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 µM (+)-CYF promoted the proliferation and disturbed the redox homeostasis of MCF-7 cells, whereas at high concentrations (≥100 µM) 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 µM concentration did not significantly affect cell proliferation, but caused cell damage at high concentrations (≥100 µM). 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.