenomas up to the highest dose of 8040 mg/kg bw/day in females., NOAEL systemic)",null,null,"Increase 10353 (Brown granular pigment deposition (6/21 females vs 5/30 controls), NOAEL systemic)",null,"Increase 10353 (Brown granular pigment deposition (3/21 females vs 0/30 controls), NOAEL systemic)",null,null,"Increase 938 (Increase in the absolute (↑42.9%) and relative-to-body (↑ 37.5%) spleen weight in females. , NOAEL systemic)","Decrease 10353 (Bodyweights were significantly lower (↓ 6.1%)., NOAEL systemic)","Change 10353 (Effects in haematological parameters indicative of mild anaemia: RBC (↓15.3%), HCT (↓7.9%), MCH (↑ 17.6%), MCHC (↑6.6%)., NOAEL systemic)",null,"Increase 10353 (Food consumption was consistently higher; findings likely due to the inclusion of the test material at a high level (5%) in the diet., NOAEL systemic)",null,"No effect (There were no treatment-related tumours., NOAEL carcinogenic)"]
[8,"DAR","1992a","Mammals","Carcinogenicity","Mouse","74, 730, 8040","mg/kg bw/day","Oral",12,"Months","Adult","Thyroid weight not measured in the 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,"Change 8040 (Brown granular pigment deposition (3/10 males vs 0/10 controls))",null,"Change 8040 (Brown granular pigment deposition (8/10 males vs 0/10 controls))",null,null,"Increase 8040 (Increase in the absolute (↑42.9%) and relative-to-body (↑ 53.7%) spleen weight in males. )","Decrease 8040 (Bodyweights were significantly lower (↓7.3%).)","Change 8040 (Effects in haematological parameters indicative of mild anaemia: RBC (↓11.4%), HCT (↓12.4%), MCH (↑ 14.7%), MCHC (↑16.3%).)"]
[8,"DAR","1992a","Mammals","Carcinogenicity","Mouse","95, 938, 10353","mg/kg bw/day","Oral",12,"Months","Adult","Thyroid weight not measured in the 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,"Change 10353 (Brown granular pigment deposition (4/10 males vs 0/10 controls))",null,"Change 10353 (Brown granular pigment deposition (2/10 males vs 0/10 controls))",null,null,"Increase 10353 (Increase in the absolute (↑114.3%) and relative-to-body (↑ 117.3%) spleen weight in females. )","No effect (Bodyweights not affected in females after 12 month treatment with the top dose of 10353 mg/kg bw/day.)","Change 10353 (Effects in haematological parameters indicative of mild anaemia: RBC (↓7.0%), HCT (↓8.8%), MCH (↑ 7.8%), MCHC (↑9.5%).)"]
[5,"DAR","1989b","Mammals","Repeated dose dermal toxicity","Rabbit","0, 1000","mg/kg bw/day","Dermal",21,"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,"No effect (No local or systemic effects in males and females)"]
[11,"DAR","1981a","Mammals","Prenatal developmental toxicity study","Rabbit","0, 150, 300, 750, 1500","mg/kg bw/day","Oral",16,"Days","Adult","High mortality, however the number of animals surviving to produce a litter exceeded the minimum specified in OECD TG 414","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,"Decrease 750 (Decreased body weight and body weight gain at the end of the study, NOAEL maternal)",null,null,"Decrease 750 (Decreased food consumption, NOAEL maternal)"]
[11,"DAR","1981a","Mammals","Prenatal developmental toxicity study","Rabbit","0, 150, 300, 750, 1500","mg/kg bw/day","Oral",16,"Days","Fetus","High mortality, however the number of animals surviving to produce a litter exceeded the minimum specified in OECD TG 414","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 (No developmental effects, NAOEL developmental)"]
[1,"DAR",2000,"Mammals","Repeated dose 90-day oral toxicity study in rodents","Rat","128.5, 387.0, 1327.3","mg/kg bw/day","Oral",90,"Days","Adult",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,"No effect (Prostate weight was slightly lower in top dose males (1327.3 mg/kg bw/day), however values did not attain statistical significance.)",null,null,"Increase 1327.3 (Mean relative testes weight was significantly higher in top dose males; this value is largely (but not entirely) attributable to one male with an unusually high absolute testes weight (5.65 g). When the outlier was excluded, the percentage fell from 9.6% to 5.5%.)","Change 1327.3 (Increase in the incidence and severity of thyroid follicular hypertrophy in high dose animals [0, 128.5, 387.0, 1327.3 mg/kg bw/day: 2/10, 1/10, 2/10, 10/10 (slight)]; affected follicles were generally smaller.)","No effect (No effect on thyroid weight in males up to the highest dose of 1327.3 mg/kg bw/day.)",null,null,null,null,null,null,null,null,"Change 1327.3 (Increase in the incidence and severity of mineral deposits located free in the renal pelvis or papilla at the top dose of 1327.3 mg/kg bw/day; a slight or minimum hyperplasia of the adjacent transitional epithelium occurred occasionally as a result of the mineral deposition causing a greater incidence of focal urothelial hyperplasia from the dose of 387.0 mg/kg bw/day in males.)",null,null,"No effect (No effect on liver weight in males up to the highest dose of 1327.3 mg/kg bw/day.)","Change 387 (Increase in the severity of splenic extramedullary haematopoiesis in males at ≥ 387 mg/kg bw/day. Increase in the severity of haemosiderin deposition in the spleen from the dose of 387 mg/kg bw/day.)","Increase 1327.3 (Significant increase in the absolute (↑14.3%) and relative-to-body (↑ 22.8%) spleen weight in males at the highest dose of 1327.3 mg/kg bw/day. Consistent with haematological findings. )","Decrease 1327.3 (Mean bodyweights and bodyweight gains of top dose males were significantly reduced (7% and 12.4% vs control, respectively).)","Change 1327.3 (Haematology: statistically significant effects on RBC parameters  consistent with mild macrocytic anaemia: RBC ( ↓ 9.1%), HGB (↓ 7.3%), HCT (↓5.6%), MCV (↑ 4.5%), MCHC (↓ 2.0%). Clinical chemistry: Statistically significant changes in: PTT (↑17%), Protein (↓ 8.7%), Globulin (↓ 17.5%), A:G ratio (↑21%), P (↓ 10.3%) in males.)"]
[1,"DAR",2000,"Mammals","Repeated dose 90-day oral toxicity study in rodents","Rat","157.9, 479.4, 1651.5","mg/kg bw/day","Oral",90,"Days","Adult",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,"No effect (No effect on ovaries weight up to the highest dose of 1651.5 mg/kg bw/day.)",null,null,null,null,null,"Change 1651.5 (Increase in the incidence and severity of thyroid follicular hypertrophy in high dose animals [0, 157.9, 479.4, 1651.5 mg/kg bw/day: 1/10, -, -, 2/10 (slight) / 6/10 (minimal)]; affected follicles were generally smaller.)","Increase 1651.5 (Significant increase in the absolute (↑17.6%) and relative-to-body (↑ 22.7%) thyroid weight in females. )",null,"No effect (No effect on uterus weight in females up to the highest dose of 479 mg/kg bw/day.)",null,null,null,null,null,null,"Change 1651.5 (Increase in the incidence and severity of mineral deposits located free in the renal pelvis or papilla from the dose of 479.4 mg/kg bw/day; a slight or minimum hyperplasia of the adjacent transitional epithelium occurred occasionally as a result of the mineral deposition causing a greater incidence of focal urothelial hyperplasia at the top dose of 1651.5 mg/kg bw/day. In addition to these changes, an increase in the severity and incidence of hydronephrosis was observed from the dose of 479.4 mg/kg bw/day in females. )",null,null,"No effect (No effect on liver weight in females up to the highest dose of 1651.5 mg/kg bw/day.)","Change 1651.5 (Increase in the severity of haemosiderin deposition at the top dose of 1651.5 mg/kg bw/day in females.)","No effect (No effect on spleen weight in females up to the highest dose of 1651.5 mg/kg bw/day.)","Decrease 1651.5 (Not stat. significant decrease on bodyweight and BW gain in females at the highest dose of 1651.5 mg/kg bw/day (4% and 11.2%, respectively).)","Change 1651.5 (Haematology: statistically significant effec ts on RBC parameters consistent with mild macrocytic anaemia: RBC ( ↓ 8.2%), HGB (↓ 7.8%), HCT (↓7.0%). Clinical chemistry:  statistically significant changes on: Globulin (↓ 17.3%), A:G ratio (↑20.2%). Not stat. sign. decrease in P (↓ 7.9%) in females.)"]
