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

描述(由申请人提供)：数百万名工人，包括在美国雇用的超过500,000名焊工，暴露在过量的金属中。人类和动物的研究已经将金属暴露与神经生理学障碍和神经退行性疾病紧密联系在一起。锰是作业人员中最重要的金属神经毒物之一。许多职业研究都证明了锰的毒性。然而，锰的暴露阈值、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记物。人体中超过40%的锰储存在骨中，这使得骨锰成为评估长期低剂量接触体内累积锰的理想生物标志物，这种模式通常见于职业性接触锰的工人。在本项目中，将开发一种新的中子活化分析技术来无创地在活体内定量骨中的锰。稍后，我们将在一个更大的项目中应用这项技术，研究暴露在工人群体中的金属混合物可能产生的协同神经毒性效应。我们要在这项建议中检验的中心假设是，可以开发和验证一种新的可移动中子激活分析技术，用于无创性地在体内定量骨中的锰。我们将进行一系列蒙特卡罗模拟来选择系统的最佳设计，在所选设计的基础上建立系统，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。在该项目完成后，将建立一种用于累积锰暴露评估的新技术。新的技术和知识将有助于填补有关适当的金属个人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。使用新的生物标记物来了解接触锰的神经毒性效应对数百万接触锰的工人来说至关重要，主要原因有两个。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，是与工作有关的伤害的主要原因。PHS 398/2590(06/09版)页面续格式页面 公共卫生相关性：拟议的研究与职业健康相关，因为它解决了一个关键问题，即开发和验证一种新技术，以评估工人中累积接触最重要的金属神经毒物之一--锰--的情况。PHS 398/2590(06/09版)页面续格式页面

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