Datasets:
javicorvi
/
pretoxtm-dataset

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NO_PRETOX_REL
There was no evidence of any findings which could be related to ~ dosing with the test compound in this animal .
[ "There", "was", "no", "evidence", "of", "any", "findings", "which", "could", "be", "related", "to", "~", "dosing", "with", "the", "test", "compound", "in", "this", "animal", "." ]
[ "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 ]
PRETOX_REL
Test article - related statistically significant decreases in mean body weight and mean body weight gain were noted in males at 60 mg / kg / day .
[ "Test", "article", "-", "related", "statistically", "significant", "decreases", "in", "mean", "body", "weight", "and", "mean", "body", "weight", "gain", "were", "noted", "in", "males", "at", "60", "mg", "/", "kg", "/", "day", "." ]
[ "O", "O", "O", "O", "O", "O", "B-MANIFESTATION_FINDING", "O", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "B-SEX", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]
[ 0, 0, 0, 0, 0, 0, 1, 0, 0, 2, 6, 0, 0, 2, 6, 6, 0, 0, 0, 5, 0, 3, 4, 4, 4, 4, 4, 0 ]
NO_PRETOX_REL
In particular , no organ toxicity was observed .
[ "In", "particular", ",", "no", "organ", "toxicity", "was", "observed", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL
On histopathological examination , the scabs were found to be foci of necrotic dermatitis , although their histological appearance did not give any indication of their pathogenesis .
[ "On", "histopathological", "examination", ",", "the", "scabs", "were", "found", "to", "be", "foci", "of", "necrotic", "dermatitis", ",", "although", "their", "histological", "appearance", "did", "not", "give", "any", "indication", "of", "their", "pathogenesis", "." ]
[ "O", "O", "O", "O", "O", "B-FINDING", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 8, 0, 0, 0, 0, 0, 0, 8, 9, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
Blood samples for hematology and clinical chemistry parameters were collected pretest and in week 2 .
[ "Blood", "samples", "for", "hematology", "and", "clinical", "chemistry", "parameters", "were", "collected", "pretest", "and", "in", "week", "2", "." ]
[ "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 compound - related effects on any of the parameters assessed .
[ "There", "were", "no", "compound", "-", "related", "effects", "on", "any", "of", "the", "parameters", "assessed", "." ]
[ "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
The treated areas of the right flank and untreated skin from the flank were examined microscopically .
[ "The", "treated", "areas", "of", "the", "right", "flank", "and", "untreated", "skin", "from", "the", "flank", "were", "examined", "microscopically", "." ]
[ "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 ]
NO_PRETOX_REL
These changes were reversible within the recovery period .
[ "These", "changes", "were", "reversible", "within", "the", "recovery", "period", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
The following investigations were performed ; mortality , clinical observations , body weight , food consumption , hematology , clinical biochemistry , organ weights , microscopic examination as well as toxicokinetics .
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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", "O" ]
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NO_PRETOX_REL
Maximum concentrations of COMPOUND_XXX in serum were determined in most cases 1 h after intragastric administration of the drug .
[ "Maximum", "concentrations", "of", "COMPOUND_XXX", "in", "serum", "were", "determined", "in", "most", "cases", "1", "h", "after", "intragastric", "administration", "of", "the", "drug", "." ]
[ "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 ]
PRETOX_REL
Mean body weight gain is dose - dependently decreased in 8 and 80 mg / kg / d males and increased in 8 and 80 mg / kg / d females .
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[ "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "O", "B-MANIFESTATION_FINDING", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "B-SEX", "O", "B-MANIFESTATION_FINDING", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "B-SEX", "O" ]
[ 0, 2, 6, 6, 0, 0, 0, 0, 1, 0, 3, 4, 4, 4, 4, 4, 4, 4, 5, 0, 1, 0, 3, 4, 4, 4, 4, 4, 4, 4, 5, 0 ]
NO_PRETOX_REL
The mean AUC ( 0 - 24h0 values of COMPOUND_XXX were 6410 , 49400 , and 122000 ng.hr / ml in females given 40 , 160 , and 400 mg / kg / day , 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", "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" ]
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PRETOX_REL
In - life findings were limited to transient decreases in bodyweight gain and food intake during the first four days of dosing , possibly due to poor palatability of the compound .
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[ "O", "O", "O", "O", "O", "O", "O", "O", "B-MANIFESTATION_FINDING", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "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 , doses less than 100 mg / kg / day ( 50 mg / kg b.i.d. ) are recommended for future COMPOUND_XXX gavage ( b.i.d. ) studies in monkeys .
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[ "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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PRETOX_REL
Degenerative cardiac lesions were observed with ultrastructural alterations in the lysosomal compartment .
[ "Degenerative", "cardiac", "lesions", "were", "observed", "with", "ultrastructural", "alterations", "in", "the", "lysosomal", "compartment", "." ]
[ "B-FINDING", "I-FINDING", "I-FINDING", "O", "O", "O", "B-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O" ]
[ 8, 9, 9, 0, 0, 0, 8, 9, 0, 0, 10, 11, 0 ]
PRETOX_REL
In the heart at 1.0 ( 1.5 ) mg / kg / day , small isolated foci of single fiber necrosis with inflammatory cell reaction and arteriitis / periarteriitis were seen in terminally sacrificed animals .
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[ "O", "O", "B-SPECIMEN", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "B-FINDING", "I-FINDING", "I-FINDING", "O", "B-FINDING", "O", "B-FINDING", "O", "O", "O", "O", "B-FINDING", "O", "O" ]
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PRETOX_REL
In the urinary bladder , edema , erosions and inflammatory cell infiltration were present at the earlier time points , particularly in the neck region of the bladder .
