javicorvi/pretoxtm-dataset huggingface dataset:
XXX - 59 ) was administered orally by gavage as a suspension in 0.5 % ( w / v ) hydroxypropylmethylcellulose ( HPMC ) Type E4M Premium , aqueous solution , to three groups of beagle dogs ( 1 / sex for the low and mid dose groups ; 2 / sex for the high dose group ) at daily doses of 6 , 20 or 60 mg / kg / day base ( equivalent to 6.4 , 21.4 and 64.1 mg / kg / day salt , respectively based on the salt / base ratio of 1.069 ) .
XXXXXX ) was administered orally by gavage as solutions in Purified Water , USP to four groups of beagle dogs ( N = 3 / sex / group ) at doses of 0 , 0.15 , 0.5 and 1.5 mg / kg / day base ( equivalent to 0 , 0.19 , 0.63 and 1.89 mg / kg COMPOUND_XXX salt , respectively ) at a dose volume of 5 mL / kg .
The liver showed : - minimal to slight eosinophilic cytoplasm in group III - minimal to moderate bile duct proliferation beginning at group | - minimal to slight periportal fibrosis beginning at group II 26 COMPOUND_XXX ( = Tosylate salt of COMPOUND_YYY ) T 7069994 The kidneys showed : - minimally to moderately increased number of basophilic tubules beginning at group I - proteinaceous casts beginning at group I !
Following changes were detected in mean organ weights : ~ Ovaries : increase in absolute and relative weights in group Ill - females Uterus / Oviduct : increase in absolute and relative weights in group Ill - females Gross - pathological and histopathological findings At the time of necropsy no changes were found in respect of the nutritional state of the animals up to and including group Ill ( see table , Animalsâ € ñutritional stateâ € oe in the appendix of the report ) .
The following investigations were performed : mortality , clinical signs , body weight , food consumption , clinical biochemistry ( incl. aspartate aminotransferase ( AST ) , creatine kinase ( CK ) , Troponin I ) , organ weights , macroscopic and microscopic observations ( limited set ) , electron microscopy ( heart and skeletal muscle , 3 animals of each 28 - day COMPOUND_XXX dose group ) and blood plasma level determinations of the test and reference item towards the end of the 14 - and 28 - day treatment periods .
The other compound related or suspected compound related effects are signs of impaired general condition , such as decrease in body weight gain starting in female animals from the mid dose of 500 μg / kg COMPOUND_XXX onwards up to body weight loss at the high dose of 2500 μg / kg COMPOUND_XXX , reduction in food consumption , retardation in growth and emaciation and slight changes in total cholesterol and protein electrophoresis observed in the high dose group , which might be related to a mild liver change .
CONCLUSION Daily oral administration of COMPOUND_XXX to Beagle dogs at dosages of 0.01 , 0.05 and 0.25 mg / kg / day during 6 months mainly induced the following treatment - related changes : Nervous clinical signs ( only in animals treated at 0.25 mg / kg / day ) : difficulties in moving ( associated with ataxia in one female ) , hind limbs outspread and head bent and / or crawling were observed on day 1 , lasting up to 2 to 6 hours after treatment , tremors were observed on days 1 and 2 , lasting up to a few hours , neck hypertonia mainly during the first week of treatment , lasting up to a few hours , deep sleep , with closed eyelids moving , state of stupor after intense stimulation , and difficulty to stand up were observed before treatment in two males on days 86 and 127 ( one occurrence each ) and in one female on days 87 , 102 and 126 , mydriasis and / or incomplete pupillary response up to day 27 in all animals .
The following compound - related effects were noted at the high dose of 9.0 mg / kg COMPOUND_XXX at the end of the treatment period : e increase in WBC due to increases in counts of neutrophils and monocytes in males and females e changes in serum protein electrophoresis such as decreases in relative albumin and albumin / globulin - quotient and increases in relative beta - and gamma - globulins in males and females Â ¢ decreases in serum iron and albumin in males and females Â ¢ increases in serum potassium and urea nitrogen in males and females e decrease in urinary volume and increase in specific gravity in males and females e slight increased occurrence of urinary protein and blood in males and females .
