Pharmaceutical-dominated organic contaminants in plateau lakes: Suspect and non-target screening, PBT risk, and structure-based risk markers.

Plateau lakes, characterized by limited mobility and enclosed hydrological conditions, are highly sensitive to anthropogenic influences. However, these water bodies remain largely understudied in the context of emerging organic contaminants. To address this gap, we systematically investigated nine plateau lakes in China using a combined approach of suspect and non-target screening, persistence-bioaccumulation-toxicity (PBT) profiling, ecological risk assessment, and structural feature analysis. A total of 1,374 organic contaminants were identified, 104 of which occurred frequently (>80% of samples). Comparative analysis revealed that pharmaceutical-related compounds were disproportionately enriched in plateau lakes compared to non-plateau lakes, highlighting a distinct pharmaceutical pollution profile driven by human activities. 60.6% of high-frequency contaminants displayed at least one hazardous PBT trait. While individual ecological risks remained low for 93.0% of quantified compounds (RQ < 0.1), their combined risk (ΣRQs = 2.68) exceeded the threshold, revealing potential mixture toxicity concerns. To support early risk identification, we extracted 51 structure-based risk markers, defined as molecular fragment features linked to PBT traits, including oxygen- and nitrogen-containing chains, heterocyclic groups, and chlorine-substituted aromatic fragments. This study provides new insights into the overlooked chemical risks in high-altitude aquatic ecosystems and underscores the importance of prioritizing pharmaceutical contaminants and their structure-based hazards in future monitoring and regulatory frameworks.