Xie_2025_Environ.Pollut_379_126527

Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant with adverse effects. Alongside PFOS, its substitutes, such as 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) and 6:2 fluorotelomer sulfonic acid (6:2 FTSA), are frequently detected in aquatic environments. While the effects of PFOS and its substitutes on the aquatic organism behavior have been observed, the underlying mechanisms of these effects remain poorly understood. In this study, an online biological monitoring system was utilized to investigate the behavioral effects of 7-day exposure to PFOS, F-53B, and 6:2 FTSA in adult zebrafish (Danio rerio), and assess alterations in neurotoxicity-related biomarker levels. Results demonstrate that exposure to PFOS, F-53B, and 6:2 FTSA significantly reduced the behavioral strength (BS) and the amplitude of circadian rhythm in zebrafish. Notably, PFOS and 6:2 FTSA exposure induced circadian rhythm phase shifts. Furthermore, acetylcholinesterase (AChE) activity and dopamine (DA)/melatonin (MT) levels showed significant reductions consistent with BS alterations across all exposure groups. Molecular docking analysis revealed that PFOS, F-53B, and 6:2 FTSA exhibited significant binding affinities to related receptors. Among the three pollutants, F-53B exerted the most pronounced effects on BS values, circadian rhythm amplitude, and levels of related biomarkers. In contrast, 6:2 FTSA displayed the most significant impact on circadian rhythm phase shifts. These findings suggest that the effects and the underlying mechanisms of PFOS and its substitutes on zebrafish behavior may vary. A comprehensive evaluation of the neurotoxicity of PFOS substitutes for aquatic organisms is required to prevent underestimation of their potential risks.