Human Health Effects of Trichloroethylene: Key Findings and Scientific Issues

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.

Medical History, Lifestyle, Family History, and Occupational Risk Factors for Peripheral T-Cell Lymphomas: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

“…Based on our data, we observed an increase in risk of PTCL and, specifically, ALCL, for textile workers. Exposures related to textile work include: dust, endotoxin (a bacterial contaminant of raw cotton fiber and cotton dust), assorted dyes, and chemicals such as trichloroethylene, which has previously been linked to lymphoma risk (33)(34)(35)(36)(37)(38). We also report that electrical fitters had increased odds of developing ALCL and angioimmunoblastic lymphoma.…”

“…The current analyses showed an increased risk of PTCL with long-term smoking and a decreased risk with alcohol consumption. Although sunlight exposure is inversely associated with NHL development (54), no such associations have previously been explored specifically for T-cell lymphomas (33). The decreased risk of ALCL that we observed in association with recreational sun exposure is thus novel and requires replication.…”

Target Organ Metabolism, Toxicity, and Mechanisms of Trichloroethylene and Perchloroethylene: Key Similarities, Differences, and Data Gaps

“…Table 3 summarizes the target organ carcinogenesis associated with TCE or PCE exposure. These data are derived from previous reports for TCE (Zhu et al, 2008;US EPA, 2011b;Chiu et al, 2013;IARC, 2014;National Toxicology Program, 2015) and PCE (US EPA, 2011a; IARC, 2014; Guyton et al, 2014).…”

Environmental Epigenomics: Applications of Epigenetic Biomarkers to Investigate Epigenetic Alterations from Environmental Exposures

“…It is a known human carcinogen (Karami et al 2012 ;Guha et al 2012 ). Its metabolites, dichloroacetic acid (DCA), and trichloroacetic acid (TCA) are known mouse liver carcinogens Herren-Freund et al 1987 ;Latendresse and Pereira 1997 ;Pereira 1996 ;Pereira and Phelps 1996 ;Pereira et al 1997 ;Chiu et al 2013 ). Increased expression of mRNA and decreased methylation of the c-jun and c-myc genes have been reported in liver tissue in mice treated with these chemicals (Latendresse and Pereira 1997 ;Nelson et al 1990 ;Tao et al 1999Tao et al , 2000a.…”