The effect of ethanol consumption on the biotransformation of 1,1,1-trichloroethane in human volunteers

There are many environmental factors that affect the toxicokinetics of organic solvents in the body. One potentially important factor is the ingestion of ethanol, as it is often consumed in multi-gram quantities. Ethanol oxidation is catalyzed in part by the same enzyme (CYP450 2E1) that mediates the metabolism of many organic solvents. This study evaluated the effect of moderate doses of ethanol over a short period of time on the biotransformation of an organic solvent, 1,1,1-trichloroethane.;A group of ten moderate drinkers were recruited and exposed via inhalation for two hours to a low concentration of 1,1,1-trichloroethane (175 ppm) on two separate occasions. Subjects were administered moderate doses of ethanol on each of the seven days preceding one of the exposures. Prior to the other exposure, subjects were given no ethanol and were asked to abstain from ethanol consumption for a two week period. Total urine was collected for 70 hours following each exposure and analyzed for the metabolites of 1,1,1-trichloroethane: trichloroethanol and trichloroacetic acid. Prior ethanol consumption resulted in mean increases of trichloroethanol (24.6%), trichloroacetic acid (31.4%), and total metabolite (25.4%) excreted and these increases were found to be significantly different from zero (paired t-test, p = 0.005, 0.009, and 0.004, respectively). The results of this study demonstrate that ethanol consumption can affect the rate of biotransformation of an organic solvent in humans. For chemicals in which the parent compound itself is toxic, this effect of ethanol consumption may be considered beneficial. However, in many instances, the metabolites of a chemical are more toxic than the chemical itself. For these chemicals, the inductive effective of ethanol consumption on the rate biotransformation would be potentially harmful. The rate of biotransformation in compounds with high hepatic extraction may not be affected by enzyme induction as it is likely that the compound is essentially completely metabolized while passing through the liver.