Methylene chloride mortality study: dose-response characterization and animal model comparison

To assess the potential chronic health effects of methylene chloride, the mortality experience of a maturing 1964 to 1970 cohort of 1,013 hourly men was evaluated through 1984. On average, employees were exposed at a rate of 26 ppm (eight-hour time-weighted average) for 22 years; median latency was 30 years. Compared with the general population, no statistically significant excesses were observed for such hypothesized causes as lung cancer (14 observed v 21.0 expected), liver cancer (0 v 0.8), and ischemic heart disease (69 v 98.1); dose-response relationships based on career methylene chloride exposure and latency were not demonstrated. Among nonhypothesized causes, a significant deficit was reported for total deaths (176 v 253.2). None of the industrial referent comparisons achieved statistical significance. Sufficient power was available to detect relative risks of 1.6 for lung malignancy and 1.3 for ischemic heart disease. In contrast, there was inadequate power to identify meaningful risk levels for hepatic cancer. With 14 combined lung and liver cancer deaths observed v 36.3 predicted (P less than .0001), the mortality estimate projected from a mathematical model derived from an animal bioassay substantially overestimated cancer mortality for these sites. This inconsistency emphasizes the need to incorporate epidemiologic evidence in assessing the human health risks associated with long-term exposure to this widely used solvent.