Human Health Effects of Trichloroethylene: Key Findings and Scientific Issues

Weihsueh A. Chiu,¹ Jennifer Jinot,¹ Cheryl Siegel Scott,¹ Susan L. Makris,¹ Glinda S. Cooper,¹ Rebecca C. Dzubow,² Ambuja S. Bale,¹ Marina V. Evans,³ Kathryn Z. Guyton,¹ Nagalakshmi Keshava,¹ John C. Lipscomb,¹ Stanley Barone Jr.,⁴ John F. Fox,¹ Maureen R. Gwinn,¹ John Schaum,⁵ and Jane C. Caldwell¹

¹National Center for Environmental Assessment, and ²Office of Children’s Health Protection, U.S. Environmental Protection Agency (EPA), Washington, DC, USA; ³National Health and Environmental Effects Research Laboratory, U.S. EPA, Research Triangle Park, North Carolina, USA; ⁴Office of Pollution Prevention and Toxics, U.S. EPA, Washington, DC, USA; ⁵U.S. EPA, Washington, DC, USA (Retired)

Abstract

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 autoimmune disease and hypersensitivity. Recent avian and in vitro mechanistic studies provided biological plausibility that TCE plays a role in developmental 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 noncancer toxicity to the central nervous system, kidney, liver, immune system, male reproductive system, and the developing embryo/fetus.

Key words: assessment, cancer/tumors, cardiovascular, epidemiology, immunologic response, Integrated Risk Information System (IRIS), meta-analysis, mode of action, physiologically based pharmacokinetic (PBPK) modeling, trichloroethylene.

Environ Health Perspect 121:303–311 (2013). http://dx.doi.org/10.1289/ehp.1205879 [Online 18 December 2012]

Address correspondence to W.A. Chiu, National Center for Environmental Assessment (8601P), U.S. EPA, Two Potomac Yard (North Building), 2733 S. Crystal Dr., Arlington, VA 22202 USA. Telephone: (703) 347-8607. E-mail: chiu.weihsueh@epa.gov

Supplemental Material is available online (http://dx.doi.org/10.1289/ehp.1205879).

This work has benefitted from advice and comments from a number of scientific reviewers—including members of the National Academies of Sciences, National Research Council panel on Trichloroethylene Health Risks, two U.S. EPA Science Advisory Board review panels, and scientists at federal agencies (including the U.S. EPA)—as well as from others who prepared public comments. We also thank P. Anastas, R. Clark, P. Preuss, D. Bussard, V. Cogliano, B. Sonawane, and P. White for providing U.S. EPA management support.

The views expressed in this article are those of the authors and do not necessarily represent the views or policies of the U.S. EPA.

The authors declare they have no actual or potential competing financial interests.

Received 10 August 2012; Accepted 17 December 2012; Online 18 December 2012.