Transporter-Mediated Mechanisms in PFAS Disposition and Elimination

: Per- and polyfluoroalkyl substances (PFAS) are highly persistent environmental contaminants. Human exposure primarily occurs through drinking water, diet, and consumer products. There is increasing evidence that the absorption, distribution, and elimination of PFAS are strongly influenced by membrane transporters. In this review, we summarize current knowledge on the transporters that handle PFAS in the intestine, liver, kidney, and other organs. Members of the SLC22A (OATs) and SLCO (OATPs) families play central roles in PFAS uptake and reabsorption, with pronounced species and chain length dependent differences. ABC efflux transporters are less well characterized regarding their PFAS transport and available data show that some, including BCRP, MDR1, MRP2, MRP4, and BSEP, are inhibited by PFAS. PFAS exposure also affects the regulation of these transporters, with multiple studies reporting altered transcription of uptake and efflux transporters in hepatic and intestinal models. Knowledge of the expression and function of these transporters help explain organ- and species specific PFAS accumulation and explain the differences in half-lives of the different PFAS. Finally, we review therapeutic strategies to enhance PFAS elimination and highlight bile acid sequestrants, which increase fecal excretion and reduce serum PFAS levels in both animal models and human studies. Available data underscore the importance of transporters in PFAS toxicokinetics, the need for additional functional characterization of efflux transporters, and the focus on emerging short-chain and replacement PFAS compounds.