Abstract
Welders are exposed to high levels of metal particles, consisting mainly of iron and manganese (Mn) oxide. Metal particles, especially those containing Mn can be neurotoxic. In this exploratory study, we evaluated associations between welding and expression of 87 putative neurology-related proteins in serum in a longitudinal approach. The study cohort from southern Sweden included welders working with mild steel (n = 56) and controls (n = 67), all male and non-smoking, which were sampled at two timepoints (T1, T2) 6-year apart. Observed associations in the longitudinal analysis (linear mixed models) were further evaluated (linear regression models) in another cross-sectional sample which included welders (n = 102) and controls (n = 89) who were sampled only once (T1 or T2). The median respirable dust levels for welders after adjusting for respiratory protection was at T1 0.6 (5–95 percentile: 0.2–4.2) and at T2 0.5 (0.1–1.8) mg/m3. The adjusted median respirable Mn concentration was at T2 0.049 mg/m3 (0.003–0.314) with a Spearman correlation between adjusted respirable dust and respirable Mn of rS = 0.88. We identified five neurology-related proteins that were differentially expressed in welders vs. controls in the longitudinal sample, of which one (nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1; NMNAT1) was also differentially expressed in the cross-sectional sample. NMNAT1, an axon-protective protein linked to Alzheimers disease, was upregulated in welders compared with controls but no associations were discerned with degree of exposure (welders only: years welding, respirable dust, cumulative exposure). However, we identified five additional proteins that were associated with years welding (GCSF, EFNA4, CTSS, CLM6, VWC2; welders only) both in the longitudinal and in the cross-sectional samples. We also observed several neurology-related proteins that were associated with age and BMI. Our study indicates that low-to-moderate exposure to welding fumes is associated with changes in circulating levels of neurology-related proteins.
Highlights
It is well-established that high exposure to manganese (Mn) is neurotoxic
We investigated the influence of welding on levels of putative neurology-related serum proteins as a proxy of exposure-related changes in the nervous system
We found that welders exposed to respirable dust concentrations below the current Swedish occupational exposure limit (OEL) (2.5 mg/m3) show change in serum levels of proteins related to neurological processes and neurologic disease
Summary
It is well-established that high exposure to manganese (Mn) is neurotoxic. Mn can accumulate in the brain and cause the condition manganism, a neurological syndrome with symptoms similar to Parkinson’s disease (referred to as Parkinsonism) including tremor, body rigidness, reduced smell, and impaired motor function and balance [1]. Welders have for a long time been considered a risk group of high Mn exposure due to the release of respirable Mn particles during welding [3, 4]. The current OEL for Mn in Sweden is 0.05 mg/m3 (8-h total weight average TWA) as respirable fraction [13]. This is in line with the OEL in the European Union [14] while other countries, such as Germany and Finland, have a lower OEL of Mn in the respirable fraction (0.02 mg/m3) [13]
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