[6,"DAR",2015,"Mammals","Repeated dose dermal toxicity","Rat","0, 50, 125, 250","mg/kg bw/day","Dermal",21,"Days","Adult",null,"Yes","Yes",null,null,null,null,null,"No effect (The statistically significant decrease in T3 in males (45.7%) was considered of no toxicological significance in the RAR. T3 was also decreased in females (22%, p>0.05). T3 was decreased in males (15%) and females (22%) but did not achieve toxicological significance.)","No effect (TSH changes were inconsistent and without statistical significance (15% increase in males and 53% decrease in females).)",null,null,null,null,null,null,null,null,null,"No effect (No effect in thyroid histopathology in males and females up to the highest dose of 250 mg/kg bw/day)","No effect (No effect in thyroid weight in males and females up to the highest dose of 250 mg/kg bw/day; The decrease observed only in mid dose females (percentage not reported) not accompanied by histopathological findings was not considered of toxicological significance)",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"No effect (No local or systemic effects in males and females)"]
[7,"DAR",1980,"Mammals","Combined chronic toxicity/carcinogenicity studies","Rat","47, 243, 1280","mg/kg bw/day","Oral",108,"Weeks","Adult",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,"No effect (No effect on ovaries weight in females up to the highest dose of 1280 mg/kg bw/day., NOAEL systemic)",null,null,null,null,null,"Change 1280 (Thyroid hyperplasia (3/50 females vs 0/50 in controls) and thyroid epithelial whorls (4/50 females vs 2/50 in controls). Enlarged thyroid (11/50 females vs 4/50 in controls). According to the RMS, the thyroid effects reported were consistent, however, within the historical control range and therefore not considered teatment-related., NOAEL systemic)",null,null,"No effect (No effect on uterus weight in females up to the highest dose of 1280 mg/kg bw/day., NOAEL systemic)","No effect (No effect on adrenals histopathology at the top dose of 1280 mg/kg bw/day in females., NOAEL systemic)",null,null,"No effect (No effect on pituitary histopathology at the top dose of 1280 mg/kg bw/day in females., NOAEL systemic)",null,null,null,null,"Change 1280 (Bile duct hyperplasia (13/50 females vs 6/50 in controls). , NOAEL systemic)","Increase 1280 (Increase in the absolute (↑10.3%) and relative-to-body (↑ 6.6%) liver weight in females. , NOAEL systemic)","Change 1280 (Prominent siderocytes (6/50 females vs 2/50 in controls) at top dose of 1280 mg/kg bw/day., NOAEL systemic)",null,"Decrease 243 (Decreased bodyweight gain (↓ 10.4% for 0-52 weeks. Data not given for 0-108 weeks). At the top dose of 1280 mg/kg bw/day: Decreased bodyweight (↓ 5.0%) and bodyweight gain (↓ 15.1% for 0-52 weeks. Data not given for 0-108 weeks)., NOAEL systemic)","No effect (Not consistent haematology changes in males up to the highest dose of 1280 mg/kg bw/day., NOAEL systemic)",null,null,null,"No effect (No evidence of treatment-related tumours in females up to the highest dose of 1280 mg/kg bw/day., NOAEL carcinogenic)"]
[7,"DAR",1980,"Mammals","Combined chronic toxicity/carcinogenicity studies","Rat","36, 180, 953","mg/kg bw/day","Oral",108,"Weeks","Adult",null,"Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,"No effect (No effect on prostate weight in males up to the highest dose of 953 mg/kg bw/day., NOAEL systemic)",null,null,"No effect (No effect on testes weight in males up to the highest dose of 953 mg/kg bw/day., NOAEL systemic)","Change 953 (Thyroid hyperplasia (11/50 males vs 0/50 in controls) and thyroid epithelial whorls (5/50 males vs 1/50 in controls). Enlarged thyroid (11/50 males vs 1/50 in controls). According to the RMS, the thyroid effects reported were consistent, however, within the historical control range and therefore not considered teatment-related., NOAEL systemic)",null,null,null,"Change 953 (Adrenals medullary hyperplasia (17/50 males vs 8/50 in controls). , NOAEL systemic)",null,null,"Change 953 (Pituitary hyperplasia (13/50 males vs 6/50 in controls). , NOAEL systemic)",null,null,null,null,"Change 953 (Bile duct hyperplasia (17/50 males vs 10/50 in controls). , NOAEL systemic)","No effect (No effect on liver weight in males up to the highest dose of 953 mg/kg bw/day., NOAEL systemic)","Change 953 (Prominent siderocytes (7/50 males vs 1/50 in controls). , NOAEL systemic)",null,"Decrease 953 (Decreased bodyweight (↓ 4.2%) and bodyweight gain (↓ 10.4% for 0-52 weeks. Data not given for 0-108 weeks)., NOAEL systemic)","No effect (Not consistent haematology changes in males up to the highest dose of 953 mg/kg bw/day. Significantly increased clotting times were noted in top dose males at Weeks 12, 14 and 24; as a result the diet was supplemented with Vit. K and similar effects were not apparent., NOAEL systemic)",null,null,null,"No effect (No evidence of treatment-related tumours in males up to the highest dose of 953 mg/kg bw/day. There is insufficient evidence that substance causes phaechromocytomas in male rats; data in the context of historical control range., NOAEL carcinogenic)"]
[9,"DAR","1981a","Mammals","Two-generation reproduction toxicity test","Rat","0, 46, 224, 1136","mg/kg bw/day","Oral",29,"Weeks","Adult (F0)","Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","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,"Decrease 1136 (Decreased body weight (8%) and body weight gain (10%) in F0 males at the end of the study, p>0.05, NOAEL parental)"]
[9,"DAR","1981a","Mammals","Two-generation reproduction toxicity test","Rat","0, 58, 278, 1456","mg/kg bw/day","Oral",29,"Weeks","Adult (F1)","Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Decrease 278 (Decreased litter size (9.1 vs 11.2 in control) in F1. Also in F2 (7.2 vs 9.3 in control, however p>0.05 and no dose response, not considered in the basis for LOAEL setting), NOAEL reproductive)",null,null,null,null,null,null,"Decrease 1456 (Decreased absolute (15.6%) and relative (8.5%) liver weight in F1 females, NOAEL parental)",null,null,"Decrease 1456 (Decreased body weight (9.4%) and body weight gain (14.5%, p>0.05) in F1 females during pre-mating period , NOAEL parental)"]
[9,"DAR","1981a","Mammals","Two-generation reproduction toxicity test","Rat","0, 46, 224, 1136","mg/kg bw/day","Oral",29,"Weeks","Adult (F1)","Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Increase 1136 (Increased absolute (25%) and relative (19.6%)thyroid weight in F1 males, NOAEL parental)",null,null,null,null,"Decrease 224 (Decreased litter size (9.1 vs 11.2 in control) in F1. Also in F2 (7.2 vs 9.3 in control, however p>0.05 and no dose response, not considered in the basis for LOAEL setting), NOAEL reproductive)"]
[9,"DAR","1981a","Mammals","Two-generation reproduction toxicity test","Rat","0, 46, 224, 1136","mg/kg bw/day","Oral",29,"Weeks","Adult (F0+F1)","Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","Yes","Yes",null,null,null,null,null,null,null,"No effect (No effect on uterus histopathology up to the highest dose of 1456 mg/kg bw/day, NOAEL parental)","No effect (No effect on epididymides histopathology up to the highest dose of 1136 mg/kg bw/day. , NOAEL parental)","No effect (No effect on ovary histopathology up to the highest dose of 1456 mg/kg bw/day, NOAEL parental)","No effect (No effect on ovarian weight up to the highest dose of 1456 mg/kg bw/day, NOAEL parental)","No effect (No effect on prostate and seminal vesicles histopathology up to the highest dose of 1136 mg/kg bw/day. No information on coagulating gland histology., NOAEL parental)","No effect (No effect on prostate weight up to the highest dose of 1136 mg/kg bw/day, NOAEL parental)","No effect (No effect on seminal vesicles histopathology up to the highest dose of 1136 mg/kg bw/day. , NOAEL parental)","No effect (No effect on testes histopathology up to the highest dose of 1136 mg/kg bw/day. , NOAEL parental)","No effect (No effect on testicular weight up to the highest dose of 1136 mg/kg bw/day, NOAEL parental)","No effect (No effect on thyroid histopathology up to the highest dose of 1456 mg/kg bw/day, NOAEL parental)",null,null,null,null,"No effect (No effect on adrenals weight up to the highest dose of 1136 (males) and 1456 (females) mg/kg bw/day., NOAEL parental)",null,"No effect (No effect on pituitary histopathology up to the highest dose of 1456 mg/kg bw/day, NOAEL parental)"]
[9,"DAR","1981a","Mammals","Two-generation reproduction toxicity test","Rat","0, 46, 224, 1136","mg/kg bw/day","Oral",29,"Weeks","Offspring (F1+F2)","Study with important deviations, however study considered sufficient to identify critical effects on reproduction. The following EATS-mediated parameters were not measured in the study: coagulating gland weight, seminal vesicles weight, oestrus cycle length, vaginal opening, preputial separation, anogenital distance, uterus weight, epididymis weight, sperm parameters.","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 (No effects in the offspring up to the highest dose of 1136 mg/kg bw/day; however animals not exposed to test material for 30 days prior to necropsy, NOAEL offpring)"]
[10,"DAR",1982,"Mammals","Prenatal developmental toxicity study","Rat","0, 500, 1000, 2000","mg/kg bw/day","Oral","Not specified",null,"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,"No effect (No maternal effects, NOAEL maternal)"]
[10,"DAR",1982,"Mammals","Prenatal developmental toxicity study","Rat","0, 500, 1000, 2000","mg/kg bw/day","Oral","Not specified",null,"Fetus",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,"Increase 2000 (Decreased ossification of the cranium (0.5% foetal incidence, 5% litter incidence vs 0 in control), short/absent 13th rib (4.1% foetal incidence, 15% litter incidence vs 1.1% and 10% in control), fused cervical arches (0.5% foetal incidence, 5% litter incidence vs 0 in control) and decreased ossification of the caudal vertebrae (2.5% foetal incidence, 5% litter incidence vs 1.1% and 5% in control), NAOEL developmental)"]