XXXX ; lactate salt ) was administered three times per week ( days 1 , 3 and 5 dosing schedule ) by oral gavage as a suspension in 0.5 % hydroxypropylcellulose NF ( Klucel ) , to one group ( n = 90 ) of male Han Wistar rats at a dose of 75 mg / kg base ( equivalent to 94.4 mg / kg / day lactate salt ) for 5 ( n = 30 ) , 12 ( n = 30 ) or 26 ( n = 30 ) days .
XXXXX ) was administered orally by gavage as solutions in Purified Water , USP to four groups of animals ( N = 10 / sex / group ) at doses of 0 ( control ) , 3 , 10 and 30 mg / kg COMPOUND_XXX base ( equivalent to 0 , 3.78 , 12.6 and 37.8 mg / kg COMPOUND_XXX salt , respectively ) at a dose volume of 10 mL / kg .
At the end of the 13 - week dosing period , mean body weight was reduced by 3.4 , 8.0 , and 10.7 % in males at doses of 0.3 , 1 , and 3 mg / kg , and by 8.1 % in females at 3 mg / kg ; mean body weight gain was reduced by 9.0 , 19.5 and 23.3 % for males , and by 14 , 12.0 and 32 % for females at doses of 0.3 , 1 and 3 mg / kg respectively , relative to concurrent controls .
SUMMARY COMPOUND_XXX , a fungicide of the SDH - carboxamide family , ( batch numbers NLL7306 - 15 and 111111 : a white powder , 99.2 and 99.4 % purity , respectively ) was administered continuously via the diet to groups of Wistar rats ( 5 / sex / group ) for at least 28 days at concentrations of 150 , 2 000 and 7 000 ppm ( equating approximately to 12 , 154 and 560 mg / kg / day in males and 13 , 169 and 648 mg / kg / day in females ) .
Following dosing of male rats with COMPOUND_XXX three times per week for 24 days , the AUC ( 0 - 24 hr ) for COMPOUND_XXX was 103 ng · hr / mL and the Cmax was 74.3 ng / mL ; for metabolite BJB432 the AUC ( 0 - 24 hr ) was 1940 ng · hr / mL and the Cmax was 105 ng / mL .
The purpose of this exploratory study in mice with COMPOUND_XXX , a partial agonist at serotonin type - 4 ( 5 - HT4 ) receptors in the gastrointestinal tract for the oral treatment of irritable bowel syndrome , was to evaluate effects on the time profile of the diamine oxidase ( DAO ) activity in the jejunum over approximately 24 hours after a 1 - week oral in - feed administration of the test item .
- decrease in red blood cell count ( p < 0.05 - p < 0.01 ) in males and females on days 25 , 53 and 84 , tendency to normalization on day 84 - decrease in hemoglobin ( p < 0.05 - p < 0.01 ) in males and females on days 25 , 53 and 84 , tendency to normalization on day 84 - decrease in packed cell volume ( p < 0.05 - p < 0.01 ) in males and females on days 53 and 84 , tendency to normalization on day 84 - decrease in mean cell volume ( n.s. ) in males and females on day 53 , reversible on day 84 - increase in mean cell hemoglobin concentration ( n.s. ) in males and females on day 53 , reversible on day 84 - decrease in platelet count ( p < 0.05 - p < 0.01 ) in males and females on day 25 and increase ( p < 0.01 ) on day 53 , reversible on day 84 - increase in AST ( p < 0.05 - p < 0.01 ) in males and females on days 2 , 25 , 53 and 84 , tendency to normalization on day 84 - slight increase in ALT ( n.s. - p < 0.01 ) in males and females on days 25 and 53 , reversible on day 84 - increase in cholesterol ( p < 0.05 - p < 0.01 ) in males and females on day 25 , reversible on day 53 - slight decrease in sodium ( n.s. - p < 0.05 ) in males and females on day 25 , reversible on day 53 - slight decrease in albumin and albumin / globulin - quotient ( n.s. - p < 0.01 ) associated with slight increase in beta globulins ( n.s. - p < 0.01 ) in males and females on days 25 , 53 and 84 , tendency to normalization on day 84 - increase of blood and protein in urine in males and females on day 23 , reversible on day 79 All other macroscopic findings noted in this study were considered to be incidental findings commonly occurring in monkeys of this species and age .
