Mutagenicity of trichloroethylene and its metabolites: Implications for the risk assessment of trichloroethylene

Moore, MM; Harrington-Brock, K

HERO ID

632714

Reference Type

Journal Article

Subtype

Review

Year

2000

Language

English

PMID

10807553

HERO ID 632714
Material Type Review
In Press No
Year 2000
Title Mutagenicity of trichloroethylene and its metabolites: Implications for the risk assessment of trichloroethylene
Authors Moore, MM; Harrington-Brock, K
Journal Environmental Health Perspectives
Volume 108
Issue Suppl. 2
Page Numbers 215-223
Abstract This article addresses the evidence that trichloroethylene (TCE) or its metabolites might mediate tumor formation via a mutagenic mode of action. We review and draw conclusions from the published mutagenicity and genotoxicity information for TCE and its metabolites, chloral hydrate (CH), dichloroacetic acid (DCA), trichloroacetic acid (TCA), trichloroethanol, S-(1, 2-dichlorovinyl)-l-cysteine (DCVC), and S-(1, 2-dichlorovinyl) glutathione (DCVG). The new U.S. Environmental Protection Agency proposed Cancer Risk Assessment Guidelines provide for an assessment of the key events involved in the development of specific tumors. Consistent with this thinking, we provide a new and general strategy for interpreting genotoxicity data that goes beyond a simple determination that the chemical is or is not genotoxic. For TCE, we conclude that the weight of the evidence argues that chemically induced mutation is unlikely to be a key event in the induction of human tumors that might be caused by TCE itself (as the parent compound) and its metabolites, CH, DCA, and TCA. This conclusion derives primarily from the fact that these chemicals require very high doses to be genotoxic. There is not enough information to draw any conclusions for trichloroethanol and the two trichloroethylene conjugates, DCVC and DCVG. There is some evidence that DCVC is a more potent mutagen than CH, DCA, or TCA. Unfortunately, definitive conclusions as to whether TCE will induce tumors in humans via a mutagenic mode of action cannot be drawn from the available information. More research, including the development and use of new techniques, is required before it is possible to make a definitive assessment as to whether chemically induced mutation is a key event in any human tumors resulting from exposure to TCE
Doi 10.1289/ehp.00108s2215
Pmid 10807553
Wosid WOS:000087149000005
Url http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1637765/
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Keyword adverse effects; Animals; Cancer; cancer risk; Carcinogens; Chemical; chemically induced; Chemicals; Chloral Hydrate; development; Dose-Response Relationship; Drug; Drug Effects; Environmental; Exposure; General; Genes; genetics; GENOTOXICITY; Glutathione; Human; Humans; metabolism; metabolites; Mutagenicity; Mutagens; Mutation; Neoplasms; Research; REVIEW; Risk; Risk Assessment; Trichloroacetic Acid; TRICHLOROETHANOL; Trichloroethylene; Tumor; United States; United States Environmental Protection Agency; USA
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