javicorvi/pretoxtm-dataset · Datasets at Hugging Face

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NO_PRETOX_REL	The control animals were treated with placebo patches of the same size and the same number as the 216 mg group .	[ "The", "control", "animals", "were", "treated", "with", "placebo", "patches", "of", "the", "same", "size", "and", "the", "same", "number", "as", "the", "216", "mg", "group", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "O", "O" ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 0 ]
PRETOX_REL	Clinical changes in rats given 400 mg / kg / day included : cold - to - touch , ataxia , labored respiration , inactivity , wasting , unthriftiness , rough coat , pallor , swollen prepuce , salivation , mouth / nose discharge , and urogenital stain .	[ "Clinical", "changes", "in", "rats", "given", "400", "mg", "/", "kg", "/", "day", "included", ":", "cold", "-", "to", "-", "touch", ",", "ataxia", ",", "labored", "respiration", ",", "inactivity", ",", "wasting", ",", "unthriftiness", ",", "rough", "coat", ",", "pallor", ",", "swollen", "prepuce", ",", "salivation", ",", "mouth", "/", "nose", "discharge", ",", "and", "urogenital", "stain", "." ]	[ "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "B-FINDING", "O", "B-FINDING", "I-FINDING", "I-FINDING", "B-FINDING", "O", "B-FINDING", "O", "B-FINDING", "O", "B-FINDING", "I-FINDING", "O", "B-FINDING", "O", "B-FINDING", "I-FINDING", "O", "B-FINDING", "O", "B-SPECIMEN", "O", "B-SPECIMEN", "B-FINDING", "O", "O", "B-FINDING", "I-FINDING", "O" ]	[ 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0, 0, 8, 9, 9, 9, 9, 0, 8, 0, 8, 9, 9, 8, 0, 8, 0, 8, 0, 8, 9, 0, 8, 0, 8, 9, 0, 8, 0, 10, 0, 10, 8, 0, 0, 8, 9, 0 ]
NO_PRETOX_REL	The study is designed to establish a no - observed - adverse - effect level ( NOAEL ) , to establish a maximal tolerated dose , to estimate the toxicokinetic profile , and to estimate the potential for reversal of any toxic effects within a 4 - week post dosing period .	[ "The", "study", "is", "designed", "to", "establish", "a", "no", "-", "observed", "-", "adverse", "-", "effect", "level", "(", "NOAEL", ")", ",", "to", "establish", "a", "maximal", "tolerated", "dose", ",", "to", "estimate", "the", "toxicokinetic", "profile", ",", "and", "to", "estimate", "the", "potential", "for", "reversal", "of", "any", "toxic", "effects", "within", "a", "4", "-", "week", "post", "dosing", "period", "." ]	[ "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" ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL	The _ reason for this is most probably a marked liver cirrhosis accompanied by several other findings ( including moderate thymic atrophy ) .	[ "The", "_", "reason", "for", "this", "is", "most", "probably", "a", "marked", "liver", "cirrhosis", "accompanied", "by", "several", "other", "findings", "(", "including", "moderate", "thymic", "atrophy", ")", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "O", "O" ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 8, 9, 0, 0, 0, 0, 0, 0, 0, 0, 8, 9, 0, 0 ]
NO_PRETOX_REL	In view of this finding a NOEL can be set at 60 mg / kg / day under the conditions of the present study .	[ "In", "view", "of", "this", "finding", "a", "NOEL", "can", "be", "set", "at", "60", "mg", "/", "kg", "/", "day", "under", "the", "conditions", "of", "the", "present", "study", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "O" ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL	Dose Level 3 At dose level 3 , absolute and relative liver weights were increased in male rats .	[ "Dose", "Level", "3", "At", "dose", "level", "3", ",", "absolute", "and", "relative", "liver", "weights", "were", "increased", "in", "male", "rats", "." ]	[ "B-DOSE", "I-DOSE", "I-DOSE", "O", "B-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "B-SPECIMEN", "B-STUDY_TESTCD", "O", "B-MANIFESTATION_FINDING", "O", "B-SEX", "O", "O" ]	[ 3, 4, 4, 0, 3, 4, 4, 0, 0, 0, 0, 10, 2, 0, 1, 0, 5, 0, 0 ]
PRETOX_REL	Tne growth plates of die kite were also thickened ( approx I - I times ) in animals given 1000 mg / kg / day , although thickening was not apparent at lower doses .	[ "Tne", "growth", "plates", "of", "die", "kite", "were", "also", "thickened", "(", "approx", "I", "-", "I", "times", ")", "in", "animals", "given", "1000", "mg", "/", "kg", "/", "day", ",", "although", "thickening", "was", "not", "apparent", "at", "lower", "doses", "." ]	[ "O", "B-SPECIMEN", "I-SPECIMEN", "O", "O", "O", "O", "O", "B-FINDING", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "O" ]	[ 0, 10, 11, 0, 0, 0, 0, 0, 8, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 15, 16, 0 ]
NO_PRETOX_REL	No changes were observed in the evaluated electrocardiography , ophthalmology , or urinalysis endpoints .	[ "No", "changes", "were", "observed", "in", "the", "evaluated", "electrocardiography", ",", "ophthalmology", ",", "or", "urinalysis", "endpoints", "." ]	[ "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	Whatever the sex , the dose and the toxicokinetic sampling day , COMPOUND_XXX concentrations were above the LLOQ up to 24 hours in all treated animals .	[ "Whatever", "the", "sex", ",", "the", "dose", "and", "the", "toxicokinetic", "sampling", "day", ",", "COMPOUND_XXX", "concentrations", "were", "above", "the", "LLOQ", "up", "to", "24", "hours", "in", "all", "treated", "animals", "." ]	[ "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" ]	[ 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 ]
PRETOX_REL	Alterations were slight , except in a single rat with pronounced alterations in the lymphoid system : The Peyer ´s patches had a slight decrease of germinal centers in some rats .	[ "Alterations", "were", "slight", ",", "except", "in", "a", "single", "rat", "with", "pronounced", "alterations", "in", "the", "lymphoid", "system", ":", "The", "Peyer", "´s", "patches", "had", "a", "slight", "decrease", "of", "germinal", "centers", "in", "some", "rats", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "O", "O", "O" ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 8, 9, 0, 0, 10, 11, 0, 0, 0, 0, 0, 0, 0, 0, 8, 9, 9, 9, 0, 0, 0, 0 ]