[12,"DAR",2016,"Mammals","Prenatal developmental toxicity study","Rat","0, 30, 45, 67.5","mg/kg bw/day","Oral","14 (GD6 to GD19)","Days","Adult","Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes",null,null,null,null,null,"No effect (No effect on T3 and T4 up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation)","No effect (No effect on TSH up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation)",null,null,null,null,null,null,null,null,null,"No effect (No effect on thyroid histopathology up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation)","No effect (No effect on thyroid weight up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation)"]
[12,"DAR",2016,"Mammals","Prenatal developmental toxicity study","Rat","0, 30, 45, 67.5","mg/kg bw/day","Oral","37 (GD6 to LD21)","Days","Adult","Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes",null,null,null,null,null,"No effect (No effect on T3 and T4 up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation and lactation)","No effect (No effect on TSH up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation and lactation)",null,null,null,null,null,null,null,null,null,"No effect (No effect on thyroid histopathology up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation and lactation)","No effect (No effect on thyroid weight up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation and lactation)"]
[12,"DAR",2016,"Mammals","Prenatal developmental toxicity study","Rat","0, 30, 45, 67.5","mg/kg bw/day","Oral","14 (GD6 to GD19)","Days","Fetus","Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes",null,null,null,null,null,"No effect (No effect on T3 and T4 in fetuses at GD20 up to the highest dose of 67.5 mg/kg bw/day )","No effect (No effect on TSH in fetuses at GD20 up to the highest dose of 67.5 mg/kg bw/day )",null,null,null,null,null,null,null,null,null,"No effect (No effect on thyroid histopathology in fetuses at GD20 up to the highest dose of 67.5 mg/kg bw/day )"]
[12,"DAR",2016,"Mammals","Prenatal developmental toxicity study","Rat","0, 30, 45, 67.5","mg/kg bw/day","Oral","35 (GD8 to LD21)","Days","Offspring (F1)","Developmental thyroid study conducted to assess thyroid development and serum thyroid hormones in young animals","Yes","Yes",null,null,null,null,null,"No effect (No effect on T3 and T4 in pups on PND4 and PND22 up to the highest dose of 67.5 mg/kg bw/day )","No effect (No effect on TSH in pups on PND4 and PND22 up to the highest dose of 67.5 mg/kg bw/day )",null,null,null,null,null,null,null,null,null,"No effect (No effect on thyroid histopathology in pups on PND4 and PND22 up to the highest dose of 67.5 mg/kg bw/day )","No effect (No effect on thyroid weight in pups on PND4 and PND22 up to the highest dose of 67.5 mg/kg bw/day )"]
[15,"US-EPA",null,"InVitroToxCast Androgen","ToxCast AR prediction model",null,null,null,null,null,null,null,null,"Yes","Yes","No effect 0 (Negative, No AR mediated agonistic effects)"]
[16,"US-EPA",null,"InVitroToxCast Androgen","ToxCast AR prediction model",null,null,null,null,null,null,null,null,"Yes","Yes","No effect 0 (Negative, No AR mediated antagonistic effects)"]
[13,"US-EPA",null,"InVitroToxCast Estrogen","ToxCast ER prediction model",null,null,null,null,null,null,null,null,"Yes","Yes",null,null,"No effect 0 (Negative, No ER mediated agonistic effects)"]
[14,"US-EPA",null,"InVitroToxCast Estrogen","ToxCast ER prediction model",null,null,null,null,null,null,null,null,"Yes","Yes",null,null,"No effect 0 (Negative, No ER mediated antagonistic effects)"]
[20,"US-EPA",null,"InVitroToxCast Steroidogenesis","TOX21_Aromatase_Inhibition","Human",null,"µM","Uptake from the medium (in vitro)",24,"Hours",null,"Biological Process Target: regulation of transcription factor activity","Yes","Yes",null,"No effect - (No effect on aromatase activity (and cell viability))"]
[17,"US-EPA",null,"InVitroToxCast Thyroid","ATG_THRa1_TRANS_up","Human ",null,"µM","Uptake from the medium (in vitro)",24,"Hours",null,"Biological Process Target: regulation of transcription factor activity","Yes","Yes",null,null,null,"No effect - (No TRα transactivation)"]
[18,"US-EPA",null,"InVitroToxCast Thyroid","Tox21_TR_LUC_GH3_Agonist","Rat",null,"µM","Uptake from the medium (in vitro)",28,"Hours",null,"Biological Process Target: regulation of transcription factor activity","Yes","Yes",null,null,null,"No effect - (No TR mediated agonistic effects)"]
[19,"US-EPA",null,"InVitroToxCast Thyroid","Tox21_TR_LUC_GH3_Antagonist","Rat",null,"µM","Uptake from the medium (in vitro)",28,"Hours",null,"Biological Process Target: regulation of transcription factor activity","Yes","Yes",null,null,null,"No effect - (No TR mediated antagonistic effects; No effect on cell viability)"]
[24,"ToxCast",null,"InVitroThyroid","Other TR in vitro assay","E. Coli (cell free)",null,"µM","Uptake from the medium (in vitro)",0.5,"Hours",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,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 0.14 (Monooxygenase activity)"]
[23,"ToxCast",null,"InVitroThyroid","Other TR in vitro assay","Porcine thyroid gland",null,"µM","Uptake from the medium (in vitro)",0.5,"Hours",null,null,null,null,null,null,null,null,"Increase 149.33 (TPO binding)"]
[22,"ToxCast",null,"InVitroThyroid","Other TR in vitro assay","Rat (cell free)",null,"µM","Uptake from the medium (in vitro)",0.5,"Hours",null,null,null,null,null,null,null,null,"Increase 21.14 (TPO binding)"]
[]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Androgen receptor","CYP19","Estrogen receptor","Thyroid receptor","Thyroperoxidase activity (TPO) (in vitro)","T3 and T4 level","Thyroid-stimulating hormone level (TSH)","Uterus histopathology (UT assay)","Epididymis histopathology","Ovary histopathology","Ovary weight","Prostate histopathology (with seminal vesicles and coagulating glands)","Prostate weight","Seminal vesicles histopathology","Testis histopathology","Testis weight","Thyroid histopathology","Thyroid weight","Uterus histopathology (with cervix)","Uterus weight (with cervix)","Adrenals histopathology","Adrenals weight","Litter size","Pituitary histopathology","Presence of anomalies (external, visceral, skeletal","Heart weight","Kidney histopathology","Kidney weight","Liver histopathology","Liver weight","Spleen histopathology","Spleen weight","Body weight","Clinical chemistry and haematology","Clinical signs","Food consumption","[Not in list]","No relevant effect observed"]
["Effect",null,null,null,null,null,null,null,null,null,null,null,null,null,null,0,0,0,0,2,0,0,0,0,0,0,0,0,0,0,3,6,6,0,0,1,1,2,1,1,0,7,1,6,2,6,5,13,10,4,3,2,0]
["No effect",null,null,null,null,null,null,null,null,null,null,null,null,null,null,2,1,2,3,0,5,5,1,1,1,3,1,4,1,2,3,9,5,1,2,1,2,0,5,0,2,0,1,0,3,1,3,4,6,0,0,1,9]
["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]

{"sheet":"Lines of evidence - T","index":11,"n_rows":146,"n_cols":15,"rows_kept":146,"cut":false,"hidden":false,"merged":[[135,3,136,3],[137,3,145,3],[87,3,94,3],[95,3,111,3],[112,3,127,3],[128,3,131,3],[132,3,134,3],[2,2,7,2],[1,12,7,12],[8,3,12,3],[8,12,17,12],[13,3,17,3],[8,2,17,2],[2,3,4,3],[5,3,6,3],[18,2,43,2],[44,2,57,2],[51,12,56,12],[18,3,32,3],[18,12,32,12],[44,3,45,3],[46,3,48,3],[49,3,50,3],[51,3,56,3],[58,14,145,14],[60,12,68,12],[33,3,43,3],[1,14,57,14],[18,13,57,13],[33,12,43,12],[44,12,48,12],[49,12,50,12],[58,12,59,12],[8,13,17,13],[1,13,7,13],[69,12,79,12],[80,12,94,12],[137,13,145,13],[58,13,136,13],[58,3,59,3],[58,2,94,2],[135,2,136,2],[135,12,136,12],[137,2,145,2],[137,12,138,12],[139,12,142,12],[95,2,134,2],[95,12,111,12],[112,12,127,12],[128,12,131,12],[132,12,134,12],[60,3,66,3],[67,3,68,3],[69,3,74,3],[75,3,79,3],[80,3,86,3]]}
["Study ID Matrix","Study principle","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"]
[21,"in silico","In silico prediction ","QSAR prediction",null,null,null,null,null,null,null,"Derek Nexus prediction: Plausible thyroid toxicity for substance (Alert 247)."]
[17,"ATG_THRa1_TRANS_up","In vitro mechanistic","Thyroid receptor","Human",1,"Hour","Uptake from the medium (in vitro)","-","µM","No effect","No TRα transactivation"]
[18,"Tox21_TR_LUC_GH3_Agonist",null,null,"Rat",28,"Hours","Uptake from the medium (in vitro)","-","µM","No effect","No TR mediated agonistic effects"]
[19,"Tox21_TR_LUC_GH3_Antagonist",null,null,"Rat",28,"Hours","Uptake from the medium (in vitro)","-","µM","No effect","No TR mediated antagonistic effects"]
[22,"ToxCast",null,"Thyroperoxidase activity (TPO) (in vitro)","Rat (cell free)","0.5","Hours","Uptake from the medium (in vitro)","21.14","µM","Increase","TPO inhibition"]
[23,"ToxCast",null,null,"Porcine thyroid gland","0.5","Hours","Uptake from the medium (in vitro)","149.33","µM","Increase","TPO inhibition"]
[24,"ToxCast",null,"[Not in list]","E. Coli (cell free)","0.5","Hours","Uptake from the medium (in vitro)","0.14","µM","Increase","Monooxygenase activity"]
[6,"Repeated dose dermal toxicity","In vivo mechanistic","T3 and T4 level","Rat",21,"Days","Dermal",null,"mg/kg bw/day","No effect","The statistically significant decrease in T3 in males (45.7%) was considered of no toxicological significance in the RAR. T3 was also decreased in females (22%, p>0.05). T3 was decreased in males (15%) and females (22%) but did not achieve toxicological significance."]
[12,"Prenatal developmental toxicity study",null,null,"Rat","14 (GD6 to GD19)","Days","Oral",null,"mg/kg bw/day","No effect","No effect on T3 and T4 up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation"]
[12,"Prenatal developmental toxicity study",null,null,"Rat","37 (GD6 to LD21)","Days","Oral",null,"mg/kg bw/day","No effect","No effect on T3 and T4 up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation and lactation"]
[12,"Prenatal developmental toxicity study",null,null,"Rat","14 (GD6 to GD19)","Days","Oral",null,"mg/kg bw/day","No effect","No effect on T3 and T4 in fetuses at GD20 up to the highest dose of 67.5 mg/kg bw/day "]
[12,"Prenatal developmental toxicity study",null,null,"Rat","35 (GD8 to LD21)","Days","Oral",null,"mg/kg bw/day","No effect","No effect on T3 and T4 in pups on PND4 and PND22 up to the highest dose of 67.5 mg/kg bw/day "]
[6,"Repeated dose dermal toxicity",null,"Thyroid-stimulating hormone level (TSH)","Rat",21,"Days","Dermal",null,"mg/kg bw/day","No effect","TSH changes were inconsistent and without statistical significance (15% increase in males and 53% decrease in females)."]
