Metabolic interactions

• Chlorinated aliphatic hydrocarbons

In vivo and in vitro studies demonstrated that combinations of tetrachloroethylene with trichloroethylene 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).

In a volunteer study, diazepam blood concentrations of 70-300 |g/l had no effect on tetrachloroethylene blood or breath concentrations during exposure to 100 ppm. There were no interactive effects of diazepam and tetrachloroethylene on neurobehavioural or neurophysiological tests (Hake and Stewart, 1977). In another study, exposure to tetrachloroethylene (25 ppm or 100 ppm) and diazepam 6 mg/day or 10 mg/ day did not affect the tetrachloroethylene blood concentration. Performance in behavioural tests was unaffected by simultaneous exposure and it was concluded that low doses of diazepam in tetrachloroethylene-exposed workers did not pose a hazard (Stewart et al., 1977).

• Enzyme inducers

Enzyme induction increases tetrachloroethylene metabolism. Pretreatment with pentobarbital or Aroclor 1254, both inducers of the hepatic mixed function oxidase system, resulted in a five- and seven-fold increase in tetrachloroethylene metabolism, respectively. Hepatic injury also occurred in the Aroclor 1254-treated animals, probably due to tetrachloroethylene metabolites (Moslen et al., 1977).

In a volunteer study, ethanol blood concentrations of 0.3-1 g/l had no effect on tetrachloroethylene blood or breath concentrations during exposure to 100 ppm. There were no interactive effects of ethanol and tetrachloroethylene on neurobehavioural or neurophysiological tests (Hake and Stewart, 1977). However, in another study, co-exposure to tetrachloroethylene (25 ppm) and ethanol doses of 0.75 and 1.5 ml of 100°-proof vodka/kg body weight (to achieve blood concentrations of 400 and 800 mg/l) significantly increased blood tetrachloroethylene concentrations. In contrast, blood tetrachloroethylene levels were not increased at 100 ppm as there was already saturation of tetrachloroethylene metabolism at this dose. Performance in behavioural tests was unaffected by simultaneous exposure and it was concluded that low doses of ethanol in tetrachloroethylene exposed workers did not pose a hazard (Stewart et al., 1977). Animal studies have shown that ethanol does not potentiate the liver toxicity of tetrachloroethylene (Cornish and Adefuin, 1966; Klassen et al., 1966).

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