In conclusion , repeated oral ( gavage ) treatment of male rats at dose levels of 60 and 180 mg / kg / day for 1 , 3 , 7 , 14 , 21 , at least 49 ( 180mg / kg / day only ) or 91 days ( 60 mg / kg / day only ) caused adverse clinical signs , reduced body weight development , moribundity and mortality mainly in animals at the high dose as early as the end of the second week of dosing .
Other treatment - related alterations that were generally consistent with those observed in earlier studies comprised : pigment deposition in various tissues , hypocellularity in the bone marrow ; lymphoid atrophy in the thymus , spleen , lymph nodes and gut - associated lymphatic tissue ; tubular degeneration in the testes ; oligospermia in the epididymides ; hemorrhagic corpora lutea in the ovaries ; fibrin thrombi in the small intestine , focal to multifocal degranulation , basophilia , single cell necrosis and fibrosis in the exocrine pancreas and abscess formation in the exocrine pancreas in an individual animal ( probably associated with a duct near the duodenum ) .
At 30 mg / kg / day , histopathology findings of the hemolymphatic system consisted of slight ( minimal to mild ) to marked lymphoid depletion in thymus , spleen , lymph nodes , and Peyer ´s patches , as well as slightly decreased extramedullary hemoatopoiesis with slight granulocytic infiltrates in the red pulp ( spleen ) : A mild hemosiderosis ( females , thymus and spleen ) and a slight to moderate acute to subacute blood resorption in lymph nodes were observed ( males and females ) .
At necropsy , poor general condition and emaciation , reddish discoloration of the stomach , small and large intestine , black - brown / hemorrhagic contents of the large intestine , nutmeg liver , opaque fluid or inspissated bile in the gall bladder , reddish discoloration of the outer surface of the gall bladder , small spleen , thymus and testes and jelly - like thymus were observed in dogs which died or were killed in a moribund condition .
COMPOUND_XXX ( Batch no. 0623003 ) was administered orally by gavage as a suspension in 0.5 % ( w / v ) hydroxypropylcellulose , type HF ( Klucel ) at an equivalent dosage volume ( 10 mL / kg ) , to 3 groups ( 20 / sex / group for Main study animals and 8 / sex / group for toxicokinetic subgroup animals ) of male and female Han Wistar rats at doses of 10 , 30 and 75 mg / kg base ( equivalent to 12.6 , 37.7 and 94.4 mg / kg lactate monohydrate salt ) for at least 26 - weeks .
Drug - related clinical signs , which were due to the exaggerated pharmacologic activities of acetylcholine , included flattened body position ( high dose ) ; ataxia , twitches , tremors , decrease in locomotor activity , pale coloring , salivation ( mid and high doses ) ; hypersensitivity to touch , increase in locomotor activity , increased grooming , increased chewing and licking and chromodacryorrhea ( all doses ) .
The AUC ( 0 - 21h ) values of COMPOUND_XXX ranged from 166 to 2647 ng ⋅ h / mL ( plasma ) , 79574 to 571536 ng ⋅ h / g ( jejunal mucosa ) and from 613395 to 7058910 ng ⋅ h / g ( jejunal content ) at 60 and 600 mg / kg / day , respectively .
XXX - 59 ) was administered orally via gavage as a suspension in 0.5 % hydroxypropylmethylcellulose ( HPMC ) Type E4M Premium , aqueous solution to 5 Wistar Hannover rats / sex / group at daily doses of 30 , 100 or 300 mg / kg / day base ( equivalent to 32 , 107 , and 321 mg / kg / day salt based on the salt / base ratio of 1.069 ) .
Relevant findings : High - dose group 20 mg / kgday : first 4 weeks of treatment - Reduced body weight gain or body weight loss ; poor general condition and weakness , findings more pronounced in females - Marked leukopenia ( mainly neutrophils ) One female , sacrificed in a moribund condition with severe leukopenia and marked body weight loss , showed lesions indicative of an infectieus - agent in the respiratory tract , exacerbated by treatment , rather than occurring as a direct effect of the Ganciclovir prodrug .
Based on the nerve fiber degeneration resulting from hypoglycemia at a dose level of 150 mg / kg / day , the no - observed 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 10,600 ng * hr / ml and 3,150 ng / ml , respectively , in males , and 17,000 ng * hr / ml and 5,770 ng / ml , respectively , on day 29 .