PDF(Pubmed)
Abstract：
A comprehensive review of published and previously unpublished studies was performed to evaluate the neonicotinoid insecticides for evidence of developmental neurotoxicity (DNT). These insecticides have favorable safety profiles, due to their preferential affinity for nicotinic receptor (nAChR) subtypes in insects, poor penetration of the mammalian blood-brain barrier, and low application rates. Nevertheless, examination of this issue is warranted, due to their insecticidal mode of action and potential exposure with agricultural and residential uses. This review identified in vitro, in vivo, and epidemiology studies in the literature and studies performed in rats in accordance with GLP standards and EPA guidelines with imidacloprid, acetamiprid, thiacloprid, clothianidin, thiamethoxam, and dinotefuran, which are all the neonicotinoids currently registered in major markets. For the guideline-based studies, treatment was administered via the diet or gavage to primiparous female rats at three dose levels, plus a vehicle control (≥20/dose level), from gestation day 0 or 6 to lactation day 21. F1 males and females were evaluated using measures of motor activity, acoustic startle response, cognition, brain morphometry, and neuropathology. The principal effects in F1 animals were associated with decreased body weight (delayed sexual maturation, decreased brain weight, and morphometric measurements) and acute toxicity (decreased activity during exposure) at high doses, without neuropathology or impaired cognition. No common effects were identified among the neonicotinoids that were consistent with DNT or the neurodevelopmental effects associated with nicotine. Findings at high doses were associated with evidence of systemic toxicity, which indicates that these insecticides do not selectively affect the developing nervous system.
摘要：
对已发表和以前未发表的研究进行了全面审查，以评估新烟碱类杀虫剂的发育神经毒性（DNT）证据。这些杀虫剂具有良好的安全性，由于它们对昆虫中烟碱受体（nAChR）亚型的优先亲和力，哺乳动物血脑屏障渗透不良，低应用率。然而，对这个问题的审查是有必要的，由于它们的杀虫作用方式和农业和住宅用途的潜在暴露。这篇综述确定了在体外，在体内，以及根据GLP标准和EPA指南使用吡虫啉在大鼠中进行的流行病学研究，啶虫脒,噻虫啉,clothianidin,噻虫嗪,还有恐龙,这些都是目前在主要市场注册的新烟碱。对于基于指南的研究，通过饮食或管饲法以三种剂量水平对初产雌性大鼠进行治疗，加上车辆控制（≥20/剂量水平），从妊娠第0天或第6天到哺乳第21天。F1男性和女性使用运动活动测量进行评估，声惊吓反应，认知，大脑形态测量,和神经病理学。F1动物的主要作用与体重减轻有关（性成熟延迟，减少大脑重量,和形态测量）和高剂量下的急性毒性（暴露期间活性降低），没有神经病理学或认知受损。在与DNT或与尼古丁相关的神经发育作用一致的新烟碱类化合物中没有发现共同作用。高剂量的研究结果与全身毒性的证据有关，这表明这些杀虫剂不会选择性地影响发育中的神经系统。
