Dose-Dependent Metabolism of Benzene in Hamsters, Rats, and Mice
The disposition of oral doses of [14C]benzene was investigated using a range of doses that included lower levels (0.02 and 0.1 mg/kg) than have been studied previously in rat, mouse, and in hamster, a species which has not been previously examined for its capacity to metabolize benzene. Saturation o...
Saved in:
Published in | Toxicological sciences Vol. 44; no. 1; pp. 14 - 21 |
---|---|
Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Cary, NC
Elsevier Science (USA)
01.07.1998
Oxford University Press |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | The disposition of oral doses of [14C]benzene was investigated using a range of doses that included lower levels (0.02 and 0.1 mg/kg) than have been studied previously in rat, mouse, and in hamster, a species which has not been previously examined for its capacity to metabolize benzene. Saturation of metabolism of benzene was apparent as the dose increased, and a considerable percentage of the highest doses (100 mg/kg) was exhaled unchanged. Most of the remainder of the radioactivity was excreted as metabolites in urine, and significant metabolite-specific changes occurred as a function of dose and species. Phenyl sulfate was the predominant metabolite in rat urine at all dose levels (64–73% of urinary radioactivity), followed by prephenylmercapturic acid (10–11%). Phenyl sulfate (24–32%) and hydroquinone glucuronide (27–29%) were the predominant metabolites formed by mice. Mice produced considerably more muconic acid (15%), which is derived from the toxic metabolite muconaldehyde, than did rats (7%) at a dose of 0.1 mg/kg. Unlike both rats and mice, hydroquinone glucuronide (24–29%) and muconic acid (19–31%) were the primary urinary metabolites formed by hamsters. Two metabolites not previously detected in the urine of rats or mice after single doses, 1,2,4-trihydroxybenzene and catechol sulfate, were found in hamster urine. These data indicate that hamsters metabolize benzene to more highly oxidized, toxic products than do rats or mice. |
---|---|
Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 1096-6080 1096-0929 |
DOI: | 10.1006/toxs.1998.2474 |