Toenail Manganese: A Sensitive and Specific Biomarker of Exposure to Manganese in Career Welders

Abstract

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.

Keywords: biomarker; exposure assessment; manganese; toenails; welding.

Figure 1.

Comparison of toenail Mn in welders versus controls. Boxplot comparison of the untransformed group toenail Mn concentrations. The whiskers show the range of the data, and top and bottom of each box represents the 1st and 3rd quartiles, respectively. The middle line represents the median, and the diamond represents the mean. Student’s t-test was used to compare the log transformed toenail Mn concentrations. ***P < 0.001.

Figure 2.

ROC curve analysis for toenail Mn to distinguish welders versus controls. Toenail Mn best discriminates between controls and welders at a toenail Mn concentration of 4.14 μg g⁻¹ , correctly classifying subjects with a specificity of 91% and a sensitivity of 94%.

Figure 3.

ROC curve analysis of the sensitivity and specificity of distinguishing subjects with average exposure above versus below the ACGIH TLV of 0.02 mg m⁻³ 7–12 months prior to the nail being clipped.

Figure 4.

Regression plots of log CEI exposure windows versus log toenail Mn concentration. (A) CEI past three months; (B) CEI past 7-12 months; (C) CEI cumulative exposure.