ABSTRACT
This chapter provides a description of approaches for using physiologically based pharmacokinetic (PBPK) models and supporting data in human health risk assessment. It focuses on the use of PBPK models in predicting internal dose at target or surrogate tissues. The dose-response analysis portion of a risk assessment can be used to determine a Point of departure for one or more of the most sensitive critical effects, based on the relationship between administered dose and observed responses in laboratory or field studies. The most robust pharmacokinetic data set needed for risk assessment would consist of the time-course data on the dose metric associated with exposure scenarios and doses used in the critical studies chosen for the assessment and relevant human exposure conditions. Risk assessments based on the use of PBPK models account for only the pharmacokinetic aspect or, more specifically, target tissue exposure to a toxic moiety.
