Computational risk assessment, occurrence and seasonality of illicit drugs in the aquatic biota of the Biobío Region, Chile.

Illicit drugs and their metabolites are increasingly detected in aquatic environments, yet their ecotoxicological impacts remain poorly understood, particularly in South America. This study assessed the environmental risks of cocaine (COC), benzoylecgonine (BENZ), and 11-nor-9Δ-tetrahydrocannabinol carboxylic acid (THCCOOH) in the Biobío Region, Chile, by integrating measured concentrations from influents of 26 wastewater treatment plants with in silico toxicity predictions from OECD Quantitative Structure-Activity Relationship (QSAR) Toolbox, VEGA, and Ecological Structure-Activity Relationship (ECOSAR). Seasonal trends were evaluated using dry- (Sep 2022-Mar 2023) and wet-season (Apr-Aug 2023) datasets, alongside a permutational multivariate analysis of variance (PERMANOVA) to test for significant seasonal differences, and non-metric multidimensional scaling (NMDS) to visualize patterns in illicit drug occurrence. BENZ was the most frequently detected compound (>90% of samples in both seasons), while COC detections dropped to 48.6% in the dry season. COC/BENZ ratios were significantly higher in the dry season, suggesting possible direct disposal or seasonal consumption shifts. QSAR predictions indicated limited experimental data availability, with THCCOOH generally predicted as most toxic across aquatic trophic levels. Risk quotient (RQ) analyses identified "Acute High Risk" and "Chronic Risk" scenarios primarily for Daphnia magna, with notable seasonal variation. COC and BENZ exhibited parallel seasonal patterns, whereas THCCOOH displayed inverse trends, likely linked to its higher log Kow. Findings highlight the role of seasonality in modulating environmental concentrations and risks of illicit drugs, the utility and limitations of computational tools in ecological risk assessment, and the need for targeted monitoring to mitigate emerging contaminant impacts in freshwater ecosystems.