[12,"Prenatal developmental toxicity study",null,null,"Rat","14 (GD6 to GD19)","Days","Oral",null,"mg/kg bw/day","No effect","No effect on TSH up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation"]
[12,"Prenatal developmental toxicity study",null,null,"Rat","37 (GD6 to LD21)","Days","Oral",null,"mg/kg bw/day","No effect","No effect on TSH up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation and lactation"]
[12,"Prenatal developmental toxicity study",null,null,"Rat","14 (GD6 to GD19)","Days","Oral",null,"mg/kg bw/day","No effect","No effect on TSH in fetuses at GD20 up to the highest dose of 67.5 mg/kg bw/day "]
[12,"Prenatal developmental toxicity study",null,null,"Rat","35 (GD8 to LD21)","Days","Oral",null,"mg/kg bw/day","No effect","No effect on TSH in pups on PND4 and PND22 up to the highest dose of 67.5 mg/kg bw/day "]
[1,"Repeated dose 90-day oral toxicity study in rodents","EATS-mediated","Thyroid histopathology","Rat",90,"Days","Oral",1327.3,"mg/kg bw/day","Change","Increase in the incidence and severity of thyroid follicular hypertrophy in high dose animals [0, 128.5, 387.0, 1327.3 mg/kg bw/day: 2/10, 1/10, 2/10, 10/10 (slight)]; affected follicles were generally smaller."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",1651.5,"mg/kg bw/day","Change","Increase in the incidence and severity of thyroid follicular hypertrophy in high dose animals [0, 157.9, 479.4, 1651.5 mg/kg bw/day: 1/10, -, -, 2/10 (slight) / 6/10 (minimal)]; affected follicles were generally smaller."]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",300,"mg/kg bw/day","Change","Thyroid follicular cell hypertrophy was seen in both sexes from the dose of 300 mg/kg bw/d; the incidence and severity of this finding was increased at the top dose level. "]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",300,"mg/kg bw/day","Change","Thyroid follicular cell hypertrophy was seen in both sexes from the dose of 300 mg/kg bw/d; the incidence and severity of this finding was increased at the top dose level. "]
[6,"Repeated dose dermal toxicity",null,null,"Rat",21,"Days","Dermal",null,"mg/kg bw/day","No effect","No effect in thyroid histopathology in males and females up to the highest dose of 250 mg/kg bw/day"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",953,"mg/kg bw/day","Change","Thyroid hyperplasia (11/50 males vs 0/50 in controls) and thyroid epithelial whorls (5/50 males vs 1/50 in controls). Enlarged thyroid (11/50 males vs 1/50 in controls). According to the RMS, the thyroid effects reported were consistent, however, within the historical control range and therefore not considered teatment-related.NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",1280,"mg/kg bw/day","Change","Thyroid hyperplasia (3/50 females vs 0/50 in controls) and thyroid epithelial whorls (4/50 females vs 2/50 in controls). Enlarged thyroid (11/50 females vs 4/50 in controls). According to the RMS, the thyroid effects reported were consistent, however, within the historical control range and therefore not considered teatment-related."]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on thyroid histopathology up to the highest dose of 1136 mg/kg bw/day"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on thyroid histopathology up to the highest dose of 1456 mg/kg bw/day"]
[12,"Prenatal developmental toxicity study",null,null,"Rat","14 (GD6 to GD19)","Days","Oral",null,"mg/kg bw/day","No effect","No effect on thyroid histopathology up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation"]
[12,"Prenatal developmental toxicity study",null,null,"Rat","37 (GD6 to LD21)","Days","Oral",null,"mg/kg bw/day","No effect","No effect on thyroid histopathology up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation and lactation"]
[12,"Prenatal developmental toxicity study",null,null,"Rat","14 (GD6 to GD19)","Days","Oral",null,"mg/kg bw/day","No effect","No effect on thyroid histopathology in fetuses at GD20 up to the highest dose of 67.5 mg/kg bw/day "]
[12,"Prenatal developmental toxicity study",null,null,"Rat","35 (GD8 to LD21)","Days","Oral",null,"mg/kg bw/day","No effect","No effect on thyroid histopathology in pups on PND4 and PND22 up to the highest dose of 67.5 mg/kg bw/day "]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",null,"mg/kg bw/day","No effect","No effect on thyroid histopathology up to the highest dose of 8040 mg/kg bw/day in males"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",null,"mg/kg bw/day","No effect","No effect on thyroid histopathology up to the highest dose of 10353 mg/kg bw/day in females"]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,"Thyroid weight","Rat",90,"Days","Oral",null,"mg/kg bw/day","No effect","No effect on thyroid weight in males up to the highest dose of 1327.3 mg/kg bw/day."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",1651.5,"mg/kg bw/day","Increase","Significant increase in the absolute (↑17.6%) and relative-to-body (↑ 22.7%) thyroid weight in females. "]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",1500,"mg/kg bw/day","Increase","Absolute and relative thyroid weight was significantly increased at the top dose of 1500 mg/kg bw/day"]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",300,"mg/kg bw/day","Increase","Absolute and relative thyroid weight was significantly increased at 300 and the top dose of 1500 mg/kg bw/day, respectively. "]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",300,"mg/kg bw/day","Increase","Mean absolute and relative thyroid weights were higher in all treated groups in a dose-related fashion; values attained statistical significance from the dose of 300 mg/kg bw/d. [300 mg/kg bw/day: 47.9% (abs) 49.8% (rel); 600 mg/kg bw/day: 67.1% (abs) 64.3% (rel)]"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",600,"mg/kg bw/day","Increase","Mean absolute and relative thyroid weights were higher in all treated groups in a dose-related fashion; values attained statistical significance at the dose of 600 mg/kg bw/d [71.7% (abs), 69.8% (rel)]."]
[6,"Repeated dose dermal toxicity",null,null,"Rat",21,"Days","Dermal",null,"mg/kg bw/day","No effect","No effect in thyroid weight in males and females up to the highest dose of 250 mg/kg bw/day; The decrease observed only in mid dose females (percentage not reported) not accompanied by histopathological findings was not considered of toxicological significance"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",1136,"mg/kg bw/day","Increase","Increased absolute (25%) and relative (19.6%)thyroid weight in F1 malesNOAEL parental"]
[12,"Prenatal developmental toxicity study",null,null,"Rat","14 (GD6 to GD19)","Days","Oral",null,"mg/kg bw/day","No effect","No effect on thyroid weight up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation"]
[12,"Prenatal developmental toxicity study",null,null,"Rat","37 (GD6 to LD21)","Days","Oral",null,"mg/kg bw/day","No effect","No effect on thyroid weight up to the highest dose of 67.5 mg/kg bw/day in dams dosed during gestation and lactation"]
[12,"Prenatal developmental toxicity study",null,null,"Rat","35 (GD8 to LD21)","Days","Oral",null,"mg/kg bw/day","No effect","No effect on thyroid weight in pups on PND4 and PND22 up to the highest dose of 67.5 mg/kg bw/day "]
[7,"Combined chronic toxicity/carcinogenicity studies","Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",108,"Weeks","Oral",953,"mg/kg bw/day","Change","Adrenals medullary hyperplasia (17/50 males vs 8/50 in controls). NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on adrenals histopathology at the top dose of 1280 mg/kg bw/day in females.NOAEL systemic"]
[4,"Subacute oral in non-rodent ",null,"Adrenals weight","Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect in adrenal weight up to the highest dose of 600 mg/kg bw/day in males"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",600,"mg/kg bw/day","Increase","Increased absolute adrenal weight (26.6%) at the highest dose of 600 mg/kg bw/day in females"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on adrenals weight up to the highest dose of 1136 (males) and 1456 (females) mg/kg bw/day."]
[9,"Two-generation reproduction toxicity test",null,"Litter size","Rat",29,"Weeks","Oral",224,"mg/kg bw/day","Decrease","Decreased litter size (9.1 vs 11.2 in control) in F1. Also in F2 (7.2 vs 9.3 in control, however p>0.05 and no dose response, not considered in the basis for LOAEL setting)NOAEL reproductive"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",278,"mg/kg bw/day","Decrease","Decreased litter size (9.1 vs 11.2 in control) in F1. Also in F2 (7.2 vs 9.3 in control, however p>0.05 and no dose response, not considered in the basis for LOAEL setting)NOAEL reproductive"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,"Pituitary histopathology","Rat",108,"Weeks","Oral",953,"mg/kg bw/day","Change","Pituitary hyperplasia (13/50 males vs 6/50 in controls). NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on pituitary histopathology at the top dose of 1280 mg/kg bw/day in females.NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",null,"mg/kg bw/day","No effect","No increased incidence in pituitary adenomas up to the highest dose of 8040 mg/kg bw/day in males.NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",null,"mg/kg bw/day","No effect","No increased incidence in pituitary adenomas up to the highest dose of 8040 mg/kg bw/day in females.NOAEL systemic"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on pituitary histopathology up to the highest dose of 1136 mg/kg bw/day"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on pituitary histopathology up to the highest dose of 1456 mg/kg bw/day"]
[10,"Prenatal developmental toxicity study",null,"Presence of anomalies (external, visceral, skeletal","Rat","Not specified",null,"Oral",2000,"mg/kg bw/day","Increase","Decreased ossification of the cranium (0.5% foetal incidence, 5% litter incidence vs 0 in control), short/absent 13th rib (4.1% foetal incidence, 15% litter incidence vs 1.1% and 10% in control), fused cervical arches (0.5% foetal incidence, 5% litter incidence vs 0 in control) and decreased ossification of the caudal vertebrae (2.5% foetal incidence, 5% litter incidence vs 1.1% and 5% in control)NAOEL developmental"]
