Gene Expression and Therapy Group, King's College London, Faculty of Life Sciences & Medicine, Department of Medical and Molecular Genetics, Guy's Hospital, London, SE1 9RT, UK.
J Appl Toxicol. 2018 Dec;38(12):1483-1491. doi: 10.1002/jat.3651. Epub 2018 Jun 27.
Few studies have investigated non-target effects of neonicotinoid insecticides on mammalian physiology. This is largely due to the widespread perception that their weak affinity for nicotinic acetylcholine receptor subtypes in vertebrates makes mammalian exposures unlikely to pose health risks. To the best of our knowledge, we describe the first investigation evaluating the interaction of seven principal neonicotinoid insecticides (thiamethoxam, imidacloprid, clothianidin, flupyradifurone, dinotefuran, nitenpyram, thiacloprid) with oestrogen and thyroid hormone receptors, as well as their adipogenic effects, in mammalian cell culture assay systems. An E-Screen with MCF-7 and T-Screen with GH3 cells respectively showed a lack of oestrogen and thyroid hormone receptor agonist effects for any of the neonicotinoids tested. Adipogenicity was assessed by the ability to stimulate lipid accumulation in adipocyte differentiated 3T3-L1 cells, with only imidacloprid scoring positive in this assay causing triglyceride accumulation from a concentration of 50 mg l . Data mining of ToxCast high-throughput screening assays revealed that this adipogenic effect of imidacloprid is probably mediated via the pregnane X receptor.
鲜有研究调查新烟碱类杀虫剂对哺乳动物生理学的非靶标效应。这主要是因为人们普遍认为，它们与脊椎动物烟碱型乙酰胆碱受体亚型的亲和力较弱，使得哺乳动物暴露于其中不太可能带来健康风险。据我们所知，我们首次评估了 7 种主要新烟碱类杀虫剂（噻虫嗪、吡虫啉、噻虫胺、氟吡呋喃酮、呋虫胺、涕灭威、噻虫啉）与雌激素和甲状腺激素受体的相互作用，以及它们在哺乳动物细胞培养测定系统中的致脂作用。使用 MCF-7 的 E-Screen 和 GH3 细胞的 T-Screen 分别显示，所测试的任何新烟碱类杀虫剂均无雌激素和甲状腺激素受体激动剂作用。通过刺激脂肪细胞分化的 3T3-L1 细胞中脂质积累的能力来评估致脂作用，只有吡虫啉在该测定中呈阳性，导致 50mg/L 浓度时甘油三酯积累。ToxCast 高通量筛选测定的数据挖掘显示，吡虫啉的这种致脂作用可能是通过妊娠相关 X 受体介导的。