NO_PRETOX_REL	On day 28 after the implantation all concentrations were below LLOQ .	[ "On", "day", "28", "after", "the", "implantation", "all", "concentrations", "were", "below", "LLOQ", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL	In the high dose â € ˜group an uncommon concentration time profile Influence of Repeated Dosing : After repeated dosing a slight change in AUC ( 0.24 ) and Cmax was observed in the low and mid dose group .	[ "In", "the", "high", "dose", "â", "€", "˜group", "an", "uncommon", "concentration", "time", "profile", "Influence", "of", "Repeated", "Dosing", ":", "After", "repeated", "dosing", "a", "slight", "change", "in", "AUC", "(", "0.24", ")", "and", "Cmax", "was", "observed", "in", "the", "low", "and", "mid", "dose", "group", "." ]	[ "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "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", "B-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "O" ]	[ 0, 0, 15, 16, 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, 12, 13, 13, 13, 13, 0 ]
NO_PRETOX_REL	Complete necropsies including macroscopic assessments were performed on all animals .	[ "Complete", "necropsies", "including", "macroscopic", "assessments", "were", "performed", "on", "all", "animals", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL	Two group III ( 30/60 mg / kg ) - females showed granulocytic infiltration in the liver paralleled by an increase in the liver weight ratio .	[ "Two", "group", "III", "(", "30/60", "mg", "/", "kg", ")", "-", "females", "showed", "granulocytic", "infiltration", "in", "the", "liver", "paralleled", "by", "an", "increase", "in", "the", "liver", "weight", "ratio", "." ]	[ "O", "B-GROUP", "I-GROUP", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "B-SEX", "O", "B-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "O", "O", "O", "B-MANIFESTATION_FINDING", "O", "O", "B-SPECIMEN", "B-STUDY_TESTCD", "O", "O" ]	[ 0, 12, 13, 0, 3, 4, 4, 4, 0, 0, 5, 0, 8, 9, 0, 0, 10, 0, 0, 0, 1, 0, 0, 10, 2, 0, 0 ]
NO_PRETOX_REL	No accumulation was observed in all the groups .	[ "No", "accumulation", "was", "observed", "in", "all", "the", "groups", "." ]	[ "O", "O", "O", "O", "O", "B-GROUP", "I-GROUP", "I-GROUP", "O" ]	[ 0, 0, 0, 0, 0, 12, 13, 13, 0 ]
NO_PRETOX_REL	COMPOUND_XXX was administered in feed to groups of 14 male and 14 female rats ( Han!bm : WIST ) for 26 weeks at the dose levels of 0 ( controls ) , 15 , 60 and 240 mg / kg / day .	[ "COMPOUND_XXX", "was", "administered", "in", "feed", "to", "groups", "of", "14", "male", "and", "14", "female", "rats", "(", "Han!bm", ":", "WIST", ")", "for", "26", "weeks", "at", "the", "dose", "levels", "of", "0", "(", "controls", ")", ",", "15", ",", "60", "and", "240", "mg", "/", "kg", "/", "day", "." ]	[ "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", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]	[ 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, 3, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0 ]
NO_PRETOX_REL	Body weight and food consumption were recorded weekly .	[ "Body", "weight", "and", "food", "consumption", "were", "recorded", "weekly", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "O", "O" ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL	Clinical pathology changes were limited to mild increases in APIT in males given 225 and 500 mg / kg / day of NS and in males given 500 mg & fday of OS .	[ "Clinical", "pathology", "changes", "were", "limited", "to", "mild", "increases", "in", "APIT", "in", "males", "given", "225", "and", "500", "mg", "/", "kg", "/", "day", "of", "NS", "and", "in", "males", "given", "500", "mg", "&", "fday", "of", "OS", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "B-MANIFESTATION_FINDING", "O", "B-STUDY_TESTCD", "O", "B-SEX", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "B-SEX", "O", "B-DOSE", "I-DOSE", "O", "O", "O", "O", "O" ]	[ 0, 0, 0, 0, 0, 0, 0, 1, 0, 2, 0, 5, 0, 3, 4, 4, 4, 4, 4, 4, 4, 0, 0, 0, 0, 5, 0, 3, 4, 0, 0, 0, 0, 0 ]
PRETOX_REL	Organ toxicity in form of focal / multifocal foam cell aggregates in the lung , to be suspected for this class of cationic amphiphilic compounds , occurred from the mid dose onwards .	[ "Organ", "toxicity", "in", "form", "of", "focal", "/", "multifocal", "foam", "cell", "aggregates", "in", "the", "lung", ",", "to", "be", "suspected", "for", "this", "class", "of", "cationic", "amphiphilic", "compounds", ",", "occurred", "from", "the", "mid", "dose", "onwards", "." ]	[ "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "O", "O" ]	[ 0, 0, 0, 0, 0, 8, 9, 9, 9, 9, 9, 0, 0, 10, 11, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 15, 16, 0, 0 ]
NO_PRETOX_REL	Concentrations of the test item in serum , heart and muscle tissues were in a roughly similar order of magnitude around the time of COMPOUND_XXX peak serum levels after 4 weeks of treatment with a trend towards slightly lower values in tissues than in serum .	[ "Concentrations", "of", "the", "test", "item", "in", "serum", ",", "heart", "and", "muscle", "tissues", "were", "in", "a", "roughly", "similar", "order", "of", "magnitude", "around", "the", "time", "of", "COMPOUND_XXX", "peak", "serum", "levels", "after", "4", "weeks", "of", "treatment", "with", "a", "trend", "towards", "slightly", "lower", "values", "in", "tissues", "than", "in", "serum", "." ]	[ "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" ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL	All the above findings proved reversible by the end of the recovery period , or showed a tendency towards recovery .	[ "All", "the", "above", "findings", "proved", "reversible", "by", "the", "end", "of", "the", "recovery", "period", ",", "or", "showed", "a", "tendency", "towards", "recovery", "." ]	[ "O", "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, 0 ]