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[ "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "B-FINDING", "O", "B-FINDING", "O", "B-FINDING", "I-FINDING", "I-FINDING", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "I-SPECIMEN", "I-SPECIMEN", "I-SPECIMEN", "O" ]
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PRETOX_REL
Hematologically , slightly decreased in red blood cell parameters indicate a slight anemia at the mid dose and higher .
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[ "O", "O", "O", "B-MANIFESTATION_FINDING", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "I-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "B-FINDING", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "O" ]
[ 0, 0, 0, 1, 0, 2, 6, 6, 6, 0, 0, 0, 8, 0, 0, 15, 16, 16, 16, 0 ]
PRETOX_REL
Increased urinary NAG and GGT levels as well as electrolyte imbalances in high dose animals point to renal impairment at the high dose of 2.0 mg / kg COMPOUND_YYY .
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[ 8, 9, 9, 0, 2, 0, 0, 0, 0, 8, 9, 0, 15, 16, 0, 0, 0, 8, 9, 0, 0, 15, 16, 0, 3, 4, 4, 4, 0, 0 ]
NO_PRETOX_REL
The animals assigned to the untreated Control group and those which had received 0.1 / 0.3 mg / ml were treated at 0.3 mg / ml and the animals assigned to the vehicle Control group and those which had received 0.2 mg / ml were treated at 0.4 mg / ml .
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[ "O", "O", "O", "O", "O", "O", "B-GROUP", "I-GROUP", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "B-GROUP", "I-GROUP", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]
[ 0, 0, 0, 0, 0, 0, 12, 13, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0, 0, 0, 3, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 12, 13, 0, 0, 0, 0, 0, 3, 4, 4, 4, 0, 0, 0, 3, 4, 4, 4, 0 ]
NO_PRETOX_REL
These effects were reversible following a 4 - week treatment - free recovery period .
[ "These", "effects", "were", "reversible", "following", "a", "4", "-", "week", "treatment", "-", "free", "recovery", "period", "." ]
[ "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
There were no differences in exposure between males and females .
[ "There", "were", "no", "differences", "in", "exposure", "between", "males", "and", "females", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
Anatomic Pathology : There were no COMPOUND_XXX - related microscopic changes at 40 mg / kg / day .
[ "Anatomic", "Pathology", ":", "There", "were", "no", "COMPOUND_XXX", "-", "related", "microscopic", "changes", "at", "40", "mg", "/", "kg", "/", "day", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]
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PRETOX_REL
High - dose group 70 mg / kg / day : week 4 to the end of the treatment period - Leukopenia and mild myeloid hypoplasia of bone marrow - Minimally to slightly decreased platelet counts - Testes : decreased weight , severe tubular atrophy , moderate vacuolation of the seminiferous epithelium , slight interstitial cell hyperplasia , absence of spermatozoa in the epididymides - Moderate to marked cortical atrophy of the thymus in 2/6 dogs Mid-dose group ( 2 mg / kg / day ) - Body weight loss in 2/5 females - Mild myeloid hypoplasia of bone marrow - Testes : decreased weight , marked tubular atrophy , moderate vacuolation of the seminiferous epithelium , slight interstitial cell hyperplasia , absence of spermatozoa in the epididymides - Slight cortical atrophy of the thymus in 2/5 dogs Low - dose group ( 0.2 mg / kg / day ) In l / 3 males : - Testes : slight tubular atrophy , moderate vacuolation of the seminiferous epithelium , moderate germ cell degeneration , oligospermia in the epididymides .
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PRETOX_REL
Following 34 weeks administration of COMPOUND_XXX at 10 / 100/75 or 50 mg / kg / day antibodies reacting against the nuclei of their own hepatocytes were found in the serum of the dogs .
[ "Following", "34", "weeks", "administration", "of", "COMPOUND_XXX", "at", "10", "/", "100/75", "or", "50", "mg", "/", "kg", "/", "day", "antibodies", "reacting", "against", "the", "nuclei", "of", "their", "own", "hepatocytes", "were", "found", "in", "the", "serum", "of", "the", "dogs", "." ]
[ "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", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "O", "O", "O", "B-SPECIMEN", "O", "O", "O", "O" ]
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NO_PRETOX_REL
Results and Discussion No mortality was observed , all animals survived until their scheduled sacrifice without showing any treatment - related clinical signs .
[ "Results", "and", "Discussion", "No", "mortality", "was", "observed", ",", "all", "animals", "survived", "until", "their", "scheduled", "sacrifice", "without", "showing", "any", "treatment", "-", "related", "clinical", "signs", "." ]
[ "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
doses of COMPOUND_XXX up to 0.50 mg / kg / day .
[ "doses", "of", "COMPOUND_XXX", "up", "to", "0.50", "mg", "/", "kg", "/", "day", "." ]
[ "B-DOSE", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]
[ 3, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0 ]
NO_PRETOX_REL
No evidence of a treatment related effect was detected in the macroscopic , or microscopic observations of the terminally sacrificed animals .
[ "No", "evidence", "of", "a", "treatment", "related", "effect", "was", "detected", "in", "the", "macroscopic", ",", "or", "microscopic", "observations", "of", "the", "terminally", "sacrificed", "animals", "." ]
[ "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 conclusion , 10 , 50 and 225 mg / kg / day COMPOUND_XXX were no effect dose levels in terms of adverse toxicological findings ( joint , skin and stomach effects ) but that the high dose of 1000 mg / kg / day induced marked lesions , both in - life and histopathologically .
[ "In", "conclusion", ",", "10", ",", "50", "and", "225", "mg", "/", "kg", "/", "day", "COMPOUND_XXX", "were", "no", "effect", "dose", "levels", "in", "terms", "of", "adverse", "toxicological", "findings", "(", "joint", ",", "skin", "and", "stomach", "effects", ")", "but", "that", "the", "high", "dose", "of", "1000", "mg", "/", "kg", "/", "day", "induced", "marked", "lesions", ",", "both", "in", "-", "life", "and", "histopathologically", "." ]
[ "O", "O", "O", "B-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", "O", "O", "B-SPECIMEN", "O", "B-SPECIMEN", "O", "B-SPECIMEN", "B-FINDING", "O", "O", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "B-FINDING", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
Clinical biochemistry investigations revealed no treatment - related changes in markers of myocardial and skeletal muscle integrity .
