However, there are quantitative differences in the fraction of benzene metabolized by the different pathways. Mice appear to have a greater overall capacity to metabolize benzene than rats or primates, based on mass balance studies conducted in vivo using radiolabeled 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. Because ring-breakage metabolites and hydroquinone have both been implicated in the toxicity of benzene, the higher formation of these metabolites in the mouse may partially explain why mice are more sensitive to benzene toxicity than are rats.
Mice also metabolize more of inhaled benzene than do rats.
For all species studied, there is a greater fractional formation of these and ring-breakage metabolites at low doses compared to high doses. This finding, along with many other factors, must be considered in attempting to extrapolate the toxicity of benzene observed at high doses to those expected at low doses. 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 the human subjects. Technical Report Series 289.