PRETOX_REL	The scores for erythema tended to be higher in the group treated with two patches / application and dosing every 6th day at the same site , than in the group treated with two patches / application and dosing every 12th day at the same site , which in turn tended to be higher than in the group treated with one patch / application and dosing every 12th day at the same site .	[ "The", "scores", "for", "erythema", "tended", "to", "be", "higher", "in", "the", "group", "treated", "with", "two", "patches", "/", "application", "and", "dosing", "every", "6th", "day", "at", "the", "same", "site", ",", "than", "in", "the", "group", "treated", "with", "two", "patches", "/", "application", "and", "dosing", "every", "12th", "day", "at", "the", "same", "site", ",", "which", "in", "turn", "tended", "to", "be", "higher", "than", "in", "the", "group", "treated", "with", "one", "patch", "/", "application", "and", "dosing", "every", "12th", "day", "at", "the", "same", "site", "." ]	[ "O", "O", "O", "B-FINDING", "O", "O", "O", "B-MANIFESTATION_FINDING", "O", "O", "B-GROUP", "I-GROUP", "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", "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", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]	[ 0, 0, 0, 8, 0, 0, 0, 1, 0, 0, 12, 13, 0, 3, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL	Post-mortem examinations revealed no macroscopic findings .	[ "Post-mortem", "examinations", "revealed", "no", "macroscopic", "findings", "." ]	[ "O", "O", "O", "O", "O", "O", "O" ]	[ 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL	In conclusion , the oral ( in - feed ) administration of COMPOUND_XXX at target dosages of 60 and 600 mg / kg / day over one week to male mice caused a dose - dependent inhibition of the diamine oxidase activity in the jejunal mucosa .	[ "In", "conclusion", ",", "the", "oral", "(", "in", "-", "feed", ")", "administration", "of", "COMPOUND_XXX", "at", "target", "dosages", "of", "60", "and", "600", "mg", "/", "kg", "/", "day", "over", "one", "week", "to", "male", "mice", "caused", "a", "dose", "-", "dependent", "inhibition", "of", "the", "diamine", "oxidase", "activity", "in", "the", "jejunal", "mucosa", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "O", "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", "O", "O", "O", "B-SEX", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O" ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 4, 4, 0, 0, 0, 0, 5, 0, 0, 0, 0, 0, 0, 8, 9, 9, 9, 9, 9, 0, 0, 10, 11, 0 ]
NO_PRETOX_REL	After a two week recovery period no statistically significant differences between mean absolute and relative liver weights of group 4 recovery males were found when compared with the controls .	[ "After", "a", "two", "week", "recovery", "period", "no", "statistically", "significant", "differences", "between", "mean", "absolute", "and", "relative", "liver", "weights", "of", "group", "4", "recovery", "males", "were", "found", "when", "compared", "with", "the", "controls", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-GROUP", "I-GROUP", "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, 12, 13, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL	After 4 , 9 , 14 , or 26 weeks of dosing , statistically significant increases in WBC counts and related parameters , or platelet counts were observed at 25 or 50 mg / kg .	[ "After", "4", ",", "9", ",", "14", ",", "or", "26", "weeks", "of", "dosing", ",", "statistically", "significant", "increases", "in", "WBC", "counts", "and", "related", "parameters", ",", "or", "platelet", "counts", "were", "observed", "at", "25", "or", "50", "mg", "/", "kg", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-MANIFESTATION_FINDING", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "O", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 2, 6, 0, 0, 0, 0, 0, 2, 6, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0 ]
NO_PRETOX_REL	After three doses per week for at least 4 weeks , exposure to COMPOUND_XXX was similar to that obtained after a single dose in rats , but there was an increase in exposure to the metabolite BJB432 .	[ "After", "three", "doses", "per", "week", "for", "at", "least", "4", "weeks", ",", "exposure", "to", "COMPOUND_XXX", "was", "similar", "to", "that", "obtained", "after", "a", "single", "dose", "in", "rats", ",", "but", "there", "was", "an", "increase", "in", "exposure", "to", "the", "metabolite", "BJB432", "." ]	[ "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" ]	[ 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 ]
PRETOX_REL	Test article - related decreases in food consumption were seen in both sexes at all doses .	[ "Test", "article", "-", "related", "decreases", "in", "food", "consumption", "were", "seen", "in", "both", "sexes", "at", "all", "doses", "." ]	[ "O", "O", "O", "O", "B-MANIFESTATION_FINDING", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "B-SEX", "I-SEX", "O", "B-DOSE", "I-DOSE", "O" ]	[ 0, 0, 0, 0, 1, 0, 2, 6, 0, 0, 0, 5, 7, 0, 3, 4, 0 ]
PRETOX_REL	Also at this dose , there were lower lymphocyte , eosinophil and basophil counts ; and lymphoid depletion ( thymic atrophy and lymphoid depletion of the mesenteric lymph nodes ) , which were attributed to the antiproliferative activity of COMPOUND_XXX .	[ "Also", "at", "this", "dose", ",", "there", "were", "lower", "lymphocyte", ",", "eosinophil", "and", "basophil", "counts", ";", "and", "lymphoid", "depletion", "(", "thymic", "atrophy", "and", "lymphoid", "depletion", "of", "the", "mesenteric", "lymph", "nodes", ")", ",", "which", "were", "attributed", "to", "the", "antiproliferative", "activity", "of", "COMPOUND_XXX", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "B-MANIFESTATION_FINDING", "B-STUDY_TESTCD", "O", "B-STUDY_TESTCD", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "B-FINDING", "I-FINDING", "O", "B-FINDING", "I-FINDING", "O", "B-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "I-SPECIMEN", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]	[ 0, 0, 0, 0, 0, 0, 0, 1, 2, 0, 2, 0, 2, 6, 0, 0, 8, 9, 0, 8, 9, 0, 8, 9, 0, 0, 10, 11, 11, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL	Whitish discoloration of teeth was noted at all doses .	[ "Whitish", "discoloration", "of", "teeth", "was", "noted", "at", "all", "doses", "." ]	[ "O", "B-FINDING", "O", "B-SPECIMEN", "O", "O", "O", "B-DOSE", "I-DOSE", "O" ]	[ 0, 8, 0, 10, 0, 0, 0, 3, 4, 0 ]
PRETOX_REL	In addition first sign of myelo - toxicity were noted in male and female animals of the high dose group .	[ "In", "addition", "first", "sign", "of", "myelo", "-", "toxicity", "were", "noted", "in", "male", "and", "female", "animals", "of", "the", "high", "dose", "group", "." ]	[ "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "O", "O", "O", "B-SEX", "I-SEX", "I-SEX", "O", "O", "O", "B-GROUP", "I-GROUP", "I-GROUP", "O" ]	[ 0, 0, 0, 0, 0, 8, 9, 9, 0, 0, 0, 5, 7, 7, 0, 0, 0, 12, 13, 13, 0 ]
