Critical review of the epidemiology literature on the potential cancer risks of methylene chloride

Objective: To critically review and summarize the epidemiological evidence published to date on the carcinogenicity of methylene chloride to humans. Methods: Papers for review were identified through Medline (National Library of Medicine) and were limited to epidemiology studies. Studies were classified using three categories. Primary studies focused on the association between methylene chloride and cancer among occupational cohorts primarily exposed to methylene chloride. Secondary studies identified methylene chloride a priori as a potential exposure of interest, and the investigators either characterized the methylene chloride exposure or described results for the methylene chloride-exposed workers separately. Tertiary studies evaluated cohorts either minimally exposed to methylene chloride or presumed exposed but for which no exposure estimation or separate classification was made. Results: No strong or consistent finding for any site of cancer was apparent despite several studies of large occupational cohorts of workers potentially exposed to high concentrations of methylene chloride. Sporadic and weak associations were reported for cancers of the pancreas, liver and biliary passages, breast, and brain. Although these studies collectively cannot rule out the possibility of any cancer risk associated with methylene chloride exposure, they do support a conclusion of no substantive cancer risk. Conclusion: Continued follow-up of the established cohorts may elucidate the few and inconsistent relationships reported to date; however, it appears likely that risks associated with methylene chloride exposure, if any, are small and limited to rare cancers. The usefulness of additional cohort studies for the evaluation of cancer risks associated with methylene chloride exposure will depend largely on whether the relevant exposure period has passed and whether exposure characterization (e.g., peak or intermittent exposure or intensity) can be improved.