Comparative fish toxicology of perfluorohexanoic acid, hexafluoropropylene oxide dimer acid, and trifluoroacetic acid.

Short-chain per- and polyfluoroalkyl substances (PFAS), including fluorinated acids, have expanded as replacements for legacy per- and polyfluoroalkyl substances, yet aquatic safety assumptions are challenged by emerging fish toxicity data and the realities of persistence and exposure. This review synthesizes fish toxicology evidence for three environmentally important short-chain fluorinated acids selected to represent distinct chemical and exposure contexts: perfluorohexanoic acid (PFHxA) as a short-chain perfluorocarboxylic acid, hexafluoropropylene oxide dimer acid (HFPO-DA) as an ether-based replacement compound, and trifluoroacetic acid (TFA) as an ultrashort terminal transformation product characterized by exceptional persistence and mobility. Across fish models, perfluorohexanoic acid is generally less bioaccumulative than many long-chain analogs, but can still elicit biologically meaningful neurobehavioral and molecular alterations depending on life stage and exposure scenario. Hexafluoropropylene oxide dimer acid, widely known as a replacement for perfluorooctanoic acid, shows patterns consistent with endocrine and metabolic disturbance in fish development, including thyroid-axis-related endpoints and transcriptomic or metabolomic disruptions. Trifluoroacetic acid differs fundamentally: it is extremely persistent and highly mobile, with evidence of increasing environmental burdens and unresolved thresholds for long-term ecological effects. The comparison is further interpreted in the context of other short-chain perfluorocarboxylic acids, particularly PFBA, PFPeA, and PFHpA, to clarify the position of the selected compounds within the broader short-chain PFAS spectrum. Overall, the comparison shows that short-chain fluorinated acids should not be interpreted through a single safety gradient, because PFHxA, HFPO-DA, and TFA represent distinct but connected risk logics shaped by exposure persistence, internal-dose dynamics, and pathway-specific biological responses. Future priorities include harmonized exposure verification, tissue-dose reporting, mixture-relevant designs, and cross-life-stage endpoints that better predict population-relevant outcomes.