NO_PRETOX_REL	No organ weight , macroscopic or microscopic changes were attributed to treatment with COMPOUND_XXX at the end of the 6 - month treatment period .	[ "No", "organ", "weight", ",", "macroscopic", "or", "microscopic", "changes", "were", "attributed", "to", "treatment", "with", "COMPOUND_XXX", "at", "the", "end", "of", "the", "6", "-", "month", "treatment", "period", "." ]	[ "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" ]	[ 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 ]
NO_PRETOX_REL	Ophthalmoscopic examinations were performed on all animals during pretest and on the control and high - dose animals during treatment .	[ "Ophthalmoscopic", "examinations", "were", "performed", "on", "all", "animals", "during", "pretest", "and", "on", "the", "control", "and", "high", "-", "dose", "animals", "during", "treatment", "." ]	[ "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" ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 15, 16, 16, 16, 16, 0, 0, 0, 0 ]
NO_PRETOX_REL	This effect was noted only in the low dose group .	[ "This", "effect", "was", "noted", "only", "in", "the", "low", "dose", "group", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "B-GROUP", "I-GROUP", "I-GROUP", "O" ]	[ 0, 0, 0, 0, 0, 0, 0, 12, 13, 13, 0 ]
NO_PRETOX_REL	This finding is to be related to treatment with the test substance .	[ "This", "finding", "is", "to", "be", "related", "to", "treatment", "with", "the", "test", "substance", "." ]	[ "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 ]
NO_PRETOX_REL	COMPOUND_XXX has a very long terminal elimination half - life in monkeys .	[ "COMPOUND_XXX", "has", "a", "very", "long", "terminal", "elimination", "half", "-", "life", "in", "monkeys", "." ]	[ "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 ]
PRETOX_REL	Decreases in body weight parameters , organ weight decreases and microscopic changes in the bone marrow , thyroid and spleen were present at doses ≥ 10 mg / kg .	[ "Decreases", "in", "body", "weight", "parameters", ",", "organ", "weight", "decreases", "and", "microscopic", "changes", "in", "the", "bone", "marrow", ",", "thyroid", "and", "spleen", "were", "present", "at", "doses", "≥", "10", "mg", "/", "kg", "." ]	[ "B-MANIFESTATION_FINDING", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "B-SPECIMEN", "B-STUDY_TESTCD", "B-MANIFESTATION_FINDING", "O", "B-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "B-SPECIMEN", "O", "B-SPECIMEN", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]	[ 1, 0, 2, 6, 0, 0, 10, 2, 1, 0, 8, 9, 0, 0, 10, 11, 0, 10, 0, 10, 0, 0, 0, 0, 0, 3, 4, 4, 4, 0 ]
PRETOX_REL	Test article - related organ weight decreases were seen in the thymus at 30 mg / kg in both sexes , thyroid at doses ≥ 3 mg / kg in both sexes , the spleen in females only at doses ≥ 10 mg / kg , and the pituitary in males only at 30 mg / kg .	[ "Test", "article", "-", "related", "organ", "weight", "decreases", "were", "seen", "in", "the", "thymus", "at", "30", "mg", "/", "kg", "in", "both", "sexes", ",", "thyroid", "at", "doses", "≥", "3", "mg", "/", "kg", "in", "both", "sexes", ",", "the", "spleen", "in", "females", "only", "at", "doses", "≥", "10", "mg", "/", "kg", ",", "and", "the", "pituitary", "in", "males", "only", "at", "30", "mg", "/", "kg", "." ]	[ "O", "O", "O", "O", "O", "B-STUDY_TESTCD", "B-MANIFESTATION_FINDING", "O", "O", "O", "O", "B-SPECIMEN", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "B-SEX", "I-SEX", "O", "B-SPECIMEN", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "B-SEX", "I-SEX", "O", "O", "B-SPECIMEN", "O", "B-SEX", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "B-SPECIMEN", "O", "B-SEX", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]	[ 0, 0, 0, 0, 0, 2, 1, 0, 0, 0, 0, 10, 0, 3, 4, 4, 4, 0, 5, 7, 0, 10, 0, 0, 0, 3, 4, 4, 4, 0, 5, 7, 0, 0, 10, 0, 5, 0, 0, 0, 0, 3, 4, 4, 4, 0, 0, 0, 10, 0, 5, 0, 0, 3, 4, 4, 4, 0 ]
NO_PRETOX_REL	The results of this study may be used for dose selection in subsequent GLP toxicity studies .	[ "The", "results", "of", "this", "study", "may", "be", "used", "for", "dose", "selection", "in", "subsequent", "GLP", "toxicity", "studies", "." ]	[ "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 ]
PRETOX_REL	Clinical examination : General observations : The following findings were considered to be compound - related : At the low dose of 1.0 mg / kg COMPOUND_XXX and higher : e Signs of local irritation at the area of administration such as reddening and / or swelling of the skin at the snout were observed in male and female animals with dose - dependent increase in severity and in onset of the finding .	[ "Clinical", "examination", ":", "General", "observations", ":", "The", "following", "findings", "were", "considered", "to", "be", "compound", "-", "related", ":", "At", "the", "low", "dose", "of", "1.0", "mg", "/", "kg", "COMPOUND_XXX", "and", "higher", ":", "e", "Signs", "of", "local", "irritation", "at", "the", "area", "of", "administration", "such", "as", "reddening", "and", "/", "or", "swelling", "of", "the", "skin", "at", "the", "snout", "were", "observed", "in", "male", "and", "female", "animals", "with", "dose", "-", "dependent", "increase", "in", "severity", "and", "in", "onset", "of", "the", "finding", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "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", "O", "O", "O", "B-FINDING", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "O", "O", "O", "B-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "I-SPECIMEN", "I-SPECIMEN", "O", "O", "O", "B-SEX", "I-SEX", "I-SEX", "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, 15, 16, 0, 3, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 8, 0, 0, 0, 0, 0, 0, 0, 8, 0, 0, 0, 8, 0, 0, 10, 11, 11, 11, 0, 0, 0, 5, 7, 7, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL	The slight increase in serum calcium at the highest dose of 500 μg / kg COMPOUND_XXX in male animals on days 10 ( p < 0.05 ) , 17 ( n. s. ) and 24 ( n. s. ) and in female animals on days 17 ( n. s. ) and 24 ( n. s. ) is a consequence of the pharmacological action of the compound intervening in the calcium metabolism .	