Laboratory toxicity testing of single compounds can produce toxicity data specific to that compound for that species, but it cannot take into account the possible toxic effects of mixtures of compounds. For example, in a 6-month carcinogenicity assay, trichloroethylene-contaminated groundwater was found to be carcinogenic in Japanese medaka fish, after initiation with diethylnitrosamine (Gardner et al. 1998). Analysis of the groundwater indicated that contamination was not limited to trichloroethylene. No tumor promotional effect was found in a follow-up laboratory study with reagent-grade trichloroethylene added to the groundwater to simulate the exposure concentration found in the contaminated groundwater. These studies implicate other water contaminants that might synergize the tumorpromoting activity of trichloroethylene.

Acute or repeated inhalation exposure to a mixture of 1,1,1-trichloroethane, 1,1-dichloroethane, trichloroethylene, and tetrachloroethylene at concentrations as low as 20 parts per million (ppm) produced neurologic impairment. Male and female weanling ICR mice were treated with a mixture of chlorinated alkanes and alkenes consisting of chloroform, 1,1-dichloroethane, 1,1-dichloroethylene, 1,1,1-trichloroethane, trichloroethylene, and tetrachloroethylene in drinking water for 16 and 18 months, respectively; male mice developed hepatocelluar neoplasms and female mice developed mammary adenocarcinoma (Wang et al. 2002). The toxicokinetics of trichloroethylene was altered in rats receiving a binary mixture of chloroform and trichloroethylene (Anand et al. 2005a). Metabolism of trichloroethylene is suppressed in humans with coexposure to tetrachloroethylene (Seiji et al. 1989). Exposure to a ternary mixture of chloroform, trichloroethylene, and allyl alcohol results in less initial liver injury in male Sprague-Dawley rats because of greater elimination of trichloroethylene (Anand et al. 2005b).

A number of commonly used drugs modify the metabolism of trichloroethylene (Leibman and McAllister 1967; Carlson 1974; Moslen et al. 1977; Pessayre et al. 1979). The opposite might also occur, resulting in important modifications of the therapeutic action of the drugs (Kelley and Brown 1974). Trichloroethylene competitively inhibits the metabolism of barbiturates, producing exaggerated effects of the drugs (Kelley and Brown 1974). Sellers and Koch-Weser (1970) observed a potentiation of the anticoagulant effect of bishydroxycoumarin (warfarin) in patients after chloral hydrate ingestion, which appears to result from displacement of plasma protein binding sites by the chloral hydrate metabolite trichloroacetic acid. Trichloroacetic acid is extensively bound to plasma proteins (Templin et al. 1995), making it likely that trichloroethylene might potentiate the effects of many other drugs that normally bind to the same protein sites. Ethanol (2 g

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