Physicochemical Factors Influencing PFAS Partitioning in Organ-Specific Models

Abstract

Per- and polyfluoroalkyl substances (PFAS) are a synthetic chemical class known as “forever chemicals” due to their persistence in nature and resistance to degradation. They were first used in the 1940s and have since been widely adopted for many commercial and industrial products and are now widespread in the environment. While PFAS exposure and bioaccumulation in humans is often assessed using blood serum concentrations, this metric may not fully capture toxicity risks or retention mechanisms in specific tissue. Consequently, organ-specific bioaccumulation is increasingly evaluated using equilibrium distribution modeling (EDM), which relies on experimentally determined distribution coefficients for proteins, lipids, and water content. However, traditional passive sampling strategies for EDM often overlook the amphiphilic, surfactant-like nature of PFAS. This property causes PFAS to accumulate at the air-water interface, creating artifacts in partitioning data. To address this, we modified the traditional C18-coated solid-phase microextraction method to remove headspace from the system. We determined that systems without headspace yielded notably higher concentrations of PFAS detected compared to samples with headspace, confirming that the headspace acts as a fourth phase where PFAS partitions to the solution surface. Using this modified method, we examined the pH-dependent partitioning behavior in a simulated fish organ system. We demonstrated that varying pH alters PFAS speciation and hydrophobicity. Specifically, analysis of perfluoroalkyl sulfonamide (FASA) compounds perfluorobutane sulfonamide (FBSA) and perfluoro-1-hexanesulfonamide (FHxSA) (both short-chain PFAS precursors) revealed that pH-dependent speciation shifts directly control their distribution equilibria between aqueous and tissue phases. These findings underscore the necessity of accounting for both surfactant behavior and physiological pH variations to accurately assess the toxicity risks of PFAS in vital organs.