Parental Lifetime PBSA Exposure Induces Neurodevelopmental Toxicity in F1 Zebrafish

2-phenylbenzimidazole-5-sulfonic acid (PBSA) is a commonly used organic ultraviolet (UV) filter frequently found in aquatic environments, raising substantial ecological health concerns. While some toxic effects of PBSA on aquatic organisms have been reported, its intergenerational developmental and neurotoxic risks remain poorly understood. In this study, we established a zebrafish life-cycle exposure model to explore the intergenerational toxicity of environmentally relevant concentrations of PBSA (0.2, 2, and 20 μg/L). Offspring were categorized into three exposure groups: parental exposure only (F0+/F1−), parental exposure with continuous F1 exposure (F0+/F1+), and only F1 exposure without parental treatment (F0−/F1+). Our findings demonstrate the transfer of PBSA from parental gonads to F1 embryos. Parental lifetime exposure significantly inhibited somitogenesis and increased mortality and malformation rates in the F1 generation, with the most pronounced developmental damage observed in the F0+/F1+ group. Whole-mount immunohistochemistry revealed that PBSA notably reduced motor neuron axon length in F1 larvae, accompanied by downregulation of developmental-related genes including gap43, mbp, and shha. Mechanistically, the F0+/F1− group exhibited a marked increase in MDA levels. Excessive ROS accumulation and reduced CAT activity were specifically observed in the F0+/F1+ group, whereas the F0+/F1− and F0−/F1+ groups showed significantly elevated CAT activity, jointly driving developmental and neurotoxic changes. In silico predictions indicated low acute aquatic toxicity of PBSA, contradicting its observed intergenerational risks. Our findings demonstrate that parental lifetime PBSA exposure can induce significant intergenerational neurodevelopmental toxicity in zebrafish offspring by disrupting oxidative balance and neural gene expression, with continuous offspring exposure further aggravating the adverse effects. This research underscores that traditional single-generation toxicity assessments underestimate the ecological dangers of UV filters. It also offers new insights into the environmental risk evaluation of PBSA and similar emerging contaminants.