Combined Toxicity Of Typical Synthetic Pyrethroids And Typical Metals To Zebrafish

Pesticides and heavy metals are important pollutants in aquatic ecosystem. Synthetic pyrethroids, a class of wide-spectrum and high-efficience bionic pesticides, show low toxicity to avian and mammals but high toxicity to aquatic organisms, like fish. In recent years, with the increasing use amount, pyrethroids have been extensively detected in the water column, posing great risk to aquatic wildlife. Based on the chemical structure, pyrethroids are divided into Ⅰ type and Ⅱ type. Comparatively, pyrethroids of type Ⅱ are of greater insecticidal potency and higher photostability. In the water system polluted with pyrethroids, co-occurrence of both types has been observed. There is great need and environmental significance to assess the combined effects of type Ⅰ and type Ⅱ pyrethroids to aquatic organisms. Heavy metal is another common class of pollutant in the water column which can be easily bioaccumulate in the organisms. Great concern has been aroused over the toxic effects of heavy metal on aquatic species. In the areas of intensive agriculture and industry, coexistence of pyrethroids and heavy metals has been detected. Assessment of the interactive effect of pyrethroids and metals is essential. Additionally, pyrethroids are an important class of chiral pesticides with 1-3 chiral centers in the chemical structure. Biological effects of the single enantiomer may be disrupted by other substance, such as inorganic metals. Therefore, there is great significance and challenge evaluating the effects of heavy metal on the toxicity of chiral pyrethroids.(1) Defect rates of embryos exposed to low concentrations of single permethrin (Ⅰ type pyrethroid, PM, ≤300μg/L) or cypermethrin (Ⅱ type pyrethroid, CP,≤30 μg/L) exhibited no statistically significant difference from the control, while the application of combination of PM and CP at sublethal concentrations resulted in deleterious effects on zebrafish embryonic development. Co-treatment of embryos with the specific sodium channel blocker MS-222 and pyrethroids (individuals or the mixture) caused a decline in the incidences of body axis curvature and spasms compared to treatment of animals with pyrethroids alone, suggesting that the developmental toxicity of PM and CP to zebrafish was related to disruption of ion channels. We further revealed that mixture of the two pyrethroids caused greater down-regulation in the mRNA levels of proneural genes. The individual pesticides had no effect on the activity of superoxide dismutase (SOD), while the mixture exposure caused significant induction. Treatment with CP or the mixture increased the activity of catalase (CAT). Taken together, our data indicated that the mixture of PM and CP caused higher incidence of morphological defects, greater inhibition in proneural herbicide dichlorprop and should be considered in future risk assessment.(2) Exposure to cypermethrin (CP) and cadmium (Cd) alone both induced the occurrence of crooked body, pericardial edema and non-inflation of swimbladder, while treatment with CP but not Cd also caused spasms in embryonic zebrafish. Co-exposure to CP and Cd produced synergistic effects on the occurrence of developmental defects. The addition of Cd significantly potentiated CP-induced spasms and caused more oxidative stress in zebrafish larvae. Additionally, coexposure to CP and Cd caused increased mortality in adult zebrafish. CP-mediated induction of transcription levels and catalytic activities of cytochrome P450 (CYP) enzyme was significantly down-regulated by Cd in both larvae and adults. Chemical analysis showed in vitro elimination of CP by CYP1A1 was inhibited by Cd. The addition of Cd caused an elevation of in vivo CP residue levels in the mixture-exposed animals. These results suggest the enhanced toxicity of CP results from the inhibitory effects of Cd on CYP-mediated biotransformation of this pesticide. Our findings suggested that heavy metals have the potential to disrupt the toxicity of pyrethroids to aquatic organisms, and it is necessary to evaluate the combined effect of these contaminants on aquatic species.(3) Cis-bifenthrin (cis-BF) is one of the most widely used pyrethroid insecticide. Racemic cis-BF (rac-cis-BF) contains two optical enantiomers:R-cis-BF and S-cis-BF. At the environmental relevant levels, coexposure to Cd/Cu/Pb (10μg/L) and rac-cis-BF (1μg/L) or R-cis-BF (1μg/L) caused increased 72 h mortality in zebrafish. Exposure to rac-cis-BF alone resulted in higher proportion of R-cis-BF residues in the fish. Additionally, the other antipode was detected in zebrafish exposed to one antipode, suggesting isomerization and racemization of BF in the organism. EF (enantiomer fraction) value in rac-cis-BF+Cd/Cu/Pb group was lower than that detected in single rac-cis-BF exposure group. Compared with R-cis-BF alone exposure group, EF value in R-cis-BF+Cd decreased, while no significant change of EF was observed in R-cis-BF+Cu/Pb groups.In S-cis-BF+Cu/Pb groups, EF values were much lower than that in single S-cis-BF group. While EF value in S-cis-BF+Cd was not significantly different from that in the S-cis-BF group. These findings suggested that the addition of heavy metals resulted in higher proportion of R-cis-BF that is more toxic than the other enantiomer, which may be the underlying mechanisms accounting for the enhanced toxicity induced by the combination of BF and heavy metals. This study indicated that the disrupted effects of the coexisted contaminant should be considered in the assessment of enantioselective toxicity of chiral pyrethroids.