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Archives of Toxicology

, Volume 70, Issue 6, pp 347–355 | Cite as

Population toxicokinetics of tetrachloroethylene

  • F. Y. Bois
  • A. Gelman
  • J. Jiang
  • D. R. Maszle
  • L. Zeise
  • G. Alexeef
ORIGINAL INVESTIGATION

Abstract

 In assessing the distribution and metabolism of toxic compounds in the body, measurements are not always feasible for ethical or technical reasons. Computer modeling offers a reasonable alternative, but the variability and complexity of biological systems pose unique challenges in model building and adjustment. Recent tools from population pharmacokinetics, Bayesian statistical inference, and physiological modeling can be brought together to solve these problems. As an example, we modeled the distribution and metabolism of tetrachloroethylene (PERC) in humans. We derive statistical distributions for the parameters of a physiological model of PERC, on the basis of data from Monster et al. (1979). The model adequately fits both prior physiological information and experimental data. An estimate of the relationship between PERC exposure and fraction metabolized is obtained. Our median population estimate for the fraction of inhaled tetrachloroethylene that is metabolized, at exposure levels exceeding current occupational standards, is 1.5% [95% confidence interval (0.52%, 4.1%)]. At levels approaching ambient inhalation exposure (0.001 ppm), the median estimate of the fraction metabolized is much higher, at 36% [95% confidence interval (15%, 58%)]. This disproportionality should be taken into account when deriving safe exposure limits for tetrachloroethylene and deserves to be verified by further experiments.

Key words Human metabolism Pharmacokinetics Population toxicokinetics Tetrachloroethylene 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • F. Y. Bois
    • 1
  • A. Gelman
    • 2
  • J. Jiang
    • 2
  • D. R. Maszle
    • 3
  • L. Zeise
    • 1
  • G. Alexeef
    • 1
  1. 1.Cal/EPA, Office of Environmental Health Hazard Assessment, 2151 Berkeley Way, Annex 11, Berkeley, CA 94704, USAUS
  2. 2.Department of Statistics, University of California at Berkeley, Berkeley, CA 94720, USAUS
  3. 3.UCB/UCSF Joint Graduate Group in Bioengineering, University of California at Berkeley, Berkeley, CA 94720, USAUS

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