[ "Clinical", "biochemistry", "investigations", "revealed", "no", "treatment", "-", "related", "changes", "in", "markers", "of", "myocardial", "and", "skeletal", "muscle", "integrity", "." ]
[ "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 ]
PRETOX_REL
Other microscopic findings comprised epithelial vacuolation / hypertrophy , pigment deposition , necrosis , fibrin thrombi and vasculitis / perivasculitis in the gall bladder ; glandular dilatation , inflammatory cell infiltration with vasculitis / perivasculitis , mucosal atrophy and erosion in the small and large intestine and epithelial necrosis / vacuolation in the epididymides and prostate .
[ "Other", "microscopic", "findings", "comprised", "epithelial", "vacuolation", "/", "hypertrophy", ",", "pigment", "deposition", ",", "necrosis", ",", "fibrin", "thrombi", "and", "vasculitis", "/", "perivasculitis", "in", "the", "gall", "bladder", ";", "glandular", "dilatation", ",", "inflammatory", "cell", "infiltration", "with", "vasculitis", "/", "perivasculitis", ",", "mucosal", "atrophy", "and", "erosion", "in", "the", "small", "and", "large", "intestine", "and", "epithelial", "necrosis", "/", "vacuolation", "in", "the", "epididymides", "and", "prostate", "." ]
[ "O", "O", "O", "O", "B-FINDING", "I-FINDING", "O", "B-FINDING", "O", "B-FINDING", "I-FINDING", "O", "B-FINDING", "O", "B-FINDING", "I-FINDING", "O", "B-FINDING", "I-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "B-FINDING", "I-FINDING", "O", "B-FINDING", "I-FINDING", "I-FINDING", "O", "B-FINDING", "I-FINDING", "I-FINDING", "O", "B-FINDING", "I-FINDING", "O", "B-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "I-SPECIMEN", "I-SPECIMEN", "O", "B-FINDING", "I-FINDING", "O", "B-FINDING", "O", "O", "B-SPECIMEN", "O", "B-SPECIMEN", "O" ]
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NO_PRETOX_REL
Based on these results , a NOEL ( no - observed - effect level ) was not established .
[ "Based", "on", "these", "results", ",", "a", "NOEL", "(", "no", "-", "observed", "-", "effect", "level", ")", "was", "not", "established", "." ]
[ "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 ]
PRETOX_REL
Administration of COMPOUND_XXX at 1.0 mg / kg / occasion resulted in diminished red blood cell parameters ( haemoglobin concentration , red blood cell count , haematocrit and calculated red blood cell indices ) and only marginally increased reticulocyte counts indicating an inadequate erythropoietic response .
[ "Administration", "of", "COMPOUND_XXX", "at", "1.0", "mg", "/", "kg", "/", "occasion", "resulted", "in", "diminished", "red", "blood", "cell", "parameters", "(", "haemoglobin", "concentration", ",", "red", "blood", "cell", "count", ",", "haematocrit", "and", "calculated", "red", "blood", "cell", "indices", ")", "and", "only", "marginally", "increased", "reticulocyte", "counts", "indicating", "an", "inadequate", "erythropoietic", "response", "." ]
[ "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "B-MANIFESTATION_FINDING", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "I-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "I-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "B-STUDY_TESTCD", "O", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "O", "O", "B-MANIFESTATION_FINDING", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "O" ]
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NO_PRETOX_REL
Maximum concentrations of the test compound were generally observed at | h after the intragastric administration of COMPOUND_XXX , indicating a moderate - fast absorption from the gastrointestinal tract .
[ "Maximum", "concentrations", "of", "the", "test", "compound", "were", "generally", "observed", "at", "|", "h", "after", "the", "intragastric", "administration", "of", "COMPOUND_XXX", ",", "indicating", "a", "moderate", "-", "fast", "absorption", "from", "the", "gastrointestinal", "tract", "." ]
[ "O", "O", "O", "O", "O", "O", "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
Treatment resulted in slightly to moderately reduced body weight development at 180 mg / kg / day and food consumption at 120 and 180 mg / kg / day .
[ "Treatment", "resulted", "in", "slightly", "to", "moderately", "reduced", "body", "weight", "development", "at", "180", "mg", "/", "kg", "/", "day", "and", "food", "consumption", "at", "120", "and", "180", "mg", "/", "kg", "/", "day", "." ]
[ "O", "O", "O", "O", "O", "O", "B-MANIFESTATION_FINDING", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]
[ 0, 0, 0, 0, 0, 0, 1, 2, 6, 0, 0, 3, 4, 4, 4, 4, 4, 0, 2, 6, 0, 3, 4, 4, 4, 4, 4, 4, 4, 0 ]
PRETOX_REL
Decreased food consumption was present beginning 1 week after the initiation of dosing at 400 mg / kg / day .
[ "Decreased", "food", "consumption", "was", "present", "beginning", "1", "week", "after", "the", "initiation", "of", "dosing", "at", "400", "mg", "/", "kg", "/", "day", "." ]
[ "B-MANIFESTATION_FINDING", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]
[ 1, 2, 6, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0 ]
PRETOX_REL
increase in liver weights of females treated at 15 mg / kg / day without no blood biochemistry or histopathological correlates .
