Bioaccumulation and Metabolism of Carbosulfan in Zebrafish (Danio rerio) and the Toxic Effects of Its Metabolites

Carbosulfan is a carbamate insecticide that has been widely used in agriculture. However, studies showed that carbosulfan could be highly toxic to aquatic organisms. The metabolism of carbosulfan in adult zebrafish is still largely unexplored, and the metabolites in individual or in combination may pose a potential threat to zebrafish. In the present study, the bioaccumulation and metabolism of carbosulfan in zebrafish (Danio rerio) were assessed, and the main metabolites, including carbofuran and 3-hydroxycarbofuran, were determined. The toxicity of carbosulfan and its metabolites individually or in combination to zebrafish was also investigated. The bioaccumulation and metabolism experiment indicated that carbosulfan was not highly accumulated in zebrafish, with a bioaccumulation factor of 18 after being exposed to carbosulfan for 15 days, and the metabolism was fast, with a half-life of 1.63 d. The two main metabolites were relatively persistent, with half-lives of 3.33 and 5.68 d for carbofuran and 3-hydroxycarbofuran, respectively. The acute toxicity assay showed that carbofuran and 3-hydroxycarbofuran had 96-h LC50 values of 0.15 and 0.36 mg/L, showing them to be more toxic than carbosulfan (96-h LC50 = 0.53 mg/L). Combinations of binary or ternary mixtures of carbosulfan and its metabolites displayed coincident synergistic effects on acute toxicity, with additive index (AI) values of 1.9-14.3. In the livers and gills of zebrafish exposed to carbosulfan, carbofuran, and 3-hydroxycarbofuran, activities of catalase, superoxide dismutase, and glutathione-S-transferase were significantly changed in most cases, and the content of malondialdehyde was greatly increased, indicating that carbosulfan and its metabolites induced varying degrees of oxidative stress. The metabolites were more persistent and toxic to zebrafish and exhibit coincident synergistic effects in combination. These results can provide evidence for the potential risk of pesticides and highlight the importance of a systematic assessment for the combination of the precursor and its metabolites.