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 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 prephenlmercapturic 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 the hamsters metabolize benzene to more highly oxidized, toxic products than do rats or mice.
Mathews
J M
JM
Center for Bioorganic Chemistry, Research Triangle Institute, North Carolina 27709, USA.
Etheridge
A S
AS
Matthews
H B
HB
D000818:Animals; D001554:Benzene / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D005243:Feces / Q000737:chemistry; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013056:Spectrophotometry, Ultraviolet
D001554:Benzene