[ "increase", "in", "liver", "weights", "of", "females", "treated", "at", "15", "mg", "/", "kg", "/", "day", "without", "no", "blood", "biochemistry", "or", "histopathological", "correlates", "." ]
[ "B-MANIFESTATION_FINDING", "O", "B-SPECIMEN", "B-STUDY_TESTCD", "O", "B-SEX", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 1, 0, 10, 2, 0, 5, 0, 0, 3, 4, 4, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL
In conclusion , administration of COMPOUND_XXX by oral gavage to beagle dogs caused reddened ears , increased alanine aminotransferase , alkaline phosphatase and total bilirubin , and microscopic changes in the liver at 60 mg / kg / day .
[ "In", "conclusion", ",", "administration", "of", "COMPOUND_XXX", "by", "oral", "gavage", "to", "beagle", "dogs", "caused", "reddened", "ears", ",", "increased", "alanine", "aminotransferase", ",", "alkaline", "phosphatase", "and", "total", "bilirubin", ",", "and", "microscopic", "changes", "in", "the", "liver", "at", "60", "mg", "/", "kg", "/", "day", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "B-SPECIMEN", "O", "B-MANIFESTATION_FINDING", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "B-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "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, 8, 10, 0, 1, 2, 6, 0, 2, 6, 0, 2, 6, 0, 0, 8, 9, 0, 0, 10, 0, 3, 4, 4, 4, 4, 4, 0 ]
PRETOX_REL
In conclusion , COMPOUND_XXX and revealed morphologic cardiac effects under the condition of the present study .
[ "In", "conclusion", ",", "COMPOUND_XXX", "and", "revealed", "morphologic", "cardiac", "effects", "under", "the", "condition", "of", "the", "present", "study", "." ]
[ "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 8, 9, 9, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
Blood samples were drawn and urine collected for routine clinical pathology evaluations from 10 animals / sex / group in Weeks 4 , 8 , 13 , 26 , 39 , 52 and 5 animals / sex / group in Week 60 ( Recovery Week 8 ) .
[ "Blood", "samples", "were", "drawn", "and", "urine", "collected", "for", "routine", "clinical", "pathology", "evaluations", "from", "10", "animals", "/", "sex", "/", "group", "in", "Weeks", "4", ",", "8", ",", "13", ",", "26", ",", "39", ",", "52", "and", "5", "animals", "/", "sex", "/", "group", "in", "Week", "60", "(", "Recovery", "Week", "8", ")", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "I-GROUP", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 12, 13, 13, 13, 13, 13, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 12, 13, 13, 13, 13, 13, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL
Dose Level 2 It is concluded that under the conditions of the study , the daily administration of the compound by intubation at dose level 2 for two weeks resulted in the appearance of bright yellow urine .
[ "Dose", "Level", "2", "It", "is", "concluded", "that", "under", "the", "conditions", "of", "the", "study", ",", "the", "daily", "administration", "of", "the", "compound", "by", "intubation", "at", "dose", "level", "2", "for", "two", "weeks", "resulted", "in", "the", "appearance", "of", "bright", "yellow", "urine", "." ]
[ "B-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", "B-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "B-SPECIMEN", "O" ]
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NO_PRETOX_REL
The toxicokinetic data showed that all animals from the groups treated with COMPOUND_XXX Nail Lacquer were systemically exposed to the drug resulting in mean AUC ( 0 - 168h ) values between 629 and 1410 ng · mL / h after the first administration .
[ "The", "toxicokinetic", "data", "showed", "that", "all", "animals", "from", "the", "groups", "treated", "with", "COMPOUND_XXX", "Nail", "Lacquer", "were", "systemically", "exposed", "to", "the", "drug", "resulting", "in", "mean", "AUC", "(", "0", "-", "168h", ")", "values", "between", "629", "and", "1410", "ng", "·", "mL", "/", "h", "after", "the", "first", "administration", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-GROUP", "I-GROUP", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "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
Summary of results No treatment - related findings occurred even with the maximum feasible dose of 30 mg / kg on ca. 15 % of the body surface with 50 mg ointment / cm2 .
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[ "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" ]
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NO_PRETOX_REL
These were generally dose - related relative to frequency and severity ( minimal to marked ) .
[ "These", "were", "generally", "dose", "-", "related", "relative", "to", "frequency", "and", "severity", "(", "minimal", "to", "marked", ")", "." ]
[ "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
Water consumption Water consumption tended to be dose - dependently lower in animals treated with COMPOUND_XXX .
[ "Water", "consumption", "Water", "consumption", "tended", "to", "be", "dose", "-", "dependently", "lower", "in", "animals", "treated", "with", "COMPOUND_XXX", "." ]
[ "O", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "O", "O", "O", "B-MANIFESTATION_FINDING", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 2, 6, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL
An increased incidence and severity of pelvic dilatation was evident in the kidney of animals at 1000 mg / kg / day Ro 32-3555/000 .
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[ "O", "B-MANIFESTATION_FINDING", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "O", "O", "O", "O", "B-SPECIMEN", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O" ]
[ 0, 1, 0, 0, 0, 0, 8, 9, 0, 0, 0, 0, 10, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0, 0, 0 ]
PRETOX_REL
Bright yellow urine in all rats and centrilobular hepatocellular hypertrophy ( minimal ) in one rat were observed due to treatment with 10 mg / kg / day .
[ "Bright", "yellow", "urine", "in", "all", "rats", "and", "centrilobular", "hepatocellular", "hypertrophy", "(", "minimal", ")", "in", "one", "rat", "were", "observed", "due", "to", "treatment", "with", "10", "mg", "/", "kg", "/", "day", "." ]
[ "B-FINDING", "I-FINDING", "B-SPECIMEN", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "O", "B-MANIFESTATION_FINDING", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]
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PRETOX_REL
The relative weight of the thyroid was increased in male rats .
[ "The", "relative", "weight", "of", "the", "thyroid", "was", "increased", "in", "male", "rats", "." ]
[ "O", "O", "B-STUDY_TESTCD", "O", "O", "B-SPECIMEN", "O", "B-MANIFESTATION_FINDING", "O", "B-SEX", "O", "O" ]
[ 0, 0, 2, 0, 0, 10, 0, 1, 0, 5, 0, 0 ]
NO_PRETOX_REL
Hematology : No treatment - related changes in hematology or coagulation parameters were observed .
