Physiologically based pharmacokinetic models to support modernized chemical safety assessment

Abstract Physiologically based pharmacokinetic (PBPK) modeling has now emerged as a critical translation tool to quantitatively bridge toxicity estimates from in vitro and in silico approaches, which collectively referred to as new approach and methodologies (NAMs) to in vivo exposure conditions within the context-based safety assessment framework. This chapter describes the emerging new role of PBPK modeling referred to as quantitative in vitro to in vivo extrapolation in modern safety assessment and how this new role is supported by rapid PBPK modeling characterized by the use of generic modeling approach coupled with in vitro–based parameterization. The ultimate goal is to support interpretation of high-volume NAMs data for chemical safety decisions in an efficient way while increasing in vivo relevance in the context of human safety.