LAUSR

Due to the global ban on PFOS, the novel PFOS alternatives 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) and sodium p-perfluorous nonenoxybenzene sulfonate (OBS) are emerging in the Chinese market, but little is known about their ecological risks. In this study, zebrafish embryos were exposed to PFOS, F-53B and OBS to evaluate their bioconcentration and acute metabolic consequences at the organismal and molecular level. Chemical analysis showed that per- and polyfluoroalkyl substances (PFASs) accumulated in zebrafish larvae in the order of F-53B > PFOS > OBS, with the bioaccumulation factors ranging from 20 to 357. Exposure to F-53B and PFOS, but not OBS, increased energy expenditure, and reduced feed intake in a concentration-dependent manner and the expression of genes involved in metabolic pathways at the transcriptional and translational levels. Molecular docking revealed that the three PFASs fitted well into the active site of zebrafish glucokinase and the binding potentials decreased in the following order: F-53B > PFOS > OBS. Finally, in order to integratively assess developing zebrafish sensitivity to metabolic disruption by PFASs, we determined the Point of Departure (PoD) using the benchmark dose method and the results indicate that metabolic endpoints at the molecular and organismal level are most sensitive to F-53B (3.8 μg/L and 6.3 μg/L) followed by PFOS (8.0 μg/L and 12.2 μg/L) and OBS (14.1 μg/L and 941.2 μg/L). Collectively, F-53B has the highest bioconcentration potential and the strongest metabolism-disrupting effects, followed by PFOS and OBS. Our findings have important implications for the assessment of early developmental metabolic effects of PFOS alternatives F-53B and OBS in wildlife and humans.