Human Health Effects of Trichloroethylene: Key Findings and Scientific Issues

BACKGROUND: In support of the Integrated Risk Information System (IRIS), the U. S. Environmental Protection Agency (EPA) completed a toxicological review of trichloroethylene (TCE) in September 2011, which was the result of an effort spanning > 20 years. OBJECTIVES: We summarized the key findings and scientific issues regarding the human health effects of TCE in the U. S. EPA's toxicological review. METHODS: In this assessment we synthesized and characterized thousands of epidemiologic, experimental animal, and mechanistic studies, and addressed several key scientific issues through modeling of TCE toxicokinetics, meta-analyses of epidemiologic studies, and analyses of mechanistic data. DISCUSSION: Toxicokinetic modeling aided in characterizing the toxicological role of the complex metabolism and multiple metabolites of TCE. Meta-analyses of the epidemiologic data strongly supported the conclusions that TCE causes kidney cancer in humans and that TCE may also cause liver cancer and non-Hodgkin lymphoma. Mechanistic analyses support a key role for mutagenicity in TCE-induced kidney carcinogenicity. Recent evidence from studies in both humans and experimental animals point to the involvement of TCE exposure in auto-immune disease and hypersensitivity. Recent avian and in vitro mechanistic studies provided biological plausibility that TCE plays a role in develop-mental cardiac toxicity, the subject of substantial debate due to mixed results from epidemiologic and rodent studies. CONCLUSIONS: TCE is carcinogenic to humans by all routes of exposure and poses a potential human health hazard for non-cancer toxicity to the central nervous system, kidney, liver, immune system, male reproductive system, and the developing embryo/fetus.