Pharmacokinetically based risk assessment of workplace exposure to benzene

Cancer risk from exposure to benzene for a working lifetime was estimated from data obtained in studies with rodents. Cancers of the Zymbal gland and the blood-forming system were selected as endpoints for the assessment because of their consistent occurrence. The combined metabolites were judged from toxicological data to be the best representative of the reactive agent. Because of similarity in the percentages of lifetime exposed in the rodent studies and in the occupational setting, the amount metabolized/day as a result of exposures 5 days a week for a lifetime was judged to be an appropriate dose paradigm for this assessment. Derived Michaelis-Menton constants were used to convert the doses of combined metabolites from the pharmacokinetic studies to the doses used in the bioassays. Scaling across species was based on allometric relationships. Experimental data were used to scale doses across species with body weight ratios raised to the exponents of 0.74 for the inhalation route and 1.0 for the oral route. The occupational lifetime cancer risk estimated from rodent data was 6 to 14 cases/1000 workers, which is consistent with the 9.5 to 174 leukemia cases/1000 estimated by others from epidemiological data. Implications of these estimates and uncertainties associated with making them are discussed.