Bridging Exposure and Mechanism: A Mechanism-Weighted Ecological Risk Assessment Reveals Divergent Priorities for Endocrine-Disrupting Chemicals in China

Abstract The proliferation of novel entities in the Anthropocene threatens aquatic biodiversity, yet traditional ecological risk assessment (ERA) may rank chemicals primarily by exposure and effect concentration, despite chemicals exhibiting widely differing receptor-mediated toxicity. To address this limitation, this study developed a mechanism-weighted ERA (mw-ERA) framework that integrates molecular docking-derived binding free energies of six key endocrine-related receptor targets (e.g., estrogen and thyroid hormone receptors) with exposure data for 139 endocrine-disrupting chemicals (EDCs) in surface water around 234 Chinese cities. Docking outputs were standardized using z-scores and transformed into a mechanism weight factor (MW) to summarize relative docking-derived receptor-binding potential and refine exposure-based ecological risk prioritization. The mw-ERA framework identified 31 EDCs with MW > 1, indicating above-average docking-derived interaction potential across the selected receptors. Among these, 20 chemicals were prioritized as candidates for endocrine-relevant testing, including bisphenols, estrogens, several phthalate esters, and antibiotics that were underestimated via exposure-only ranking. Conversely, most per- and polyfluoroalkyl substances showed MW < 1, reflecting weaker predicted binding potential with the selected receptors relative to the study data set. By integrating receptor-mediated mechanism information with exposure data, this framework provides a biologically grounded, near-term actionable, and computationally efficient approach for prioritizing EDCs for ecological risk management.