Large-Scale Study and Molecular Insights Reveal City-Level Socioeconomic Links to Whole Wastewater Toxicity

Wastewater treatment plants (WWTPs) are widely deployed across China to reduce whole wastewater toxicity and mitigate its adverse impact on aquatic ecosystems. However, insufficient analysis of influent toxicity and its city-level socioeconomic drivers has limited the development of effective wastewater management and treatment strategies. Here, we hypothesize that city-level socioeconomic conditions influence whole wastewater toxicity through specific molecular mediators, and we test this hypothesis using large-scale data from 100 WWTPs across China. The results indicated that cities with higher gross domestic product, greater population density, and more intensive industrial activity tend to produce influent with significantly higher toxicity ( p < 0.05, generalized additive models). Mechanistically, this elevated toxicity was mediated by distinct molecular features, as CHO-class specific toxic precursors ( R 2 = 0.84), particularly unsaturated hydrocarbon–, condensed hydrocarbon–, and amino sugar–like compounds, were identified as the dominant molecular contributors to this toxicity based on ultrahigh-resolution mass spectrometry. Together, these findings demonstrate a molecular mediation pathway linking socioeconomic development to whole wastewater toxicity, highlighting the need for precision toxicity control strategies that prioritize economically developed cities, wherein WWTPs should target specific CHO-class toxic precursors.