Physiologically-based pharmacokinetic (PBPK) models in toxicity testing and risk assessment

Area of Science:

• Pharmacokinetics
• Toxicology
• Computational Biology

Background:

• Physiologically-based pharmacokinetic (PBPK) modeling provides a robust framework for understanding chemical disposition.
• It integrates mechanistic data on absorption, distribution, metabolism, and elimination (ADME).

Purpose of the Study:

• To present the principles and practice of PBPK modeling.
• To highlight the application of PBPK models in toxicity testing and health risk assessment.
• To demonstrate how PBPK models reduce and refine animal use in studies.

Main Methods:

• PBPK models integrate in vitro and in silico data.
• These models predict the time-course of parent chemicals, metabolites, or biomarkers.
• They forecast the impact of mechanistic processes on tissue dose.

Main Results:

• PBPK models enable prediction of tissue dosimetry in whole animals.
• They facilitate the integration of diverse data sources.
• The models support reduced and refined animal testing.

Conclusions:

• PBPK modeling is a valuable tool for pharmacokinetic and toxicological assessments.
• It enhances the scientific basis for predicting chemical exposure effects.
• PBPK models contribute to more accurate health risk assessments and reduced animal usage.