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检查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含有多环芳烃和金属，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，职业暴露于MWF发生在高浓度-数量级高于环境空气污染-提供了进一步的支持感兴趣的假设。该建议建立在我们最近的应用g-估计控制健康工人幸存者效应（HWSE）在密歇根州汽车工人暴露于MWF的队列研究，这种因果关系的方法在职业研究中的第一次实施。自我们上次提交以来，基于g-估计报告的新结果表明，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疾病导致的死亡风险。这两种关系只有在调整HWSE后才能检测到。我们现在建议将g-估计框架从二进制暴露扩展到浓度-通过利用MWF（mg/m3）的尺寸分级颗粒质量（PM）的现有定量测量。美国汽车工人联合会-通用汽车公司队列研究由于其规模（近40，000名受试者）、多样性、60年生命状态随访期以及暴露于油基和水基MWF（PM3.5和PM3.5-9.8）的定量指标而成为丰富的资源。使用现有的样品，我们将比较MWF的物理化学组成与空气污染和香烟烟雾-通过PM3.5和PM3.5-9.8的粒度分数-使用常见的分析技术。这些化学结果将补充流行病学调查结果。MWF没有具体的健康标准;它们只受未另行规定的颗粒的一般接触限值的约束。2010年4月，美国汽车工人联合会再次向OSHA申请MWF标准，以哮喘、过敏性肺炎和癌症为基础，强调了这一申请的重要性和及时性。该提案解决了关于一般小颗粒职业暴露的心肺健康风险，特别是MWF的知识方面的关键差距。随着绿色制造业的发展，节能汽车、轻轨汽车和风力涡轮机系统，暴露于MWF的工人数量可能会增加。鉴于广泛的工业接触加上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.