Cancer dose-response modeling of epidemiological data on worker exposures to aldrin and dieldrin

The paper applies classical statistical principles to yield new tools for r isk assessment and makes new use of epidemiological data for human risk ass essment. An extensive clinical and epidemiological study of workers engaged in the manufacturing and formulation of aldrin and dieldrin provides occup ational hygiene and biological monitoring data on individual exposures over the years of employment and provides unusually accurate measures of indivi dual lifetime average daily doses. In the cancer dose-response modeling, ea ch worker is treated as a separate experimental unit with his own unique do se. Maximum likelihood estimates of added cancer risk are calculated for mu ltistage, multistage-Weibull, and proportional hazards models. Distribution al characterizations of added cancer risk are based on bootstrap and relati ve likelihood techniques. The cancer mortality data on these male workers s uggest that low-dose exposures to aldrin and dieldrin do not significantly increase human cancer risk and may even decrease the human hazard rate for all types of cancer combined at low doses (e.g., 1 mu g/kg/day). The appare nt hermetic effect in the best fitting dose-response models for this data s et is statistically significant. The decrease in cancer risk at low doses o f aldrin and dieldrin is in sharp contrast to the U.S. Environmental Protec tion Agency's upper bound on cancer potency based on mouse liver tumors. Th e EPA's upper bound implies that lifetime average daily doses of 0.0000625 and 0.00625 mu g/kg body weight/day would correspond to increased cancer ri sks of 0.000001 and 0.0001, respectively. However, the best estimate from t he Pernis epidemiological data is that there is no increase in cancer risk in these workers at these doses or even at doses as large as 2 mu g/kg/day.