Toxicity Impacts of Trace-Level of F-53B in Atmospheric Particles: Implications for Low-Exposure Risk Assessment

Although previous toxicological studies on F-53B (a substitute for perfluorooctanesulfonic acid) have primarily employed relatively high exposure doses, none have simulated environmentally relevant concentrations of F-53B found in atmospheric particulate matter (PM) to assess its contribution to particle-induced toxicity. In this study, we addressed this gap by using real-world F-53B concentrations adsorbed onto PM_2.5 as a basis for setting exposure levels. Pure carbon particles were used as a surrogate for atmospheric particles, and their toxicological effects-alone and in combination with trace-level F-53B-were comprehensively evaluated using an A549/THP-1 coculture model. Despite its extremely low concentration, F-53B significantly amplified the toxicity of carbon particles, as demonstrated by decreased mitochondrial activity, elevated oxidative stress, and disruptions in cell cycle regulation. Carbon particles alone suppressed the expression of most inflammatory and tissue-repair cytokines, while F-53B alone modestly increased several pro-inflammatory mediators. The combined exposure dampened some of the immune responses triggered by F-53B alone, indicating a complex interplay between these pollutants. Integrated potency analyses further confirmed that coexposure resulted in greater overall toxicity than exposure to carbon particles alone. These findings highlight the need to account for trace-level emerging pollutants such as F-53B when assessing the health risks associated with atmospheric PM.