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Physiologically Based Pharmacokinetic Modeling of Chemical Mixtures

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Chemical Mixtures and Combined Chemical and Nonchemical Stressors

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Abstract

Physiologically based pharmacokinetic (PBPK) modeling is a tool that is increasingly being used for xenobiotics exposure assessment and target tissue dosimetry simulations in risk assessment and in pharmaceutical sciences. Because this tool can use chemical and physiological information/data from different sources (i.e., in vitro, in vivo, in silico), it is also being increasingly used for mixture exposures, especially for mixtures containing chemicals that toxicokinetically interact, at the physiological, physicochemical, and biochemical level. The aim of this chapter is to give an overview of what PBPK modeling is and how it can be used in the context of mixture toxicology. Known mechanisms of toxicokinetic interactions between xenobiotics are described, and mathematical representations are given when available. Existing modeling approaches that are available in the literature are presented for mixtures of various complexities. Current methods and their limitations are reported, and future directions are put forward.

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  1. Department of Occupational & Environmental Health, School of Public Health, Public Health Research Institute of Université de Montréal, Université de Montréal, Montreal, QC, Canada

    Sami Haddad

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  1. National Toxicology Program, National Institute of Environmental, Health Sciences, Research Triangle Park, North Carolina, USA

    Cynthia V. Rider

  2. National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA

    Jane Ellen Simmons

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Haddad, S. (2018). Physiologically Based Pharmacokinetic Modeling of Chemical Mixtures. In: Rider, C., Simmons, J. (eds) Chemical Mixtures and Combined Chemical and Nonchemical Stressors. Springer, Cham. https://doi.org/10.1007/978-3-319-56234-6_12

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