Environmental toxicology of neonicotinoid pesticides: effects on central nervous system function in small mammals

在过去的二十年中，新烟碱类杀虫剂已成为全球五大化学杀虫剂中最重要和增长最快的一类。顾名思义，这些化合物在乙酰胆碱受体（nAchRs）的烟碱亚类中起激动剂作用，导致“过度刺激”，导致神经肌肉麻痹。它们通常用作种子处理，也直接应用于植物，并用作家畜（包括狗和猫）的“跳蚤粉”。虽然nachr是所有脊椎动物（以及无脊椎动物）生理的基础，但新烟碱类已被批准并广泛使用，基于毒理学数据表明，它们与昆虫nachr的结合比哺乳动物nachr具有更高的亲和力；与有机磷或氨基甲酸甲酯等其他种类的杀虫剂相比，具有更大的“安全边际”。然而，这一结论几乎完全是基于对目标物种产生致死的相对效力（LD50）的比较。然而，这些化合物在哺乳动物中的亚致死毒性比较较少。关于这些化合物对脊椎动物的繁殖和免疫抑制的影响的数据有限，但几乎没有关于这些化合物对哺乳动物的神经发育毒性或低剂量暴露的长期影响的数据。对大鼠和小鼠等物种缺乏了解，这些物种会消耗处理过的种子，进而成为高级哺乳动物（如狐狸）或猛禽等鸟类物种（如猫头鹰、鹰等）的猎物，这是我们目前对新烟碱类药物使用对环境影响的理解中的一个主要空白，Gibbons等人（2015年）最近的一篇综述强调了这一点，该综述对这些化合物对脊椎动物的影响提出了严重的问题。

Over the last two decades the neonicotinoids have become the most important and fastest growing of the five major chemical classes of insecticides worldwide. As the name suggests, these compounds act as agonists at the nicotinic subclass of acetylcholine receptors (nAchRs) resulting in “over-stimulation” that leads to neuromuscular paralysis. Commonly used as seed treatments they are also applied directly to plants and are used as “flea powders” for domestic animals including dogs and cats. Although nAChRs are fundamental to the physiology of all vertebrate species (as well as invertebrates) the neonicotinoids have been approved and used widely based on toxicological data indicating that they bind with substantially higher affinity to insect nAChRs than mammalian nAChRs; conferring a larger “margin of safety” than other classes of insecticides such as organophosphates or methylcarbamates. This conclusion, however, is based almost exclusively on comparisons of the relative potency to produce lethality (LD50 ) in the target species. Comparisons of sublethal toxicity of these compounds in mammals, however, are comparatively sparse. There is some limited data of effects on reproduction and immunosuppression in vertebrates but almost no available data on either the neurodevelopmental toxicity of these compounds in mammals or the long-term effects of low dose exposure. This lack of knowledge in species such as rats and mice that would consume treated seed and in turn become prey for higher-order mammals (e.g. foxes) or avian species such as raptors (owls, hawks, etc.) is a major gap in our current understanding of the environmental consequences of neonicotinoid use, and was highlighted in a recent review by Gibbons et al. (2015) that raises serious questions about the effects of these compounds on vertebrate wildlife.