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ToxSci Advance Access published online on October 10, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl129
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Published by Oxford University Press 2006.
Received July 5, 2006
Accepted October 9, 2006

Original Article

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

Weihsueh A. Chiu 1 *, Sandrine Micallef 2, Aart C. Monster 3, and Frédéric Y. Bois 2

1 National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington DC 20460, USA
2 Institut National de L'Environnement Industriel et des Risques, Unité de Toxicologie Expérimentale, Parc Alata, BP2, 60550 Vernuil-En-Halatte, France
3 Coronel Institute, Academic Medical Centre, University of Amsterdam, P.O. Box 22660, 1100 DD, Amsterdam, The Netherlands

* To whom correspondence should be addressed.
Weihsueh A. Chiu, E-mail: chiu.weihsueh{at}epa.gov


  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 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 inter-individual and inter-occasion variability remain to be determined.

Keywords: Biotransformation and Toxicokinetics - pharmacokinetics/toxicokinetics, Risk Assessment - dosimetry, Agents - volatile organic compounds.

Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency.

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

Financial Disclosure: The authors declare that they have no competing financial interests.


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