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ToxSci Advance Access published online on April 25, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj210
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Published by Oxford University Press 2006.
Received February 23, 2006
Accepted April 19, 2006

Biotransformation and Toxicokinetics

Ethanol Induced Increase in the Metabolic Clearance of 1,1,1-Trichloroethane in Human Volunteers

Douglas O. Johns 1, William E. Daniell 1, Danny D. Shen 2, David A. Kalman 1, Russell L. Dills 1, and Michael S. Morgan 1 *

1 Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA
2 Department of Pharmacy, University of Washington, Seattle, WA, USA

* To whom correspondence should be addressed.
Michael S. Morgan, E-mail: mmorgan{at}u.washington.edu


  Abstract

This study evaluated the effect of moderate doses of ethanol over a short period of time on the toxicokinetics 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 ethanol (0.35 g per kg body weight) on each of the seven days preceding one of the exposures. Blood and urine samples were collected during and following each exposure, with blood analyzed for 1,1,1-trichloroethane and urine analyzed for the metabolites of 1,1,1-trichloroethane: trichloroethanol and trichloroacetic acid. Prior ethanol consumption resulted in a significant increase in apparent metabolic clearance of 1,1,1-trichloroethane (mean increase = 25.4%). The results of this study demonstrate that ethanol consumption over time can affect the rate at which an organic solvent is cleared through metabolism in humans. For chemicals with toxic metabolic products, this inductive effective of ethanol consumption on the rate of biotransformation could be potentially harmful to exposed individuals. Metabolic clearance of compounds with high hepatic extraction may not be affected by enzyme induction as it is likely that these compounds are essentially completely metabolized while passing through the liver.

Keywords: 1,1,1-Trichloroethane; Methyl chloroform; Ethanol; Enzyme induction; Biotransformation.

The authors certify that all research involving human subjects was done under full compliance with all government policies and the Helsinki Declaration.


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