Risk Assessment of Per- and Polyfluoroalkyl Substance Mixtures: A Relative Potency Factor Approach.

Per- and polyfluoroalkyl substances (PFAS) often occur together as contamination in exposure media such as drinking water or food. The relative potency factor (RPF) methodology facilitates the risk assessment of mixture exposure. A database of liver endpoints was established for 16 PFAS, using data with the same species (rat), sex (male), and exposure route (oral) and comparable exposure duration (42-90 d). Dose-response analysis was applied to derive the relative potencies of 3 perfluoroalkyl sulfonic acids (perfluorobutane sulfonic acid, perfluorohexane sulfonic acid, perfluorooctane sulfonic acid), 8 perfluoroalkyl carboxylic acids (perfluorobutanoic acid, perfluorohexanoic acid, perfluorononanoic acid, perfluoroundecanoic acid, perfluorododecanoic acid, perfluorotetradecanoic acid, perfluorohexadecanoic acid, perfluorooctadecanoic acid), 2 perfluoroalkyl ether carboxylic acids (tetrafluoro-2-[heptafluoropropoxy]propanoic acid, 3H-perfluoro-3-[(3-methoxy-propoxy)propanoic acid]), and 2 fluorotelomer alcohols (6:2 FTOH, 8:2 FTOH) compared to perfluorooctanoic acid (PFOA), based on liver effects. In addition, the RPFs of 7 other perfluoroalkyl acids were estimated based on read-across. This resulted in the relative potencies of 22 PFAS compared to the potency of index compound PFOA. The obtained RPFs can be applied to measured PFAS quantities, resulting in the sum of PFOA equivalents in a mixture. This sum can be compared with an established PFOA concentration limit (e.g., in drinking water or food) or an external health-based guidance value (e.g., tolerable daily intake, acceptable daily intake, or reference dose) to estimate the risk resulting from direct oral exposure to mixtures. Assessing mixture exposure is particularly relevant for PFAS, with omnipresent exposure in our daily lives. Environ Toxicol Chem 2021;40:859-870.