Mortality in a 1942-1990 cohort of 858 men and 21 women employed in the manufacture and use of hydroquinone was evaluated through 1991. Average exposure concentrations, 1949-1990, ranged from 0.1 to 6.0 mg/m3 for hydroquinone dust and from less than 0.1 to 0.3 for quinone vapor (estimated 8-h time-weighted averages). Compared with general population and occupational referents, there were statistically significant deficits in total mortality and deaths due to cancer. No significant excesses were observed for such hypothesized causes as kidney cancer [2 observed vs 1.3 expected (both control groups), P approximately 0.39], liver cancer (0 vs 0.8, 1.3), and leukemia (0 vs 2.3, 2.7). Dose-response analyses of selected causes of death, including renal carcinoma, demonstrated no statistically significant heterogeneities or linear trends according to estimated career hydroquinone exposure (mg/m3-years) or time from first exposure.

The mortality experience of two overlapping cohorts of employees engaged in the manufacture of photographic film support was evaluated to assess the potential chronic health effects of methylene chloride exposure. In the first analysis, we examined causes of death among 1311 men initially employed between 1946 (when the solvent was first used) and 1970; in the second, we updated mortality in a 1964 to 1970 employed cohort of 1013 men. Follow-up was through 1994. The mean exposure among members of the 1946 to 1970 cohort was 39 ppm (8-hour time-weighted average) for 17 years, and the median length of follow-up from first exposure was 34 years. Members of the 1964 to 1970 cohort received an average exposure of 26 ppm for 24 years; median time from first exposure was 35 years. Compared with general population vital statistics, mortality in both cohorts was below expectation for all causes of death, ischemic heart disease, and cancer, including such sites as the lung and liver, which were target organs identified in animal toxicology studies. No statistically significant increases were observed for any cause of death. The combined results of this study and three others in the photographic film and textile fibers industries (approximately 7300 subjects) show that long-term exposure to methylene chloride does not increase the risk of death from any cause including specific diagnoses that have been associated with this widely used solvent.

A call for risk assessment approaches that better characterize and quantify uncertainty has been made by the scientific and regulatory community. This paper responds to that call by demonstrating a distributional approach that draws upon human data to derive potency estimates and to identify and quantify important sources of uncertainty. The approach is rooted in the science of decision analysis and employs an influence diagram, a decision tree, probabilistic weights, and a distribution of point estimates of carcinogenic potency. Its results estimate the likelihood of different carcinogenic risks (potencies) for a chemical under a specific scenario. For this exercise, human data on formaldehyde were employed to demonstrate the approach. Sensitivity analyses were performed to determine the relative impact of specific levels and alternatives on the potency distribution. The resulting potency estimates are compared with the results of an exercise using animal data on formaldehyde. The paper demonstrates that distributional risk assessment is readily adapted to situations in which epidemiologic data serve as the basis for potency estimates. Strengths and weaknesses of the distributional approach are discussed. Areas for further application and research are recommended.

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