[4,"Subacute oral in non-rodent ","Target organ toxicity","Heart weight","Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","Absolute and relative heart weights were slightly lower in both sexes at the top dose level, however values do not attain statistical significance"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","Absolute and relative heart weights were slightly lower in both sexes at the top dose level, however values do not attain statistical significance"]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,"Kidney histopathology","Rat",90,"Days","Oral",387,"mg/kg bw/day","Change","Increase in the incidence and severity of mineral deposits located free in the renal pelvis or papilla at the top dose of 1327.3 mg/kg bw/day; a slight or minimum hyperplasia of the adjacent transitional epithelium occurred occasionally as a result of the mineral deposition causing a greater incidence of focal urothelial hyperplasia from the dose of 387.0 mg/kg bw/day in males."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",1327.3,"mg/kg bw/day","Change","Increase in the incidence and severity of mineral deposits located free in the renal pelvis or papilla at the top dose of 1327.3 mg/kg bw/day; a slight or minimum hyperplasia of the adjacent transitional epithelium occurred occasionally as a result of the mineral deposition causing a greater incidence of focal urothelial hyperplasia from the dose of 387.0 mg/kg bw/day in males."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",479,"mg/kg bw/day","Change","Increase in the incidence and severity of mineral deposits located free in the renal pelvis or papilla from the dose of 479.4 mg/kg bw/day; a slight or minimum hyperplasia of the adjacent transitional epithelium occurred occasionally as a result of the mineral deposition causing a greater incidence of focal urothelial hyperplasia at the top dose of 1651.5 mg/kg bw/day. In addition to these changes, an increase in the severity and incidence of hydronephrosis was observed from the dose of 479.4 mg/kg bw/day in females. "]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",1651.5,"mg/kg bw/day","Change","Increase in the incidence and severity of mineral deposits located free in the renal pelvis or papilla from the dose of 479.4 mg/kg bw/day; a slight or minimum hyperplasia of the adjacent transitional epithelium occurred occasionally as a result of the mineral deposition causing a greater incidence of focal urothelial hyperplasia at the top dose of 1651.5 mg/kg bw/day. In addition to these changes, an increase in the severity and incidence of hydronephrosis was observed from the dose of 479.4 mg/kg bw/day in females. "]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",10353,"mg/kg bw/day","Increase","Brown granular pigment deposition (6/21 females vs 5/30 controls)NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",8040,"mg/kg bw/day","Change","Brown granular pigment deposition (3/10 males vs 0/10 controls)"]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",10353,"mg/kg bw/day","Change","Brown granular pigment deposition (4/10 males vs 0/10 controls)"]
[3,"Subacute oral in non-rodent ",null,"Kidney weight","Dog",26,"Weeks","Oral",1500,"mg/kg bw/day","Increase","Relative kidney weight was significantly higher in top dose"]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",1500,"mg/kg bw/day","No effect","No effect on kidney weight up to the top dose of 1500 mg/kg bw/day"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,"Liver histopathology","Rat",108,"Weeks","Oral",953,"mg/kg bw/day","Change","Bile duct hyperplasia (17/50 males vs 10/50 in controls). NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",1280,"mg/kg bw/day","Change","Bile duct hyperplasia (13/50 females vs 6/50 in controls). NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",8040,"mg/kg bw/day","Increase","Brown granular pigment deposition (2/28 males vs 0/28 controls)NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",10353,"mg/kg bw/day","Increase","Brown granular pigment deposition (3/21 females vs 0/30 controls)NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",8040,"mg/kg bw/day","Change","Brown granular pigment deposition (8/10 males vs 0/10 controls)"]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",10353,"mg/kg bw/day","Change","Brown granular pigment deposition (2/10 males vs 0/10 controls)"]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,"Liver weight","Rat",90,"Days","Oral",null,"mg/kg bw/day","No effect","No effect on liver weight in males up to the highest dose of 1327.3 mg/kg bw/day."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",null,"mg/kg bw/day","No effect","No effect on liver weight in females up to the highest dose of 1651.5 mg/kg bw/day."]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on liver weight in males up to the highest dose of 953 mg/kg bw/day.NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",1280,"mg/kg bw/day","Increase","Increase in the absolute (↑10.3%) and relative-to-body (↑ 6.6%) liver weight in females. NOAEL systemic"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",1456,"mg/kg bw/day","Decrease","Decreased absolute (15.6%) and relative (8.5%) liver weight in F1 femalesNOAEL parental"]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,"Spleen histopathology","Rat",90,"Days","Oral",387,"mg/kg bw/day","Change","Increase in the severity of splenic extramedullary haematopoiesis in males at ≥ 387 mg/kg bw/day. Increase in the severity of haemosiderin deposition in the spleen from the dose of 387 mg/kg bw/day."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",1651.5,"mg/kg bw/day","Change","Increase in the severity of haemosiderin deposition at the top dose of 1651.5 mg/kg bw/day in females."]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",300,"mg/kg bw/day","Change","Gross necropsy revealed increased incidences of ‘small’ spleen at the top dose, corresponding to the organ weight findings. Microscopically, a marginally increased incidence and/or severity of splenic haemosiderosis/sclerosiderosis was seen from the dose of 300 mg/kg bw/d. Findings are not considered to be of clear toxicological significance in the absence of any treatment-related effects on red blood cell parameters."]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on spleen histopathology up to the highest dose of 600 mg/kg bw/day"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",953,"mg/kg bw/day","Change","Prominent siderocytes (7/50 males vs 1/50 in controls). NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",243,"mg/kg bw/day","Change","Prominent siderocytes (6/50 females vs 2/50 in controls). Same incidence at top dose of 1280 mg/kg bw/day.NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",1280,"mg/kg bw/day","Change","Prominent siderocytes (6/50 females vs 2/50 in controls) at top dose of 1280 mg/kg bw/day."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,"Spleen weight","Rat",90,"Days","Oral",1327.3,"mg/kg bw/day","Increase","Significant increase in the absolute (↑14.3%) and relative-to-body (↑ 22.8%) spleen weight in males at the highest dose of 1327.3 mg/kg bw/day. Consistent with haematological findings. "]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",null,"mg/kg bw/day","No effect","No effect on spleen weight in females up to the highest dose of 479 mg/kg bw/day."]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","Spleen weight (abs & rel) was slightly (but not significantly) lower (7%) at the top dose of 600 mg/kg bw/day"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect in spleen weight up to the highest dose of 600 mg/kg bw/day"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",730,"mg/kg bw/day","Increase","Increase in the absolute (↑69.2%) and relative-to-body (↑ 78.2%) spleen weight in males. NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",938,"mg/kg bw/day","Increase","Increase in the absolute (↑42.9%) and relative-to-body (↑ 37.5%) spleen weight in females. NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",8040,"mg/kg bw/day","Increase","Increase in the absolute (↑42.9%) and relative-to-body (↑ 53.7%) spleen weight in males. "]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",10353,"mg/kg bw/day","Increase","Increase in the absolute (↑114.3%) and relative-to-body (↑ 117.3%) spleen weight in females. "]
[1,"Repeated dose 90-day oral toxicity study in rodents","Systemic toxicity","Body weight","Rat",90,"Days","Oral",1327.3,"mg/kg bw/day","Decrease","Mean bodyweights and bodyweight gains of top dose males were significantly reduced (7% and 12.4% vs control, respectively)."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",1651.5,"mg/kg bw/day","Decrease","Not stat. significant decrease on bodyweight and BW gain in females at the highest dose of 1651.5 mg/kg bw/day (4% and 11.2%, respectively)."]
[2,"Subchronic oral toxicity in rodents",null,null,"Mouse",8,"Weeks","Oral",5103,"mg/kg bw/day","Decrease","Body weight was stat. significantly decreased (-8%) and -13% at the highest dose of 9022 mg/kg bw/day"]
[2,"Subchronic oral toxicity in rodents",null,null,"Mouse",8,"Weeks","Oral",10828,"mg/kg bw/day","Decrease","Transient weight loss was observed at the top dose"]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",1500,"mg/kg bw/day","Decrease","10.8% decrease at the top dose (not stat. significant)"]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect in BW up to the top dose of 1500 mg/kg bw/day (2.8% decrease)"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect in BW and BW gain up to the highest dose of 600 mg/kg bw/day"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect in BW and BW gain up to the highest dose of 600 mg/kg bw/day"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",953,"mg/kg bw/day","Decrease","Decreased bodyweight (↓ 4.2%) and bodyweight gain (↓ 10.4% for 0-52 weeks. Data not given for 0-104 weeks).NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",243,"mg/kg bw/day","Decrease","Decreased bodyweight gain (↓ 10.4% for 0-52 weeks. Data not given for 0-104 weeks). At the top dose of 1280 mg/kg bw/day: Decreased bodyweight (↓ 5.0%) and bodyweight gain (↓ 15.1% for 0-52 weeks. Data not given for 0-104 weeks).NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",8040,"mg/kg bw/day","Decrease","Bodyweights were significantly lower (↓ 5.1%).NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",10353,"mg/kg bw/day","Decrease","Bodyweights were significantly lower (↓ 6.1%).NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",8040,"mg/kg bw/day","Decrease","Bodyweights were significantly lower (↓7.3%)."]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",null,"mg/kg bw/day","No effect","Bodyweights not affected in females after 12 month treatment with the top dose of 10353 mg/kg bw/day."]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",1136,"mg/kg bw/day","Decrease","Decreased body weight (8%) and body weight gain (10%) in F0 males at the end of the study, p>0.05NOAEL parental"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",1456,"mg/kg bw/day","Decrease","Decreased body weight (9.4%) and body weight gain (14.5%, p>0.05) in F1 females during pre-mating period NOAEL parental"]
[11,"Prenatal developmental toxicity study",null,null,"Rabbit",16,"Days","Oral",750,"mg/kg bw/day","Decrease","Decreased body weight and body weight gain at the end of the studyNOAEL maternal"]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,"Clinical chemistry and haematology","Rat",90,"Days","Oral",387,"mg/kg bw/day","Change","Clinical chemistry: Statistically significant changes in: Globulin (↓ 12%), A:G ratio (↑13.3%) in males"]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",157.9,"mg/kg bw/day","Change","Clinical chemistry: statistically significant changes on: A:G ratio (↑11.8%), not stati. Sign. Change on Globulin (↓ 8.8%) in females."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",1327.3,"mg/kg bw/day","Change","Haematology: statistically significant effects on RBC parameters  consistent with mild macrocytic anaemia: RBC ( ↓ 9.1%), HGB (↓ 7.3%), HCT (↓5.6%), MCV (↑ 4.5%), MCHC (↓ 2.0%). Clinical chemistry: Statistically significant changes in: PTT (↑17%), Protein (↓ 8.7%), Globulin (↓ 17.5%), A:G ratio (↑21%), P (↓ 10.3%) in males."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",1651.5,"mg/kg bw/day","Change","Haematology: statistically significant effec ts on RBC parameters consistent with mild macrocytic anaemia: RBC ( ↓ 8.2%), HGB (↓ 7.8%), HCT (↓7.0%). Clinical chemistry:  statistically significant changes on: Globulin (↓ 17.3%), A:G ratio (↑20.2%). Not stat. sign. decrease in P (↓ 7.9%) in females."]
