Characterization of manganese exposure biomarkers among welder apprentices

描述（由申请人提供）：尽管有证据表明暴露于焊接烟雾，特别是锰（Mn）会对健康产生不利影响，但暴露的生物标志物知之甚少，并且尚未在纵向设计中进行彻底评估。本研究旨在评估特征明确的吸入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。我们将招募一个80名学徒焊工的队列，并在密集暴露四周后，在队列成员中集中评估空气中Mn浓度和Mn暴露的生物标志物，然后在暴露停止四周后再次评估。在暴露期间，每个参与者每周两次测量个人空气中Mn和其他焊接烟雾成分的暴露量。此外，还将评估Mn和总焊烟颗粒的粒径分布，以确定其对暴露生物标志物的影响。所有受试者的短期暴露生物标志物是血锰和尿锰。将在20名受试者的子集中评估长期暴露的生物标志物是头发Mn和脑组织中Mn浓度的两种测量方法，苍白指数（PI）和T1松弛时间，通过磁共振成像（MRI）评估。还将在所有受试者中评估生物效应的生物标志物，以便与暴露指数进行比较。临床运动功能测试（UDPRS3和Purdue Pegboard测试）将对接受MRI评估的受试者进行，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。所有受试者将通过问卷调查评估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、吸烟状况和既往健康状况。我们将使用混合效应分布滞后模型来模拟空气暴露水平和暴露生物标志物之间的关系，以便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。空气或基于生物标志物的暴露与生物标志物的影响之间的关系也将类似地建模。该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。

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.