Datasets:
javicorvi
/
pretoxtm-dataset

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NO_PRETOX_REL
Each cycle consisted of 3 consecutive days of dosing followed by a 4 - day washout period .
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[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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PRETOX_REL
Compound - related organ weight ( absolute and covariant ) decreases were present at doses ≥ 10 mg / kg and included decreases in submaxillary salivary gland weights ( doses ≥ 10 mg / kg in males ; doses ≥ 30 mg / kg in females ) , adrenal ( doses ≥ 30 mg / kg in males and females ) , liver weights ( doses ≥ 30 mg / kg in males and 75 mg / kg in females ) and prostate weights ( males at ≥ 10 mg / kg ) .
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NO_PRETOX_REL
Following a 4 - week recovery period , the hematology and urinalysis parameters for animals receiving 1.2 mg / kg were comparable to vehicle control values .
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NO_PRETOX_REL
Merely one analysed formulation of the high dose group ( N 6437A - 9 ) exceeded with 132 % the acceptance criteria of + 15 % of the nominal concentration .
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PRETOX_REL
Dermal irritation consisting of very slight erythema only was noted in animals dosed twice a week .
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PRETOX_REL
Minimal to moderate decreases in platelet counts occurred at ~ 0.05 mg / kg in males and at ~ 0.3 mglkg in females but was resolved by the end of recovery .
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NO_PRETOX_REL
The area under the curve was not calculated based on two data points only and therefore any accumulation could not be assessed for this dose group .
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NO_PRETOX_REL
Clinical chemistry parameters showed no clear treatment - related changes in any dose groups .
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[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-GROUP", "I-GROUP", "I-GROUP", "O" ]
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NO_PRETOX_REL
There were no clinical observations or toxicologically relevant effects on body weight development indicating a relationship to the treatment with COMPOUND_XXX .
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[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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PRETOX_REL
Slight body weight losses were seen on day 4 in individual males at doses t 100 mg / kg / day and in individual females at all doses .
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NO_PRETOX_REL
XXXXXX , was administered to male rats at dosages of 60 and 180 mg / kg / day ( at a dosage volume of 5 mL / kg ) , once daily , for either 1 , 3 , 7 , 14 , 21 or at least 49 ( 180mg / kg / day only ) or 91 days ( 60 mg / kg / day only ) .
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PRETOX_REL
Total WBC and absolute lymphocyte counts in group 4 males remained reduced as compared to control after the 4 - week recovery period .
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NO_PRETOX_REL
There was no relevant effect on body weight development and food intake at 20 mg / kg .
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NO_PRETOX_REL
Further groups of 2 male and 2 female minipigs were treated with the placebo formulation or the 200 mg / g formulation and observed after cessation of treatment for 6 weeks to investigate the reversibility of treatment - related effects .
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PRETOX_REL
The decrease in the absolute organ weight of the seminal vesicles from the mid dose of 200 μg / kg COMPOUND_XXX and the additional decrease in the relative organ weight of the seminal vesicles at the high dose of 500 μg / kg COMPOUND_XXX are suspected of being compound related as the decrease is dose dependend .
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NO_PRETOX_REL
Ophthalmologic evaluations were conducted on all animals during pretest and on all control and high - dose animals on day 24 during week 4 .
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PRETOX_REL
Food consumption Food consumption was significantly reduced in animals treated with COMPOUND_XXX at a daily dose of 160 umol / kg bw .
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PRETOX_REL
Based on decreased organ weight in the thyroid , a no - toxic - effect level ( NTEL ) was not established .
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NO_PRETOX_REL
Analytical measurements from removed patches revealed that 46 - 68 % and 34 - 63 % of COMPOUND_XXX were released from the patches on days 1 and 14 , respectively .
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[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
These signs abated during the recovery phase in all affected animals .
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[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
Clinical signs , body weights and food consumption determination were performed on all animals during the study .
