Characterization of manganese exposure biomarkers among welder apprentices

描述（由申请人提供）：尽管有证据表明焊接烟尘尤其是锰（Mn）暴露会对健康产生不良影响，但对暴露的生物标志物了解甚少，并且尚未在纵向设计中进行彻底评价。本研究旨在评估充分表征的吸入性锰暴露与锰暴露的一些短期和长期生物标志物之间的关系。我们将招募一组80名学徒焊工，并集中评估空气中的锰浓度和锰暴露的生物标志物之间的队列成员超过四周的密集暴露，然后再次暴露停止后四周。在暴露期间，将每周两次测量每个参与受试者的Mn和焊接烟尘其他成分的个人空气暴露。此外，还将评估Mn和总焊接烟尘颗粒的粒度分布，以确定其对暴露生物标志物的影响。在所有受试者中评价的短期暴露生物标志物为血Mn和尿Mn。将在20名受试者的亚组中评估暴露的长期生物标志物是头发Mn和脑组织中Mn浓度的两个测量值，即通过磁共振成像（MRI）评价的苍白球指数（PI）和T1弛豫时间。还将在所有受试者中评价生物效应的生物标志物，以与暴露指数进行比较。将对接受MRI评价的受试者进行临床运动功能测试（UDPRS 3和Purdue Pegboard测试），以探索脑组织中Mn暴露的生物标志物与运动任务表现之间的关系。将通过问卷调查评估所有受试者的可能影响空气和生物标志物浓度之间关系的个体特征，包括饮食、吸烟状态和既存健康状况。我们将使用混合效应分布滞后模型对空气暴露水平和暴露生物标志物之间的关系进行建模，以描述和测试最近和累积暴露对每个观察到的生物标志物的贡献。空气或生物标志物暴露与效应生物标志物之间的关系将以类似方式建模。这些结果将为未来焊接或锰相关健康影响研究中的流行病学暴露评估提供信息，并为各种暴露背景下锰生物标志物结果的解释提供指导。 公共卫生相关性：虽然有证据表明，职业暴露于吸入锰的结果对健康的不利影响，暴露于锰的生物标志物知之甚少。这项研究将探讨空气中锰浓度和各种锰暴露的生物标志物之间的关系，包括血液，尿液，头发和脑组织（通过磁共振成像评估），随着时间的推移，在一组学徒焊工。

DESCRIPTION (provided by applicant): Despite evidence of adverse health effects resulting from exposure to welding fume and in particular to manganese (Mn), biomarkers of exposure are poorly understood and have not been thoroughly evaluated in a longitudinal design. This study is designed to evaluate the relationship between well-characterized inhaled Mn exposure and a number of short- and long-term biomarkers of Mn exposure. We will recruit a cohort of 80 apprentice welders and intensively evaluate airborne Mn concentrations and biomarkers of Mn exposure among members of the cohort over four weeks of intensive exposure, and then again four weeks after exposure cessation. Personal airborne exposures to Mn and other components of welding fume will be measured twice weekly on each participating subject during the exposure period. In addition, the particle size distribution of Mn and total welding fume particulate will be evaluated to determine its influence on exposure biomarkers. Short-term biomarkers of exposure to be evaluated in all subjects are blood Mn and urine Mn. Long-term biomarkers of exposure which will be assessed among a subset of 20 subjects are hair Mn and two measures of Mn concentration in brain tissue, the Pallidal Index (PI) and T1 relaxation time, evaluated via magnetic resonance imaging (MRI). Biomarkers of biological effect will also be evaluated among all subjects for comparison with the exposure indices. Clinical motor function tests (UDPRS3 and Purdue Pegboard test) will be administered to subjects undergoing MRI evaluation to allow for exploration of the relationship between biomarkers of Mn exposure in brain tissue and motor task performance. Individual characteristics with the potential to influence the relationship between air and biomarker concentrations, including diet, smoking status, and pre-existing health conditions, will be assessed in all subjects via questionnaire. We will model the relationships between air exposure levels and exposure biomarkers using a mixed effects distributed lag model to allow for description and testing of the contribution of recent and cumulative exposure on each observed biomarker. Relationships between air or biomarker-based exposures and biomarkers of effect will be similarly modeled. The results will inform future epidemiological exposure assessment in studies of welding or Mn- related health effects and provide guidance on interpretation of Mn biomarker results in a variety of exposure contexts. PUBLIC HEALTH RELEVANCE: Although there is evidence that occupational exposure to inhaled manganese results in adverse health effects, biomarkers of exposure to manganese are poorly understood. This study will explore the relationships between airborne manganese concentrations and a variety of biomarkers of manganese exposure, including blood, urine, hair, and brain tissue (assessed via magnetic resonance imaging), over time in a group of apprentice welders.