新烟碱类杀虫剂对稀有鮈鲫内分泌干扰及致癌效应机理研究

The neonicotinoid insecticides, which are outstanding potency to insects,low toxicity to mammals and broad spectrum of activity,have become best-selling insecticide worldwide , and some of them have been detected in surface water at μg/L levels.Although a small amount of data shows that some of neonicotinoid insecticides have toxicity effects in fish, little is known about their endocrine disrupting and carcinogenic effects. In this research, Chinese rare minnow will be selected,and endocrine disruping and carcinogenic effects of neonicotinoid insecticides will be studied by acute and sub-chronic toxicity test.Moreover,different life stages of rare minnow including early-life,junvenile growth and reproduction stages,will be used to confirm endocrine disrupting and carcinogenic effects of neonicotinoid insecticides, which are selected by acute and sub-chronic toxicity test.Multi-generation exposure will be carried out, and population breeding, carcinogenesis and reversibe toxicity effects will be futher study. A series of method such as microarray,growth indexes, hormone levels and histological analysis will be used to study the interactions of endocrine disrupting axes,and the toxicity mechanisms and carcinogenic effects of neonicotinoid insecticides will be focus on different life stages at environmentally concentrations.Based on these results,it will be possible to predict the adverse effects of neonicotinoid insecticides,and provide risk assesment to non-target aquatic organisms.

新烟碱类杀虫剂因高效、低毒和广谱的特点，已成为全球销售量增长最快的一类杀虫剂，在地表水中检出浓度在μg/L级。部分研究表明新烟碱类杀虫剂对水生生物存在毒性效应，但缺少对于鱼类内分泌干扰效应和致癌效应的相关研究。本课题以稀有鮈鲫为实验生物，通过急性毒性和亚慢性毒性实验筛选具有潜在内分泌干扰及致癌效应的杀虫剂；利用不同生命阶段（早期、幼鱼生长和繁殖阶段）暴露实验确定内分泌干扰效应及致癌效应的敏感时期；通过多代长期暴露实验研究种群繁殖、肿瘤发生过程及毒性效应的可逆性。利用功能基因芯片技术，结合生长指标、激素水平分析和组织病理学观察等方法阐明内分泌作用轴之间的相互作用关系，探讨环境浓度新烟碱类杀虫剂对鱼类生长、繁殖等不同生命阶段的毒理作用模式和作用机制以及潜在的致癌效应，为预测新烟碱类杀虫剂危害提供分子毒理学基础，为水环境中非靶标生物毒性风险评估提供依据。

新烟碱类杀虫剂因高效、低毒和广谱的特点得到广泛使用，其环境中尤是水体中具有较高检出率。目前，关于新烟碱类杀虫剂对非靶标生物毒的性数据尚不完善，本研究以本土种稀有鮈鲫和国际通用种青鳉两种小型模式鱼类开展毒性暴露实验。结果表明，噻虫嗪和噻虫胺28d亚慢性毒性暴露可导致稀有鮈鲫成鱼组织损伤，大量内分泌及癌症相关基因在转录水平存在表达差异。噻虫嗪90d暴露导致稀有鮈鲫成鱼肝脏损伤、病变及潜在的繁殖毒性；低剂量处理组中雄鱼体内雌雄激素比例失衡，雌、雄鱼血浆T4浓度下降均表明噻虫嗪具有内分泌干扰效应；功能基因芯片杂交结果表明噻虫嗪抑制稀有鮈鲫胆固醇生物合成和癌症信号通路相关基因表达。噻虫嗪对幼鱼具有致死和致畸效应，同时存在潜在的致癌风险。噻虫嗪暴露导致青鳉早期生命阶段胚胎发育滞后，孵化率降低，平均孵化时间增加。组织病理学分析结果表明其可导致成鱼肝脏、性腺组织受损，并伴随肿瘤发生。转录组测序结果，表明药物处理导致不同处理组及性别间存在表达差异，具有潜在的内分泌干扰效应及致癌效应。研究认为噻虫嗪对非靶标生物鱼类具有潜在的内分泌干扰效应和致癌效应。