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 dow 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-toacquire biomarker of Mn exposure, which is feasible to be used in an industrial welder population.

Periconceptional and prenatal exposure to metal mixtures in relation to behavioral development at 3 years of age

“…Toenails are promising biomarkers of metal exposure for their noninvasive collection, easy storage and handling procedures, and capacity to reflect exposures from months prior. 24 – 27 , 54 For As, 24 , 27 , 55 Mn, 54 – 56 Se, 54 , 57 , 58 and Zn, 54 toenail metal concentrations have demonstrated relations with known exposure sources and/or established biomarkers. For other metals in our study, including Cu 54 and Pb, 59 their validity is less well characterized.…”

Development of a Cumulative Exposure Index (CEI) for Manganese and Comparison with Bone Manganese and Other Biomarkers of Manganese Exposure

“…Our observed FMn of 13.5 µg/g is somewhat higher than FMn values reported among a Brazilian community living near the ferromanganese industry (6.9 µg/g) [ 47 ]; this is not surprising as an occupationally exposed population would be expected to have higher exposure compared to a population with environmental exposure. Studies among United States welders have reported median toenail Mn concentration of 0.81 µg/g [ 55 ] and mean toenail Mn concentration of 6.87 µg/g [ 23 ]. Both measures are lower than our results; this difference could be due to the different occupations (welding versus ferroalloy worker) or the different matrix (toenail versus fingernail).…”

“…There is still very limited evidence regarding cumulative biomarkers of Mn exposure; thus a significant strength of this study is our use of bone manganese. Prior work has introduced CEIs which reflect different time periods [ 14 , 23 ]; our incorporation of two CEIs is also a strength of this analysis as it allowed us to expand upon prior work by demonstrating differences in Mn biomarker-CEI associations based on exposure duration.…”

“…Mn levels in toenails and hair have also been suggested as potential biomarkers of Mn exposure [ 14 , 21 , 22 ]. Two recent studies report that toenail Mn is reflective of external Mn exposure in the prior 7–12 months among welders [ 14 , 23 ]. Hair Mn can also be reflective of several months of Mn exposure [ 21 , 22 ].…”

Dietary Manganese Exposure in the Adult Population in Germany—What Does it Mean in Relation to Health Risks?

“…For example, Ward et al. who studied manganese levels in toenails of welders reported that dietary manganese intake did not significantly influence the manganese levels in toenails …”