Species differences in the metabolism of benzene.

The pathways of metabolism of benzene appear to be qualitatively similar in all species studied thus far. However, there are quantitative differences in the fraction of benzene metabolized by the different pathways. These species differences become important for risk assessments based on animal data. Mice have a greater overall capacity to metabolize benzene than rats or primates, based on mass balance studies conducted in vivo using radiolabled benzene. Mice and monkeys metabolize more of the benzene to hydroquinone metabolites than do rats or chimpanzees, especially at low doses. Nonhuman primates metabolize less of the benzene to muconic acid than do rodents or humans. In all species studied, a greater proportion of benzene is converted to hydroquinone and ring-breakage metabolites at low doses than at high doses. This finding should be considered in attempting to extrapolate the toxicity of benzene observed at high doses to predicted toxicity at low doses. Because ring-breakage metabolites and hydroquinone have both been implicated in the toxicity of benzene, the higher formation of those metabolites in the mouse may partially explain why mice are more sensitive to benzene than are rats. Metabolism of benzene in humans, the species of interest, does not exactly mimic that of any animal species studied. More information on the urinary and blood metabolites of occupationally exposed people is required to determine the fractional conversion of benzene to putative toxic metabolites and the degree of variability present in human subjects.