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[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
Findings were as follows : Toxicokinetics : Generally greater than dose proportional increases were observed in AUC0 - 24 hr on both toxicokinetic sampling days for both genders .
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[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
In conclusion , the dose level of 5 mg / kg is determined as the maximum tolerated dose ( MTD ) in dogs .
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[ "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
After the recovery period , signs of reversibility were observed in individual animals .
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[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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PRETOX_REL
Based on body weight loss and reduced food consumption in two females from the high - dose recovery group , dosing was discontinued for all group 4 animals and recovery was initiated a day earlier than originally scheduled .
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NO_PRETOX_REL
Blood samples for toxicokinetic analyses were collected on all animals for determination of COMPOUND_XXX plasma levels during week 2 ( day 8 ) at 0 , 2 , 4 , 6 and 18 hours following the second dose of the day .
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PRETOX_REL
Treatment - related clinical signs consisted of fecal changes ( females at doses ≥ 0.2 mg / kg ; males at 1.2 mg / kg ) and limited hindlimb usage / abnormal gait ( individual males at 0.2 and 1.2 mg / kg ; 3/5 females at 1.2 mg / kg ) with affected limbs often red , slightly swollen and warm to touch .
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PRETOX_REL
Post mortem examinations : - cholestasis ( intrahepatocellular and in the bile canaliculi ) , hydropic and fatty degeneration of hepatocytes and centrilobular necrosis in male and female animals .
[ "Post", "mortem", "examinations", ":", "-", "cholestasis", "(", "intrahepatocellular", "and", "in", "the", "bile", "canaliculi", ")", ",", "hydropic", "and", "fatty", "degeneration", "of", "hepatocytes", "and", "centrilobular", "necrosis", "in", "male", "and", "female", "animals", "." ]
[ "O", "O", "O", "O", "O", "B-FINDING", "O", "O", "O", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "B-FINDING", "I-FINDING", "O", "B-SEX", "I-SEX", "I-SEX", "O", "O" ]
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PRETOX_REL
Lymphocyte counts were reduced for males at 300 mg / kg / day and decreased monocyte and eosinophil counts were present at dosages of 75 mg / kg / day or above .
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NO_PRETOX_REL
There was no apparent difference in exposure between males and females as measured by both AUC and Cmax · There was also no increase in exposure between weeks 1 and 39 .
[ "There", "was", "no", "apparent", "difference", "in", "exposure", "between", "males", "and", "females", "as", "measured", "by", "both", "AUC", "and", "Cmax", "·", "There", "was", "also", "no", "increase", "in", "exposure", "between", "weeks", "1", "and", "39", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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PRETOX_REL
In addition , the male showed a moderate increase in neutrophils ( +308 % ) and the female showed a slight decrease in albumin ( - 23 % ) and total protein ( - 19 % ) .
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NO_PRETOX_REL
There was no mortality , ocular changes , abnormal electrocardiographic or hematological findings attributable to treatment with COMPOUND_XXX .
[ "There", "was", "no", "mortality", ",", "ocular", "changes", ",", "abnormal", "electrocardiographic", "or", "hematological", "findings", "attributable", "to", "treatment", "with", "COMPOUND_XXX", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
Complete necropsies were performed and macroscopic observations were recorded .
[ "Complete", "necropsies", "were", "performed", "and", "macroscopic", "observations", "were", "recorded", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
Additional control and high dose animals ( 2 / sex / group ) served as recovery animals for a 4 - week recovery period .
[ "Additional", "control", "and", "high", "dose", "animals", "(", "2", "/", "sex", "/", "group", ")", "served", "as", "recovery", "animals", "for", "a", "4", "-", "week", "recovery", "period", "." ]
[ "O", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "O", "O", "B-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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PRETOX_REL
Treatment at 50 mg / kg / day resulted in slightly increased AST , ALT , total protein , albumin and globulin and slightly decreased A / G ratio , sodium , cholesterol and triglycerides .