[ "Hematology", ":", "No", "treatment", "-", "related", "changes", "in", "hematology", "or", "coagulation", "parameters", "were", "observed", "." ]
[ "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
The disparity between males and females in the present study is more likely a reflection of a gender difference in sensitivity such that the relatively slight insult was only discernible in the more sensitive gender .
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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", "O", "O", "O", "O", "O" ]
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PRETOX_REL
b. Mortality Animal H 937 / group lil had to be sacrificed prematurely in week 3 of the study ( see also  » Clinical findings " ) .
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[ "O", "O", "O", "O", "O", "O", "B-GROUP", "I-GROUP", "O", "O", "O", "B-FINDING", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
Protocol - specified organs were weighed and tissues were collected , processed and microscopically examined on all animals .
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[ "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
Thereafter , plasma concentrations decreased rapidly depending on dose .
[ "Thereafter", ",", "plasma", "concentrations", "decreased", "rapidly", "depending", "on", "dose", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL
Relevant hematological findings were slightly increased platelet counts at the high dose level .
[ "Relevant", "hematological", "findings", "were", "slightly", "increased", "platelet", "counts", "at", "the", "high", "dose", "level", "." ]
[ "O", "O", "O", "O", "O", "B-MANIFESTATION_FINDING", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "O", "O" ]
[ 0, 0, 0, 0, 0, 1, 2, 6, 0, 0, 15, 16, 0, 0 ]
PRETOX_REL
Based upon lymphocyte decreases at doses ≥ 0.2 mg / kg a NOAEL was not established in this study .
[ "Based", "upon", "lymphocyte", "decreases", "at", "doses", "≥", "0.2", "mg", "/", "kg", "a", "NOAEL", "was", "not", "established", "in", "this", "study", "." ]
[ "O", "O", "B-STUDY_TESTCD", "B-MANIFESTATION_FINDING", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 2, 1, 0, 0, 0, 3, 4, 4, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
At the highest dose , the exposure was increased after multiple doses .
[ "At", "the", "highest", "dose", ",", "the", "exposure", "was", "increased", "after", "multiple", "doses", "." ]
[ "O", "O", "B-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 3, 4, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL
Muscle acetylcholinesterase activity increased 28 % in the high dose males and 45 % in the high dose female rats .
[ "Muscle", "acetylcholinesterase", "activity", "increased", "28", "%", "in", "the", "high", "dose", "males", "and", "45", "%", "in", "the", "high", "dose", "female", "rats", "." ]
[ "B-SPECIMEN", "B-STUDY_TESTCD", "O", "B-MANIFESTATION_FINDING", "O", "O", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "B-SEX", "O", "O", "O", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "B-SEX", "O", "O" ]
[ 10, 2, 0, 1, 0, 0, 0, 0, 15, 16, 5, 0, 0, 0, 0, 0, 15, 16, 5, 0, 0 ]
NO_PRETOX_REL
Organ weight analysis did not reveal any clearly treatment - related findings .
[ "Organ", "weight", "analysis", "did", "not", "reveal", "any", "clearly", "treatment", "-", "related", "findings", "." ]
[ "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
Based on the actual food consumption , the mean test item intake was 21.8 and 122.5 mg salt / kg / day during the first 3 days , 20.1 and 158.3 mg salt / kg / day during the next 4 days and 20.7 and 187.7 mg salt / kg / day during the last 7 days .
[ "Based", "on", "the", "actual", "food", "consumption", ",", "the", "mean", "test", "item", "intake", "was", "21.8", "and", "122.5", "mg", "salt", "/", "kg", "/", "day", "during", "the", "first", "3", "days", ",", "20.1", "and", "158.3", "mg", "salt", "/", "kg", "/", "day", "during", "the", "next", "4", "days", "and", "20.7", "and", "187.7", "mg", "salt", "/", "kg", "/", "day", "during", "the", "last", "7", "days", "." ]
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NO_PRETOX_REL
Other groups of females had similar body weight curves to that of the control .
[ "Other", "groups", "of", "females", "had", "similar", "body", "weight", "curves", "to", "that", "of", "the", "control", "." ]
[ "B-GROUP", "I-GROUP", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 12, 13, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
At initiation of dosing , the males weighed 28.6 - 32.9 grams and the females weighed 21.1 - 27.1 grams .
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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" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL
on , treatment with COMPOUND_XXX was associated with reddenings of the skin compatible with histamine induced vasodilations .
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[ "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "O", "O", "O", "B-FINDING", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 8, 9, 9, 9, 0, 0, 0, 0, 8, 0 ]
PRETOX_REL
The higher exposure in females resulted in compound - related effects seen either exclusively or at lower doses in females , including partly to completely reversible clinical chemistry changes in males at 110 mg / kg / day and females at ≥ 30 mg / kg / day ; irreversible increases in adrenal gland and kidney weight and partially reversible liver weight increases in females at 110 mg / kg / day ; reversible macroscopic light pale colored kidneys in females at ≥ 30 mg / kg / day ; and partially to completely reversible microscopic kidney findings in males at 110 mg / kg / day and females at ≥ 10 mg / kg / day , as well as reversible and nonadverse microscopic liver findings in females at 110 mg / kg / day .
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[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "O", "B-SEX", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "B-SEX", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "B-MANIFESTATION_FINDING", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "B-SPECIMEN", "B-STUDY_TESTCD", "O", "O", "O", "B-SPECIMEN", "B-STUDY_TESTCD", "B-MANIFESTATION_FINDING", "O", "B-SEX", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "B-FINDING", "O", "B-SPECIMEN", "O", "B-SEX", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "O", "B-SEX", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "B-SEX", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O", "O", "B-SPECIMEN", "B-FINDING", "O", "B-SEX", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O" ]
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NO_PRETOX_REL
Ophthalmological examinations were performed prior to dosing and during study week 3 .
