Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-products Quality and Safety Control in Storage and Transport Process/Laboratory of Agro-products Quality Safety Risk Assessment, Ministry of Agriculture and Rural Affairs, Beijing, 100193, PR China.
State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China.
Chemosphere. 2023 Jun;325:138431. doi: 10.1016/j.chemosphere.2023.138431. Epub 2023 Mar 16.
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 (LD) values, indicating low toxicity. In contrast, for bee mites and red spider mites, LD 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.
氰氟虫腙（CYF）是一种新型手性杀螨剂，通过与谷胱甘肽 S-转移酶结合，对靶标生物表现出对映体特异性效应。然而，对于非靶标生物对 CYF 的反应，包括对映体选择性毒性，知之甚少。在这项研究中，我们研究了外消旋氰氟虫腙（rac-CYF）及其两种对映体（+）-CYF 和（-）-CYF 对 MCF-7 细胞以及非靶标（蜜蜂）和靶标（蜜蜂螨虫和红叶螨）生物的影响。结果表明，与雌二醇类似，1μM（+）-CYF 促进 MCF-7 细胞的增殖并扰乱其氧化还原稳态，而在高浓度（≥100μM）下，它对细胞活力的负面影响比（-）-CYF 或 rac-CYF 要强得多。在 1μM 浓度下，（-）-CYF 和 rac-CYF 对细胞增殖没有显著影响，但在高浓度（≥100μM）下会导致细胞损伤。对非靶标和靶标生物的急性 CYF 毒性分析表明，对于蜜蜂，所有 CYF 样品的致死剂量（LD）值都很高，表明毒性低。相比之下，对于蜜蜂螨虫和红叶螨，LD 值较低，而（+）-CYF 的 LD 值最低，表明（+）-CYF 的毒性比其他 CYF 样品更高。蛋白质组学分析揭示了与蜜蜂能量代谢、应激反应和蛋白质合成相关的潜在 CYF 靶标蛋白。雌激素诱导的 FAM102A 蛋白类似物的上调表明，CYF 可能通过扰乱雌二醇的产生和改变蜜蜂中依赖雌激素的蛋白质表达来发挥雌激素作用。我们的研究结果表明，CYF 以对映体特异性方式作为非靶标生物的内分泌干扰物发挥作用，这表明对手性农药进行一般性生态风险评估的必要性。
