SAT-243 Assessment of PFAS ‘Forever Chemicals’ on Viability of Triple-Negative Breast Cancer Cells

Abstract Disclosure: M. La Merrill: None. D. Guzman: None. S. Singh Johal: None. B.J. Mengeling: None. Abstract Body: Per- and polyfluoroalkyl substances (PFAS) are pervasive environmental pollutants found in household items such as non-stick cookware, stain-resistant fabrics, and food packaging. Certain PFAS, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have shown to persist in the environment due to their chemical stability, leading to widespread contamination in water supplies and human tissues. The International Agency for Research on Cancer classifies PFOA as carcinogenic to humans (Group 1), based in part on sufficient evidence of epigenetic alterations and immunosuppression, in exposed humans. Moreover, PFOS is classified as possibly carcinogenic to humans (Group 2B). Consequently, the U.S. EPA has regulated PFOA and PFOS, leading to alternatives being introduced into the marketplace. However the replacement PFAS, such as hexafluoropropylene oxide trimer acid (HFPO-TA), hexafluoropropylene oxide tetrameric acid (HFPO-TeA), and chlorinated polyfluoroalkyl ether sulfonic acid (F-53B), remain largely untested for their toxicological properties. This study investigates the effects of HFPO-TA, HFPO-TeA, and F-53B on the viability of Hs578T triple-negative breast cancer cells. Hs578T cells were exposed to concentrations of 10 µM, 1 µM, 100 nM, and 10 nM of HFPO-TA, HFPO-TeA, and F-53B and cell viability measured at 12h, 24h, and 48h time points. All three compounds contributed to varying levels of cell-membrane deterioration. F-53B, in particular, significantly decreased cell viability across all four concentrations, with 10 nM significantly decreasing cell viability at all three time points. To further investigate the cytotoxicity of low F-53B concentrations, Hs578T cells were exposed to F-53B concentrations ranging from 10 nM to 19.5 pM. F-53B significantly reduced cell viability at low concentration levels of 10, 5, and 2.5 nM. Furthermore, exposure to F-53B at these concentrations for both 12h and 48h durations significantly reduced cell viability, indicating sustained effects of low F-53B concentrations on human cell viability. F-53B levels that are cytotoxic to Hs578T human triple-negative breast cancer cells in our research are within the range of the levels of F-53B that are cytotoxic to non-cancerous human cells (e.g. neuroblastoma and umbilical vein endothelial cells) and to the levels found in human serum (∼9 nM). These results indicate that F-53B may be cytotoxic at levels typically found in humans. This raises significant public health concerns as blood concentrations of this replacement PFAS are rising. Presentation: Saturday, July 12, 2025