Cancer Dose‐Response Modeling of Epidemiological Data on Worker Exposures to Aldrin and Dieldrin

Abstract

The paper applies classical statistical principles to yield new tools for risk assessment and makes new use of epidemiological data for human risk assessment. An extensive clinical and epidemiological study of workers engaged in the manufacturing and formulation of aldrin and dieldrin provides occupational hygiene and biological monitoring data on individual exposures over the years of employment and provides unusually accurate measures of individual lifetime average daily doses. In the cancer dose-response modeling, each worker is treated as a separate experimental unit with his own unique dose. Maximum likelihood estimates of added cancer risk are calculated for multistage, multistage-Weibull, and proportional hazards models. Distributional characterizations of added cancer risk are based on bootstrap and relative likelihood techniques. The cancer mortality data on these male workers suggest 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 microgram/kg/day). The apparent hormetic effect in the best fitting dose-response models for this data set is statistically significant. The decrease in cancer risk at low doses of aldrin and dieldrin is in sharp contrast to the U.S. Environmental Protection Agency's upper bound on cancer potency based on mouse liver tumors. The EPA's upper bound implies that lifetime average daily doses of 0.0000625 and 0.00625 microgram/kg body weight/day would correspond to increased cancer risks of 0.000001 and 0.0001, respectively. However, the best estimate from the 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 micrograms/kg/day.

Cancer risk and parental pesticide application in children of Agricultural Health Study participants.

“…This could be a chance finding, because recent reviews have suggested that aldrin is unlikely to have significant carcinogenic potential (IARC 1987;Sielken et al 1999;Stevenson et al 1999). This finding should be interpreted with caution given the lack of evidence of carcinogenicity, and lack of associations between other specific pesticide exposures and childhood cancer in our study.…”

Cancer mortality in workers exposed to dieldrin and aldrin: over 50 years of follow up

“…It is estimated that over 75% of the cohort had dieldrin exposure levels that exceeded the assumed human equivalent dose rate corresponding to the lowest positive dose rate for female mice in a cancer bioassay in which the incidence of liver tumors had doubled. Sielken et al (1999), based on an earlier study of this cohort, have reported a cancer risk assessment for dieldrin and aldrin. The overall mortality for cancer of that study was slightly lower than the Dutch general population (46 observed deaths with an SMR of 96.8, 95% CI = 71-129).…”