Application of biological data in cancer risk estimations of chlordane and heptachlor

Regulatory agencies traditionally use doses associated with ambient concentrations of contaminants in environmental media to estimate lifetime excess cancer risks. This approach is, however, limited by the errors inherent in making several default assumptions such as daily water and food intakes and organ absorption factors. A methodology was developed in this study to estimate daily human doses of chlordane and heptachlor from measured metabolites in adipose tissue. Human biomonitoring data, pharmacodynamic and pharmacokinetic parameters in humans and animals, and selected dose-response data from animal carcinogenicity studies were utilized in this procedure for cancer risk assessment in man. Conversion factors, based on body surface area, were used for animal-to-man extrapolation. Conservative estimates from the Global 82 linearized multistage mathematical model (95% upper confidence limit) associate a 1 x 10(-5) risk probability level to chlordane and heptachlor doses of 1.1 x 10(-4) and 4.0 x 10(-5) mg/kg-day, respectively, via all potential routes of exposure. The unit cancer risks associated with "internal" dose estimates from human adipose tissue concentrations were calculated and compared with U.S. Environmental Protection Agency (1986a, Carcinogenicity Assessment of Chlordane and Heptachlor/Heptachlor Epoxide, EPA-600/6-87-004) unit risks in air and water. The implications and uncertainties associated with the risk estimates were also discussed.