Unveiling the molecular effects of replacement and legacy PFASs: Transcriptomic analysis of zebrafish embryos reveals surprising similarities and potencies.
Date
2024-10-11
Authors
Mahoney, Hannah
Ankley, Phillip
Roberts, Catherine
Lamb, Alicia
Schultz, Matthew
Zhou, Yutong
Giesy, John
Brinkmann, Markus
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American Chemical Society
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Article
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Abstract
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.
Description
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Environmental Science & Technology, copyright © 2024 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.est.4c04246.
Keywords
transcriptomic benchmark concentration, perfluoroalkyl substances, perfluoroethylcyclohexanesulfonate, perfluorobutane sulphamide, perfluorooctanesulfonic acid, risk assessment, adverse outcome pathway, network-based analysis
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DOI
10.1021/acs.est.4c04246