title: Physiologically-based pharmacokinetic (PBPK) models in toxicity testing and risk assessment.
abstract: Physiologically-based pharmacokinetic (PBPK) modeling offers a scientifically-sound framework for integrating mechanistic data on absorption, distribution, metabolism and elimination to predict the time-course of parent chemical, metabolite(s) or biomarkers in the exposed organism. A major advantage of PBPK models is their ability to forecast the impact of specific mechanistic processes and determinants on the tissue dose. In this regard, they facilitate integration of data obtained with in vitro and in silico methods, for making predictions of the tissue dosimetry in the whole animal, thus reducing and/or refining the use of animals in pharmacokinetic and toxicity studies. This chapter presents the principles and practice of PBPK modeling, as well as the application of these models in toxicity testing and health risk assessments.
authors.affiliation: US Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment, Cincinnati, Ohio, USA. lipscomb.john@epa.gov
authors.forename: John C
authors.initials: JC
authors.lastname: Lipscomb
authors.forename: Sami
authors.initials: S
authors.lastname: Haddad
authors.forename: Torka
authors.initials: T
authors.lastname: Poet
authors.forename: Kannan
authors.initials: K
authors.lastname: Krishnan
mesh_terms: D000818:Animals; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics; D018570:Risk Assessment / Q000379:methods*; D018675:Toxicity Tests / Q000379:methods*