Comparing Toxicologic and Epidemiologic Studies: Methylene Chloride-A Case Study

Exposure to methylene chloride induces lung and liver cancers in mice. The mouse bioassay data have been used as the basis for several cancer risk assessments. ^(1,2) The results from epidemiologic studies of workers exposed to methylene chloride have been mixed with respect to demonstrating an increased cancer risk. The results from a negative epidemiologic study of Kodak workers have been used by two groups of investigators to test the predictions from the EPA risk assessment models.^(3,4) These two groups used very different approaches to this problem, which resulted in opposite conclusions regarding the consistency between the animal model predictions and the Kodak study results. The results from the Kodak study are used to test the predictions from OSHA's multistage models of liver and lung cancer risk. Confidence intervals for the standardized mortality ratios (SMRs) from the Kodak study are compared with the predicted confidence intervals derived from OSHA's risk assessment models. Adjustments for the "healthy worker effect," differences in length of follow-up, and dosimetry between animals and humans were incorporated into these comparisons. Based on these comparisons, we conclude that the negative results from the Kodak study are not inconsistent with the predictions from OSHA's risk assessment model.