Concentration-dependent toxicokinetics of novel PFOS alternatives and their chronic combined toxicity in adult zebrafish

The increasing use of perfluorooctanesulfonate (PFOS) alternatives has led to their release into the aquatic environ-ment. This study sought to determine the effects of exposure concentration on the toxicokinetics of PFOS and its alter-natives, including perfluorobutanesulfonic acid (PFBS), perfluorohexanesulfonic acid (PFHxS), chlorinated polyfluorinated ether sulfonate (F-53B) and sodium p-perfluorous nonenoxybenzenesulfonate (OBS) in adult zebrafish by exposure to mixtures of the five per-and polyfluoroalkyl substances (PFAS) at 1, 10, and 100 ng/mL for 28-day, followed by a 14-day depuration. PFAS predominantly accumulated in the blood and liver, and the bioconcentration factor (BCF) decreased in the order of F-53B > PFOS > OBS >> PFHxS > PFBS in whole-fish homogenates. The uptake rate constants and BCF of the short-chain PFAS (<= C6) positively correlated with increasing exposure concentra-tion, while the long-chain PFAS (>= C8) exhibited a pattern of first increasing and then decreasing. A consistent in-crease in the elimination rate constants of short-and long-chain PFAS was observed with increasing exposure concentration. All PFAS form tight conformations with ZSA and ZL-FABP via hydrogen bonding as revealed by mo-lecular docking analysis. Furthermore, chronic combined exposure to PFAS induced the occurrence of vacuolation and oxidative stress in the zebrafish liver. Our findings uniquely inform the concentration-dependent bioconcentration potential and health risks to aquatic organisms of these PFOS alternatives in the environment.

Automated summary

This study investigates the toxicokinetics and health effects of PFOS alternatives in adult zebrafish, and reveals the concentration-dependent bioconcentration potential and health risks of these substances to aquatic organisms in the environment. The study also uncovers the molecular interactions between PFAS and ZSA/ZL-FABP, and identifies the occurrence of vacuolation and oxidative stress in the zebrafish liver with chronic combined exposure to PFAS.