[2,"Subchronic oral toxicity in rodents",null,null,"Mouse",8,"Weeks","Oral",null,"mg/kg bw/day","No effect","Plasma, erythrocyte and cholinesterase activities were comparable in all groups"]
[2,"Subchronic oral toxicity in rodents",null,null,"Mouse",8,"Weeks","Oral",null,"mg/kg bw/day","No effect","Plasma, erythrocyte and cholinesterase activities were comparable in all groups"]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",300,"mg/kg bw/day","Decrease","Red blood cell parameters (erythrocyte count, haemoglobin concentration and haematocrit) were stat. significantly depressed in top dose males at Week 26. Dose-related increase in glucose. The total WBC count was significantly lower in treated groups at the majority of time points."]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",300,"mg/kg bw/day","Change","No effect in RBC parameters up to the highest dose tested. The total WBC count was significantly lower in treated groups at the majority of time points."]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect in heamatological and clinical chemistry parameters up to the highest dose of 600 mg/kg bw/day"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect in haematological and clinical chemistry parameters up to the highest dose of 600 mg/kg bw/day. Slightly elevated AST, ALP and CK activities however they were sporadic with no dose-response relationship and no stat. significance was reached."]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","Not consistent haematology changes in males up to the highest dose of 953 mg/kg bw/day. Significantly increased clotting times were noted in top dose males at Weeks 12, 14 and 24; as a result the diet was supplemented with Vit. K and similar effects were not apparent.NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","Not consistent haematology changes in males up to the highest dose of 1280 mg/kg bw/day.NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",8040,"mg/kg bw/day","Change","Effects in haematological parameters indicative of mild anaemia: RBC (↓11%), HCT (↓8.6%), MCH (↑ 19.2%), MCHC (↑16.3%).NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",10353,"mg/kg bw/day","Change","Effects in haematological parameters indicative of mild anaemia: RBC (↓15.3%), HCT (↓7.9%), MCH (↑ 17.6%), MCHC (↑6.6%).NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",8040,"mg/kg bw/day","Change","Effects in haematological parameters indicative of mild anaemia: RBC (↓11.4%), HCT (↓12.4%), MCH (↑ 14.7%), MCHC (↑16.3%)."]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",10353,"mg/kg bw/day","Change","Effects in haematological parameters indicative of mild anaemia: RBC (↓7.0%), HCT (↓8.8%), MCH (↑ 7.8%), MCHC (↑9.5%)."]
[3,"Subacute oral in non-rodent ",null,"Clinical signs","Dog",26,"Weeks","Oral",1500,"mg/kg bw/day","Increase","Vomiting immediately following dosing was observed with increased incidence at the top dose"]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",300,"mg/kg bw/day","Increase","Vomiting immediately following dosing was observed with increased incidence from the dose of 300 mg/kg bw/day"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",300,"mg/kg bw/day","Increase","Salivation and vomiting with increasing incidence and severity. Slight salivation was observed from the dose of 100 mg/kg bw/day but was not considered adverse."]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",300,"mg/kg bw/day","Increase","Salivation and vomiting with increasing incidence and severity from the dose of 300 mg/kg bw/day."]
[8,"Carcinogenicity",null,"Food consumption","Mouse",24,"Months","Oral",8040,"mg/kg bw/day","Change","Food consumption was consistently higher; findings likely due to the inclusion of the test material at a high level (5%) in the diet.NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",10353,"mg/kg bw/day","Change","Food consumption was consistently higher; findings likely due to the inclusion of the test material at a high level (5%) in the diet.NOAEL systemic"]
[11,"Prenatal developmental toxicity study",null,null,"Rabbit",16,"Days","Oral",750,"mg/kg bw/day","Decrease","Decreased food consumptionNOAEL maternal"]
[3,"Subacute oral in non-rodent ","[Not in list]","[Not in list]","Dog",26,"Weeks","Oral",1500,"mg/kg bw/day","Decrease","Absolute (stat. significant) and relative lung weights were lower in top dose males"]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",1500,"mg/kg bw/day","No effect","No effect on lung weight up to the top dose of 1500 mg/kg bw/day"]
[5,"Repeated dose dermal toxicity","No relevant effect observed","No relevant effect observed","Rabbit",21,"Days","Dermal",null,"mg/kg bw/day","No effect","No local or systemic effects in males and females"]
[6,"Repeated dose dermal toxicity",null,null,"Rat",21,"Days","Dermal",null,"mg/kg bw/day","No effect","No local or systemic effects in males and females"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","No evidence of treatment-related tumours in males up to the highest dose of 953 mg/kg bw/day. There is insufficient evidence that substance causes phaechromocytomas in male rats; data in the context of historical control range.NOAEL carcinogenic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","No evidence of treatment-related tumours in females up to the highest dose of 1280 mg/kg bw/day.NOAEL carcinogenic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",null,"mg/kg bw/day","No effect","There were no treatment-related tumours.NOAEL carcinogenic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",null,"mg/kg bw/day","No effect","There were no treatment-related tumours.NOAEL carcinogenic"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effects in the offspring, however animals not exposed to test material for 30 days prior to necropsyNOAEL offpring"]
[10,"Prenatal developmental toxicity study",null,null,"Rat","Not specified",null,"Oral",null,"mg/kg bw/day","No effect","No maternal effectsNOAEL maternal"]
[11,"Prenatal developmental toxicity study",null,null,"Rabbit",16,"Days","Oral",null,"mg/kg bw/day","No effect","No developmental effectsNAOEL developmental"]

{"sheet":"Lines of evidence - EAS","index":12,"n_rows":130,"n_cols":18,"rows_kept":130,"cut":false,"hidden":false,"merged":[[79,13,118,13],[28,12,29,12],[30,12,32,12],[6,13,27,13],[28,13,41,13],[42,13,78,13],[33,12,34,12],[116,3,118,3],[119,3,120,3],[121,3,129,3],[1,12,2,12],[3,12,4,12],[8,12,10,12],[12,12,15,12],[26,12,27,12],[64,3,70,3],[71,3,78,3],[79,3,95,3],[96,3,111,3],[112,3,115,3],[42,3,43,3],[44,3,50,3],[51,3,52,3],[53,3,58,3],[59,3,63,3],[26,3,27,3],[28,3,29,3],[30,3,32,3],[33,3,34,3],[35,3,40,3],[121,2,129,2],[1,13,5,13],[1,3,2,3],[3,3,4,3],[42,2,78,2],[6,2,27,2],[17,3,18,3],[19,12,24,12],[17,12,18,12],[28,2,41,2],[79,2,118,2],[119,2,120,2],[1,2,5,2],[8,3,10,3],[12,3,15,3],[19,3,24,3]]}
["Study ID Matrix","Study principle","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"]
[15,"ToxCast AR prediction model","In vitro mechanistic","Androgen receptor",null,null,null,null,0,null,"No effect","No AR mediated agonistic effects"]
[16,"ToxCast AR prediction model",null,null,null,null,null,null,0,null,"No effect","No AR mediated antagonistic effects"]
[13,"ToxCast ER prediction model",null,"Estrogen receptor",null,null,null,null,0,null,"No effect","No ER mediated agonistic effects"]
[14,"ToxCast ER prediction model",null,null,null,null,null,null,0,null,"No effect","No ER mediated antagonistic effects"]
[20,"TOX21_Aromatase_Inhibition",null,"CYP19","Human breast cancer cells",24,"Hours",null,"-","μΜ","No effect","No effect on aromatase activity",null,null,null,null,null," "]
[9,"Two-generation reproduction toxicity test","EATS-mediated","Epididymides histopathology","Rat",26,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on epididymides histopathology up to the highest dose of 1136 mg/kg bw/day. "]
[9,"Two-generation reproduction toxicity test",null,"Ovary histopathology","Rat",26,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on ovary histopathology up to the highest dose of 1456 mg/kg bw/day"]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,"Ovary weight","Rat",90,"Days","Oral",null,"mg/kg bw/day","No effect","No effect on ovaries weight in females up to the highest dose of 479 mg/kg bw/day."]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on ovaries weight in females up to the highest dose of 1280 mg/kg bw/day. "]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on ovarian weight up to the highest dose of 1456 mg/kg bw/day"]
[9,"Two-generation reproduction toxicity test",null,"Prostate histopathology","Rat",29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on prostate and seminal vesicles histopathology up to the highest dose of 1136 mg/kg bw/day. No information on coagulating gland histology."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,"Prostate weight","Rat",90,"Days","Oral",null,"mg/kg bw/day","No effect","Prostate weight was slightly lower in top dose males (1327.3 mg/kg bw/day), however values did not attain statistical significance."]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","Prostate weight (abs & rel) was slightly (but not significantly) lower at the top dose of 600 mg/kg bw/day"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on prostate weight in males up to the highest dose of 953 mg/kg bw/day. "]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on prostate weight up to the highest dose of 1136 mg/kg bw/day"]
[9,"Two-generation reproduction toxicity test",null,"Seminal vesicles histopathology",null,29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on seminal vesicles histopathology up to the highest dose of 1136 mg/kg bw/day. "]
[8,"Carcinogenicity",null,"Testis histopathology","Mouse",24,"Months","Oral",null,"mg/kg bw/day","No effect","Incidence of testes mineralisation: 7, 7, 10, 12 males at 74, 730, 8040 mg/kg bw/day, respectively. In RAR, not considered treatment-related adverse effect. "]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on testes histopathology up to the highest dose of 1136 mg/kg bw/day. "]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,"Testis weight","Rat",90,"Days","Oral",1327.3,"mg/kg bw/day","Increase","Mean relative testes weight was significantly higher in top dose males; this value is largely (but not entirely) attributable to one male with an unusually high absolute testes weight (5.65 g). When the outlier was excluded, the percentage fell from 9.6% to 5.5%."]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",1500,"mg/kg bw/day","Decrease","Mean absolute testes weight was significantly lower at the top dose of 1500 mg/kg bw/day (25% decrease)"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",600,"mg/kg bw/day","Decrease","Abs. testes weight were slightly (but not significantly) lower in top dose males (13.2%). "]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on testes weight in males up to the highest dose of 953 mg/kg bw/day."]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",null,"mg/kg bw/day","No effect","No effect on testes weight in males up to the highest dose of 8040 mg/kg bw/day."]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on testicular weight up to the highest dose of 1136 mg/kg bw/day"]
[8,"Carcinogenicity",null,"Uterus histopathology (with cervix)","Mouse",24,"Months","Oral",null,"mg/kg bw/day","No effect","Incidence of uterine corpus cystic endometrial hyperplasia: 23, 30, 40, 36 females at 74, 730, 8040 mg/kg bw/day, respectively. In RAR, not considered treatment-related adverse effect. "]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,"Uterus weight (with cervix)","Rat",90,"Days","Oral",null,"mg/kg bw/day","No effect","No effect on uterus weight in females up to the highest dose of 479 mg/kg bw/day."]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on uterus weight in females up to the highest dose of 1280 mg/kg bw/day."]
