Methods for Addressing Uncertainty and Variability to Characterize Potential Health Risk from Trichloroethylene-Contaminated Ground Water at Beale Air Force Base in California:Integration of Uncertainty and Variability in Pharmacokinetics and Dose-Response

Traditional estimates of health risk are typically inflated, particularly if cancer is the dominant endpoint and there is fundamental uncertainty as to mechanism(s) of action. Risk is more realistically characterized if it accounts for joint uncertainty and interindividual variability within a systematic probabilistic framework to integrate the joint effects on risk of distributed parameters of all (linear as well as nonlinear) risk-extrapolation models involved. Such a framework was used to characterize risks to potential future residents posed by trichloroethylene (TCE) in ground water at an inactive landfill site on Beale Air Force Base in California. Variability and uncertainty were addressed in exposure-route-specific estimates of applied dose, in pharmacokinetically based estimates of route-specific metabolized fractions of absorbed TCE, and in corresponding biologically effective doses estimated under a genotoxic/linear (MA{sub G}) vs. a cytotoxic/nonlinear (MA{sub c}) mechanistic assumption for TCE-induced cancer. Increased risk conditional on effective dose was estimated under MA{sub G} based on seven rodent-bioassay data sets, and under MA{sub c} based on mouse hepatotoxicity data. Mean and upper-bound estimates of combined risk calculated by the unified approach were <10{sup -6} and 10{sup -4}, respectively, while corresponding estimates based on traditional deterministic methods were >10{sup -5} and 10{sup -4}, respectively. It was estimated that no TCE-related harm is likely to occur due to any plausible residential exposure scenario involving the site. The systematic probabilistic framework illustrated is particularly suited to characterizing risks that involve uncertain and/or diverse mechanisms of action.