Project 2: Toxicity of Metallic Nanoparticles and Carbon Nanotubes

纳米技术对新型化学传感器的开发和应用具有巨大的潜力 超级基金和其他有毒废物场地的补救方法。然而，纳米材料可能会导致 在制造、使用和处置过程中对健康和环境的不利影响 产品生命周期。在新兴的纳米毒理学领域中，一个主要的担忧是将商业 以及非商业性石棉纤维和碳纳米管在几何形状、纵横比、硬度、 表面反应性和生物持久性。黄曲霉基本理化特性的鉴定 需要与其潜在毒性相关的纳米材料来防止对健康的不利影响，同时保留 它们在环境传感和修复方面的独特性能。一个跨学科研究团队，位于 布朗大学包括一名材料科学家，一名毒理学病理学家和一名分子生物学家 开发了一种由闪石石棉纤维、金属纳米颗粒和碳纳米材料组成的面板，并 纳米毒物分析的创新方法。这一模型纳米材料小组将扩大到 包括经过严格毒理学相关表征的选定商业材料 材料特性。碳纳米管是在金属催化剂存在的情况下进行商业生产的 包括单独或组合的Fe、Ni或Y。这项SBRP生物医学研究项目的重点是 含镍纳米材料。难溶的镍化合物被归类为已知的人类 在短期的啮齿动物肺部毒性试验中，致癌物和镍纳米颗粒具有高度毒性。建议数 实验将集中在从金属镍中动员镍的生物利用度和潜在的毒性。 纳米粒子和碳纳米管。三氯甲烷急性毒性的生化机制 或对提纯的商业碳纳米管样品进行评估(具体目标1)。潜力 共同暴露于镍加Y催化剂残留物的协同或拮抗效应将在人体内进行评估 肺上皮细胞(特异靶2)。最后，将对含镍纳米材料进行活化测试 镍致癌的表观遗传途径(具体目标3和4)。这些实验将 提供机械信息，以支持制造方法和后处理的开发 尽量减少或减轻纳米材料对健康和环境的不利影响的步骤。

Nanotechnology has great potential for development and application of novel chemical sensors and remediation approaches at Superfund and other toxic waste sites. However, nanomaterials may cause adverse health and environmental impacts during manufacturing, application, and disposal at the end of product life-cycle. A major concern in the emerging field of nanotoxicology is the analogy between commercial and noncommercial asbestos fibers and carbon nanotubes with respect to geometry, aspect ratio, rigidity, surface reactivity, and biopersistence. Identification of the fundamental physicochemical characteristics of nanomaterials relevant for their potential toxicity is required to prevent adverse health effects while retaining their unique properties for environmental sensing and remediation. An interdisciplinary research team at Brown University including a materials scientist, a toxicologic pathologist, and a molecular biologist has developed a panel of amphibole asbestos fibers, metallic nanoparticles, and carbon nanomaterials and innovative approaches for nanotoxicology assays. This panel of model nanomaterials will be expanded to include selected commercial materials subjected to rigorous characterization of toxicologically relevant materials properties. Carbon nanotubes are commercially produced in the presence of metal catalysts including Fe, Ni, or Y alone or in combination. The focus of this SBRP biomedical research project is on nickel-containing nanomaterials. Poorly-soluble nickel compounds are classified as known human carcinogens and nickel nanoparticles are highly toxic in short-term rodent lung toxicity assays. The proposed experiments will focus on the bioavailability and potential toxicity of nickel mobilized from metallic nickel nanoparticles and carbon nanotubes. The biochemical mechanisms responsible for acute toxicity of asproduced or purified commercial carbon nanotube samples will be assessed (Specific Aim 1). The potential synergistic or antagonistic effects of co-exposures to Ni plus Y catalyst residues will be assessed using human lung epithelial cells (Specific Aim 2). Finally, nickel-containing nanomaterials will be tested for activation of epigenetic pathways involved in nickel carcinogenesis (Specific Aims 3 and 4). These experiments will provide mechanistic information that will enable development of manufacturing methods and post processing steps to minimize or mitigate adverse health and environmental impacts of nanomaterials.