PHARMACOKINETICALLY BASED RISK ASSESSMENT OF WORKPLACE EXPOSURE OF BENZENE

Abstract

Cancer risk from exposure to benzene for a working lifetime was estimated from data obtained in studies with rodents. ancers of the Zymbal gland and the blood-forming system were selected as endpoints for the assessment because of their consistent occurrence. he combined metabolites were judged from toxicological data to be the best representative of the reactive agent. ecause 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. erived Michael isMenton constants were used to convert the doses of combined metabolites from the pharmacokinetic studies to the doses used in the bioassays. caling across species was based on allometric relationships. xperimental 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. he occupational lifetime cancer risk estimated from rodent data was 6 to 14 cases/lOOO workers, which is consistent with the 9.5 to 174 leukemia cases/lOOO estimated by others from epidemiological data. implications of these estimates and uncertainties associated with making them are discussed.

Citation

Beliles, R. AND L. Totman. PHARMACOKINETICALLY BASED RISK ASSESSMENT OF WORKPLACE EXPOSURE OF BENZENE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-89/005 (NTIS PB89235089), 1989.

Additional Information

Regulatory Tox and Pharm, 9:186-195, 1989

• PHARMACOKINETICALLY BASED RISK ASSESSMENT OF WORKPLACE EXPOSURE OF BENZENE