School of Health Sciences, Purdue University, USA.
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, USA.
Ann Work Expo Health. 2017 Dec 15;62(1):101-111. doi: 10.1093/annweh/wxx091.
Manganese (Mn) is an essential trace metal. It is also a component of welding fume. Chronic inhalation of manganese from welding fume has been associated with decreased neurological function. Currently, there is not a universally recognized biomarker for Mn exposure; however, hair and toenails have shown promise. In a cohort of 45 male welders and 35 age-matched factory control subjects, we assessed the sensitivity and specificity of toenail Mn to distinguish occupationally exposed subjects from unexposed controls. Further we examined the exposure time window that best correlates with the proposed biomarker, and investigated if non-occupational exposure factors impacted toenail Mn concentrations. Toenail clippings were analyzed for Mn using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Exposure to respirable Mn-containing particles (<4 µm) was estimated using an exposure model that combines personal air monitoring, work history information, and dietary intake to estimate an individual's exposure to Mn from inhalation of welding fume. We assessed the group differences in toenail concentrations using a Student's t-test between welders and control subjects and performed a receiver operating characteristic (ROC) curve analysis to identify a threshold in toenail concentration that has the highest sensitivity and specificity in distinguishing welders from control subjects. Additionally, we performed mixed-model regressions to investigate the association between different exposure windows and toenail Mn concentrations. We observed that toenail Mn concentrations were significantly elevated among welders compared to control subjects (6.87 ± 2.56 versus 2.70 ± 1.70 µg g-1; P < 0.001). Our results show that using a toenail Mn concentration of 4.14 µg g-1 as cutoff allows for discriminating between controls and welders with 91% specificity and 94% sensitivity [area under curve (AUC) = 0.98]. Additionally, we found that a threshold of 4.66 µg g-1 toenail Mn concentration enables a 90% sensitive and 90% specific discrimination (AUC = 0.96) between subjects with average exposure above or below the American Conference of Governmental Industrial Hygienist (ACGIH) Threshold Limit Value (TLV) of 0.02 mg m-3 during the exposure window of 7-12 months prior to the nail being clipped. Investigating which exposure window was best reflected by toenail Mn reproduced the result from another study of toenail Mn being significantly (P < 0.001) associated with exposure 7-12 months prior to the nail being clipped. Lastly, we found that dietary intake, body mass index, age, smoking status, and ethnicity had no significant effect on toenail Mn concentrations. Our results suggest that toenail Mn is a sensitive, specific, and easy-to-acquire biomarker of Mn exposure, which is feasible to be used in an industrial welder population.
锰（Mn）是一种必需的微量元素。它也是焊接烟尘的成分之一。慢性吸入焊接烟尘中的锰与神经功能下降有关。目前，尚无普遍认可的锰暴露生物标志物；然而，头发和指甲显示出了希望。在 45 名男性焊工和 35 名年龄匹配的工厂对照受试者的队列中，我们评估了指甲锰作为职业暴露区分暴露组和未暴露对照组的敏感性和特异性。进一步，我们研究了与建议的生物标志物相关性最佳的暴露时间窗口，并调查了非职业暴露因素是否会影响指甲锰浓度。使用电感耦合等离子体质谱法（ICP-MS）分析指甲中的锰。使用一种暴露模型来估计可吸入的含锰颗粒（<4 µm）的暴露，该模型结合了个人空气监测、工作历史信息和饮食摄入数据，以估计个体通过吸入焊接烟尘而吸入的锰的暴露量。我们使用学生 t 检验在焊工和对照组之间评估指甲浓度的组间差异，并进行接收者操作特征（ROC）曲线分析，以确定指甲浓度的阈值，该阈值在区分焊工和对照组受试者方面具有最高的敏感性和特异性。此外，我们还进行了混合模型回归分析，以调查不同暴露窗口与指甲锰浓度之间的关联。我们观察到，与对照组相比，焊工的指甲锰浓度明显升高（6.87 ± 2.56 与 2.70 ± 1.70 µg g-1；P < 0.001）。我们的结果表明，使用指甲锰浓度为 4.14 µg g-1 作为截断值，可以在 91%特异性和 94%敏感性的情况下区分对照组和焊工[曲线下面积（AUC）= 0.98]。此外，我们发现指甲锰浓度为 4.66 µg g-1 的阈值可实现 90%的敏感性和 90%的特异性区分（AUC = 0.96），用于区分暴露于美国政府工业卫生学家会议（ACGIH）阈值（0.02 mg m-3）以下或以上的受试者在指甲被剪下之前的 7-12 个月暴露窗口内。研究哪个暴露窗口最能反映指甲锰的情况，与指甲锰与指甲被剪下前 7-12 个月的暴露显著相关（P < 0.001）的另一项研究结果一致。最后，我们发现饮食摄入、体重指数、年龄、吸烟状况和种族对指甲锰浓度没有显著影响。我们的结果表明，指甲锰是一种敏感、特异且易于获得的锰暴露生物标志物，适用于工业焊工人群。
