ABSORPTION AND DISTRIBUTION

There are three types of exposures to consider for humans and laboratory animals: inhalation, oral, and dermal. Exposure is usually either from trichloroethylene vapor or from trichloroethylene in drinking water. In either form, trichloroethylene is rapidly and extensively absorbed through the lungs and gastrointestinal tract, and less so dermally. Absorbed trichloroethylene is then distributed to different target organs (e.g., lungs, liver, kidneys, nervous system) via the circulatory system. Trichloroethylene readily equilibrates from the circulation into richly perfused tissues, with reported partition coefficients for liver:blood or richly perfused tissue:blood for male rats of approximately 1.2 (Dallas et al. 1991; Fisher et al. 1991). Most trichloroethylene taken into the body is metabolized, but it can also be eliminated via exhalation.

Species differences exist in the fraction of administered dose of trichloroethylene that becomes available for conversion to toxic metabolites in the target organs because of differences in blood flow and overall metabolic rate. For example, blood concentrations of the three metabolites of trichloroethylene—chloral hydrate, trichloroethanol, and trichloroacetic acid— over time after administration of an oral dose of trichloroethylene at 1,000 mg/kg to male Osborne-Mendel rats and male B6C3F1 mice were markedly higher in mice than in rats, whereas concentrations for trichloroethylene were higher in rats than in mice, indicating more rapid metabolism and elimination of trichloroethylene (Prout et al. 1985). Similarly, higher peak plasma concentrations of trichloroacetic acid, the metabolite thought to be primarily responsible for liver effects (Bull 2000), were found in male and female mice than in male and female rats. These observations suggest species differences in susceptibility to the toxic effects of trichloroethylene.

PHARMACOKINETICS

Orally administered trichloroethylene is readily absorbed into the systemic circulation. In rats dosed with [36Cl]trichloroethylene by stomach tube (60 mg/kg), 90% to 95% of the radiolabel was recovered in expired air and urine (Daniel 1963). Administration of a range of doses of labeled trichloroethylene (10-2,000 mg/kg) to rats and mice yielded peak blood concentrations in 1 hour in mice and in 3 hours in rats (Dekant et al. 1984; Prout et al. 1985). Using classic pharmacokinetic analysis, D’Souza et al. (1985) reported that oral and intravenous bioavailability of trichloroethylene was 60% to 90% in nonfasted rats and greater than 90% in fasted rats. Peak blood concentrations occurred between 6 and 10 minutes and blood concentrations were two to three times higher in the fasted rats than in the nonfasted rats. Lee et al. (1996) showed that elimination of low doses



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