Developmental Toxicity of Chlorinated Polyfluorinated Ether Sulfonate (F-53B), a Perfluorooctane Sulfonate (PFOS) Alternative, in Embryos and Larvae of Blotched Snakehead (Channa maculata)

Chlorinated polyfluoroalkyl ether sulfonate (F-53B), a common substitute for perfluorooctane sulfonate (PFOS), exhibits similar environmental persistence and bioaccumulation potential, raising concerns about its ecological and health impacts. However, comprehensive toxicological data remain limited for adequate environmental risk assessment. In this study, we evaluated the developmental toxicity of F-53B using embryos/larvae of a commercially important benthic fish, blotched snakehead (<i>Channa maculata</i>). Embryos (<1 h post-fertilization, hpf) were exposed to various concentrations of F-53B (0.002, 0.02, 0.2, and 2 mg/L) for 120 h. Exposure resulted in concentration-dependent adverse effects, including reduced hatching success, increased mortality, and morphological malformations (yolk sac edema, spinal curvature). Histopathological analysis revealed substantial hepatic injury (vacuolization, nuclear pyknosis) and intestinal damage (villi atrophy) at higher concentrations (0.2 and 2 mg/L). Mechanistically, F-53B induced oxidative stress through inhibition of superoxide dismutase (SOD) and catalase (CAT), depletion of glutathione (GSH), and elevated malondialdehyde (MDA). Additionally, the observed immune dysregulation was characterized by the up-regulation of pro-inflammatory cytokines, including interleukin 1β (<i>IL-1β</i>), interleukin 8 (<i>IL-8</i>), and tumor necrosis factor-α (<i>TNF-α</i>), consistent with activation of the TLR-MAPK signaling pathway, and coincided with a shift from metabolic adaptation to pronounced inflammation. These integrated findings indicate that F-53B impairs early development in <i>C. maculata</i> through pathways involving oxidative damage, tissue injury, and immune disruption. This underscores the ecological risk F-53B poses to aquatic organisms and highlights the need for more comprehensive environmental risk assessment.