Project 2: Toxicity of Metallic Nanoparticles and Carbon Nanotubes

纳米技术在新型化学传感器的开发和应用方面具有巨大的潜力， 在超级基金和其他有毒废物场地采取补救办法。然而，纳米材料可能会导致 在生产、应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的一个主要关注是商业之间的类比 以及非商业石棉纤维和碳纳米管的几何形状、纵横比、刚性 表面活性和生物持久性。基本理化特性的鉴定 需要与其潜在毒性相关的纳米材料，以防止对健康的不利影响， 它们在环境传感和修复方面的独特性能。一个跨学科的研究团队， 布朗大学包括一名材料科学家，一名毒理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， 纳米毒理学检测的创新方法。这个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 材料性能碳纳米管是在金属催化剂存在下商业化生产的 包括Fe、Ni或Y单独或组合。SBRP生物医学研究项目的重点是 含镍纳米材料。难溶性镍化合物被归类为已知的人类 致癌物和镍纳米颗粒在短期啮齿动物肺毒性试验中具有高毒性。拟议 实验将集中于从金属镍中迁移出来的镍的生物利用度和潜在毒性 纳米颗粒和碳纳米管。其急性毒性的生化机制 或纯化的商业碳纳米管样品将进行评估（具体目标1）。的潜在 将使用人体试验评估共暴露于Ni加Y催化剂残留物的协同或拮抗作用。 肺上皮细胞（特异性目标2）。最后，将测试含镍纳米材料的活化性能， 镍致癌作用中的表观遗传途径（具体目标3和4）。这些实验将 提供机械信息，使制造方法和后处理的发展成为可能 采取措施尽量减少或减轻纳米材料对健康和环境的不利影响。

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.