Dose-Dependent Metabolism of Benzene in Hamsters, Rats, and Mice

• Published in: Toxicological sciences Vol. 44; no. 1; pp. 14 - 21
• Main Authors: Mathews, James M., Etheridge, Amy S., Matthews, H.B.
• Format: Journal Article
• Language: English
• Published: Cary, NC Elsevier Science (USA) 01.07.1998; Oxford University Press
• Subjects: Animals; Benzene - administration & dosage; Benzene - pharmacokinetics; Biological and medical sciences; Biotransformation; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; Chromatography, High Pressure Liquid; Cricetinae; Feces - chemistry; Male; Medical sciences; Mice; Mice, Inbred Strains; Rats; Rats, Inbred F344; Species Specificity; Spectrophotometry, Ultraviolet; Tumors; Hydrocarbon; Isotope labelling; Rat; Interspecific comparison; Rodentia; Elimination; Metabolism; Ingestion; Dose activity relation; Toxicokinetics; Carcinogen; Vertebrata; Mammalia; Mouse; Animal; Benzene; Aromatic compound; Carbon 14; Hamster
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1006/toxs.1998.2474

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.