[ "Treatment", "at", "50", "mg", "/", "kg", "/", "day", "resulted", "in", "slightly", "increased", "AST", ",", "ALT", ",", "total", "protein", ",", "albumin", "and", "globulin", "and", "slightly", "decreased", "A", "/", "G", "ratio", ",", "sodium", ",", "cholesterol", "and", "triglycerides", "." ]
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NO_PRETOX_REL
The purpose of this study was to investigate alterations in the thyroid in male rats administered COMPOUND_XXX at 75 mg / kg / day for 5 , 12 or 26 days ( 3 doses per week ) , compared with a positive control agent , propylthiouracil , which has known effects on the thyroid .
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NO_PRETOX_REL
The purpose of this study was to evaluate the potential toxicity of COMPOUND_XXX when administered to mice once daily or twice weekly by dermal skin painting for 28 days .
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[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
At necropsy , gross pathology and organ weights were evaluated , and histopathologic examination of tissue specimens was conducted subsequently .
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PRETOX_REL
The initial high dose of 1.5 mg / kg / day caused intolerable side effects , which resulted in a dose reduction to 1.0 mg / kg / day in Week 1 .
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[ "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "B-FINDING", "I-FINDING", "I-FINDING", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O" ]
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NO_PRETOX_REL
The animals were regularly monitored for viability .
[ "The", "animals", "were", "regularly", "monitored", "for", "viability", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
Comparable to the parent , the tissue concentrations of COMPOUND_XXX - D6 in the different tissues investigated were : cortex ≈ liver > pelvis at 60 mg / kg / day and liver >> cortex >> pelvis at 180 mg / kg / day .
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NO_PRETOX_REL
As these changes were slight to moderate in severity at 75 and 150 mg / kg / day , it is recommended that the high dosage should not exceed 150 mg / kg / day in the forthcoming 13 - week study in this species .
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NO_PRETOX_REL
The increase in exposure was generally dose - proportional in both male and female dogs after both a single dose and after three doses / week for more than three weeks .
[ "The", "increase", "in", "exposure", "was", "generally", "dose", "-", "proportional", "in", "both", "male", "and", "female", "dogs", "after", "both", "a", "single", "dose", "and", "after", "three", "doses", "/", "week", "for", "more", "than", "three", "weeks", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
The cause of death could not be determined in any of these animals however , they were considered treatment - related .
[ "The", "cause", "of", "death", "could", "not", "be", "determined", "in", "any", "of", "these", "animals", "however", ",", "they", "were", "considered", "treatment", "-", "related", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
No signs were observed during the first 14 days oftreatment nor during the nine day extension period .
[ "No", "signs", "were", "observed", "during", "the", "first", "14", "days", "oftreatment", "nor", "during", "the", "nine", "day", "extension", "period", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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PRETOX_REL
There was a local transient erythema at the application site .
[ "There", "was", "a", "local", "transient", "erythema", "at", "the", "application", "site", "." ]
[ "O", "O", "O", "O", "O", "B-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O" ]
[ 0, 0, 0, 0, 0, 8, 0, 0, 10, 11, 0 ]
NO_PRETOX_REL
Ophthalmologic evaluations were conducted on all animals during pretest and on all control and high - dose animals during week 4 .
[ "Ophthalmologic", "evaluations", "were", "conducted", "on", "all", "animals", "during", "pretest", "and", "on", "all", "control", "and", "high", "-", "dose", "animals", "during", "week", "4", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "O", "O", "O", "O", "O" ]
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PRETOX_REL
Dark livers were noted in 4/5 females and enlarged livers in 3/5 females .
