Multilevel assessment of ivermectin effects using different zebrafish life stages

Several studies have shown high toxicity of the veterinary pharmaceutical ivermectin (a semisynthetic avermectin) for aquatic invertebrates however, few data is found for fish species. The present study evaluated the toxicity of ivermectin, to embryos, juveniles, and adults of zebrafish at different levels of biological organization including developmental, behavioural and biochemical. Toxicity tests were performed based on OECD protocols and mortality and behavioural changes were assed for all stages. Biochemical responses were assessed in adults and embryos and included cholinesterases (ChEs), catalase (CAT) (only in embryos), glutathione-S-Transferase (GST), lactate dehydrogenase (LDH) and vitellogenin (VTG) like proteins (only in embryos). Genotoxicity was evaluated in adults. Results showed a higher sensitivity of juvenile and adults of zebrafish (96 h-LC10 values of 14.0 and 55.4 μg/L, respectively). For embryos a 96 h-LC10 of 147.1 μg/L was calculated, moreover developmental anomalies and hatching inhibition were observed only at high concentrations (> 400 μg/L), whereas biochemical and behavioural responses occurred at lower concentrations (< 60 μg/L). Behavioural responses (lethargy) occurred in all life stages. Biochemical responses were observed including the inhibition of GST in adults and changes in ChE, CAT, LDH activities and VTG levels in embryos. Ivermectin did not show to be genotoxic for adult fish. The species sensitivity distribution analysis, based on fish and invertebrate species, indicated a Hazardous Concentration for 5% of the population (HC5) value of 0.057 μg/L; suggesting high sensitivity of both groups to ivermectin and a high risk of this compound to aquatic ecosystems.