[ "Ophthalmological", "examinations", "were", "performed", "prior", "to", "dosing", "and", "during", "study", "week", "3", "." ]
[ "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
Each dose level was administered to one group daily and to another group two times per week .
[ "Each", "dose", "level", "was", "administered", "to", "one", "group", "daily", "and", "to", "another", "group", "two", "times", "per", "week", "." ]
[ "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 ]
PRETOX_REL
The peripheral neuropathy present in the sciatic nerves was considered secondary to persistent hypoglycemia .
[ "The", "peripheral", "neuropathy", "present", "in", "the", "sciatic", "nerves", "was", "considered", "secondary", "to", "persistent", "hypoglycemia", "." ]
[ "O", "B-FINDING", "I-FINDING", "O", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "O" ]
[ 0, 8, 9, 0, 0, 0, 10, 11, 0, 0, 0, 0, 8, 9, 0 ]
NO_PRETOX_REL
Body weight , body weight gain and food consumption did not show any treatment - related changes during the treatment and recovery period .
[ "Body", "weight", ",", "body", "weight", "gain", "and", "food", "consumption", "did", "not", "show", "any", "treatment", "-", "related", "changes", "during", "the", "treatment", "and", "recovery", "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" ]
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NO_PRETOX_REL
After dilution of the samples with the mobile phase , COMPOUND_XXX concentrations were measured by HPLC coupled to a UV detector set at 214 nm , and they were quantified by using the area under the peak .
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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", "O", "O", "O", "O", "O", "O", "O" ]
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NO_PRETOX_REL
Complete necropsies were performed on all animals , organ weights were recorded , and protocol specified tissues and gross lesions were collected and processed .
[ "Complete", "necropsies", "were", "performed", "on", "all", "animals", ",", "organ", "weights", "were", "recorded", ",", "and", "protocol", "specified", "tissues", "and", "gross", "lesions", "were", "collected", "and", "processed", "." ]
[ "O", "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 50 mg / kg / day , microscopic findings consisted of hemorrhagic and / or cystic corpora lutea lutea and hemosiderin - laden macrophages in ovaries , foamy macrophage accumulation in lungs , focal angiectasis of the adrenal cortex , hypertrophy of the masseter muscle , focal mineralization and hyperplasia of renal pelvic epithelium , and focal new bone formation .
[ "At", "50", "mg", "/", "kg", "/", "day", ",", "microscopic", "findings", "consisted", "of", "hemorrhagic", "and", "/", "or", "cystic", "corpora", "lutea", "lutea", "and", "hemosiderin", "-", "laden", "macrophages", "in", "ovaries", ",", "foamy", "macrophage", "accumulation", "in", "lungs", ",", "focal", "angiectasis", "of", "the", "adrenal", "cortex", ",", "hypertrophy", "of", "the", "masseter", "muscle", ",", "focal", "mineralization", "and", "hyperplasia", "of", "renal", "pelvic", "epithelium", ",", "and", "focal", "new", "bone", "formation", "." ]
[ "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "B-FINDING", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "B-SPECIMEN", "I-SPECIMEN", "B-FINDING", "I-FINDING", "I-FINDING", "O", "B-SPECIMEN", "I-SPECIMEN", "B-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "B-FINDING", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "B-FINDING", "I-FINDING", "O", "B-FINDING", "O", "B-SPECIMEN", "I-SPECIMEN", "I-SPECIMEN", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O" ]
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NO_PRETOX_REL
Conclusions The repeated daily intragastric administration of COMPOUND_XXX at doses of 0.2 , 2 and 20 mg / kg to female Cynomolgus monkeys over a period of 4 weeks followed by an additional recovery period of 4 weeks in the high dose group resulted in minor reversible changes from the lowest dose upwards .
[ "Conclusions", "The", "repeated", "daily", "intragastric", "administration", "of", "COMPOUND_XXX", "at", "doses", "of", "0.2", ",", "2", "and", "20", "mg", "/", "kg", "to", "female", "Cynomolgus", "monkeys", "over", "a", "period", "of", "4", "weeks", "followed", "by", "an", "additional", "recovery", "period", "of", "4", "weeks", "in", "the", "high", "dose", "group", "resulted", "in", "minor", "reversible", "changes", "from", "the", "lowest", "dose", "upwards", "." ]
[ "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", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-GROUP", "I-GROUP", "I-GROUP", "O", "O", "O", "O", "O", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "O", "O" ]
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NO_PRETOX_REL
No test article - related macroscopic findings were observed .
[ "No", "test", "article", "-", "related", "macroscopic", "findings", "were", "observed", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
At the end of the 4 - week post-treatment period the remaining animals were sacrificed , complete necropsies were performed , weights of selected organs were recorded and gross lesions were evaluated microscopically .
[ "At", "the", "end", "of", "the", "4", "-", "week", "post-treatment", "period", "the", "remaining", "animals", "were", "sacrificed", ",", "complete", "necropsies", "were", "performed", ",", "weights", "of", "selected", "organs", "were", "recorded", "and", "gross", "lesions", "were", "evaluated", "microscopically", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "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
Administration of COMPOUND_XXX resulted in decreases in alkaline phosphatase at doses of ≥ 0.15 mg / kg / occasion , cholesterol at doses of ≥ 0.5 mg / kg / occasion and alanine aminotransferase at doses of 1.0 mg / kg / occasion .