[ "Dark", "livers", "were", "noted", "in", "4/5", "females", "and", "enlarged", "livers", "in", "3/5", "females", "." ]
[ "B-FINDING", "B-SPECIMEN", "O", "O", "O", "O", "B-SEX", "O", "B-FINDING", "B-SPECIMEN", "O", "O", "B-SEX", "O" ]
[ 8, 10, 0, 0, 0, 0, 5, 0, 8, 10, 0, 0, 5, 0 ]
PRETOX_REL
No clinical signs were observed in males and females at any time point except in one male of the 75 mg / kg / day group that showed piloerection for a few days during the treatment period .
[ "No", "clinical", "signs", "were", "observed", "in", "males", "and", "females", "at", "any", "time", "point", "except", "in", "one", "male", "of", "the", "75", "mg", "/", "kg", "/", "day", "group", "that", "showed", "piloerection", "for", "a", "few", "days", "during", "the", "treatment", "period", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-SEX", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "B-FINDING", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
Although in some instances variations from control attained levels of statistical significance , they were either of insufficient magnitude or showed no pattern to indicate an effect of treatment .
[ "Although", "in", "some", "instances", "variations", "from", "control", "attained", "levels", "of", "statistical", "significance", ",", "they", "were", "either", "of", "insufficient", "magnitude", "or", "showed", "no", "pattern", "to", "indicate", "an", "effect", "of", "treatment", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
Animals were dosed for 4 cycles , at doses of 0 ( control ) , 0.05 , 0.3 and 0.9 mglkg at a dose volume of 2 mL / kg .
[ "Animals", "were", "dosed", "for", "4", "cycles", ",", "at", "doses", "of", "0", "(", "control", ")", ",", "0.05", ",", "0.3", "and", "0.9", "mglkg", "at", "a", "dose", "volume", "of", "2", "mL", "/", "kg", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
This study was designed to estimate a no - toxic - effect - level , the toxicokinetic profile , and the potential for reversal of any toxic effects within a 4 - week postdosing / recovery phase .
[ "This", "study", "was", "designed", "to", "estimate", "a", "no", "-", "toxic", "-", "effect", "-", "level", ",", "the", "toxicokinetic", "profile", ",", "and", "the", "potential", "for", "reversal", "of", "any", "toxic", "effects", "within", "a", "4", "-", "week", "postdosing", "/", "recovery", "phase", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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PRETOX_REL
At 1.0 and 7.5 mg / kg / day , hunched posture was evident in both sexes , and “ Holding body close to cage floor ” , partially closed eyes and limb extension were also noted in males only at 1.0 mg / kg / day and both sexes at 7.5 mg / kg / day .
[ "At", "1.0", "and", "7.5", "mg", "/", "kg", "/", "day", ",", "hunched", "posture", "was", "evident", "in", "both", "sexes", ",", "and", "“", "Holding", "body", "close", "to", "cage", "floor", "”", ",", "partially", "closed", "eyes", "and", "limb", "extension", "were", "also", "noted", "in", "males", "only", "at", "1.0", "mg", "/", "kg", "/", "day", "and", "both", "sexes", "at", "7.5", "mg", "/", "kg", "/", "day", "." ]
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PRETOX_REL
Three group 4 ( 1000 mg / kg ) males showed respiratory sounds .
[ "Three", "group", "4", "(", "1000", "mg", "/", "kg", ")", "males", "showed", "respiratory", "sounds", "." ]
[ "O", "B-GROUP", "I-GROUP", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "B-SEX", "O", "B-FINDING", "I-FINDING", "O" ]
[ 0, 12, 13, 0, 3, 4, 4, 4, 0, 5, 0, 8, 9, 0 ]
NO_PRETOX_REL
Histopathologic evaluation of the tissues examined in this study did not detect any toxicity .
[ "Histopathologic", "evaluation", "of", "the", "tissues", "examined", "in", "this", "study", "did", "not", "detect", "any", "toxicity", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
All other concentrations were within specifications .
[ "All", "other", "concentrations", "were", "within", "specifications", "." ]
[ "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL
Treatment - related very slight or well - defined erythema occasionally occurred at the application sites in groups 2 , 3 and 4 for maximally 3 days after patch removal .
