Unveiling the Molecular Effects of Replacement and Legacy PFASs: Transcriptomic Analysis of Zebrafish Embryos Reveals Surprising Similarities and Potencies

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