[ "The", "slight", "increase", "in", "serum", "calcium", "at", "the", "highest", "dose", "of", "500", "μg", "/", "kg", "COMPOUND_XXX", "in", "male", "animals", "on", "days", "10", "(", "p", "<", "0.05", ")", ",", "17", "(", "n.", "s.", ")", "and", "24", "(", "n.", "s.", ")", "and", "in", "female", "animals", "on", "days", "17", "(", "n.", "s.", ")", "and", "24", "(", "n.", "s.", ")", "is", "a", "consequence", "of", "the", "pharmacological", "action", "of", "the", "compound", "intervening", "in", "the", "calcium", "metabolism", "." ]	[ "O", "O", "B-MANIFESTATION_FINDING", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "B-SEX", "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" ]	[ 0, 0, 1, 0, 2, 6, 0, 0, 15, 16, 0, 3, 4, 4, 4, 0, 0, 5, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL	Complete necropsies were conducted with macroscopic observations recorded .	[ "Complete", "necropsies", "were", "conducted", "with", "macroscopic", "observations", "recorded", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "O", "O" ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL	COMPOUND_XXX ( Batch no. 0351002 ) was administered orally by gavage as solutions in 0.5 % ( w / v ) hydroxypropylmethylcellulose ( 0.5 % HPMC ) Type E4M Premium , aqueous solution to three groups ( 10 / sex / group ) of IGS Wistar Hannover Crl : WI ( Glx / BRL / Han ) IGS BR rats at doses of 6/6 .4 , 20/21 and 60/64 mg / kg / day ( base / salt ) for at least 4 weeks .	[ "COMPOUND_XXX", "(", "Batch", "no.", "0351002", ")", "was", "administered", "orally", "by", "gavage", "as", "solutions", "in", "0.5", "%", "(", "w", "/", "v", ")", "hydroxypropylmethylcellulose", "(", "0.5", "%", "HPMC", ")", "Type", "E4M", "Premium", ",", "aqueous", "solution", "to", "three", "groups", "(", "10", "/", "sex", "/", "group", ")", "of", "IGS", "Wistar", "Hannover", "Crl", ":", "WI", "(", "Glx", "/", "BRL", "/", "Han", ")", "IGS", "BR", "rats", "at", "doses", "of", "6/6", ".4", ",", "20/21", "and", "60/64", "mg", "/", "kg", "/", "day", "(", "base", "/", "salt", ")", "for", "at", "least", "4", "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", "O", "O", "O", "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", "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", "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, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 12, 13, 13, 13, 13, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL	The dosing volume for all dose groups was 5 mL / kg .	[ "The", "dosing", "volume", "for", "all", "dose", "groups", "was", "5", "mL", "/", "kg", "." ]	[ "O", "O", "O", "O", "B-GROUP", "I-GROUP", "I-GROUP", "O", "O", "O", "O", "O", "O" ]	[ 0, 0, 0, 0, 12, 13, 13, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL	Slight reductions in food consumption occurred in the mid and high dose groups for both sexes .	[ "Slight", "reductions", "in", "food", "consumption", "occurred", "in", "the", "mid", "and", "high", "dose", "groups", "for", "both", "sexes", "." ]	[ "O", "B-MANIFESTATION_FINDING", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "B-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "O", "B-SEX", "I-SEX", "O" ]	[ 0, 1, 0, 2, 6, 0, 0, 0, 12, 13, 13, 13, 13, 0, 5, 7, 0 ]
PRETOX_REL	Food consumption correlated with the body weight loss .	[ "Food", "consumption", "correlated", "with", "the", "body", "weight", "loss", "." ]	[ "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "B-MANIFESTATION_FINDING", "O" ]	[ 2, 6, 0, 0, 0, 2, 6, 1, 0 ]
NO_PRETOX_REL	There was no consistent difference in exposure to COMPOUND_XXX or BJB432 between males and females .	[ "There", "was", "no", "consistent", "difference", "in", "exposure", "to", "COMPOUND_XXX", "or", "BJB432", "between", "males", "and", "females", "." ]	[ "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	There were no essential differences in the body weight development of the 4 groups .	[ "There", "were", "no", "essential", "differences", "in", "the", "body", "weight", "development", "of", "the", "4", "groups", "." ]	[ "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 ]
PRETOX_REL	Focal necrotic inflammation in the glandular mucosa of the stomach was apparent in half the animals at 1000 mg / kg / day , but was not evident at lower doses and was not seen at the end of the recovery period at any dosage .	[ "Focal", "necrotic", "inflammation", "in", "the", "glandular", "mucosa", "of", "the", "stomach", "was", "apparent", "in", "half", "the", "animals", "at", "1000", "mg", "/", "kg", "/", "day", ",", "but", "was", "not", "evident", "at", "lower", "doses", "and", "was", "not", "seen", "at", "the", "end", "of", "the", "recovery", "period", "at", "any", "dosage", "." ]	[ "B-FINDING", "I-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "O", "B-SPECIMEN", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-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" ]	[ 8, 9, 9, 0, 0, 10, 11, 0, 0, 10, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL	Two albino NZW male rabbits were dermally exposed to the vehicle Placebo Nail Formulation ( vehicle 1 ) , and test items J Nail Nail Formulation 200 / o ( variant 12 ) .	[ "Two", "albino", "NZW", "male", "rabbits", "were", "dermally", "exposed", "to", "the", "vehicle", "Placebo", "Nail", "Formulation", "(", "vehicle", "1", ")", ",", "and", "test", "items", "J", "Nail", "Nail", "Formulation", "200", "/", "o", "(", "variant", "12", ")", "." ]	[ "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" ]	[ 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 ]
NO_PRETOX_REL	Ophthalmoscopy : There were no COMPOUND_XXX - related rats given 40 , 160 , or 400 mglkgfday .	[ "Ophthalmoscopy", ":", "There", "were", "no", "COMPOUND_XXX", "-", "related", "rats", "given", "40", ",", "160", ",", "or", "400", "mglkgfday", "." ]	[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]	[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 4, 0 ]
NO_PRETOX_REL	Overall , considering AUC0 - 24 ratios between males and females , no obvious sex effect was observed .	[ "Overall", ",", "considering", "AUC0", "-", "24", "ratios", "between", "males", "and", "females", ",", "no", "obvious", "sex", "effect", "was", "observed", "." ]	[ "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	COMPOUND_XXX lactate salt ( Batch no .	[ "COMPOUND_XXX", "lactate", "salt", "(", "Batch", "no", "." ]	[ "O", "O", "O", "O", "O", "O", "O" ]	[ 0, 0, 0, 0, 0, 0, 0 ]