[ "Treatment", "-", "related", "very", "slight", "or", "well", "-", "defined", "erythema", "occasionally", "occurred", "at", "the", "application", "sites", "in", "groups", "2", ",", "3", "and", "4", "for", "maximally", "3", "days", "after", "patch", "removal", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "O", "O", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "B-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 8, 0, 0, 0, 0, 10, 11, 0, 12, 13, 13, 13, 13, 13, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL
An increase in the incidence of generally minimal inflammatory foci in the heart was present at 60 mg / kg , but the toxicological significance is equivocal .
[ "An", "increase", "in", "the", "incidence", "of", "generally", "minimal", "inflammatory", "foci", "in", "the", "heart", "was", "present", "at", "60", "mg", "/", "kg", ",", "but", "the", "toxicological", "significance", "is", "equivocal", "." ]
[ "O", "B-MANIFESTATION_FINDING", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 1, 0, 0, 0, 0, 0, 0, 8, 9, 0, 0, 10, 0, 0, 0, 3, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
Enlarged livers were observed in 4/5 males and 2/5 females .
[ "Enlarged", "livers", "were", "observed", "in", "4/5", "males", "and", "2/5", "females", "." ]
[ "O", "B-SPECIMEN", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 10, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL
At 50 mg / kg / day , swelling ( one female ) , swollen appendages , limping , red feet , dry perineal staining and an increased incidence and frequency of swollen muzzles were noted .
[ "At", "50", "mg", "/", "kg", "/", "day", ",", "swelling", "(", "one", "female", ")", ",", "swollen", "appendages", ",", "limping", ",", "red", "feet", ",", "dry", "perineal", "staining", "and", "an", "increased", "incidence", "and", "frequency", "of", "swollen", "muzzles", "were", "noted", "." ]
[ "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "B-FINDING", "O", "O", "B-SEX", "O", "O", "B-FINDING", "I-FINDING", "O", "B-FINDING", "O", "B-FINDING", "I-FINDING", "O", "B-FINDING", "I-FINDING", "I-FINDING", "O", "O", "B-MANIFESTATION_FINDING", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "O", "O", "O" ]
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PRETOX_REL
At clinical pathology examination , the very few compound - related findings consisted of prolongations of Prothrombin Times in both animals at 100 mg / kg / day , related to the pharmacological activity of the compound , and variations in urinalysis parameters from 30 mg / kg / day ( increases in urine volumes and presence of proteins , reversible ) .
[ "At", "clinical", "pathology", "examination", ",", "the", "very", "few", "compound", "-", "related", "findings", "consisted", "of", "prolongations", "of", "Prothrombin", "Times", "in", "both", "animals", "at", "100", "mg", "/", "kg", "/", "day", ",", "related", "to", "the", "pharmacological", "activity", "of", "the", "compound", ",", "and", "variations", "in", "urinalysis", "parameters", "from", "30", "mg", "/", "kg", "/", "day", "(", "increases", "in", "urine", "volumes", "and", "presence", "of", "proteins", ",", "reversible", ")", "." ]
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PRETOX_REL
The mesenteric lymph nodes showed multifocal red discolorations in females .
[ "The", "mesenteric", "lymph", "nodes", "showed", "multifocal", "red", "discolorations", "in", "females", "." ]
[ "O", "B-SPECIMEN", "I-SPECIMEN", "I-SPECIMEN", "O", "O", "B-FINDING", "I-FINDING", "O", "B-SEX", "O" ]
[ 0, 10, 11, 11, 0, 0, 8, 9, 0, 5, 0 ]
NO_PRETOX_REL
d ) Mortalities There were no mortalities during the course of the study .
[ "d", ")", "Mortalities", "There", "were", "no", "mortalities", "during", "the", "course", "of", "the", "study", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
during the treatment period as well as during the recovery period ( p < 0.01 , Dunnett test ) .
