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ToxSci Advance Access originally published online on October 10, 2006
Toxicological Sciences 2007 95(1):23-36; doi:10.1093/toxsci/kfl129
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Published by Oxford University Press 2006.

Toxicokinetics of Inhaled Trichloroethylene and Tetrachloroethylene in Humans at 1 ppm: Empirical Results and Comparisons with Previous Studies

Weihsueh A. Chiu*,1, Sandrine Micallef{dagger}, Aart C. Monster{ddagger} and Frédéric Y. Bois{dagger}

* National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington, DC 20460 {dagger} Institut National de L'Environnement Industriel et des Risques, Unité de Toxicologie Expérimentale, 60550 Vernuil-En-Halatte, France {ddagger} Coronel Institute, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands

1 To whom correspondence should be addressed at U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW, Mail Code 8623D, Washington, DC 20460. Fax: (202) 565-0079. E-mail: chiu.weihsueh{at}epa.gov.

Received July 5, 2006; accepted October 9, 2006


  Abstract

Trichloroethylene (TRI) and tetrachloroethylene (TETRA) are solvents that have been widely used in a variety of industries, and both are widespread environmental contaminants. In order to provide a better basis for understanding their toxicokinetics at environmental exposures, seven human volunteers were exposed by inhalation to 1 ppm of TRI or TETRA for 6 h, with biological samples collected for analysis during exposure and up to 6-days postexposure. Concentrations of TRI, TETRA, free trichloroethanol (TCOH), total TCOH (free TCOH plus glucuronidated TCOH), and trichloroacetic acid (TCA) were determined in blood and urine; TRI and TETRA concentrations were measured in alveolar breath. Toxicokinetic time courses and empirical analyses of classical toxicokinetic parameters were compared with those reported in previous human volunteer studies, most of which involved exposures that were at least 10-fold higher. Qualitatively, TRI and TETRA toxicokinetics were consistent with previous human studies. Quantitatively, alveolar retention and clearance by exhalation were similar to those found previously but blood and urine data suggest a number of possible toxicokinetic differences. For TRI, data from the current study support lower apparent blood-air partition coefficients, greater apparent metabolic clearance, less TCA production, and greater glucuronidation of TCOH as compared to previous studies. For TETRA, the current data suggest TCA formation that is similar or slightly lower than that of previous studies. Variability and uncertainty in empirical estimates of total TETRA metabolism are substantial, with confidence intervals among different studies substantially overlapping. Relative contributions to observed differences from concentration-dependent toxicokinetics and interindividual and interoccasion variability remain to be determined.

Key Words: biotransformation and toxicokinetics; pharmacokinetics/toxicokinetics; risk assessment; dosimetry; volatile organic compounds.


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