javicorvi/pretoxtm-dataset huggingface dataset:
Summary of results and discussion All relevant or suspected treatment - or compound - related effects after implantation of the ELEMENT_XXX ( release rate : 5.5 μg / day COMPOUND_XXX ) can briefly be summarized as follows : Alterations in the endometrium such as atrophy and flattening of the lumenal epithelium ( by pressure ) , focal necrosis at the edges of the device and focal subepithelial hemorrhage were observed in the microscopical examination .
Mean concentrations of COMPOUND_XXX in mouse plasma Target dose ( mg / kg / day ) Mean COMPOUND_XXX concentration ( ng / ml ) ( SD ) 60 5.66 ( 3.59 ) 200 40.4 ( 19.9 ) 600 86.9 ( 34.4 ) At microscopic examination , dose - dependent mucosal hyperplasia was observed m the jejunum ( minimal to slight ) and ileum ( minimal ) at 200 and 600 mg / kg / day .
The positive control article propylthiouracil ( PTU ) was administered daily at a dose of 10 mg / kg via oral gavage at a dose volume of 5 mL / kg as a suspension in 0.25 % methylcellulose , to an additional group of 90 male Han Wistar rats , for 5 ( n = 30 ) , 12 ( n = 30 ) or 26 ( n = 30 ) days .
The changes were more pronounced after treatment with COMPOUND_XXX when compared to treatment with , i.e. at the end of the 28 - day treatment period , foci of acute myocardial necrosis were noted in several rats treated with COMPOUND_XXX at > 120 mg / kg / day and the incidence and severity of inflammatory focus , characterized by granulation tissue with or without inflammatory cell infiltration , were increased after COMPOUND_XXX treatment at > 120 mg / kg / day when compared to control animals or rats treated with .
In females , there was a reduced mean body weight gain of 1.4 g / day compared to 2.4 g / day in the control group between Days 1 - 8 and of 0.9 g / day compared to 1.8 g / day in the control group between Days 15 - 22 , representing a reduction of cumulative body weight gain of 47 % between Days 1 - 8 and of 26 % between Days 1 - 22 .
Necropsy Changes observed at the end of treatment period : From low dose ( 5 mg / kg COMPOUND_XXX ) and higher : e â € " Cysts ( mainly bilateral ) in the ovaries of single animals of group 2 and 3 e Diminished size of uterine horns , cervix and uterus body e Increased incidence and severity of ovarian follicular cysts Â ¢ Atrophy of uterine horn , body and cervix in most animals Findings from the mid dose of 15 mg / kg COMPOUND_XXX and higher : e Increased incidence and severity of focal / multifocal foam cell aggregates in all animals of group 3 Additional findings at the high dose ( 50 mg / kg COMPOUND_XXX ) : e Emaciation of single animals e â € " Gray - white foci in all lobes of the lungs in single animals e Diminished size of ovaries , thymus and iliac lymph nodes in single animals e Diffuse adrenocortical atrophy and associated lipid depletion e Diffuse hepatocellular hypertrophy e Vacuolation of Kupffer cells e Diffuse alveolar foam cell ( i.e. histiocytes ) aggregation ( with associated acute / mixed inflammation and hyperplasia of alveolar type II pneumocytes ) e Accumulation of multinucleated giant cells in the BALT of single animals e Hypocellularity of the femoral and sternal bone marrow and associated congestion in most rats e Lobuloalveolar histologic pattern in the mammary gland .
SUMMARY COMPOUND_XXX , a fungicide of the SDH - carboxamide family , ( batch number NLL 111111 : a white solid , 98.6 % purity ) was administered continuously via the diet to groups of C57BL / 6J mice ( 5 / sex / group ) for 28 days at concentrations of 150 , 3 500 and 7 000 ppm ( equating approximately to 26 , 632 and 1 274 mg / kg / day in males and 31 , 741 and 1 585 mg / kg / day in females ) .
CONCLUSION The oral administration of COMPOUND_XXX for 1 month to rats at doses of 10 , 30 and 100 mg / kg / day resulted in compound - related mortality in 1/16 males at 100 mg / kg / day ; no clinical signs and no ocular abnormalities at whatever the dose ; body weight gain decreases throughout the study primarily in males treated at 100 mg / kg / day , with decreases in food intake .
Food consumption was markedly reduced ( up to 100 % ) and resulted in a body weight decrease ( up to 17 % ) in dogs treated with 60 mg / kg / d. Hematology showed equivocal changes of the red blood cell parameters and a slight increase in the relative prothrombin time after treatment with 20/60 mg / kg / d. Clinical pathology revealed a slight decrease in electrolytes ( up to 24 % ) and a slight increase in metabolic parameters ( up to 61 % ) .