[ "Administration", "of", "COMPOUND_XXX", "resulted", "in", "decreases", "in", "alkaline", "phosphatase", "at", "doses", "of", "≥", "0.15", "mg", "/", "kg", "/", "occasion", ",", "cholesterol", "at", "doses", "of", "≥", "0.5", "mg", "/", "kg", "/", "occasion", "and", "alanine", "aminotransferase", "at", "doses", "of", "1.0", "mg", "/", "kg", "/", "occasion", "." ]
[ "O", "O", "O", "O", "O", "B-MANIFESTATION_FINDING", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "B-STUDY_TESTCD", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "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, 1, 0, 2, 6, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0, 2, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0, 2, 6, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0 ]
NO_PRETOX_REL
Body weight gain and food consumption were normal .
[ "Body", "weight", "gain", "and", "food", "consumption", "were", "normal", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL
Conclusions The dose of 1 mg / kg COMPOUND_XXX lead to toxicity up to anticipated mortality in one out of two female and male animals each .
[ "Conclusions", "The", "dose", "of", "1", "mg", "/", "kg", "COMPOUND_XXX", "lead", "to", "toxicity", "up", "to", "anticipated", "mortality", "in", "one", "out", "of", "two", "female", "and", "male", "animals", "each", "." ]
[ "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "O", "O", "O", "O", "B-SEX", "O", "B-SEX", "O", "O", "O" ]
[ 0, 0, 0, 0, 3, 4, 4, 4, 0, 0, 0, 8, 9, 9, 9, 9, 0, 0, 0, 0, 0, 5, 0, 5, 0, 0, 0 ]
PRETOX_REL
The only other treatment related clinical sign was considered to be liquid / soft faeces , which was observed at 1.5 mg / kg / occasion up to Week 7 of treatment .
[ "The", "only", "other", "treatment", "related", "clinical", "sign", "was", "considered", "to", "be", "liquid", "/", "soft", "faeces", ",", "which", "was", "observed", "at", "1.5", "mg", "/", "kg", "/", "occasion", "up", "to", "Week", "7", "of", "treatment", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "O", "O", "O" ]
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PRETOX_REL
A slight increase of water consumption was seen in group 3 ( 300 mg / kg ) and 4 ( 1000 mg / kg ) females during the treatment period , statistical significance was noted from day 3 - 7 ( group 4 only ) , then on days 7 - 10 , 17 - 21 , and day 21 - 28 in both groups .
[ "A", "slight", "increase", "of", "water", "consumption", "was", "seen", "in", "group", "3", "(", "300", "mg", "/", "kg", ")", "and", "4", "(", "1000", "mg", "/", "kg", ")", "females", "during", "the", "treatment", "period", ",", "statistical", "significance", "was", "noted", "from", "day", "3", "-", "7", "(", "group", "4", "only", ")", ",", "then", "on", "days", "7", "-", "10", ",", "17", "-", "21", ",", "and", "day", "21", "-", "28", "in", "both", "groups", "." ]
[ "O", "O", "B-MANIFESTATION_FINDING", "O", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "B-GROUP", "I-GROUP", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "B-SEX", "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", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-GROUP", "I-GROUP", "O" ]
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NO_PRETOX_REL
After repeated dosing , no clear trend was evident in terms of accumulation .
[ "After", "repeated", "dosing", ",", "no", "clear", "trend", "was", "evident", "in", "terms", "of", "accumulation", "." ]
[ "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
Clinical signs , body weight and estimated food consumption determinations were performed on all the animals .
[ "Clinical", "signs", ",", "body", "weight", "and", "estimated", "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", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
PRETOX_REL
No specific target organ toxicity has been observed , although typical signs of excessive cholinergic stimulation occur at high doses in the gastrointestinal tract and central nervous system .
[ "No", "specific", "target", "organ", "toxicity", "has", "been", "observed", ",", "although", "typical", "signs", "of", "excessive", "cholinergic", "stimulation", "occur", "at", "high", "doses", "in", "the", "gastrointestinal", "tract", "and", "central", "nervous", "system", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "O", "B-DOSE_QUALIFICATION", "I-DOSE_QUALIFICATION", "O", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "B-SPECIMEN", "I-SPECIMEN", "I-SPECIMEN", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 8, 9, 9, 9, 9, 0, 0, 15, 16, 0, 0, 10, 11, 0, 10, 11, 11, 0 ]
PRETOX_REL
Clinical signs and reduced body weight occurred in rats that received 200 or 800 mg / kg / day of COMPOUND_XXX .
[ "Clinical", "signs", "and", "reduced", "body", "weight", "occurred", "in", "rats", "that", "received", "200", "or", "800", "mg", "/", "kg", "/", "day", "of", "COMPOUND_XXX", "." ]
[ "B-FINDING", "I-FINDING", "O", "B-MANIFESTATION_FINDING", "B-STUDY_TESTCD", "I-STUDY_TESTCD", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O" ]
[ 8, 9, 0, 1, 2, 6, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 4, 4, 0, 0, 0 ]
NO_PRETOX_REL
There was no indication for an accumulation of the test compound when administered daily over 29 days .
[ "There", "was", "no", "indication", "for", "an", "accumulation", "of", "the", "test", "compound", "when", "administered", "daily", "over", "29", "days", "." ]
[ "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 ]
NO_PRETOX_REL
Electrocardiography evaluations were performed on all animals in pretest and in week 13 at approximately 30 minutes post dose .
[ "Electrocardiography", "evaluations", "were", "performed", "on", "all", "animals", "in", "pretest", "and", "in", "week", "13", "at", "approximately", "30", "minutes", "post", "dose", "." ]
[ "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
Females appeared more sensitive than the males to this compound .
[ "Females", "appeared", "more", "sensitive", "than", "the", "males", "to", "this", "compound", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
In males , AUC were 677 ± 182 h.ng / ml , 2191 ± 672 h.ng / ml , 12532 ± 8255 h.ng / ml for 5 , 15 and 70 mg / kg / day respectively .
