Development and utilization of physiologically based pharmacokinetic models for toxicological applications

Abstract

Recent advances in physiologically based pharmacokinetic (PB‐PK) modeling have introduced novel approaches for evaluating toxicological problems. Because PB‐PK models are amenable to extrapolation of tissue dosimetry, they are increasingly being applied to chemical risk assessment. This paper reviews the development of PB‐PK modeling for toxicological applications. It briefly compares and contrasts the fundamental differences between conventional compartmental analysis and PB‐PK modeling. The theory and principles, data requirements and the methodologies to obtain them, and the steps to construct PB‐PK models are described. A comprehensive listing of PB‐PK models for environmental chemicals developed to date is referenced. Salient applications of PB‐PK modeling to toxicological problems are illustrated with examples. Finally, the uncertainties and limitations in PB‐PK modeling are also discussed.