Chemical risk assessment in food animals via physiologically based pharmacokinetic modeling - Part II: Environmental pollutants on animal and human health assessments

Human activities generate a large amount of environmental pollutants, including drugs and agricultural and industrial chemicals that are released into the air, water, and soil. Environmental pollutants can enter food animals through contaminated feed and water, posing risks to human health via the food chain. Physiologically based pharmacokinetic (PBPK) modeling is used to predict the target organ dosimetry informing human health risk assessment. However, there is a lack of critical reviews concerning PBPK models for environmental pollutants in food animals in the last several years (2020-2024). This review is part of a series of reviews focusing on applications of PBPK models for drugs and environmental chemicals in food animals to inform human health and food safety assessments. Part I is focused on veterinary drugs. The present article is Part II and focuses on environmental chemicals, including pesticides, polychlorinated biphenyls (PCBs), bisphenols, and per- and polyfluoroalkyl substances (PFAS). This article discusses the existing challenges in developing PBPK models for environmental pollutants and shares our perspectives on future directions, including the combinations of in vitro to in vivo extrapolation (IVIVE), machine learning and artificial intelligence, read-across approaches, and quantitative pharmacodynamic modeling to enhance the potential applications of PBPK models in assessing human health and food safety.