[ "during", "the", "treatment", "period", "as", "well", "as", "during", "the", "recovery", "period", "(", "p", "<", "0.01", ",", "Dunnett", "test", ")", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
Clinical signs , body weight and food consumption determinations were performed on all the animals .
[ "Clinical", "signs", ",", "body", "weight", "and", "food", "consumption", "determinations", "were", "performed", "on", "all", "the", "animals", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
Data from recovery animals was generally unremarkable .
[ "Data", "from", "recovery", "animals", "was", "generally", "unremarkable", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL
The histopathological findings observed in the heart were paralleled by an increase in the heart weight ratio in group III ( 30/60 mg / kg ) - females .
[ "The", "histopathological", "findings", "observed", "in", "the", "heart", "were", "paralleled", "by", "an", "increase", "in", "the", "heart", "weight", "ratio", "in", "group", "III", "(", "30/60", "mg", "/", "kg", ")", "-", "females", "." ]
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PRETOX_REL
In addition , at the mid dose of 2 mg / kg COMPOUND_XXX and higher : - decreased body weight gain in week 4 as well as over the whole treatment period ; - acinar hypertrophy in the intraorbital lacrimal gland .
[ "In", "addition", ",", "at", "the", "mid", "dose", "of", "2", "mg", "/", "kg", "COMPOUND_XXX", "and", "higher", ":", "-", "decreased", "body", "weight", "gain", "in", "week", "4", "as", "well", "as", "over", "the", "whole", "treatment", "period", ";", "-", "acinar", "hypertrophy", "in", "the", "intraorbital", "lacrimal", "gland", "." ]
[ "O", "O", "O", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "B-MANIFESTATION_FINDING", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "I-SPECIMEN", "O" ]
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PRETOX_REL
In the teeth , dose - dependent degeneration and decreased iron contents in ameloblasts corresponded to discoloration of the incisors at 10 mg / kg and higher .
[ "In", "the", "teeth", ",", "dose", "-", "dependent", "degeneration", "and", "decreased", "iron", "contents", "in", "ameloblasts", "corresponded", "to", "discoloration", "of", "the", "incisors", "at", "10", "mg", "/", "kg", "and", "higher", "." ]
[ "O", "O", "B-SPECIMEN", "O", "O", "O", "O", "B-FINDING", "O", "B-MANIFESTATION_FINDING", "B-STUDY_TESTCD", "O", "O", "O", "O", "O", "B-FINDING", "O", "O", "B-SPECIMEN", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O" ]
[ 0, 0, 10, 0, 0, 0, 0, 8, 0, 1, 2, 0, 0, 0, 0, 0, 8, 0, 0, 10, 0, 3, 4, 4, 4, 0, 0, 0 ]
PRETOX_REL
Piloerection was observed in all animals receiving 300 mg / kg / day .
[ "Piloerection", "was", "observed", "in", "all", "animals", "receiving", "300", "mg", "/", "kg", "/", "day", "." ]
[ "B-FINDING", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]
[ 8, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0 ]
NO_PRETOX_REL
Samples of treated and Control skin were retained and the treated skin of all animals was examined microscopically .
[ "Samples", "of", "treated", "and", "Control", "skin", "were", "retained", "and", "the", "treated", "skin", "of", "all", "animals", "was", "examined", "microscopically", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
At the end of the dosing period , at 1.0 mg / kg , the mean AUC ( 0 - 24h ) was 76.7 ± 18.5 ng.h / mL and 88.4 ± 37.8 ng.h / mL for males and females respectively , Cmax , was 23.2 ± 6.63 ng / mL and 22.9 ± 8.44 ng / mL for males and females respectively and tmax , was 0.5 ± 0 h and 0.6 ± 0.3 h for males and females respectively .
