Healthy Worker Effect, Occupational Exposure to PM and Cardiopulmonary Mortality

描述（由申请人提供）：本修订提案的目的是研究长期定量暴露于金属加工液（MWF）与心肺死亡率之间的关系。MWF是油和化学添加剂的复杂混合物，广泛用于工业环境中冷却和润滑金属加工操作。油基MWF含有多芳烃和金属，这些成分也存在于交通相关空气污染的细颗粒物（PM2.5）中，这是一种公认的心血管危害。此外，职业性接触MWF发生在高浓度下——比环境空气污染高几个数量级——为相关假设提供了进一步的支持。该建议建立在我们最近在密歇根州暴露于MWF的汽车工人队列研究中应用g估计来控制健康工人幸存者效应（HWSE）的基础上；这是这种因果方法在职业研究中的首次应用。自我们之前的报告以来，基于g估计的新结果表明，暴露于油基MWF的持续时间显著增加了缺血性心脏病和慢性阻塞性肺病的死亡风险。这两种关系仅在调整HWSE后才被发现。我们现在建议将g估计框架从二元暴露扩展到浓度-利用现有的MWF的粒径分馏颗粒质量（PM） （mg/m3）的定量测量。美国汽车工人联合会-通用汽车队列研究是一个丰富的资源，因为它的规模（近40,000名受试者），多样性，60年的生命状态随访期，以及暴露于石油和水基MWF （PM3.5和PM3.5-9.8）的定量指标。利用现有的样品，我们将使用常见的分析技术，通过PM3.5和PM3.5-9.8的颗粒大小来比较MWF与空气污染和香烟烟雾的物理化学成分。这些化学结果将补充流行病学的发现。对MWF没有具体的卫生标准；它们仅受未受其他规定的颗粒的一般暴露限值的约束。2010年4月，美国汽车工人联合会再次向OSHA请愿，要求在哮喘、过敏性肺炎和癌症的基础上制定MWF标准，强调了这一申请的重要性和及时性。该建议解决了关于一般职业接触小颗粒，特别是接触微空气的心肺健康风险的知识方面的一个重大空白。随着绿色制造业的发展，例如节能汽车、轻轨汽车和风力涡轮机系统，接触MWF的工人人数可能会增加。考虑到广泛的工业接触和这些慢性病的高发病率，即使死亡率略有上升也意味着巨大的职业负担。

DESCRIPTION (provided by applicant): The goal of this revised proposal is to examine the relation between long-term quantitative exposure to metalworking fluids (MWF) and cardiopulmonary mortality. MWF are complex mixtures of oils and chemical additives widely used in industrial settings to cool and lubricate metal machining operations. Oil-based MWF contain polyaromatic hydrocarbons and metals, constituents also present in the fine particulate mass (PM2.5) of traffic-related air pollution, a well established cardiovascular hazard. Moreover, occupational exposure to MWF occurs at high concentrations - orders of magnitude higher than ambient air pollution - providing further support for the hypotheses of interest. The proposal builds on our recent application of g-estimation to control for healthy worker survivor effect (HWSE) in a cohort study of Michigan autoworkers exposed to MWF; the first implementation of this causal method in an occupational study. New results based on g-estimation reported since our previous submission suggest that duration of exposure to oil-based MWF significantly increases the risk of mortality due to both ischemic heart disease and chronic obstructive pulmonary disease. Both relationships were only detected after adjustment for HWSE. We now propose to extend the g-estimation framework from binary exposure to concentration - by taking advantage of existing quantitative measures of size fractionated particle mass (PM) of MWF (mg/m3). The United Autoworkers - General Motors cohort study is a rich resource due to its size (almost 40,000 subjects), diversity, 60 year vital status follow-up period, and quantitative metrics of exposure to oil-and water-based MWF (PM3.5 and PM3.5-9.8). Using available samples, we will compare the physicochemical composition of MWF with air pollution and cigarette smoke - by particle size fractions of PM3.5 and PM3.5-9.8 - using common analytic techniques. These chemical results will complement the epidemiologic findings. There is no specific health standard for MWF; they are subject only to generic exposure limits for particles not otherwise regulated. In April 2010, the United Autoworkers again petitioned OSHA for a MWF standard on the basis of asthma, hypersensitivity pneumonitis and cancer, underscoring the significance and timeliness of this application. The proposal addresses a critical gap in knowledge about the cardiopulmonary health risks of occupational exposures to small particles in general, and to MWF in particular. With the growth of the green manufacturing sector, e.g., fuel efficient automobiles, light rail cars and wind turbine systems, the number of workers exposed to MWF will likely increase. Given widespread industrial exposure combined with the high incidence of these chronic diseases, even a modestly elevated mortality rate ratio would imply a substantial occupational burden.