Human Health Effects of Tetrachloroethylene: Key Findings and Scientific Issues
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Citation: Guyton KZ, Hogan KA, Siegel Scott C, Cooper GS, Bale AS, Kopylev L, Barone S Jr, Makris SL, Glenn B, Subramaniam RP, Gwinn MR, Dzubow RC, Chiu WA. Human Health Effects of Tetrachloroethylene: Key Findings and Scientific Issues. Environ Health Perspect; http://dx.doi.org/10.1289/ehp.1307359.
Received: 12 July 2013
Accepted: 11 February 2014
Advance Publication: 14 February 2014
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Background: In support of the Integrated Risk Information System (IRIS), the US Environmental Protection Agency (EPA) completed a Toxicological Review of Tetrachloroethylene (Perchloroethylene) in February, 2012.
Objectives: This article reviews key findings and scientific issues regarding the human health effects of tetrachloroethylene in EPA’s Toxicological Review.
Methods: This assessment synthesized and characterized a substantial database of epidemiologic, experimental animal, and mechanistic studies. Key scientific issues were addressed through modeling of tetrachloroethylene toxicokinetics, synthesis of evidence from neurological studies, and analyses of toxicokinetic, mechanistic, and other factors (tumor latency, severity, and background rate) in interpreting experimental animal cancer findings. Considerations in evaluating epidemiologic studies included the quality (e.g., specificity) of the exposure assessment methods and other essential design features, and the potential for alternative explanations for observed associations (e.g., bias or confounding).
Discussion: Toxicokinetic modeling aided in characterizing the complex metabolism and multiple metabolites that contribute to tetrachloroethylene toxicity. The exposure assessment approach was a key evaluation factor for epidemiologic studies of bladder cancer, non Hodgkin lymphoma, and multiple myeloma, which provided suggestive evidence of carcinogenicity. Bioassay data provided conclusive evidence of carcinogenicity in experimental animals. Neurotoxicity was identified as a sensitive non-cancer health effect, occurring at low exposures, a conclusion supported by multiple studies. Evidence was integrated from human, experimental animal, and mechanistic datasets in assessing adverse health effects of tetrachloroethylene.
Conclusions: Tetrachloroethylene is likely to be carcinogenic to humans. Neurotoxicity is a sensitive adverse health effect of tetrachloroethylene.
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