[ "At", "the", "end", "of", "the", "dosing", "period", ",", "at", "1.0", "mg", "/", "kg", ",", "the", "mean", "AUC", "(", "0", "-", "24h", ")", "was", "76.7", "±", "18.5", "ng.h", "/", "mL", "and", "88.4", "±", "37.8", "ng.h", "/", "mL", "for", "males", "and", "females", "respectively", ",", "Cmax", ",", "was", "23.2", "±", "6.63", "ng", "/", "mL", "and", "22.9", "±", "8.44", "ng", "/", "mL", "for", "males", "and", "females", "respectively", "and", "tmax", ",", "was", "0.5", "±", "0", "h", "and", "0.6", "±", "0.3", "h", "for", "males", "and", "females", "respectively", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
A concurrent control group received the vehicle control article on a comparable regimen .
[ "A", "concurrent", "control", "group", "received", "the", "vehicle", "control", "article", "on", "a", "comparable", "regimen", "." ]
[ "O", "O", "B-GROUP", "I-GROUP", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 12, 13, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
The purpose of this 2 - week study in rats was to aid in the selection of dosages for a proposed 13 - week study in this species .
[ "The", "purpose", "of", "this", "2", "-", "week", "study", "in", "rats", "was", "to", "aid", "in", "the", "selection", "of", "dosages", "for", "a", "proposed", "13", "-", "week", "study", "in", "this", "species", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
The test article was formulated as patches , each with a content of 18 mg COMPOUND_XXX , Batch Nos XXXXXX and YYYY or 0 mg , placebo Batch Nos ZZZZZ and WWWWWW .
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PRETOX_REL
In conclusion , dermal skin painting of COMPOUND_XXX Nail Lacquer at doses of 100 , 200 , and 270 mg / kg / day for 28 days produced test - article related findings in the treated skin sections when applied daily .
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NO_PRETOX_REL
Plasma levels had decreased below the limit of quantification at 24 hours in all animals , and the area under the curve could only be determined from 5 minutes to 3 hours post injection .
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NO_PRETOX_REL
After once weekly dosing for at least 13 weeks , exposure to COMPOUND_XXX and BJB432 was similar to the exposure after a single dose in both male and female dogs .
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[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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PRETOX_REL
However , there was a reduction in overall weight gain for females given ≥ 0.6 mg / kg which appeared to correlate with slight decreases in food consumption during the treatment period .
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PRETOX_REL
Four males and 10 females given 400 mg / kg / day died or were euthanatized within 7 to 22 days after initiation of treatment .
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NO_PRETOX_REL
In the low dose group tiast was observed between 4 and 24 h post-dose .
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[ "O", "O", "B-GROUP", "I-GROUP", "I-GROUP", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
Females showed slightly higher exposure levels at doses of 30 and 100 mg / kg / day .
[ "Females", "showed", "slightly", "higher", "exposure", "levels", "at", "doses", "of", "30", "and", "100", "mg", "/", "kg", "/", "day", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]
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NO_PRETOX_REL
volume of drug or vehicle administered was 10 ml ; kg / day .
[ "volume", "of", "drug", "or", "vehicle", "administered", "was", "10", "ml", ";", "kg", "/", "day", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]
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NO_PRETOX_REL
Out of the 18 rats / sex / group from the toxicity study , 12 rats / sex / group were sacrificed after at least 4 weeks of treatment and the remaining 6 rats / sex / group ( based on survival ) were sacrificed after at least 4 weeks of recovery .
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PRETOX_REL
The trachea showed a mild to moderate pyogranulomatous inflammation in single rats , in males with increased incidences of mixed subepithelial infiltrates .
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[ "O", "B-SPECIMEN", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "O", "O", "O", "O", "O", "B-SEX", "O", "B-MANIFESTATION_FINDING", "O", "O", "O", "B-FINDING", "I-FINDING", "O" ]
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PRETOX_REL
Test article - related decreases in estimated food consumption were noted in both sexes at 80 mglkg / day .
