A Multi-Route Permeability-Limited Physiologically-Based Kinetic Model for Perfluorooctanoic Acid (PFOA) Exposure of in Male and Female Rats

Per- and polyfluoroalkyl substances (PFAS), persistent synthetic chemicals prevalent in industrial and consumer applications. Among them, perfluorooctanoic acid (PFOA) is one of the most studied congeners due to its widespread detection in humans. Notably, it has been detected in up to 99% of individuals in the U.S. population and is linked to various adverse health effects [1]. While ingestion of contaminated food and water is the primary exposure route, inhalation also contributes to human PFOA intake, particularly in occupational settings. In this context, the present study develops a detailed physiologically-based kinetic (PBK) model for rats that offers a mechanistic framework for simulating the absorption, distribution, and excretion of PFOA across various organs and tissues and understanding key processes that affect its internal disposition.