XXXX responses to acute, subchronic, and chronic oral administrations of @entity30170 to rodents.

@entity137 @entity30170 @entity39 @entity19 @entity5 @entity4336 @entity35
Acute (single exposure), 14-d repeated exposure, 91-d subchronic, and 103-wk chronic @entity137 studies of orally administered (gavage, in @entity4336 oil) @entity30170 were conducted in male and female Fischer-344 @entity35 and B6C3F1 hybrid @entity19 . A single exposure to 4000 mg/kg was lethal to male and female @entity35 , while a single exposure to a dose as low as 1000 mg/kg was lethal to @entity19 . Fourteen daily exposures to 1000 mg/kg caused death in @entity35 of both sexes, but neither survival nor clinical health were compromised at 500 mg/kg in @entity35 or @entity19 . In the 91-d studies, wherein @entity30170 was administered once daily, 5 d/wk, survival was reduced by doses of 500 mg/kg and higher in @entity35 , and by doses of 250 mg/kg and higher in @entity19 . Dose-dependent @entity39 of the liver (hepatocytes), @entity39 of the renal proximal tubules, and lymphoid or myeloid depletion of the spleen, bone marrow, and thymus (mild to severe) were produced by doses of 250 mg/kg or greater of @entity30170 in both sexes of @entity35 and @entity19 , although the incidences of these lesions varied considerably by sex and species. Consistent changes in the circulating blood components were not observed, but a mild porphyrinuria was detected at the higher doses. No toxic effects were observed at doses of 125 mg/kg or less. In the 2-yr studies, wherein @entity30170 was administered once daily, 5 d/wk, doses of 30 or 60 mg/kg in male @entity19 and 60 or 120 mg/kg in female @entity19 and male and female @entity35 did not produce any evidence of @entity137 . Doses of 60 or 120 mg/kg caused slight (statistically significant at 120 mg/kg; p less than 0.05) increases in the frequencies of male @entity35 with neoplastic nodules of the liver. Increased @entity5 frequencies were not observed in female @entity35 or in male or female @entity19 receiving @entity30170 .