NO_PRETOX_REL

The control animals were treated with placebo patches of the same size and the same number as the 216 mg group .

[ "The", "control", "animals", "were", "treated", "with", "placebo", "patches", "of", "the", "same", "size", "and", "the", "same", "number", "as", "the", "216", "mg", "group", "." ]

[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "O", "O" ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 0, 0 ]

PRETOX_REL

Clinical changes in rats given 400 mg / kg / day included : cold - to - touch , ataxia , labored respiration , inactivity , wasting , unthriftiness , rough coat , pallor , swollen prepuce , salivation , mouth / nose discharge , and urogenital stain .

[ "Clinical", "changes", "in", "rats", "given", "400", "mg", "/", "kg", "/", "day", "included", ":", "cold", "-", "to", "-", "touch", ",", "ataxia", ",", "labored", "respiration", ",", "inactivity", ",", "wasting", ",", "unthriftiness", ",", "rough", "coat", ",", "pallor", ",", "swollen", "prepuce", ",", "salivation", ",", "mouth", "/", "nose", "discharge", ",", "and", "urogenital", "stain", "." ]

[ "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "B-FINDING", "O", "B-FINDING", "I-FINDING", "I-FINDING", "B-FINDING", "O", "B-FINDING", "O", "B-FINDING", "O", "B-FINDING", "I-FINDING", "O", "B-FINDING", "O", "B-FINDING", "I-FINDING", "O", "B-FINDING", "O", "B-SPECIMEN", "O", "B-SPECIMEN", "B-FINDING", "O", "O", "B-FINDING", "I-FINDING", "O" ]

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NO_PRETOX_REL

The study is designed to establish a no - observed - adverse - effect level ( NOAEL ) , to establish a maximal tolerated dose , to estimate the toxicokinetic profile , and to estimate the potential for reversal of any toxic effects within a 4 - week post dosing period .

[ "The", "study", "is", "designed", "to", "establish", "a", "no", "-", "observed", "-", "adverse", "-", "effect", "level", "(", "NOAEL", ")", ",", "to", "establish", "a", "maximal", "tolerated", "dose", ",", "to", "estimate", "the", "toxicokinetic", "profile", ",", "and", "to", "estimate", "the", "potential", "for", "reversal", "of", "any", "toxic", "effects", "within", "a", "4", "-", "week", "post", "dosing", "period", "." ]

[ "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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PRETOX_REL

The _ reason for this is most probably a marked liver cirrhosis accompanied by several other findings ( including moderate thymic atrophy ) .

[ "The", "_", "reason", "for", "this", "is", "most", "probably", "a", "marked", "liver", "cirrhosis", "accompanied", "by", "several", "other", "findings", "(", "including", "moderate", "thymic", "atrophy", ")", "." ]

[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "O", "O" ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 8, 9, 0, 0, 0, 0, 0, 0, 0, 0, 8, 9, 0, 0 ]

NO_PRETOX_REL

In view of this finding a NOEL can be set at 60 mg / kg / day under the conditions of the present study .

[ "In", "view", "of", "this", "finding", "a", "NOEL", "can", "be", "set", "at", "60", "mg", "/", "kg", "/", "day", "under", "the", "conditions", "of", "the", "present", "study", "." ]

[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "O" ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0 ]

PRETOX_REL

Dose Level 3 At dose level 3 , absolute and relative liver weights were increased in male rats .

[ "Dose", "Level", "3", "At", "dose", "level", "3", ",", "absolute", "and", "relative", "liver", "weights", "were", "increased", "in", "male", "rats", "." ]

[ "B-DOSE", "I-DOSE", "I-DOSE", "O", "B-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "B-SPECIMEN", "B-STUDY_TESTCD", "O", "B-MANIFESTATION_FINDING", "O", "B-SEX", "O", "O" ]

[ 3, 4, 4, 0, 3, 4, 4, 0, 0, 0, 0, 10, 2, 0, 1, 0, 5, 0, 0 ]

PRETOX_REL

Tne growth plates of die kite were also thickened ( approx I - I times ) in animals given 1000 mg / kg / day , although thickening was not apparent at lower doses .

[ "Tne", "growth", "plates", "of", "die", "kite", "were", "also", "thickened", "(", "approx", "I", "-", "I", "times", ")", "in", "animals", "given", "1000", "mg", "/", "kg", "/", "day", ",", "although", "thickening", "was", "not", "apparent", "at", "lower", "doses", "." ]

[ "O", "B-SPECIMEN", "I-SPECIMEN", "O", "O", "O", "O", "O", "B-FINDING", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "O" ]

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NO_PRETOX_REL

No changes were observed in the evaluated electrocardiography , ophthalmology , or urinalysis endpoints .

[ "No", "changes", "were", "observed", "in", "the", "evaluated", "electrocardiography", ",", "ophthalmology", ",", "or", "urinalysis", "endpoints", "." ]

[ "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

Whatever the sex , the dose and the toxicokinetic sampling day , COMPOUND_XXX concentrations were above the LLOQ up to 24 hours in all treated animals .

[ "Whatever", "the", "sex", ",", "the", "dose", "and", "the", "toxicokinetic", "sampling", "day", ",", "COMPOUND_XXX", "concentrations", "were", "above", "the", "LLOQ", "up", "to", "24", "hours", "in", "all", "treated", "animals", "." ]

[ "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" ]

[ 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 ]

PRETOX_REL

Alterations were slight , except in a single rat with pronounced alterations in the lymphoid system : The Peyer ´s patches had a slight decrease of germinal centers in some rats .

