title: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Center for Environmental Assessment, U.S. Environmental Protection Agency (EPA), Washington, DC, USA. chiu.weihsueh@epa.gov
authors.forename: Weihsueh A
authors.initials: WA
authors.lastname: Chiu
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jinot
authors.forename: Cheryl Siegel
authors.initials: CS
authors.lastname: Scott
authors.forename: Susan L
authors.initials: SL
authors.lastname: Makris
authors.forename: Glinda S
authors.initials: GS
authors.lastname: Cooper
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Dzubow
authors.forename: Ambuja S
authors.initials: AS
authors.lastname: Bale
authors.forename: Marina V
authors.initials: MV
authors.lastname: Evans
authors.forename: Kathryn Z
authors.initials: KZ
authors.lastname: Guyton
authors.forename: Nagalakshmi
authors.initials: N
authors.lastname: Keshava
authors.forename: John C
authors.initials: JC
authors.lastname: Lipscomb
authors.forename: Stanley
authors.initials: S
authors.lastname: Barone
authors.forename: John F
authors.initials: JF
authors.lastname: Fox
authors.forename: Maureen R
authors.initials: MR
authors.lastname: Gwinn
authors.forename: John
authors.initials: J
authors.lastname: Schaum
authors.forename: Jane C
authors.initials: JC
authors.lastname: Caldwell
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D006801:Humans; D014241:Trichloroethylene / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D014241:Trichloroethylene