A Review of the Toxicokinetics of Benzene

Abstract

Benzene is an important, widely used industrial solvent (Yin et al. 1987), and a common pollutant in indoor air (Wallace et al. 1984), cigarette smoke (Wallace et al. 1984; Jermini et al. 1976), and gasoline vapors (Wallace et al. 1984; Kalf 1987). Epidemiology studies have demonstrated an increase in both leukemia and aplastic anemia in exposed people (Aksoy and Erdem 1978; Goldstein 1977). Toxicity has also been demonstrated in laboratory animals. For example, in studies conducted by the National Toxicology Program, rats and mice were exposed orally to benzene for 2 years (National Toxicology Program 1986). Increased incidences of lymphomas and other tumors were noted in benzene-treated mice compared to controls. Rats responded differently to the carcinogenic effects of benzene. One hypothesis for the difference in species response is that there are significant species differences in benzene metabolism. An approach to addressing this hypothesis is to compare the metabolism of benzene in rats and mice and develop toxicokinetic models to describe this metabolism. In studies conducted in rats and mice exposed to a range of oral and inhaled concentrations, distinct species differences in benzene metabolism were noted (Sabourin et al. 1987, 1988a, b, 1989). A toxicokinetic model describing benzene disposition has been developed (Medinsky et al. 1988, 1989a, b). One of the most important observations from both the animal studies and the toxicokinetic model was related to the nonlinear nature of benzene metabolism. This nonlinear metabolism has important implications for risk assessment and is discussed in detail here.