[ "Alterations", "were", "slight", ",", "except", "in", "a", "single", "rat", "with", "pronounced", "alterations", "in", "the", "lymphoid", "system", ":", "The", "Peyer", "´s", "patches", "had", "a", "slight", "decrease", "of", "germinal", "centers", "in", "some", "rats", "." ]

[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "O", "O", "O" ]

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NO_PRETOX_REL

On day 28 after the implantation all concentrations were below LLOQ .

[ "On", "day", "28", "after", "the", "implantation", "all", "concentrations", "were", "below", "LLOQ", "." ]

[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

NO_PRETOX_REL

In the high dose â € ˜group an uncommon concentration time profile Influence of Repeated Dosing : After repeated dosing a slight change in AUC ( 0.24 ) and Cmax was observed in the low and mid dose group .

[ "In", "the", "high", "dose", "â", "€", "˜group", "an", "uncommon", "concentration", "time", "profile", "Influence", "of", "Repeated", "Dosing", ":", "After", "repeated", "dosing", "a", "slight", "change", "in", "AUC", "(", "0.24", ")", "and", "Cmax", "was", "observed", "in", "the", "low", "and", "mid", "dose", "group", "." ]

[ "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "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", "B-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "O" ]

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NO_PRETOX_REL

Complete necropsies including macroscopic assessments were performed on all animals .

[ "Complete", "necropsies", "including", "macroscopic", "assessments", "were", "performed", "on", "all", "animals", "." ]

[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

PRETOX_REL

Two group III ( 30/60 mg / kg ) - females showed granulocytic infiltration in the liver paralleled by an increase in the liver weight ratio .

[ "Two", "group", "III", "(", "30/60", "mg", "/", "kg", ")", "-", "females", "showed", "granulocytic", "infiltration", "in", "the", "liver", "paralleled", "by", "an", "increase", "in", "the", "liver", "weight", "ratio", "." ]

[ "O", "B-GROUP", "I-GROUP", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "B-SEX", "O", "B-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "O", "O", "O", "B-MANIFESTATION_FINDING", "O", "O", "B-SPECIMEN", "B-STUDY_TESTCD", "O", "O" ]

[ 0, 12, 13, 0, 3, 4, 4, 4, 0, 0, 5, 0, 8, 9, 0, 0, 10, 0, 0, 0, 1, 0, 0, 10, 2, 0, 0 ]

NO_PRETOX_REL

No accumulation was observed in all the groups .

[ "No", "accumulation", "was", "observed", "in", "all", "the", "groups", "." ]

[ "O", "O", "O", "O", "O", "B-GROUP", "I-GROUP", "I-GROUP", "O" ]

[ 0, 0, 0, 0, 0, 12, 13, 13, 0 ]

NO_PRETOX_REL

COMPOUND_XXX was administered in feed to groups of 14 male and 14 female rats ( Han!bm : WIST ) for 26 weeks at the dose levels of 0 ( controls ) , 15 , 60 and 240 mg / kg / day .

[ "COMPOUND_XXX", "was", "administered", "in", "feed", "to", "groups", "of", "14", "male", "and", "14", "female", "rats", "(", "Han!bm", ":", "WIST", ")", "for", "26", "weeks", "at", "the", "dose", "levels", "of", "0", "(", "controls", ")", ",", "15", ",", "60", "and", "240", "mg", "/", "kg", "/", "day", "." ]

[ "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", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]

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NO_PRETOX_REL

Body weight and food consumption were recorded weekly .

[ "Body", "weight", "and", "food", "consumption", "were", "recorded", "weekly", "." ]

[ "O", "O", "O", "O", "O", "O", "O", "O", "O" ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

PRETOX_REL

Clinical pathology changes were limited to mild increases in APIT in males given 225 and 500 mg / kg / day of NS and in males given 500 mg & fday of OS .

[ "Clinical", "pathology", "changes", "were", "limited", "to", "mild", "increases", "in", "APIT", "in", "males", "given", "225", "and", "500", "mg", "/", "kg", "/", "day", "of", "NS", "and", "in", "males", "given", "500", "mg", "&", "fday", "of", "OS", "." ]

[ "O", "O", "O", "O", "O", "O", "O", "B-MANIFESTATION_FINDING", "O", "B-STUDY_TESTCD", "O", "B-SEX", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "B-SEX", "O", "B-DOSE", "I-DOSE", "O", "O", "O", "O", "O" ]

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PRETOX_REL

Organ toxicity in form of focal / multifocal foam cell aggregates in the lung , to be suspected for this class of cationic amphiphilic compounds , occurred from the mid dose onwards .

[ "Organ", "toxicity", "in", "form", "of", "focal", "/", "multifocal", "foam", "cell", "aggregates", "in", "the", "lung", ",", "to", "be", "suspected", "for", "this", "class", "of", "cationic", "amphiphilic", "compounds", ",", "occurred", "from", "the", "mid", "dose", "onwards", "." ]

[ "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "O", "O" ]

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NO_PRETOX_REL

Concentrations of the test item in serum , heart and muscle tissues were in a roughly similar order of magnitude around the time of COMPOUND_XXX peak serum levels after 4 weeks of treatment with a trend towards slightly lower values in tissues than in serum .

[ "Concentrations", "of", "the", "test", "item", "in", "serum", ",", "heart", "and", "muscle", "tissues", "were", "in", "a", "roughly", "similar", "order", "of", "magnitude", "around", "the", "time", "of", "COMPOUND_XXX", "peak", "serum", "levels", "after", "4", "weeks", "of", "treatment", "with", "a", "trend", "towards", "slightly", "lower", "values", "in", "tissues", "than", "in", "serum", "." ]

[ "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

All the above findings proved reversible by the end of the recovery period , or showed a tendency towards recovery .

[ "All", "the", "above", "findings", "proved", "reversible", "by", "the", "end", "of", "the", "recovery", "period", ",", "or", "showed", "a", "tendency", "towards", "recovery", "." ]

[ "O", "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, 0 ]

PRETOX_REL

The scores for erythema tended to be higher in the group treated with two patches / application and dosing every 6th day at the same site , than in the group treated with two patches / application and dosing every 12th day at the same site , which in turn tended to be higher than in the group treated with one patch / application and dosing every 12th day at the same site .

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NO_PRETOX_REL

Post-mortem examinations revealed no macroscopic findings .

