Metabolism of [14C]benzene by cynomolgus monkeys and chimpanzees

Toxicology and Applied Pharmacology
P J SabourinR F Henderson

Abstract

Rodent bioassays indicate that B6C3F1 mice are more sensitive to the carcinogenicity of benzene than are rats. The urinary profile of benzene metabolites is different in rats vs mice. Mice produce higher proportions of hydroquinone conjugates and muconic acid, indicators of metabolism via pathways leading to putative toxic metabolites, than do rats. In both species, metabolism to hydroquinone and muconic acid is favored at low concentrations of benzene, indicating that these pathways are easily saturated. These species differences in the metabolism of benzene make it difficult to predict the health risk to humans and how this risk varies with dose. For this reason, the metabolism of [14C]benzene by cynomolgus monkeys and chimpanzees, animals phylogenetically closer to humans than rodents, was studied. Monkeys were dosed ip with 5, 50, or 500 mg [14C]benzene/kg body wt. Urine was collected for up to 24 hr following exposure and was analyzed for benzene metabolites. The proportion of the administered 14C excreted in the urine of monkeys decreased from approximately 50 to 15% as the dose increased. Phenyl sulfate was the major urinary metabolite. The proportion of hydroquinone conjugates and muconic acid in the monkey's urine decr...Continue Reading

References

Jun 15, 1989·Toxicology and Applied Pharmacology·M A MedinskyR F Henderson
Oct 1, 1987·Toxicology and Applied Pharmacology·D A EastmondR D Irons
Feb 1, 1989·British Journal of Industrial Medicine·O InoueM Ikeda
Jul 1, 1988·Journal of Analytical Toxicology·W E BechtoldR F Henderson
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Jan 1, 1988·Annals of the New York Academy of Sciences·J E HuffJ K Haseman

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Citations

Apr 7, 1995·Journal of Chromatography. B, Biomedical Applications·T RuppertF Adlkofer
Jan 27, 2000·Toxicology·M W Powley, G P Carlson
May 29, 2004·Mutation Research·John WhysnerElizabeth A Lax
Jul 1, 1994·Journal of Toxicology and Environmental Health·A BartczakW E Bechtold
Feb 1, 1995·Journal of Toxicology and Environmental Health·E M KenyonM A Medinsky
Dec 1, 1996·Environmental Health Perspectives·R F Henderson
Sep 6, 2005·Chemico-biological Interactions·Kun-Ming ChenAssieh A Melikian
Jun 20, 2002·Critical Reviews in Toxicology·Robert Snyder
Nov 22, 2008·Toxicology and Industrial Health·S WilburO Faroon
Sep 16, 2003·Journal of Exposure Analysis and Environmental Epidemiology·Clifford P WeiselGisela Witz
Jan 1, 1994·Critical Reviews in Toxicology·R Snyder, G F Kalf

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