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Combined anti-androgenic effects of mixtures of agricultural pesticides using in vitro and in silico methods

文献类型： 外文期刊

作者： Ma, Mengmeng 1 ; Chen, Chen 1 ; Yang, Guiling 2 ; Wang, Yanhua 2 ; Wang, Tiancai 1 ; Li, Yun 1 ; Qian, Yongzhong 1 ;

作者机构： 1.Chinese Acad Agr Sci, Inst Qual Stand & Testing Technol Agroprod, Key Lab Agroprod Qual & Safety, Minist Agr, 12 Zhong Guan Cun South St, Beijing 100081, Peoples R China

2.Zhejiang Acad Agr Sci, Lab Hangzhou Risk Assessment Agr Prod, Inst Qual & Stand Agr Prod, Minist Agr, Hangzhou 310021, Zhejiang, Peoples R China

关键词： Pesticides mixtures; Combined effects; Anti-androgenic activity; MDA-kb2 cells; Molecular docking

期刊名称：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY （ 影响因子：6.291； 五年影响因子：6.393 ）

ISSN： 0147-6513

年卷期： 2019 年 186 卷

页码：

收录情况： SCI

摘要： Humans and wildlife are continuously and simultaneously exposed to various pesticides that have been identified as endocrine disruptors which interfere with regulations of sexual differentiation and fertility. Low-dose effects of combined exposure from mixtures of pesticides have been extensively reported and need to be addressed in the context of human health risk assessment. The objective of the study is to assess the individual and combined anti-androgenic effects of twelve widely used pesticides in MDA-kb2 cells. The order of potency for seven pesticides with moderate anti-androgenic activities was in the order: fenitrothion > dimethomorph > difenoconazole > bromopropylate > prochloraz > imazalil > endosulfan, which was induced by the androgen receptor (AR) antagonism rather than cytotoxicity (with the exception of endosulfan which exhibited the highest cytotoxicity). The other five pesticides exhibited lower anti-androgenic activities. At 10% of AR antagonistic effect, three mixtures comprised of the seven pesticides (Mix-Ee(10), Mix-EC20, and Mix-EC25) at equi-effect concentrations showed summed concentrations of 6.75E-11, 17.63 and 25.21 mu M, respectively. The combined effects were essentially close to the predicted of concentration addition (CA) at realistically low concentrations. In addition, molecular docking simulation indicated that hydrophobic interaction and polar functional groups of the pesticides contributed to the binding energy, which might be responsible for the AR antagonism. Our findings provide a basis for defining similarly acting antagonists in the context of cumulative risk assessment for pesticides in foods.

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