[ "In", "males", ",", "AUC", "were", "677", "±", "182", "h.ng", "/", "ml", ",", "2191", "±", "672", "h.ng", "/", "ml", ",", "12532", "±", "8255", "h.ng", "/", "ml", "for", "5", ",", "15", "and", "70", "mg", "/", "kg", "/", "day", "respectively", "." ]
[ "O", "O", "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", "O" ]
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PRETOX_REL
As expected from previous studies , minimal heart weight increases were present after 4 weeks at both dosages , but without correlating findings in clinical biochemistry or histopathology .
[ "As", "expected", "from", "previous", "studies", ",", "minimal", "heart", "weight", "increases", "were", "present", "after", "4", "weeks", "at", "both", "dosages", ",", "but", "without", "correlating", "findings", "in", "clinical", "biochemistry", "or", "histopathology", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "B-SPECIMEN", "B-STUDY_TESTCD", "B-MANIFESTATION_FINDING", "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, 10, 2, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
Based on these results , the exposure period for the main study is selected to be 119 hours ( every five days for 28 days ) .
[ "Based", "on", "these", "results", ",", "the", "exposure", "period", "for", "the", "main", "study", "is", "selected", "to", "be", "119", "hours", "(", "every", "five", "days", "for", "28", "days", ")", "." ]
[ "O", "O", "O", "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 ]
NO_PRETOX_REL
All animals survived the scheduled study period .
[ "All", "animals", "survived", "the", "scheduled", "study", "period", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
Clinical observations , body weight and food consumption determinations , ophthalmoscopic and clinical pathology examinations were performed on all groups .
[ "Clinical", "observations", ",", "body", "weight", "and", "food", "consumption", "determinations", ",", "ophthalmoscopic", "and", "clinical", "pathology", "examinations", "were", "performed", "on", "all", "groups", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-GROUP", "I-GROUP", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 12, 13, 0 ]
NO_PRETOX_REL
Exposure increased proportionally with dosage for both males and females .
[ "Exposure", "increased", "proportionally", "with", "dosage", "for", "both", "males", "and", "females", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0 ]
NO_PRETOX_REL
The corresponding dosages in terms of base were 43.3 and 433.2 mg / kg , respectively .
[ "The", "corresponding", "dosages", "in", "terms", "of", "base", "were", "43.3", "and", "433.2", "mg", "/", "kg", ",", "respectively", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "B-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "I-DOSE", "O", "O", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 0, 3, 4, 4, 4, 4, 4, 0, 0, 0 ]
PRETOX_REL
At the histopathological examination , a minimal hypertrophy of the centrilobular hepatocytes in the liver was noted in 2/5 males .
[ "At", "the", "histopathological", "examination", ",", "a", "minimal", "hypertrophy", "of", "the", "centrilobular", "hepatocytes", "in", "the", "liver", "was", "noted", "in", "2/5", "males", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "I-FINDING", "O", "O", "B-SPECIMEN", "O", "O", "O", "O", "B-SEX", "O" ]
[ 0, 0, 0, 0, 0, 0, 0, 8, 9, 9, 9, 9, 0, 0, 10, 0, 0, 0, 0, 5, 0 ]
PRETOX_REL
In conclusion , based on the results of this study , a no toxic effect level was not established , and while it appears that most of the adverse effects produced by administration ofCOMPOUND_XXX at the 0.6 mg / kg / day dose are reversible within a four - week recovery period , the insults to the thyroid and lymphoid tissues , although less severe , persisted .
[ "In", "conclusion", ",", "based", "on", "the", "results", "of", "this", "study", ",", "a", "no", "toxic", "effect", "level", "was", "not", "established", ",", "and", "while", "it", "appears", "that", "most", "of", "the", "adverse", "effects", "produced", "by", "administration", "ofCOMPOUND_XXX", "at", "the", "0.6", "mg", "/", "kg", "/", "day", "dose", "are", "reversible", "within", "a", "four", "-", "week", "recovery", "period", ",", "the", "insults", "to", "the", "thyroid", "and", "lymphoid", "tissues", ",", "although", "less", "severe", ",", "persisted", "." ]
[ "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "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", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-FINDING", "O", "O", "B-SPECIMEN", "O", "B-SPECIMEN", "I-SPECIMEN", "O", "O", "O", "O", "O", "O", "O" ]
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PRETOX_REL
A marked decrease in thymus weight was noted following I month treatment at 1000 mg / kg / day , this did not correspond to any histopathological finding in the thymus and appeared to be reversible .
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[ "O", "O", "B-MANIFESTATION_FINDING", "O", "B-SPECIMEN", "B-STUDY_TESTCD", "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" ]
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NO_PRETOX_REL
Food Consumption : There were no treatment - related changes in food consumption .
[ "Food", "Consumption", ":", "There", "were", "no", "treatment", "-", "related", "changes", "in", "food", "consumption", "." ]
[ "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 ]
PRETOX_REL
Reverse T3 was significantly increased on day 5 , but significantly decreased on days 12 and 26 compared to vehicle control - treated animals .
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PRETOX_REL
Since no histological heart lesions related to treatment with COMPOUND_XXX were observed at 80 mg / kg after 4 weeks treatment or 60 mg / kg after 4 or 26 weeks treatment in previous toxicity studies in rats ( Studies 0510076 , 0370146 and 0580158 ) at similar systemic exposure to COMPOUND_XXX , the increase of these foci in some treated animals appears to be more likely an exacerbation of a background lesion due to treatment or an incidental finding not related to treatment rather than a direct effect of COMPOUND_XXX .
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PRETOX_REL
At 75 and 225 mg / kg a slightly lower mean daily food consumption was observed in female animals during the first weeks of gestation that resulted in minimal changes ( about 5 % less than controls ) in mean body weight of these two groups at the end of gestation and up to end of the study ( Day 4 of lactation ) .
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NO_PRETOX_REL
At the end of the treatment period all main study animals were sacrificed , complete necropsies were performed , weights of selected organs were recorded and selected tissues were evaluated microscopically .
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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", "O" ]
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