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ToxSci Advance Access published online on January 18, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj107
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received October 11, 2005
Accepted November 29, 2005

Review

Trichloroethylene: Mechanisms of Renal Toxicity and Renal Cancer and Relevance to Risk Assessment

Edward A. Lock 1 * and Celia J. Reed 1

1 School of Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, United Kingdom

* To whom correspondence should be addressed.
Edward A. Lock, E-mail: edwardlock_600{at}hotmail.com


  Abstract

1,1,2-Trichloroethylene (TCE) is an important solvent that is widespread in the environment. We have reviewed carcinogenicity data from seven bioassays with regard to renal injury and renal tumors. We report a consistent but low incidence of renal tubule carcinoma in male rats. Epidemiology studies on workers exposed to TCE (and other chlorinated solvents) indicate a weak association between high-level exposure and renal cancer. There appears to be a threshold below which no renal injury or carcinogenicity is expected to arise. TCE is not acutely nephrotoxic to rats or mice, but subchronic exposure to rats produces a small increase in urinary markers of renal injury. Following chronic exposure, pathological changes (toxic nephrosis and a high incidence of cytomegaly and karyomegaly) were observed. The basis for the chronic renal injury probably involves bioactivation of TCE. Based on the classification by Lock & Hard (2004) of chemicals that induce renal tubule tumors, we found no clear evidence to place TCE in category 1 or 2 (chemicals that directly or indirectly interact with renal DNA), category 4 (direct cytotoxicity and sustained tubule cell regeneration), category 5 (indirect cytotoxicity and sustained tubule cell regeneration associated with {alpha}2u-globulin accumulation), or category 6 (exacerbation of spontaneous chronic progressive nephropathy). TCE is best placed in category 3, chemicals that undergo conjugation with GSH and subsequent enzymatic activation to a reactive species. The implication for human risk assessment is that TCE should not automatically be judged by linear default methods; benchmark methodology could be used.

Keywords: Trichloroethylene; renal toxicity; renal cancer; mechanisms of toxicity; risk assessment.
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