Silica Exposure & Silicosis: Effect of Mixed Exposures

描述（由申请人提供）： 暴露于结晶二氧化硅和矽肺的发展是不确定的 尽管有一些研究。不确定性是由于以下原因造成的： (a)曝光重建通常基于稀疏数据 显著不确定性;（B）获得累积剂量的剂量重建 工人的肺负担，不考虑同时暴露于 有毒粉尘，归类为未另行分类的颗粒（PNOC）。的 本研究的目的是获得定量的剂量-反应关系 结晶二氧化硅和硅肺之间的联系， 三个问题。北卡罗来纳州的Dusty Trades项目提供了大量数据， 1935 - 1980年人类接触二氧化硅和PNOC及矽肺病例的一组数据 为此目的。一种新的贝叶斯方法， 判断，暴露模型和历史测量将用于 曝光重建将使用药代动力学建模来估计 二氧化硅和PNOC的累积肺剂量，和PNOC，以及巨噬细胞 在这种混合暴露的情况下过载。将进行病例对照研究， 进行比较矽肺和无病参考，并测试 以下假设：（1）累积暴露指标，包括两者 二氧化硅和PNOC，与矽肺的发展比 单独累积二氧化硅暴露，（2）巨噬细胞过载的时间是 （3）在粉尘行业中， 由于暴露于二氧化硅和PNOC的混合物， 与矽肺患者首次发病时间有关。

DESCRIPTION (provided by applicant): The quantitative relationship between exposure to crystalline silica and development of silicosis is uncertain despite a number of studies. The uncertainty is due to the following reasons: (a) exposure reconstructions are typically based on sparse data with significant uncertainty; (b) dose reconstructions that obtain the cumulative lung burden of the worker, do not account for simultaneous exposures to less toxic dusts, categorized as particles not otherwise classified (PNOC). The purpose of this study is to obtain the quantitative dose-response relationship between crystalline silica and silicosis in a manner that addresses the above three issues. The North Carolina Dusty Trades program, provides a large data set of human exposures to silica and PNOC and silicosis cases from 1935-1980 for this purpose. A novel Bayesian methodology that synthesizes expert judgment, exposure models, and historical measurements will be used for exposure reconstruction. Pharmacokinetic modeling will be used to estimate the cumulative lung does of silica and PNOC, and PNOC, and the time to macrophage overload in this mixed exposure scenario. A case-control study will be conducted to compare silicotics and disease free referents and test the following hypotheses: (1) A cumulative exposure metric, which includes both silica and PNOC, is more related to the development of silicosis than cumulative silica exposure alone, (2) The time to macrophage overload is shorter among cases than non-cases employed in the dusty trades, (3) The time to macrophage overload, due to exposures to mixtures of silica and PNOC, is related to the time from first exposure to disease among silicosis cases.