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[ "O", "O", "O", "O", "O", "O", "O" ]

[ 0, 0, 0, 0, 0, 0, 0 ]

PRETOX_REL

In conclusion , the oral ( in - feed ) administration of COMPOUND_XXX at target dosages of 60 and 600 mg / kg / day over one week to male mice caused a dose - dependent inhibition of the diamine oxidase activity in the jejunal mucosa .

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NO_PRETOX_REL

After a two week recovery period no statistically significant differences between mean absolute and relative liver weights of group 4 recovery males were found when compared with the controls .

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PRETOX_REL

After 4 , 9 , 14 , or 26 weeks of dosing , statistically significant increases in WBC counts and related parameters , or platelet counts were observed at 25 or 50 mg / kg .

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NO_PRETOX_REL

After three doses per week for at least 4 weeks , exposure to COMPOUND_XXX was similar to that obtained after a single dose in rats , but there was an increase in exposure to the metabolite BJB432 .

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PRETOX_REL

Test article - related decreases in food consumption were seen in both sexes at all doses .

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[ 0, 0, 0, 0, 1, 0, 2, 6, 0, 0, 0, 5, 7, 0, 3, 4, 0 ]

PRETOX_REL

Also at this dose , there were lower lymphocyte , eosinophil and basophil counts ; and lymphoid depletion ( thymic atrophy and lymphoid depletion of the mesenteric lymph nodes ) , which were attributed to the antiproliferative activity of COMPOUND_XXX .

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PRETOX_REL

Whitish discoloration of teeth was noted at all doses .

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[ "O", "B-FINDING", "O", "B-SPECIMEN", "O", "O", "O", "B-DOSE", "I-DOSE", "O" ]

[ 0, 8, 0, 10, 0, 0, 0, 3, 4, 0 ]

PRETOX_REL

In addition first sign of myelo - toxicity were noted in male and female animals of the high dose group .

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NO_PRETOX_REL

No organ weight , macroscopic or microscopic changes were attributed to treatment with COMPOUND_XXX at the end of the 6 - month treatment period .

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NO_PRETOX_REL

Ophthalmoscopic examinations were performed on all animals during pretest and on the control and high - dose animals during treatment .

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NO_PRETOX_REL

This effect was noted only in the low dose group .

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[ "O", "O", "O", "O", "O", "O", "O", "B-GROUP", "I-GROUP", "I-GROUP", "O" ]

[ 0, 0, 0, 0, 0, 0, 0, 12, 13, 13, 0 ]

NO_PRETOX_REL

This finding is to be related to treatment with the test substance .

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[ "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 ]

NO_PRETOX_REL

COMPOUND_XXX has a very long terminal elimination half - life in monkeys .

[ "COMPOUND_XXX", "has", "a", "very", "long", "terminal", "elimination", "half", "-", "life", "in", "monkeys", "." ]

[ "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 ]

PRETOX_REL

Decreases in body weight parameters , organ weight decreases and microscopic changes in the bone marrow , thyroid and spleen were present at doses ≥ 10 mg / kg .

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PRETOX_REL

Test article - related organ weight decreases were seen in the thymus at 30 mg / kg in both sexes , thyroid at doses ≥ 3 mg / kg in both sexes , the spleen in females only at doses ≥ 10 mg / kg , and the pituitary in males only at 30 mg / kg .

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NO_PRETOX_REL

The results of this study may be used for dose selection in subsequent GLP toxicity studies .

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PRETOX_REL

Clinical examination : General observations : The following findings were considered to be compound - related : At the low dose of 1.0 mg / kg COMPOUND_XXX and higher : e Signs of local irritation at the area of administration such as reddening and / or swelling of the skin at the snout were observed in male and female animals with dose - dependent increase in severity and in onset of the finding .

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PRETOX_REL

The slight increase in serum calcium at the highest dose of 500 μg / kg COMPOUND_XXX in male animals on days 10 ( p < 0.05 ) , 17 ( n. s. ) and 24 ( n. s. ) and in female animals on days 17 ( n. s. ) and 24 ( n. s. ) is a consequence of the pharmacological action of the compound intervening in the calcium metabolism .

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NO_PRETOX_REL

Complete necropsies were conducted with macroscopic observations recorded .

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[ "O", "O", "O", "O", "O", "O", "O", "O", "O" ]

[ 0, 0, 0, 0, 0, 0, 0, 0, 0 ]

NO_PRETOX_REL

COMPOUND_XXX ( Batch no. 0351002 ) was administered orally by gavage as solutions in 0.5 % ( w / v ) hydroxypropylmethylcellulose ( 0.5 % HPMC ) Type E4M Premium , aqueous solution to three groups ( 10 / sex / group ) of IGS Wistar Hannover Crl : WI ( Glx / BRL / Han ) IGS BR rats at doses of 6/6 .4 , 20/21 and 60/64 mg / kg / day ( base / salt ) for at least 4 weeks .

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NO_PRETOX_REL

The dosing volume for all dose groups was 5 mL / kg .

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PRETOX_REL

Slight reductions in food consumption occurred in the mid and high dose groups for both sexes .

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PRETOX_REL

Food consumption correlated with the body weight loss .

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[ 2, 6, 0, 0, 0, 2, 6, 1, 0 ]

NO_PRETOX_REL

There was no consistent difference in exposure to COMPOUND_XXX or BJB432 between males and females .

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NO_PRETOX_REL

There were no essential differences in the body weight development of the 4 groups .

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[ "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 ]

PRETOX_REL

Focal necrotic inflammation in the glandular mucosa of the stomach was apparent in half the animals at 1000 mg / kg / day , but was not evident at lower doses and was not seen at the end of the recovery period at any dosage .

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NO_PRETOX_REL

Two albino NZW male rabbits were dermally exposed to the vehicle Placebo Nail Formulation ( vehicle 1 ) , and test items J Nail Nail Formulation 200 / o ( variant 12 ) .

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NO_PRETOX_REL

Ophthalmoscopy : There were no COMPOUND_XXX - related rats given 40 , 160 , or 400 mglkgfday .

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[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 4, 0 ]

NO_PRETOX_REL

Overall , considering AUC0 - 24 ratios between males and females , no obvious sex effect was observed .

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NO_PRETOX_REL

COMPOUND_XXX lactate salt ( Batch no .

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[ "O", "O", "O", "O", "O", "O", "O" ]

[ 0, 0, 0, 0, 0, 0, 0 ]