Development and Validation of a Novel In Vivo Neutron Activation Analysis Technol

描述（由申请人提供）：数百万工人，包括美国雇用的50多万焊工，已经暴露在过量的金属中。人体和动物研究已将金属接触与神经生理障碍和神经退行性疾病密切联系起来。锰（Mn）是工人中最重要的金属神经毒物之一。许多职业研究已经证实了锰的毒性。然而，锰暴露的阈值、锰的毒性机制以及锰与其他金属（如铅和汞）的相互作用尚不清楚，因此值得进一步研究。评估锰暴露的一个悬而未决的问题是选择合适的生物标志物。人体中超过40%的锰储存在骨骼中，这使得骨锰成为评估长期低剂量暴露（在职业暴露于锰的工人中通常看到的模式）时体内累积锰的理想生物标志物。在本项目中，将开发一种新的中子活化分析技术来无创地定量体内骨中的锰。稍后，我们将把这项技术应用到一个更大的项目中，研究工人群体接触金属混合物可能产生的协同神经毒性效应。我们在本提案中要测试的中心假设是，一种新的可转移中子激活分析技术可以被开发和验证，用于骨中Mn的非侵入性体内定量。我们将进行一系列的蒙特卡罗模拟来选择系统的最佳设计，根据所选的设计建立系统，通过实验优化设计，并开发新的算法来分析数据和校准系统。本项目完成后，将建立一种新的锰累积暴露评估技术。新技术和知识将有助于填补关于适当的金属个体暴露评估的数据空白，并为锰暴露和毒性的早期诊断提供有价值的信息。使用新的生物标志物来了解暴露于锰的神经毒性作用对数百万暴露于锰的工人至关重要，主要有两个原因。首先，神经生理障碍是这些工人的主要健康问题之一；其次，神经损伤降低了工人的生产力，是工伤的主要原因。小灵通398/2590 （Rev. 06/09）页延续格式页

DESCRIPTION (provided by applicant): Millions of workers, including over 500,000 welders employed in the United States, have been exposed to excessive metals. Human and animal studies have strongly linked metal exposure to neurophysiological disorders and neurodegenerative diseases. Manganese (Mn) is one of the most significant metal neuro- toxicants among workers. Many occupational studies have documented Mn toxicity. However, the threshold of Mn exposure, the mechanism of the toxicity of Mn, and the interaction of Mn with other metals (such as lead and mercury) are unknown and therefore deserve further investigation. One pending issue in assessment of Mn exposure pertains to the selection of proper biomarker. Over 40% of Mn in human body is stored in bone, which renders bone Mn to be the ideal biomarkers to assess cumulative Mn in the body with long-term, low dose exposure, a pattern typically seen among workers occupationally exposed to Mn. In this project, a novel neutron activation analysis technology will be developed to noninvasively quantify Mn in bone in vivo. Later we will apply this technology in a larger project to study the possible synergistic neurotoxic effect of the exposure of metal mixtures among worker populations. Our central hypothesis to be tested in this proposal is that a novel transportable neutron activation analysis technology can be developed and validated for non invasive in vivo quantification of Mn in bone. We will conduct a series of Monte Carlo simulations to select the best design of the system, set up the system based on the chosen design, optimize the design with experiments, and develop new algorithms to analyze the data and calibrate the system. At the completion of this project, a novel technology for cumulative Mn exposure assessment will be established. The new technology and knowledge will help to fill the data gaps regarding appropriate individual exposure assessment of metals and to provide valuable information on early diagnose of Mn exposure and toxicity. The use of new biomarker to understand the neurotoxic effects of exposure to Mn is critical to millions of workers who have been exposed to Mn for two main reasons. First, neurophysiological disorder is one of the main health issues for these workers; second, neurological impairment reduces the workers' productivity and is a major cause for work related injuries. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page PUBLIC HEALTH RELEVANCE: The proposed research is relevant to occupation health because it addresses a critical problem regarding the development and validation of a novel technology to assess cumulative exposure to one of the most significant metal neuro-toxicants, manganese, among workers. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page