Enantioselective activity and toxicity of chiral acaricide cyflumetofen toward target and non-target organisms

Cyflumetofen (CYF), a novel chiral acaricide, exert enantiomer-specific effects on target organisms by binding to glutathione S-transferase. However, there is limited knowledge regarding the response of non-target organisms to CYF, including enantioselective toxicity. In this study, we investigated the effects of racemic CYF (rac-CYF) and its two enantiomers (+)-CYF and (-)-CYF on MCF-7 cells and non-target (honeybees) and target (bee mites and red spider mites) organisms. The results showed that similar to estradiol, 1 mu M (+)-CYF promoted the prolif-eration and disturbed the redox homeostasis of MCF-7 cells, whereas at high concentrations (>= 100 mu M) it exerted a negative effect on cell viability that was substantially stronger than that of (-)-CYF or rac-CYF. (-)-CYF and rac-CYF at 1 mu M concentration did not significantly affect cell proliferation, but caused cell damage at high concentrations (>= 100 mu M). Analysis of acute CYF toxicity against non-target and target organisms revealed that for honeybees, all CYF samples had high lethal dose (LD50) values, indicating low toxicity. In contrast, for bee mites and red spider mites, LD50 values were low, whereas those of (+)-CYF were the lowest, suggesting higher toxicity of (+)-CYF than that of the other CYF samples. Proteomics profiling revealed potential CYF-targeted proteins in honeybees related to energy metabolism, stress responses, and protein synthesis. Upregulation of estrogen-induced FAM102A protein analog indicated that CYF might exert estrogenic effects by dysregulating estradiol production and altering estrogen-dependent protein expression in bees. Our findings suggest that CYF functions as an endocrine disruptor in non-target organisms in an enantiomer-specific manner, indicating the necessity for general ecological risk assessment for chiral pesticides.

Automated summary

This study investigated the effects of CYF on non-target (honeybees) and target (bee mites and red spider mites) organisms. It was found that (+)-CYF had a stronger negative effect on cell viability compared to (-)-CYF and rac-CYF in MCF-7 cells. Acute toxicity analysis showed that honeybees had low toxicity to CYF, while bee mites and red spider mites were more sensitive to (+)-CYF. Proteomics profiling revealed potential CYF-targeted proteins in honeybees related to energy metabolism, stress responses, and protein synthesis.