[7,"Combined chronic toxicity/carcinogenicity studies","Sensitive to, but not diagnostic of, EATS","Adrenals histopathology","Rat",108,"Weeks","Oral",953,"mg/kg bw/day","Change","Adrenals medullary hyperplasia (17/50 males vs 8/50 in controls). NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on adrenals histopathology at the top dose of 1280 mg/kg bw/day in females.NOAEL systemic"]
[4,"Subacute oral in non-rodent ",null,"Adrenals weight","Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect in adrenal weight up to the highest dose of 600 mg/kg bw/day in males"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",600,"mg/kg bw/day","Increase","Increased absolute adrenal weight (26.6%) at the highest dose of 600 mg/kg bw/day in females"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on adrenals weight up to the highest dose of 1136 (males) and 1456 (females) mg/kg bw/day."]
[9,"Two-generation reproduction toxicity test",null,"Litter size","Rat",29,"Weeks","Oral",224,"mg/kg bw/day","Decrease","Decreased litter size (9.1 vs 11.2 in control) in F1. Also in F2 (7.2 vs 9.3 in control, however p>0.05 and no dose response, not considered in the basis for LOAEL setting)NOAEL reproductive"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",278,"mg/kg bw/day","Decrease","Decreased litter size (9.1 vs 11.2 in control) in F1. Also in F2 (7.2 vs 9.3 in control, however p>0.05 and no dose response, not considered in the basis for LOAEL setting)NOAEL reproductive"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,"Pituitary histopathology","Rat",108,"Weeks","Oral",953,"mg/kg bw/day","Change","Pituitary hyperplasia (13/50 males vs 6/50 in controls). NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on pituitary histopathology at the top dose of 1280 mg/kg bw/day in females.NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",null,"mg/kg bw/day","No effect","No increased incidence in pituitary adenomas up to the highest dose of 8040 mg/kg bw/day in males.NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",null,"mg/kg bw/day","No effect","No increased incidence in pituitary adenomas up to the highest dose of 8040 mg/kg bw/day in females.NOAEL systemic"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on pituitary histopathology up to the highest dose of 1136 mg/kg bw/day"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on pituitary histopathology up to the highest dose of 1456 mg/kg bw/day"]
[10,"Prenatal developmental toxicity study",null,"Presence of anomalies (external, visceral, skeletal","Rat","Not specified",null,"Oral",2000,"mg/kg bw/day","Increase","Decreased ossification of the cranium (0.5% foetal incidence, 5% litter incidence vs 0 in control), short/absent 13th rib (4.1% foetal incidence, 15% litter incidence vs 1.1% and 10% in control), fused cervical arches (0.5% foetal incidence, 5% litter incidence vs 0 in control) and decreased ossification of the caudal vertebrae (2.5% foetal incidence, 5% litter incidence vs 1.1% and 5% in control)NAOEL developmental"]
[4,"Subacute oral in non-rodent ","Target organ toxicity","Heart weight","Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","Absolute and relative heart weights were slightly lower in both sexes at the top dose level, however values do not attain statistical significance"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","Absolute and relative heart weights were slightly lower in both sexes at the top dose level, however values do not attain statistical significance"]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,"Kidney histopathology","Rat",90,"Days","Oral",387,"mg/kg bw/day","Change","Increase in the incidence and severity of mineral deposits located free in the renal pelvis or papilla at the top dose of 1327.3 mg/kg bw/day; a slight or minimum hyperplasia of the adjacent transitional epithelium occurred occasionally as a result of the mineral deposition causing a greater incidence of focal urothelial hyperplasia from the dose of 387.0 mg/kg bw/day in males."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",1327.3,"mg/kg bw/day","Change","Increase in the incidence and severity of mineral deposits located free in the renal pelvis or papilla at the top dose of 1327.3 mg/kg bw/day; a slight or minimum hyperplasia of the adjacent transitional epithelium occurred occasionally as a result of the mineral deposition causing a greater incidence of focal urothelial hyperplasia from the dose of 387.0 mg/kg bw/day in males."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",479,"mg/kg bw/day","Change","Increase in the incidence and severity of mineral deposits located free in the renal pelvis or papilla from the dose of 479.4 mg/kg bw/day; a slight or minimum hyperplasia of the adjacent transitional epithelium occurred occasionally as a result of the mineral deposition causing a greater incidence of focal urothelial hyperplasia at the top dose of 1651.5 mg/kg bw/day. In addition to these changes, an increase in the severity and incidence of hydronephrosis was observed from the dose of 479.4 mg/kg bw/day in females. "]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",1651.5,"mg/kg bw/day","Change","Increase in the incidence and severity of mineral deposits located free in the renal pelvis or papilla from the dose of 479.4 mg/kg bw/day; a slight or minimum hyperplasia of the adjacent transitional epithelium occurred occasionally as a result of the mineral deposition causing a greater incidence of focal urothelial hyperplasia at the top dose of 1651.5 mg/kg bw/day. In addition to these changes, an increase in the severity and incidence of hydronephrosis was observed from the dose of 479.4 mg/kg bw/day in females. "]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",10353,"mg/kg bw/day","Increase","Brown granular pigment deposition (6/21 females vs 5/30 controls)NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",8040,"mg/kg bw/day","Change","Brown granular pigment deposition (3/10 males vs 0/10 controls)"]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",10353,"mg/kg bw/day","Change","Brown granular pigment deposition (4/10 males vs 0/10 controls)"]
[3,"Subacute oral in non-rodent ",null,"Kidney weight","Dog",26,"Weeks","Oral",1500,"mg/kg bw/day","Increase","Relative kidney weight was significantly higher in top dose"]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",1500,"mg/kg bw/day","No effect","No effect on kidney weight up to the top dose of 1500 mg/kg bw/day"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,"Liver histopathology","Rat",108,"Weeks","Oral",953,"mg/kg bw/day","Change","Bile duct hyperplasia (17/50 males vs 10/50 in controls). NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",1280,"mg/kg bw/day","Change","Bile duct hyperplasia (13/50 females vs 6/50 in controls). NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",8040,"mg/kg bw/day","Increase","Brown granular pigment deposition (2/28 males vs 0/28 controls)NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",10353,"mg/kg bw/day","Increase","Brown granular pigment deposition (3/21 females vs 0/30 controls)NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",8040,"mg/kg bw/day","Change","Brown granular pigment deposition (8/10 males vs 0/10 controls)"]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",10353,"mg/kg bw/day","Change","Brown granular pigment deposition (2/10 males vs 0/10 controls)"]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,"Liver weight","Rat",90,"Days","Oral",null,"mg/kg bw/day","No effect","No effect on liver weight in males up to the highest dose of 1327.3 mg/kg bw/day."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",null,"mg/kg bw/day","No effect","No effect on liver weight in females up to the highest dose of 1651.5 mg/kg bw/day."]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on liver weight in males up to the highest dose of 953 mg/kg bw/day.NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",1280,"mg/kg bw/day","Increase","Increase in the absolute (↑10.3%) and relative-to-body (↑ 6.6%) liver weight in females. NOAEL systemic"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",1456,"mg/kg bw/day","Decrease","Decreased absolute (15.6%) and relative (8.5%) liver weight in F1 femalesNOAEL parental"]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,"Spleen histopathology","Rat",90,"Days","Oral",387,"mg/kg bw/day","Change","Increase in the severity of splenic extramedullary haematopoiesis in males at ≥ 387 mg/kg bw/day. Increase in the severity of haemosiderin deposition in the spleen from the dose of 387 mg/kg bw/day."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",1651.5,"mg/kg bw/day","Change","Increase in the severity of haemosiderin deposition at the top dose of 1651.5 mg/kg bw/day in females."]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",300,"mg/kg bw/day","Change","Gross necropsy revealed increased incidences of ‘small’ spleen at the top dose, corresponding to the organ weight findings. Microscopically, a marginally increased incidence and/or severity of splenic haemosiderosis/sclerosiderosis was seen from the dose of 300 mg/kg bw/d. Findings are not considered to be of clear toxicological significance in the absence of any treatment-related effects on red blood cell parameters."]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect on spleen histopathology up to the highest dose of 600 mg/kg bw/day"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",953,"mg/kg bw/day","Change","Prominent siderocytes (7/50 males vs 1/50 in controls). NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",243,"mg/kg bw/day","Change","Prominent siderocytes (6/50 females vs 2/50 in controls). Same incidence at top dose of 1280 mg/kg bw/day.NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",1280,"mg/kg bw/day","Change","Prominent siderocytes (6/50 females vs 2/50 in controls) at top dose of 1280 mg/kg bw/day."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,"Spleen weight","Rat",90,"Days","Oral",1327.3,"mg/kg bw/day","Increase","Significant increase in the absolute (↑14.3%) and relative-to-body (↑ 22.8%) spleen weight in males at the highest dose of 1327.3 mg/kg bw/day. Consistent with haematological findings. "]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",null,"mg/kg bw/day","No effect","No effect on spleen weight in females up to the highest dose of 479 mg/kg bw/day."]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","Spleen weight (abs & rel) was slightly (but not significantly) lower (7%) at the top dose of 600 mg/kg bw/day"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect in spleen weight up to the highest dose of 600 mg/kg bw/day"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",730,"mg/kg bw/day","Increase","Increase in the absolute (↑69.2%) and relative-to-body (↑ 78.2%) spleen weight in males. NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",938,"mg/kg bw/day","Increase","Increase in the absolute (↑42.9%) and relative-to-body (↑ 37.5%) spleen weight in females. NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",8040,"mg/kg bw/day","Increase","Increase in the absolute (↑42.9%) and relative-to-body (↑ 53.7%) spleen weight in males. "]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",10353,"mg/kg bw/day","Increase","Increase in the absolute (↑114.3%) and relative-to-body (↑ 117.3%) spleen weight in females. "]
[1,"Repeated dose 90-day oral toxicity study in rodents","Systemic toxicity","Body weight","Rat",90,"Days","Oral",1327.3,"mg/kg bw/day","Decrease","Mean bodyweights and bodyweight gains of top dose males were significantly reduced (7% and 12.4% vs control, respectively)."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",1651.5,"mg/kg bw/day","Decrease","Not stat. significant decrease on bodyweight and BW gain in females at the highest dose of 1651.5 mg/kg bw/day (4% and 11.2%, respectively)."]
