Ethanol-Induced Changes in Trichloroethylene Toxicity
Abstract
This project was aimed at determining the extent to which the metabolism of trichloroethylene (TCE) to trichloroacetate (TCA) was responsible for its hepatotoxic effects in rodents. Originally ethanol co-administration was to be used to selectively decrease the production of TCA. Although the basic tenants of the hypothesis driving this study have been confirmed, the interaction produces variable internal exposures to TCA. Consequently, the project has shifted focus to more quantitative identification of the effects of TCA and dichloroacetate (DCA) in quantitative terms and use the metabolism studies to determine whether sufficient amounts of these metabolites are produced to account for the hepatotoxic and hepatocarcinogenic effects of TCE. It has been established that both TCA and DCA are capable of rapidly producing hepatic tumors in B6C3F1 mouse. They are much more potent than TCE in this regard. Although closely related, these metabolites differ significantly in their hepatotoxic effects. DCA induces a severe hypertrophic effect on the liver that is associated with focal necrotic lesions, an effect not observed with TCA. This effect does greatly enhance tumor formation at high doses of DCA, but at lower doses TCA appears to be the more potent carcinogen. TCA had previously been shown the more potent inducer of single strand breaks in hepatic DNA in mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 30, 1988
- Accession Number
- ADA201245
Entities
People
- Richard J. Bull
Organizations
- Washington State University