Based on toxicology, metabolism, animal studies, and human studies, occupational exposure to chlorinated aliphatic solvents (methanes, ethanes, and ethenes) has been associated with numerous adverse health effects, including central nervous system, reproductive, liver, and kidney toxicity, and carcinogenicity. However, many of these solvents remain in active; large-volume use. This article reviews the recent occupational epidemiology literature on the most widely used solvents, methylene chloride, chloroform, trichloroethylene, and tetrachloroethylene, and discusses other chlorinated aliphatics. The impact of studies to date has been lessened because of small study size, inability to control for confounding factors, particularly smoking and mixed occupational exposures, and the lack of evidence for a solid pathway from occupational exposure to biological evidence of exposure, to precursors of health effects, and to health effects. International differences in exposure limits may provide a "natural experiment" in the coming years if countries that have lowered exposure limits subsequently experience decreased adverse health effects among exposed workers. Such decreases could provide some evidence that higher levels of adverse health effects were associated with higher levels of solvent exposure. The definitive studies, which should be prospective biomarker studies incorporating body burden of solvents as well as markers of effect, remain to be done.
National Institute for Occupational Safety and Health, MS R-16, 4676 Columbia Parkway, Cincinnati, OH 45226