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

最近的科学工作主要集中在研究仅在源材料中制造的纳米颗粒（MNP）的毒性。由于没有在接触点对MNP进行评估，这些努力未能解决消费产品衍生的MNP是否对公共卫生和环境造成影响的相关问题。拟议的美英联盟“消费品中使用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和项目，用于预测与使用选定的消费品相关的潜在人类和环境风险，这些消费品分别是氧化锌、银和二氧化铈纳米颗粒。RAMNUC项目的总体假设是，人类和水生动物接触点的MNP在理化和毒理学特性方面与来源（实验室合成或商业获得）的MNP有很大差异。这些差异可能对MNP的生物利用度、免疫力改变、氧化应激诱导、炎症、疾病过程和其他毒性措施产生显著影响。我们将评估细胞内和细胞外的生物利用度和毒性的选定的MNP，合成和纳入消费品，使用在体外和体内实验。测试的MNP将被控制或很好地表征其物理（例如，尺寸、形状、附聚/聚集状态）和化学性质（例如，组成、功能化、表面化学）。因此，我们拟定的体外和体内研究将产生基于机制的结果，这些结果将毒性作用与MNP理化性质相关。RAMNUC联盟还将包括一项新的人体接触模拟研究，该研究将对消费者接触MNP的情况进行现实的估计。从这些机制实验产生的数据将被整合到两个现有的源-到-消除-剂量-到-效应建模系统的基于机制的计算模块中，从而在MNP风险评估中进行合理的外推和推广。基于机构间专家结构，RAMNUC联盟作为一个模型，系统地解决与MNP风险评估相关的复杂问题，并将产生结果，这将有助于我们对与使用纳米技术相关的健康风险非常有限的知识基于消费品。

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.