2. Academic Validation
  3. Combined anti-androgenic effects of mixtures of agricultural pesticides using in vitro and in silico methods

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

  • Ecotoxicol Environ Saf. 2019 Dec 30;186:109652. doi: 10.1016/j.ecoenv.2019.109652.
Mengmeng Ma 1,  Chen Chen 2,  Guiling Yang 3,  Yanhua Wang 3,  Tiancai Wang 4,  Yun Li 4,  Yongzhong Qian 5
Affiliations

Affiliations

  • 1 Key Laboratory of Agro-Product Quality and Safety of Ministry of Agriculture, Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, NO.12 Zhong-guan-cun South Street, Haidian District, Beijing, 100081, China. Electronic address: mmmhongxinzmm@sina.com.
  • 2 Key Laboratory of Agro-Product Quality and Safety of Ministry of Agriculture, Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, NO.12 Zhong-guan-cun South Street, Haidian District, Beijing, 100081, China. Electronic address: chenchen02@caas.cn.
  • 3 Lab (Hangzhou) for Risk Assessment of Agricultural Products of Ministry of Agriculture, Institute of Quality and Standard for Agricultural Products, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China.
  • 4 Key Laboratory of Agro-Product Quality and Safety of Ministry of Agriculture, Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, NO.12 Zhong-guan-cun South Street, Haidian District, Beijing, 100081, China.
  • 5 Key Laboratory of Agro-Product Quality and Safety of Ministry of Agriculture, Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, NO.12 Zhong-guan-cun South Street, Haidian District, Beijing, 100081, China. Electronic address: qyzcaas@163.com.
PMID: 31605955 DOI: 10.1016/j.ecoenv.2019.109652
Abstract

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-EC10, Mix-EC20, and Mix-EC25) at equi-effect concentrations showed summed concentrations of 6.75E-11, 17.63 and 25.21 μM, 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.

Keywords

Anti-androgenic activity; Combined effects; MDA-kb2 cells; Molecular docking; Pesticides mixtures.

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