Needs for research on benzene metabolism and dosimetry.

In the past, benzene was used extensively in the production of paints, resins, rubber, inks, and dyes. Evidence that persons exposed to high levels of benzene for extended periods of time suffer an increased risk of aplastic anemia and acute myelogenous leukemia (AML) (Ayres & Taylor, 1989), prompted the adoption of regulations by the U.S. government that limited occupational exposures to benzene (Wallace et al., 1990). Recent reports of increased hematotoxicity and leukemia among benzene-exposed workers in China corroborate the existing evidence that benzene causes both aplastic anemia and AML (Travis et al., 1994; Xia et al., 1995). As in previous studies, AML in the Chinese cohort was associated with constant, highlevel exposures or high cumulative exposures. Benzene is found in gasoline at a relative abundance of 1% by volume and is used in the chemical industry as a feedstock for the synthesis of many organic chemicals (Infante et al., 1977). Common sources of environmental exposure include gasoline fumes, automobile exhaust, and both mainstream and sidestream tobacco smoke (Runion & Scott, 1985). A clear concern is whether or not these ubiquitous, low-level exposure present a significant health risk to humans for AML, and what level of exposure can be considered to be of negligible risk. From a risk-management viewpoint, the purpose in understanding and quantifying the dosimetry and metabolism of benzene and its metabolites would be to use this information in characterizing the exposure-dose relationship for benzene. In particular, one would like to know how the concentration of key metabolites in bone marrow, including phenol, hydroquinone, muconaldehyde, and possibly benzene oxide, relates to the level of benzene to which an individual is exposed. These metabolites (with the possible exception of benzene oxide, the effects of which have not been investigated) appear to play an important role in benzene-induced myelotoxicity (Smith, 1996; Barale et al., 1990) and likely are significant in the induction of AML. Therefore, any nonlinearity in the exposure-dose relationship for these metabolites would be expected, in turn, to lead to nonlinearity in the exposure-response relationship for benzene-induced AML. Hence, determining or quantifying the shape of these exposure-dose relationships should