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Next Generation Risk Assessment of Emerging PFOA Alternatives Using Integrated New Approach Methodologies.

You Song1, Xueqi Fan2, Maria T Hultman1

  • 1Norwegian Institute for Water Research (NIVA), Økernveien 94, N-0579 Oslo, Norway.

Environmental Science & Technology
|November 21, 2025
PubMed
Summary

Emerging per- and polyfluoroalkyl substances (PFASs) alternatives pose local environmental risks, with some showing cytotoxicity and embryo toxicity. New Approach Methodologies (NAMs) within a Next Generation Risk Assessment (NGRA) framework effectively evaluated these risks.

Keywords:
AOPNAMNGRAPFASSSDtPODweight of evidencezebrafish

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Area of Science:

  • Environmental Chemistry
  • Toxicology
  • Risk Assessment

Background:

  • Global restrictions on legacy per- and polyfluoroalkyl substances (PFASs), like perfluorooctanoic acid (PFOA), have spurred the development and increased environmental presence of alternative chemicals.
  • Evaluating the environmental impact of these emerging PFAS alternatives is crucial for safeguarding ecosystems and human health.

Purpose of the Study:

  • To assess and compare the local environmental risks associated with eight PFOA alternatives.
  • To demonstrate the utility of a Next Generation Risk Assessment (NGRA) framework utilizing New Approach Methodologies (NAMs).

Main Methods:

  • Application of a NGRA framework integrating targeted chemical analysis of wastewater and surface waters.
  • Hazard characterization using in silico modeling, in vitro zebrafish liver cell assays, in vivo zebrafish embryo toxicity tests, and transcriptomic profiling.
  • Derivation of multiple points of departure (PODs), including benchmark concentrations (BMC) and transcriptomic POD (tPOD), and calculation of risk quotients (RQ).

Main Results:

  • HFPO-TA and HFPO-TeA exhibited cytotoxicity; HFPO-DA, HFPO-TA, and HFPO-TeA caused significant embryo toxicity.
  • HFPO-TeA was identified as the most potent alternative, with transcriptomic data suggesting disruption of metabolic and cardiovascular functions.
  • Risk quotients for HFPO-DA exceeded concern thresholds, while adjusted risk quotients for HFPO-TA and HFPO-TeA indicated reduced concern.

Conclusions:

  • Emerging PFOA alternatives can pose significant local environmental risks, necessitating careful evaluation.
  • The NAM-based NGRA framework provides a robust and effective approach for assessing the risks of alternative chemicals.
  • Findings underscore the importance of proactive environmental risk assessment for chemical substitutions.