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[ "O", "O", "O", "O", "B-MANIFESTATION_FINDING", "O", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "B-SEX", "I-SEX", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]
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PRETOX_REL
In conclusion , intravenous administration of COMPOUND_XXX at doses of 0.3 , 1.0 and 3 mg / kg for 13 weeks using a once weekly dosing schedule was associated with compound - related decreases in body weight parameters , food consumption , white blood cell counts and lymphocyte counts at doses ≥ 0.3 mg / kg .
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NO_PRETOX_REL
Additional histopathological findings , observed with comparable incidence in both controls and treated rats ( KO ) in this study were considered to be spontaneous or incidental and none of these finding was attributed to effects of the test item .
[ "Additional", "histopathological", "findings", ",", "observed", "with", "comparable", "incidence", "in", "both", "controls", "and", "treated", "rats", "(", "KO", ")", "in", "this", "study", "were", "considered", "to", "be", "spontaneous", "or", "incidental", "and", "none", "of", "these", "finding", "was", "attributed", "to", "effects", "of", "the", "test", "item", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
CONCLUSION Toxicokinetic results showed that following a 4 - week repeated oral administration at doses of 80 to 480 mg / kg / day of COMPOUND_XXX , all macaques were exposed to COMPOUND_XXX on dosing Days 1 and 29 .
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NO_PRETOX_REL
Administration of 50111 of COMPOUND_XXX at a concentration of0 .4 mg / ml was considered to be close to the maximum tolerated dose .
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NO_PRETOX_REL
The study was mainly focused on the histopathological , electron microscopical , and molecular biological evaluation of tissues of the heart and skeletal muscle .
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[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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PRETOX_REL
Pathological examination revealed increased mastocytes ( grade 3 ) in 5/12 high dose animals and in 1/8 low dose recovery animals as swell as increased histiocytes in the mesenteric lymph nodes ( grade 3 ) in 2/19 control , 7/20 high dose , and in 2/8 high dose recovery rats .
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PRETOX_REL
Discussion Bone and tooth changes observed in this study were related to increased exposure to fluoride with its accumulation , and were also consistent with skeletal / dental fluorosis in rats reported in the literature ( NTP , 1990 ; Maurer et al , 1990 ; Ream , 1981 ) .
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[ "O", "B-SPECIMEN", "O", "B-SPECIMEN", "B-FINDING", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
The potential systemic toxicity , and reversibility of toxic effects of the test article , COMPOUND_XXX , were evaluated in this one - month study ( with a one - month recovery period ) in Crl : WI ( GLx / BRL / HAN ) IGS BR rats .
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NO_PRETOX_REL
The following rounded values of Cmax and AUC ( o - 24h ) were observed on day 14 : COMPOUND_XXX Male Female COMPOUND_XXX - 666 Male Female 11 121 120 14 10 53 14 103 102 17 16 60 185 1810 1113 199 168 735 247 1637 1003 242 239 942 Cmax ( ng / ml ) 36 mg / day 108 mg / day 216 mg / day AUC o - 24h ( h.ng / ml ) 36 mg / day 108 mg / day 216 mg / day Because of the great between - animal variability , an increase of the concentration with the dose could not be demonstrated .
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NO_PRETOX_REL
Electrocardiography was performed at pretest , and on day 13 .
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PRETOX_REL
In general , there were no differences in the severity of the findings between the two treated groups with the exception of the pancreatic lesions which were mainly observed at 10 / 100/75 mg / kg / day .
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PRETOX_REL
In the stomach , minimal multifocal acute hemorrhages were found in the glandular stomach .
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PRETOX_REL
Determination of organ weights revealed a dose - dependent increase of the relative kidney weights in 40 and 8 mg / kg / d males .
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NO_PRETOX_REL
Blood samples were taken prior to treatment ( on the first day ) , and at approximately 2 , 6 , and 24 h following patch application on the 1st and 14th days .
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