Atrophy of the pars distalis of the pituitary gland e Atrophy of the vaginal epithelium Changes observed at the end of 4 - week treatment - free recovery period : e Diffuse adrenocortical atrophy in single animals e Diffuse alveolar foam cell ( i.e. histiocytes ) aggregation ( with associated acute / mixed inflammation and hyperplasia of alveolar type II pneumocytes ) with associated minimal fibroplasias e â € " Granulomas and / or granulomatous inflammation and associated reactive lymphoid hyperplasia in the mediastinal lymph nodes of single animals Â ¢ â € " Lobuloalveolar histologic pattern in the mammary gland e Increased incidence and severity of follicular cysts in the ovaries e â € " Atrophy of the pars distalis of the pituitary gland in most animals e Atrophy of uterine horn , body and cervix e Atrophy of the epithelium of the vagina e = Thymic involution with increased lymphocytolysis in single animals is considered to be suspected compound - related
Summary of the report and discussion 3 groups of 4 female Cynomolgus monkeys ( Macaca fascicularis ) each were treated daily intravenously over a period of 28 to 31 days with daily dosages of 0.8 , 2.0 and 5.0 mg COMPOUND_XXX / kg body weight at an application volume of 0.4 , 1.0 and 2.5 mL / kg respectively .
Based on the sciatic nerve degeneration resulting from severe hypoglycemia at dose levels of 150 and 450 mg / kg / day , the no - observable adverse effect level ( NOAEL ) for the current study is 50 mg / kg / day which corresponds to COMPOUND_XXX AUC 0 - 24 hr and C max values of 8,730 ng * hr / ml and 1,440 ng / ml , in males and 18,600 ng * hr / ml and 4,390 ng / ml in females , respectively , on day 15 .
Additional compound - related microscopic changes were present in the lymph nodes ( decreases in presence and activity of germinal centers in both sexes at doses ≥ 0.6 mg / kg ) , thymus ( lymphoid atrophy in males at 1.2 mg / kg ) and thyroid ( reduced follicular colloid with occasional instances of follicular epithelial hypertrophy in both sexes at 1.2 mg / kg ) .
Test article - related microscopic changes were noted in the thyroid ( decreased colloid , epithelial vacuolation ) , bone marrow ( reduced cellularity ) , prostate ( epithelial attenuation ) , epididymis ( luminal debris ) , testes ( degeneration ) , stomach ( glandular atrophy ) , small intestine ( dilated crypts , necrotic debris ) and lymphoid tissue ( atrophy / depletion ) .
In satellite group animals treated with COMPOUND_XXX at 120 or 180 mg / kg / day for 28 days , COMPOUND_XXX and COMPOUND_XXX heart tissue concentrations were markedly increased compared to plasma concentrations ( heart / plasma concentration ratios : COMPOUND_XXX : 29 - 38 , COMPOUND_XXX : 35 - 49 ) thus indicating accumulation of COMPOUND_XXX and its metabolite COMPOUND_XXX in the heart .
Haematology revealed low red blood cell parameters ( haemaglobin concentration , red blood cell count , haematocrit and calculated red blood cell indices ) , reticulocyte count ( Week 4 ) , white blood cell count ( differential counts for lymphocytes , eosinophils and basophils ) and high platelet and increased activated partial thromboplastin times in animals receiving 1.5 mg / kg / occasion during the treatment period when compared with the Controls .
Forty ( 40 ) young adult male Charles River CD rats ( Sprague - Dawley ) were randomly divided into four groups of 10 animals each and administered 212 - 713 ( COMPOUND_XXX ; hydrogen tartrate salt ) in suspension ( 1 % CMC plus 0.2 % Tween 80 ) by gavage ( rigid oral feeding needle ) for 15 consecutive days as follows : Group I , Control ; Group II , 0.04 mg ; kgjday ; Group III , 0.4 mg / kg / day ; Group IV , 4 mgjkgjday ( base equivalent dose levels : 0 , 0.025 , 0.25 and 2.5 mg / kgjday , respectively ) .
Changes unrelated to COMPOUND_XXX : None Food Consumption ( Tables 1 - 1 to 1 - 30 and 3 - 1 to 3 - 3 , Appendices 1 - 1 to 1 - 90 and 3 - 1 to 3 - 10 ) Changes related to COMPOUND_XXX : In some animals at 25 and 50 mg / kg , food was left sporadically .