[2,"Subchronic oral toxicity in rodents",null,null,"Mouse",8,"Weeks","Oral",5103,"mg/kg bw/day","Decrease","Body weight was stat. significantly decreased (-8%) and -13% at the highest dose of 9022 mg/kg bw/day"]
[2,"Subchronic oral toxicity in rodents",null,null,"Mouse",8,"Weeks","Oral",10828,"mg/kg bw/day","Decrease","Transient weight loss was observed at the top dose"]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",1500,"mg/kg bw/day","Decrease","10.8% decrease at the top dose (not stat. significant)"]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect in BW up to the top dose of 1500 mg/kg bw/day (2.8% decrease)"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect in BW and BW gain up to the highest dose of 600 mg/kg bw/day"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect in BW and BW gain up to the highest dose of 600 mg/kg bw/day"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",953,"mg/kg bw/day","Decrease","Decreased bodyweight (↓ 4.2%) and bodyweight gain (↓ 10.4% for 0-52 weeks. Data not given for 0-104 weeks).NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",243,"mg/kg bw/day","Decrease","Decreased bodyweight gain (↓ 10.4% for 0-52 weeks. Data not given for 0-104 weeks). At the top dose of 1280 mg/kg bw/day: Decreased bodyweight (↓ 5.0%) and bodyweight gain (↓ 15.1% for 0-52 weeks. Data not given for 0-104 weeks).NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",8040,"mg/kg bw/day","Decrease","Bodyweights were significantly lower (↓ 5.1%).NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",10353,"mg/kg bw/day","Decrease","Bodyweights were significantly lower (↓ 6.1%).NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",8040,"mg/kg bw/day","Decrease","Bodyweights were significantly lower (↓7.3%)."]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",null,"mg/kg bw/day","No effect","Bodyweights not affected in females after 12 month treatment with the top dose of 10353 mg/kg bw/day."]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",1136,"mg/kg bw/day","Decrease","Decreased body weight (8%) and body weight gain (10%) in F0 males at the end of the study, p>0.05NOAEL parental"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",1456,"mg/kg bw/day","Decrease","Decreased body weight (9.4%) and body weight gain (14.5%, p>0.05) in F1 females during pre-mating period NOAEL parental"]
[11,"Prenatal developmental toxicity study",null,null,"Rabbit",16,"Days","Oral",750,"mg/kg bw/day","Decrease","Decreased body weight and body weight gain at the end of the studyNOAEL maternal"]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,"Clinical chemistry and haematology","Rat",90,"Days","Oral",387,"mg/kg bw/day","Change","Clinical chemistry: Statistically significant changes in: Globulin (↓ 12%), A:G ratio (↑13.3%) in males"]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",157.9,"mg/kg bw/day","Change","Clinical chemistry: statistically significant changes on: A:G ratio (↑11.8%), not stati. Sign. Change on Globulin (↓ 8.8%) in females."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",1327.3,"mg/kg bw/day","Change","Haematology: statistically significant effects on RBC parameters  consistent with mild macrocytic anaemia: RBC ( ↓ 9.1%), HGB (↓ 7.3%), HCT (↓5.6%), MCV (↑ 4.5%), MCHC (↓ 2.0%). Clinical chemistry: Statistically significant changes in: PTT (↑17%), Protein (↓ 8.7%), Globulin (↓ 17.5%), A:G ratio (↑21%), P (↓ 10.3%) in males."]
[1,"Repeated dose 90-day oral toxicity study in rodents",null,null,"Rat",90,"Days","Oral",1651.5,"mg/kg bw/day","Change","Haematology: statistically significant effec ts on RBC parameters consistent with mild macrocytic anaemia: RBC ( ↓ 8.2%), HGB (↓ 7.8%), HCT (↓7.0%). Clinical chemistry:  statistically significant changes on: Globulin (↓ 17.3%), A:G ratio (↑20.2%). Not stat. sign. decrease in P (↓ 7.9%) in females."]
[2,"Subchronic oral toxicity in rodents",null,null,"Mouse",8,"Weeks","Oral",null,"mg/kg bw/day","No effect","Plasma, erythrocyte and cholinesterase activities were comparable in all groups"]
[2,"Subchronic oral toxicity in rodents",null,null,"Mouse",8,"Weeks","Oral",null,"mg/kg bw/day","No effect","Plasma, erythrocyte and cholinesterase activities were comparable in all groups"]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",300,"mg/kg bw/day","Decrease","Red blood cell parameters (erythrocyte count, haemoglobin concentration and haematocrit) were stat. significantly depressed in top dose males at Week 26. Dose-related increase in glucose. The total WBC count was significantly lower in treated groups at the majority of time points."]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",300,"mg/kg bw/day","Change","No effect in RBC parameters up to the highest dose tested. The total WBC count was significantly lower in treated groups at the majority of time points."]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect in heamatological and clinical chemistry parameters up to the highest dose of 600 mg/kg bw/day"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effect in haematological and clinical chemistry parameters up to the highest dose of 600 mg/kg bw/day. Slightly elevated AST, ALP and CK activities however they were sporadic with no dose-response relationship and no stat. significance was reached."]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","Not consistent haematology changes in males up to the highest dose of 953 mg/kg bw/day. Significantly increased clotting times were noted in top dose males at Weeks 12, 14 and 24; as a result the diet was supplemented with Vit. K and similar effects were not apparent.NOAEL systemic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","Not consistent haematology changes in males up to the highest dose of 1280 mg/kg bw/day.NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",8040,"mg/kg bw/day","Change","Effects in haematological parameters indicative of mild anaemia: RBC (↓11%), HCT (↓8.6%), MCH (↑ 19.2%), MCHC (↑16.3%).NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",10353,"mg/kg bw/day","Change","Effects in haematological parameters indicative of mild anaemia: RBC (↓15.3%), HCT (↓7.9%), MCH (↑ 17.6%), MCHC (↑6.6%).NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",8040,"mg/kg bw/day","Change","Effects in haematological parameters indicative of mild anaemia: RBC (↓11.4%), HCT (↓12.4%), MCH (↑ 14.7%), MCHC (↑16.3%)."]
[8,"Carcinogenicity",null,null,"Mouse",12,"Months","Oral",10353,"mg/kg bw/day","Change","Effects in haematological parameters indicative of mild anaemia: RBC (↓7.0%), HCT (↓8.8%), MCH (↑ 7.8%), MCHC (↑9.5%)."]
[3,"Subacute oral in non-rodent ",null,"Clinical signs","Dog",26,"Weeks","Oral",1500,"mg/kg bw/day","Increase","Vomiting immediately following dosing was observed with increased incidence at the top dose"]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",300,"mg/kg bw/day","Increase","Vomiting immediately following dosing was observed with increased incidence from the dose of 300 mg/kg bw/day"]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",300,"mg/kg bw/day","Increase","Salivation and vomiting with increasing incidence and severity. Slight salivation was observed from the dose of 100 mg/kg bw/day but was not considered adverse."]
[4,"Subacute oral in non-rodent ",null,null,"Dog",52,"Weeks","Oral",300,"mg/kg bw/day","Increase","Salivation and vomiting with increasing incidence and severity from the dose of 300 mg/kg bw/day."]
[8,"Carcinogenicity",null,"Food consumption","Mouse",24,"Months","Oral",8040,"mg/kg bw/day","Change","Food consumption was consistently higher; findings likely due to the inclusion of the test material at a high level (5%) in the diet.NOAEL systemic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",10353,"mg/kg bw/day","Change","Food consumption was consistently higher; findings likely due to the inclusion of the test material at a high level (5%) in the diet.NOAEL systemic"]
[11,"Prenatal developmental toxicity study",null,null,"Rabbit",16,"Days","Oral",750,"mg/kg bw/day","Decrease","Decreased food consumptionNOAEL maternal"]
[3,"Subacute oral in non-rodent ","[Not in list]","[Not in list]","Dog",26,"Weeks","Oral",1500,"mg/kg bw/day","Decrease","Absolute (stat. significant) and relative lung weights were lower in top dose males"]
[3,"Subacute oral in non-rodent ",null,null,"Dog",26,"Weeks","Oral",1500,"mg/kg bw/day","No effect","No effect on lung weight up to the top dose of 1500 mg/kg bw/day"]
[5,"Repeated dose dermal toxicity","No relevant effect observed","No relevant effect observed","Rabbit",21,"Days","Dermal",null,"mg/kg bw/day","No effect","No local or systemic effects in males and females"]
[6,"Repeated dose dermal toxicity",null,null,"Rat",21,"Days","Dermal",null,"mg/kg bw/day","No effect","No local or systemic effects in males and females"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","No evidence of treatment-related tumours in males up to the highest dose of 953 mg/kg bw/day. There is insufficient evidence that substance causes phaechromocytomas in male rats; data in the context of historical control range.NOAEL carcinogenic"]
[7,"Combined chronic toxicity/carcinogenicity studies",null,null,"Rat",108,"Weeks","Oral",null,"mg/kg bw/day","No effect","No evidence of treatment-related tumours in females up to the highest dose of 1280 mg/kg bw/day.NOAEL carcinogenic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",null,"mg/kg bw/day","No effect","There were no treatment-related tumours.NOAEL carcinogenic"]
[8,"Carcinogenicity",null,null,"Mouse",24,"Months","Oral",null,"mg/kg bw/day","No effect","There were no treatment-related tumours.NOAEL carcinogenic"]
[9,"Two-generation reproduction toxicity test",null,null,"Rat",29,"Weeks","Oral",null,"mg/kg bw/day","No effect","No effects in the offspring, however animals not exposed to test material for 30 days prior to necropsyNOAEL offpring"]
[10,"Prenatal developmental toxicity study",null,null,"Rat","Not specified",null,"Oral",null,"mg/kg bw/day","No effect","No maternal effectsNOAEL maternal"]
[11,"Prenatal developmental toxicity study",null,null,"Rabbit",16,"Days","Oral",null,"mg/kg bw/day","No effect","No developmental effectsNAOEL developmental"]