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Reconstructing population exposures from dose biomarkers: inhalation of trichloroethylene (TCE) as a case study

Journal of Exposure Science & Environmental Epidemiology volume 14, pages 204–213 (2004)Cite this article

Abstract

Physiologically based pharmacokinetic (PBPK) modeling is a well-established toxicological tool designed to relate exposure to a target tissue dose. The emergence of federal and state programs for environmental health tracking and the availability of exposure monitoring through biomarkers creates the opportunity to apply PBPK models to estimate exposures to environmental contaminants from urine, blood, and tissue samples. However, reconstructing exposures for large populations is complicated by often having too few biomarker samples, large uncertainties about exposures, and large interindividual variability. In this paper, we use an illustrative case study to identify some of these difficulties, and for a process for confronting them by reconstructing population-scale exposures using Bayesian inference. The application consists of interpreting biomarker data from eight adult males with controlled exposures to trichloroethylene (TCE) as if the biomarkers were random samples from a large population with unknown exposure conditions. The TCE concentrations in blood from the individuals fell into two distinctly different groups even though the individuals were simultaneously in a single exposure chamber. We successfully reconstructed the exposure scenarios for both subgroups — although the reconstruction of one subgroup is different than what is believed to be the true experimental conditions. We were however unable to predict with high certainty the concentration of TCE in air.

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Acknowledgements

This work was supported in part by the US Environmental Protection Agency National Exposure Reasearch Laboratory through Interagency Agreement # DW-988-38190-01-0 and carried out at Lawrence Berkley National Laboratory through the US Department of Energy under contract Grant No. DE-AC03-76SF00098. This work was also supported in part by the Health Tracking Center of Excellence at the University of California Berkley, and funded by interagency agreement No. U50CCUT922409-01 with US Centers for Disease Control. We thank M. Rigas and F.Power from the US EPA for their help in developing the PBPK model. We also thank M.Macleod, W.Riley, and the reviewers for their helpful comments on an earlier version of this manuscript.

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Authors and Affiliations

  1. Lawrence Berkeley National Laboratory, Berkeley, 94720, California, USA

    Michael D Sohn & Thomas E McKone

  2. University of California, Berkeley, 94720, California, USA

    Thomas E McKone

  3. National Exposure Research Laboratory, United State Environmental Protection Agency, Las Vegas, 89193, Nevada, USA

    Jerry N Blancato

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  1. Michael D Sohn
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  2. Thomas E McKone
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  3. Jerry N Blancato
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Correspondence to Michael D Sohn.

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The United States Environmental Protection Agency through its Office of Research and Development funded and collaborated in the research described here under Interagency Assistance Agreement to Lawrence Berkeley National Laboratory (IAG #89938190). It has been subjected to Agency review and approved for publication.

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Sohn, M., McKone, T. & Blancato, J. Reconstructing population exposures from dose biomarkers: inhalation of trichloroethylene (TCE) as a case study. J Expo Sci Environ Epidemiol 14, 204–213 (2004). https://doi.org/10.1038/sj.jea.7500314

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