Establishing an aquatic toxicity assessment framework for environmental pollutants: safety threshold derivation for...

Standardized toxicity assessment frameworks for environmental pollutants are still lacking, limiting their effective regulation. Here, we develop a multi-level toxicity assessment framework using sodium p-perfluorous nonenoxybenzene sulfonate (OBS), a widely used alternative for perfluorooctane sulfonate (PFOS), as a case study with the zebrafish model. Acute toxicity testing revealed 96 h-median lethal concentration (LC₅₀) of 30 mg/L for embryos and 10 mg/L for newly hatched larvae, identifying larvae as a more sensitive life stage for hazard screening. Larvae were then exposed to sublethal OBS concentrations (0.1, 10, and 1000 μg/L), and a suite of targeted toxicity assessments were implemented to capture organismal-level and molecular-level responses. OBS at 10 μg/L caused significant reductions in body length and weight, and OBS at 1000 μg/L induced significant delay in swimming behavior, while antioxidant and immune biomarkers exhibited significant alterations accompanied by a multi-system transcriptional dysregulation. By integrating sensitive indicators of growth, swimming behavior, antioxidant function, immune response, and endocrine-related molecular effects, our framework provided a holistic assessment of OBS toxicity. We conducted benchmark dose (BMD) modeling across all parameters and derived Points of Departure (PoD) for each level of biological responses. The lowest median benchmark dose lower confidence limit (BMDL) of 5.569 μg/L was selected as a health-protective PoD for early-life-stage fish and was compared against reported environmental concentrations of OBS in China. The comparison revealed that OBS concentrations at some locations approached or exceeded the PoD, indicating potential ecological risk. Overall, this study proposes an effective and expandable toxicity assessment system for pollutants, and provides a methodological basis for deriving safety thresholds for a wide range of environmental pollutants and a basis for water quality assessment.