Insights into the circadian rhythm alterations of the novel PFOS substitutes F-53B and OBS on adult zebrafish

As alternatives to perfluorooctane sulfonate (PFOS), 6:2 Cl-PFESA (F-53B) and sodium p-perfluorous nonenoxybenzene sulfonate (OBS) are frequently detected in aquatic environments, but little is known about their neurotoxicity, especially in terms of circadian rhythms. In this study, adult zebrafish were chronically exposed to 1 μM PFOS, F-53B and OBS for 21 days taking circadian rhythm-dopamine (DA) regulatory network as an entry point to comparatively investigate their neurotoxicity and underlying mechanisms. The results showed that PFOS may affect the response to heat rather than circadian rhythms by reducing DA secretion due to disruption of calcium signaling pathway transduction caused by midbrain swelling. In contrast, F-53B and OBS altered the circadian rhythms of adult zebrafish, but their mechanisms of action were different. Specifically, F-53B might alter circadian rhythms by interfering with amino acid neurotransmitter metabolism and disrupting blood-brain barrier (BBB) formation, whereas OBS mainly inhibited canonical Wnt signaling transduction by reducing cilia formation in ependymal cells and induced midbrain ventriculomegaly, finally triggering imbalance in DA secretion and circadian rhythm changes. Our study highlights the need to focus on the environmental exposure risks of PFOS alternatives and the sequential and interactive mechanisms of their multiple toxicities.