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

Abstract

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.

Keywords: Cyflumetofen; Enantioselective toxicity; Estrogen; Honeybees; MCF-7.