Ecotoxicological risk and environmental assessment of mebendazole: A comprehensive study using freshwater snails as non-target species.

The increasing use of veterinary pharmaceuticals, like mebendazole, raises ecological concerns due to their environmental persistence and non-target toxicity, which may negatively affect biodiversity. While its antiparasitic efficacy is well-established, its ecotoxicological effects on non-target gastropods remain unexplored. Here, we identified mebendazole's strong toxicity to freshwater snails, including Pomacea canaliculata (LC₅₀=0.307 mg/L), Biomphalaria glabrata (0.110 mg/L), Biomphalaria straminea (0.138 mg/L) and Cipangopaludina cathayensis (0.205 mg/L), with marked species selectivity, and exhibiting significantly lower toxicity to zebrafish (5.398 mg/L). Integrating transcriptomic analysis, qPCR, enzymatic profiling, histopathology, and molecular docking revealed that mebendazole interacts with the colchicine-binding site of tubulin, disrupting microtubule polymerization in hepatopancreas and kidneys and inducing organelle vacuolization and structural disintegration. Furthermore, mebendazole dysregulated the neuroactive ligand-receptor interaction pathway and altered enzymatic activities (acid phosphatase upregulation, alkaline phosphatase downregulation), indicating neural and metabolic dysregulation and signaling broader metabolic cascades. Field validation at 0.25-0.50 mg/L resulted in high mortality of freshwater snails, highlighting the ecological hazards associated with mebendazole exposure. These findings provide critical evidence of mebendazole's ecological risks to non-target species, highlighting the urgency for dose optimization frameworks and ecosystem-level risk assessments to balance veterinary drug efficacy with environmental sustainability and biodiversity preservation in aquaculture systems.