Uncertainty and Variability in Physiologically-Based Pharmacokinetic (PBPK) Models: Key Issues and Case Studies (Final Report)

Chemical risk and safety assessments increasingly rely upon tissue dosimetry estimates in animals and humans obtained from physiologically-based pharmacokinetic (PBPK) modeling. However, risk assessment also increasingly requires characterization of uncertainty and variability; such characterization for PBPK model predictions represents a continuing challenge to both modelers and users. Current practices show significant progress in specifying deterministic biological models and the non-deterministic (often statistical) models, estimating their parameters using diverse data sets from multiple sources, and using them to make predictions and characterize uncertainty and variability. This report summarizes some of the recent progress in this area that has been conducted or supported by the National Center for Environmental Assessment (NCEA). These include the identification of the state-of-the science on key issues in this area, as well as priority research or implementation needs. In addition, a number of case examples of chemical-specific applications have demonstrated some of the methods and issues associated with characterizing uncertainty and variability in PBPK modeling.

This is the final report.