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Using Physiologically-Based Pharmacokinetic Models to Incorporate Chemical and Non-Chemical Stressors into Cumulative Risk Assessment: A Case Study of Pesticide Exposures

Author

Listed:
  • Susan C. Wason

    (Department of Environmental Health, Harvard School of Public Health, 401 Park Drive West, Boston, MA 02215, USA)

  • Thomas J. Smith

    (Department of Environmental Health, Harvard School of Public Health, 401 Park Drive West, Boston, MA 02215, USA)

  • Melissa J. Perry

    (Department of Environmental Health, Harvard School of Public Health, 401 Park Drive West, Boston, MA 02215, USA
    Department of Environmental and Occupational Health, School of Public Health and Health Service, George Washington University, 2300 Eye St. NW, Washington, DC 20037, USA)

  • Jonathan I. Levy

    (Department of Environmental Health, Harvard School of Public Health, 401 Park Drive West, Boston, MA 02215, USA
    Department of Environmental Health, Boston University School of Public Health, 715 Albany St., Boston, MA 02118, USA)

Abstract

Cumulative risk assessment has been proposed as an approach to evaluate the health risks associated with simultaneous exposure to multiple chemical and non-chemical stressors. Physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models can allow for the inclusion and evaluation of multiple stressors, including non-chemical stressors, but studies have not leveraged PBPK/PD models to jointly consider these disparate exposures in a cumulative risk context. In this study, we focused on exposures to organophosphate (OP) pesticides for children in urban low-income environments, where these children would be simultaneously exposed to other pesticides (including pyrethroids) and non-chemical stressors that may modify the effects of these exposures (including diet). We developed a methodological framework to evaluate chemical and non-chemical stressor impacts on OPs, utilizing an existing PBPK/PD model for chlorpyrifos. We evaluated population-specific stressors that would influence OP doses or acetylcholinesterase (AChE) inhibition, the relevant PD outcome. We incorporated the impact of simultaneous exposure to pyrethroids and dietary factors on OP dose through the compartments of metabolism and PD outcome within the PBPK model, and simulated combinations of stressors across multiple exposure ranges and potential body weights. Our analyses demonstrated that both chemical and non-chemical stressors can influence the health implications of OP exposures, with up to 5-fold variability in AChE inhibition across combinations of stressor values for a given OP dose. We demonstrate an approach for modeling OP risks in the presence of other population-specific environmental stressors, providing insight about co-exposures and variability factors that most impact OP health risks and contribute to children’s cumulative health risk from pesticides. More generally, this framework can be used to inform cumulative risk assessment for any compound impacted by chemical and non-chemical stressors through metabolism or PD outcomes.

Suggested Citation

  • Susan C. Wason & Thomas J. Smith & Melissa J. Perry & Jonathan I. Levy, 2012. "Using Physiologically-Based Pharmacokinetic Models to Incorporate Chemical and Non-Chemical Stressors into Cumulative Risk Assessment: A Case Study of Pesticide Exposures," IJERPH, MDPI, vol. 9(5), pages 1-13, May.
    • Handle: RePEc:gam:jijerp:v:9:y:2012:i:5:p:1971-1983:d:17891
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    References listed on IDEAS

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    1. Yu-Mei Tan & Harvey Clewell & Jerry Campbell & Melvin Andersen, 2011. "Evaluating Pharmacokinetic and Pharmacodynamic Interactions with Computational Models in Supporting Cumulative Risk Assessment," IJERPH, MDPI, vol. 8(5), pages 1-18, May.
    2. Jonathan I. Levy, 2008. "Is Epidemiology the Key to Cumulative Risk Assessment?," Risk Analysis, John Wiley & Sons, vol. 28(6), pages 1507-1513, December.
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