Metabolic interactions

Trichloroethylene is metabolised principally in the liver by two pathways, one of which is by oxidation via cytochrome P450. Induction of this isoenzyme system by acetone may increase the metabolism of trichloroethylene to toxic metabolites.

• Aliphatic organochlorines

In vivo and in vitro studies demonstrated that combinations of trichloroethylene with tetrachloroethylene or 1,1,1-trichloroethane or both, were more toxic than the individual chemicals alone. Measures of effects were parameters of cell integrity (leak of potassium, lactate dehydrogenase and alanine aminotransferase in hepatocytes) for the in vitro tests and measures of hepatic and renal function (liver weight, alanine aminotransferase, sorbital dehydrogenase and urea) in rats. The effect of the three solvents together was greater than mixtures of two. This study did not investigate the mechanism of interaction (Stacey, 1989).

• Carbon tetrachloride

Carbon tetrachloride induced hepatotoxicity in rats is enhanced by the simultaneous administration of trichloroethylene and this response is potentiated by pre-treatment with acetone (Charbonneau et al., 1988). This may be relevant for individuals who work with a mixture of solvents.

• Cimetidine

Cimetidine (which inhibits the hepatic microoxygenase system) decreased the in vivo metabolism of trichloroethylene in experimental animals (Landriault et al., 1989).

Alcohol dehydrogenase is thought to be one of the main enzymes involved in the metabolism of trichloroethylene. Concurrent exposure to ethanol appears to greatly alter the metabolism of trichloroethylene, increasing the concentration of trichloroethylene and its metabolites. There may also be an increase in ethanol and acetaldehyde concentrations (Hills and Venable, 1982; Köppel et al., 1988).

In one study, volunteers inhaled 50 ppm trichloroethylene for 6 hours per day for 5 days. Simultaneous ethanol ingestion (blood ethanol level 600 mg/l) inhibited the metabolism of trichloroethylene to trichloroethanol and trichloroacetic acid by approximately 40%. During this time, the blood trichloroethylene concentration increased by 2.5-fold and that in the expired air rose by 4-fold, as compared to trichloroethylene inhalation without concomitant ethanol ingestion. The alcohol intolerance noted after exposure to trichloroethylene is due to the accumulation of trichloroethylene in the CNS resulting from the inhibition of the oxidation of trichloroethylene (Müller et al., 1975).

Ingestion of ethanol before or during work (but not after work), produced increases in the blood trichloroethylene concentration and decreases in the urinary excretion rates of trichloroethylene metabolites. This effect lasted until the next day. These effects were smaller with increased exposure concentrations of trichloroethylene. Induction of trichloroethylene metabolism by consumption of ethanol the evening before work caused small changes in trichloroethylene metabolism at 50 ppm, but greater changes at 500 ppm (Sato et al., 1991).

Ethanol may also enhance the hepatotoxic effects of trichloroethylene. Studies in rats found that ethanol potentiated trichloroethylene hepatotoxicity at trichloroethylene concentrations as low as 500 ppm (Nakajima et al., 1988). In another animal study, rats receiving ethanol prior to trichloroethylene exposure had AST concentrations approximately 75% higher than trichloroethylene exposed animals without ethanol pre-treatment (Cornish and Adefuin, 1966).

One effect of the combination of ethanol and trichloroethylene has been termed 'degreasers flush'. Workers exposed to 200 ppm of trichloroethylene daily for three weeks reported extreme dermal flushing and red blotches on the face, neck and shoulders after consumption of as little as one-half pint of beer (Stewart et al., 1974).

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