Chemical mixture risk drivers and their heterogeneity in European freshwaters

Chemical pollution of aquatic environments involves diverse substance combinations that can provoke combined biological and toxicological effects even when individual concentrations remain below effect thresholds. Multiple efforts are ongoing to better consider mixture effects in chemical safety regulation, but debate continues over whether a few substances drive aquatic mixture risks or whether a large heterogeneous set of drivers must be considered. We employed a data re-use strategy to investigate the heterogeneity of chemical mixture risk drivers to aquatic species in Europe. Initially, we derived 201 risk-driving chemicals from a single measurement campaign, allowing driver comparisons between sites based on consistently measured substances. We then extended our analysis to extensive chemical monitoring data of the NORMAN network, originating from different campaigns focusing on diverging substance sets measured at different times and locations. Data were aggregated quarterly and sites clustered per quarter according to measured substances. Using a robust definition of risk drivers (the most significant chemicals whose cumulative toxic units contribute ≥75% of total risk), our study concludes that at least 580 different substances drive chemical mixture risks in European freshwaters, with high heterogeneity between locations. Notably, mixture risk drivers were species-specific, exhibited temporal variability, and belonged to different chemical use groups considered in various safety regulations. We also found that monitoring data gaps prevented more precise analysis, particularly regarding temporal variability. These findings have important implications for future chemical monitoring strategies and mixture risk regulation in Europe, highlighting the complexity and heterogeneity of chemical mixture risks in aquatic environments.