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Lecture in “The use of physiologically based pharmacokinetic modelling to incorporate chemical-specific information in risk assessments
March 2010

Harvey J. Clewell III, Ph.D., DABT
Director, Center for Human Health Assessment
The Hamner Institutes for Health Sciences
6 Davis Drive (P.O. Box 12137)
Research Triangle Park, NC 27703
919-558-1211 (FAX 1301)



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In recent years, physiologically based pharmacokinetic (PBPK) modeling has become increasingly popular as a tool for use during environmental risk assessment.  The ultimate aim of using PBPK modeling in risk assessment is to provide a measure of target tissue exposure that better represents the "biologically effective dose"; that is, the dose that is causally related to the outcome of interest.  The tissue exposure metric can then be used in place of traditional dose metrics (such as administered dose) to provide more accurate predictions for human doses.  The motivation for applying PBPK in risk assessment is the expectation that the target tissue effects of a chemical will be more simply and directly related to a measure of target tissue exposure than to a measure of administered dose.  A highly valuable feature of PBPK modeling is its ability to integrate the interpretation of kinetic data across different animal species and dosing routes.  In particular, a PBPK model can be used to perform the high-to-low dose, dose-route, and interspecies extrapolations necessary for estimating human risk on the basis of animal toxicology studies.  PBPK models are also useful for predicting exposures in the fetus and infant, for evaluating the impact of metabolic polymorphisms, and for investigating the impact of human interindividual variability.  This presentation provides a brief overview of the nature of PBPK modeling, and describes examples of the application of PBPK modeling to improve risk assessments by incorporating chemical-specific data. 





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