Risk Assessment for Manufactured Nanoparticles Used in Consumer Products (RAMNUC)

最近的大多数科学努力都集中在检查仅存在于原始材料中的人造纳米颗粒(MNPs)的毒性。由于没有在接触点对MNPs进行评估，这些努力未能解决消费性产品衍生的MNPs是否对公众健康和环境构成关切的相关问题。拟议中的美英联盟“用于消费品的人造纳米颗粒的风险评估(RAMNUC)”提供了一种系统的、多学科的方法，包括实验和计算工具以及项目，用于预测与使用分别含有氧化锌、银和二氧化铈纳米颗粒的选定消费产品相关的潜在人类和环境风险。RAMNUC项目的总体假设是，对于人类和水生动物来说，接触点上的MNPs在物理化学和毒理学性质上都与源头上的MNPs有很大不同(实验室合成或商业获得)。这些差异可能会对MNPs的生物利用度、免疫变化、氧化应激诱导、炎症、疾病过程和其他毒性措施产生重大影响。我们将使用体外和体内实验评估选定的MNPs的细胞内和细胞外生物利用度和毒性，这些MNPs是合成的，并加入到消费产品中。测试的MNPs将根据其物理(例如，大小、形状、团聚/聚集状态)和化学性质(例如，组成、官能化、表面化学)进行控制或很好地表征。因此，我们建议的体外和体内研究将产生基于机制的结果，将毒性效应与MNP的物理化学性质联系起来。RAMNUC联盟还将包括一项新的人体暴露模拟研究，该研究将产生对消费者的MNP暴露的真实估计。这些机械实验产生的数据将被整合到两个现有的源-暴露-剂量-效应建模系统的基于机制的计算模块中，以便在MNP风险评估中进行合理的外推和推广。在机构间专家结构的基础上，RAMNUC联盟作为系统地解决与MNP风险评估相关的复杂问题的模式，并将产生的结果将有助于我们对与使用基于纳米技术的消费产品相关的健康风险的有限了解。

Most recent scientific efforts have focused on examining toxicities of manufactured nano-particles (MNPs) only in source materials. By not evaluating MNPs at the point of exposure, these efforts fail to address the relevant question of whether or not consumer-product-derived MNPs are of concern to public health and the environment. The proposed US-UK consortium, 'Risk Assessment for Manufactured Nanoparticles Used in Consumer Products (RAMNUC)', provides a systematic, multidisciplinary approach, including both experimental and computational tools and projects, for predicting potential human and environmental risks associated with the use of selected consumer products that respectively incorporatezinc oxide, silver, and cerium dioxide nanoparticles. The overall hypothesis of the RAMNUC project is that MNPs at the point of exposure for both humans and aquatic animals will substantially differ in both physicochemical and toxicological properties from MNPs at the source (synthesized in the laboratory or acquired commercially). These differences may have significant consequences with respect to MNPs' bioavailability, alterations of immunity, induction of oxidative stress, inflammation, disease processes, and other toxicity measures. We will assess intracellular and extracellular bioavailability and toxicity of the selected MNPs, as synthesized and as incorporated in consumer products, using both in vitro and in vivo experiments. Tested MNPs will be controlled or well characterized for their physical (e.g., size, shape, state of agglomeration/aggregation) and chemical properties (e.g., composition, functionalization, surface chemistry). Hence, our proposed in vitro and in vivo studies will produce mechanism-based results relating toxic effects to MNP physicochemical properties. The RAMNUC Consortium will also include a novel human exposure simulation study that will produce realistic estimates of MNP exposures to consumers. Data generated from these mechanistic experiments will be integrated into the mechanism-based computational modules of two existing source-to-exposure-dose-to-effects modeling systems, allowing for rational extrapolation and generalization in MNP risk assessment. Built upon the inter-institutional expert structure, the RAMNUC consortium serves as a model for systematically addressing complex problems associated with MNP risk assessment and will generate results that will contribute to our very limited knowledge about health risks associated with the use of nano-technology based consumer products.