Office of Research and Development, National Center for Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Toxicol Sci. 2013 Aug;134(2):225-42. doi: 10.1093/toxsci/kft109. Epub 2013 May 24.
Increasing use of engineered nanomaterials (ENM) in consumer products and commercial applications has helped drive a rise in research related to the environmental health and safety (EHS) of these materials. Within the cacophony of information on ENM EHS to date are data indicating that these materials may be neurotoxic in adult animals. Evidence of elevated inflammatory responses, increased oxidative stress levels, alterations in neuronal function, and changes in cell morphology in adult animals suggests that ENM exposure during development could elicit developmental neurotoxicity (DNT), especially considering the greater vulnerability of the developing brain to some toxic insults. In this review, we examine current findings related to developmental neurotoxic effects of ENM in the context of identifying research gaps for future risk assessments. The basic risk assessment paradigm is presented, with an emphasis on problem formulation and assessments of exposure, hazard, and dose response for DNT. Limited evidence suggests that in utero and postpartum exposures are possible, while fewer than 10 animal studies have evaluated DNT, with results indicating changes in synaptic plasticity, gene expression, and neurobehavior. Based on the available information, we use current testing guidelines to highlight research gaps that may inform ENM research efforts to develop data for higher throughput methods and future risk assessments for DNT. Although the available evidence is not strong enough to reach conclusions about DNT risk from ENM exposure, the data indicate that consideration of ENM developmental neurotoxic potential is warranted.
随着工程纳米材料（ENM）在消费品和商业应用中的使用日益增多，有关这些材料环境健康和安全（EHS）的研究也有所增加。在迄今为止有关 ENM EHS 的大量信息中，有数据表明这些材料在成年动物中可能具有神经毒性。在成年动物中，炎症反应升高、氧化应激水平增加、神经元功能改变以及细胞形态改变的证据表明，在发育过程中接触 ENM 可能会引发发育性神经毒性（DNT），尤其是考虑到发育中的大脑对某些有毒物质的敏感性更高。在这篇综述中，我们在确定未来风险评估的研究空白的背景下，检查了与 ENM 发育神经毒性效应相关的现有发现。提出了基本的风险评估范式，重点是制定问题以及对 DNT 的暴露、危害和剂量反应进行评估。有限的证据表明，宫内和产后暴露是可能的，而少于 10 项动物研究评估了 DNT，结果表明突触可塑性、基因表达和神经行为发生了变化。根据现有信息，我们使用当前的测试指南来突出研究空白，这些空白可能为开发更高通量方法的数据和 DNT 的未来风险评估提供信息。尽管现有证据还不够充分，无法就 ENM 暴露导致 DNT 的风险得出结论，但数据表明，有必要考虑 ENM 的发育神经毒性潜力。
