title: Target Organ Metabolism, Toxicity, and Mechanisms of Trichloroethylene and Perchloroethylene: Key Similarities, Differences, and Data Gaps.
abstract: Trichloroethylene (TCE) and perchloroethylene or tetrachloroethylene (PCE) are high-production volume chemicals with numerous industrial applications. As a consequence of their widespread use, these chemicals are ubiquitous environmental contaminants to which the general population is commonly exposed. It is widely assumed that TCE and PCE are toxicologically similar; both are simple olefins with three (TCE) or four (PCE) chlorines. Nonetheless, despite decades of research on the adverse health effects of TCE or PCE, few studies have directly compared these two toxicants. Although the metabolic pathways are qualitatively similar, quantitative differences in the flux and yield of metabolites exist. Recent human health assessments have uncovered some overlap in target organs that are affected by exposure to TCE or PCE, and divergent species- and sex-specificity with regard to cancer and noncancer hazards. The objective of this minireview is to highlight key similarities, differences, and data gaps in target organ metabolism and mechanism of toxicity. The main anticipated outcome of this review is to encourage research to 1) directly compare the responses to TCE and PCE using more sensitive biochemical techniques and robust statistical comparisons; 2) more closely examine interindividual variability in the relationship between toxicokinetics and toxicodynamics for TCE and PCE; 3) elucidate the effect of coexposure to these two toxicants; and 4) explore new mechanisms for target organ toxicity associated with TCE and/or PCE exposure.
authors: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas (J.A.C., W.A.C., I.R.); International Agency for Research on Cancer, Lyon, France (K.Z.G., N.G.); Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan (L.H.L.).
authors: Joseph A
authors: JA
authors: Cichocki
authors: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas (J.A.C., W.A.C., I.R.); International Agency for Research on Cancer, Lyon, France (K.Z.G., N.G.); Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan (L.H.L.).
authors: Kathryn Z
authors: KZ
authors: Guyton
authors: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas (J.A.C., W.A.C., I.R.); International Agency for Research on Cancer, Lyon, France (K.Z.G., N.G.); Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan (L.H.L.).
authors: Neela
authors: http://orcid.org/0000-0003-3991-4662
authors: N
authors: Guha
authors: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas (J.A.C., W.A.C., I.R.); International Agency for Research on Cancer, Lyon, France (K.Z.G., N.G.); Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan (L.H.L.).
authors: Weihsueh A
authors: http://orcid.org/0000-0002-7575-2368
authors: WA
authors: Chiu
authors: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas (J.A.C., W.A.C., I.R.); International Agency for Research on Cancer, Lyon, France (K.Z.G., N.G.); Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan (L.H.L.) l.h.lash@wayne.edu irusyn@tamu.edu.
authors: Ivan
authors: http://orcid.org/0000-0001-9340-7384
authors: I
authors: Rusyn
authors: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas (J.A.C., W.A.C., I.R.); International Agency for Research on Cancer, Lyon, France (K.Z.G., N.G.); Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan (L.H.L.) l.h.lash@wayne.edu irusyn@tamu.edu.
authors: Lawrence H
authors: http://orcid.org/0000-0003-3239-4481
authors: LH
authors: Lash
mesh_terms: D000818:Animals; D004785:Environmental Pollutants / Q000378:metabolism* / Q000633:toxicity*; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced / Q000473:pathology; D013750:Tetrachloroethylene / Q000378:metabolism* / Q000633:toxicity*; D014241:Trichloroethylene / Q000378:metabolism* / Q000633:toxicity*
chemical_list: D004785:Environmental Pollutants; D014241:Trichloroethylene; D013750:Tetrachloroethylene