A field-monitoring-informed assessment for effect-based prioritization of pharmaceutically active compounds in freshwater lakes: A case study in Taihu Lake, China

Pharmaceutically active compounds (PhACs) are emerging contaminants of increasing ecological concern due to their persistence, bioactivity, and potential for bioaccumulation in aquatic ecosystems. Here, we propose a field-monitoring-informed framework for identifying priority substances and screening priority areas to support targeted pharmaceutical pollution control in large freshwater lakes. Using Taihu Lake, China, as a case study, four-season surface-water monitoring together with summer biota sampling revealed the widespread occurrence of 44 PhACs in surface water, fish, and benthic macroinvertebrates. Among these, caffeine (CAFF), carbamazepine (CBZ), and sulfamethoxazole (SMX) were identified as priority substances mainly because of their high occurrence frequencies, elevated ecological risk quotients, and retained Tier 1 status under a threshold-first evidence matrix that separated risk severity from ubiquity. Bioaccumulation analysis revealed species- and tissue-specific enrichment, whereas the field-based BAFs should be interpreted cautiously because water and biota sampling were not fully synchronous and neither CAFF nor CBZ showed statistically significant trophic magnification. By integrating spatial patterns of concentrations and ecological risks, northern and western lake regions were further identified as priority control areas. To examine whether measured ambient concentrations could elicit adverse biological effects, representative compounds (CAFF, CBZ, SMX, and mirtazapine) and a fixed-ratio mixture based on the compound-specific ambient maxima measured in this study were tested in zebrafish. Single and combined exposures induced developmental, behavioral, and transcriptomic responses associated with neurodevelopment, endocrine regulation, and energy metabolism, and a descriptive treatment-mean Bliss-independence benchmark suggested that observed mixture effects were generally lower than Bliss-expected effects, with no evidence of greater-than-Bliss responses. Overall, this study provides a field-monitoring-informed and effect-based framework for identifying priority pharmaceutical pollutants and potential control areas, offering a practical basis for targeted pollution management in freshwater ecosystems.