SAT-234 Hepatotoxic Effects of HFPO Homologues in Mice: Evaluating the Safety of PFOA and PFOS Replacements

Abstract Disclosure: M. La Merrill: None. D. Guzman: None. M.L. Goodson: None. B. Lachter: None. A. Ehrlich: None. Presentation Type: Traditional Poster Presentation (Printed Poster)Science Type and Topic: Basic Scientific Research Authors: David Guzman, Michael Goodson, Bea Lachter, Allison Ehrlich, Michele La MerrillDisclosures: Nothing to discloseCOI and Permissions: No conflict of interest. Permissions = NAAbstract Body: Widespread drinking water contamination by the well-studied per- and polyfluoroalkyl substances (PFAS) perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) has recently been restricted due to their toxicity. Their replacements include hexafluoropropylene oxide (HFPO) homologues, including dimer acid (HFPO-DA), trimer acid (HFPO-TA), and tetramer acid (HFPO-TeA). However, their toxicity is relatively uncharacterized. This study evaluated the immunotoxic and hepatotoxic effects of these HFPO homologues in adult female C57BL/6J mice. Mice were orally exposed to HFPO-DA (5880 ng/ml), HFPO-TA (58.8, 5.88, or 0.59 ng/ml), or HFPO-TeA (58.8, 5.88, or 0.59 ng/ml) or a vehicle control (drinking water) for 28 days, with immunotoxicity assessed through a T-cell-dependent antibody response (TDAR) assay following immunization with sheep red blood cells (SRBCs) (n = 8 per treatment group). Additional mice underwent a 14-day exposure to HFPO-DA (588 ng/ml), HFPO-TA (588, 58.8, or 5.88 ng/ml), HFPO-TeA (588, 58.8, or 5.88 ng/ml), or a vehicle control (drinking water), without SRBC immunization (n = 8 per treatment group). Analysis revealed a dose-dependent increase in liver weight associated with HFPO-TA in both exposure studies, indicating significant hepatotoxicity, while no similar effects were observed for HFPO-DA or HFPO-TeA. Efforts to ensure scientific rigor included the use of appropriate controls, statistical analysis of liver weight changes, and replication of findings. Biological variables, such as average body weight per cage, were controlled to reduce variability, and adequate sample sizes ensured robust detection of dose-dependent trends. These findings demonstrate the hepatotoxic potential of HFPO-TA and highlight the need for further mechanistic and long-term toxicity studies to assess the safety of HFPO homologues as replacements for PFOA and PFOS. Submission Questions:1.Michele La Merrill2. No religious conflicts3.Embargo and Publication Restriction - Yes4.Does not cover quality improvement and patient safety5.Opt-out of Rising Star Power Talk Awards: Opt-in if possible Presentation: Saturday, July 12, 2025