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Linking Indoor Air and Pharmacokinetic Models to Assess Tetrachloroethylene Risk

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  • Kenneth T. Bogen
  • Thomas E. McKone

Abstract

Physiologically based pharmacokinetic (PBPK) models describing the uptake, metabolism, and excretion of xenobiotic compounds are now proposed for use in regulatory health‐risk assessments. In this study we investigate the extent of PCE metabolism arising from domestic respiratory exposure to tetrachloroethylene (PCE) from ground water, as predicted using a PBPK model. Indoor exposure patterns we use as input to the PBPK model are realistic ones generated from a three‐compartment model describing volatilization of PCE from domestic water into household air. Values we use for the metabolic parameters of the PBPK model are estimated from data on urinary metabolites in workers exposed to PCE. It is shown that for respiratory PCE exposure due to typical levels of PCE in ground water, use of time‐weighted average air concentrations with a steady‐state PBPK model yields estimates of total metabolized PCE similar to those obtained using completely dynamic modeling, despite considerable uncertainty in key exposure‐ and metabolic‐model parameters. These findings suggest that, for PCE, risk estimation taking pharmacokinetics into account may be accomplished using a simple analytic approach.

Suggested Citation

  • Kenneth T. Bogen & Thomas E. McKone, 1988. "Linking Indoor Air and Pharmacokinetic Models to Assess Tetrachloroethylene Risk," Risk Analysis, John Wiley & Sons, vol. 8(4), pages 509-520, December.
    • Handle: RePEc:wly:riskan:v:8:y:1988:i:4:p:509-520
    DOI: 10.1111/j.1539-6924.1988.tb01191.x
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    References listed on IDEAS

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    1. Brown, H.S. & Bishop, D.R. & Rowan, C.A., 1984. "The role of skin absorption as a route of exposure for volatile organic compounds (VOCs) in drinking water," American Journal of Public Health, American Public Health Association, vol. 74(5), pages 479-484.
    2. Elizabeth L. Anderson, 1983. "Quantitative Approaches in Use to Assess Cancer Risk," Risk Analysis, John Wiley & Sons, vol. 3(4), pages 277-295, December.
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    Cited by:

    1. Robert L. Chinery & A. Kevin Gleason, 1993. "A Compartmental Model for the Prediction of Breath Concentration and Absorbed Dose of Chloroform After Exposure While Showering," Risk Analysis, John Wiley & Sons, vol. 13(1), pages 51-62, February.
    2. Dale Hattis & Paul White & Paul Koch, 1993. "Uncertainties in Pharmacokinetic Modeling for Perchloroethylene: II. Comparison of Model Predictions with Data for a Variety of Different Parameters," Risk Analysis, John Wiley & Sons, vol. 13(6), pages 599-610, December.
    3. Louis Anthony Cox, 1995. "Simple Relations Between Administered and Internal Doses in Compartmental Flow Models," Risk Analysis, John Wiley & Sons, vol. 15(2), pages 197-204, April.
    4. Kenneth T. Bogen, 2006. "Comment on “Steady State Solutions to PBPK Models and Their Applications to Risk Assessment I: Route to Route Extrapolation of Volatile Chemicals,” by Chiu and White in Risk Analysis, 26(3), 769–780," Risk Analysis, John Wiley & Sons, vol. 26(6), pages 1415-1415, December.
    5. Judith S. Schreiber, 1993. "Predicted Infant Exposure to Tetrachloroethene in Human Breastmilk," Risk Analysis, John Wiley & Sons, vol. 13(5), pages 515-524, October.
    6. Dale Hattis & Paul White & Laura Marmorstein & Paul Koch, 1990. "Uncertainties in Pharmacokinetic Modeling for Perchloroethylene. I. Comparison of Model Structure, Parameters, and Predictions for Low‐Dose Metabolism Rates for Models Derived by Different Authors," Risk Analysis, John Wiley & Sons, vol. 10(3), pages 449-458, September.
    7. Kenneth T. Bogen, 1995. "Methods to Approximate Joint Uncertainty and Variability in Risk," Risk Analysis, John Wiley & Sons, vol. 15(3), pages 411-419, June.

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