Unveiling the Molecular\nEffects of Replacement and\nLegacy PFASs: Transcriptomic Analysis of Zebrafish Embryos Reveals\nSurprising Similarities and Potencies

The prevalence of per- and poly fluoroalkyl substances\n(PFASs)\nin the environment has prompted restrictions on legacy PFASs due to\ntheir recognized toxic effects. Consequently, alternative “replacement”\nPFASs have been introduced and are prevalent in environmental matrices.\nFew studies have investigated the molecular effects of both legacy\nand replacement PFASs under short-term exposures. This study aimed\nto address this by utilizing transcriptomic sequencing to compare\nthe molecular impacts of exposure to concentrations 0.001–5\nmg/L of the legacy PFOS and two of its replacements, PFECHS and FBSA.\nUsing zebrafish embryos, the research assessed apical effects (mortality,\nmorphology, and growth), identified differentially expressed genes\n(DEGs) and enriched pathways, and determined transcriptomic points\nof departure (tPoDs) for each compound. Results indicated that PFOS\nexhibited the highest relative potency, followed by PFECHS and then\nFBSA. While similarities were observed among the ranked DEGs across\nall compounds, over-representation analysis revealed slight differences.\nNotably, PFOS demonstrated the lowest tPoD identified to date. These\nfindings raise concerns regarding the safety of emerging replacement\nPFASs and challenge assumptions about PFAS toxicity solely resulting\nfrom their accumulative potential. As replacement PFASs proliferate\nin the environment, this study underscores the need for heightened\nscrutiny of their effects and questions current regulatory thresholds.