Abstract

Background
Increasing evidence suggests that welding fume exposure is associated with systemic inflammation. Although celluar metabolites may be associated with inflammation, there is limited information on metabolomic changes during welding fume exposure. Such changes may play an important role in the occurrence, development, and prevention of metal-associated diseases. We aim to investigate human metabolomics changes pre- and post-welding fume exposure.

Methods
This study included 52 boilermakers totally. We collected plasma samples pre- and post-shift welding fume exposure and prepared samples using the automated MicroLab STAR® system. Metabolite concentrations were measured using ultra performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS) methods. Two-way analysis of variance was used to test the significance of metabolite changes with false discovery rate correction.

Results
Analysis detected several metabolic changes after welding fume exposure, mainly involved in the lipid pathway [glucocorticoid class (cortisol, corticosterone, and cortisone), acylcarnitine class, and DiHOME species (9,10-DiHOME and 12,13-DiHOME)], amino acid utilization (isoleucine, proline and phenylalanine), and S-(3-hydroxypropyl) mercapturic acid (3-HPMA). These compounds are all associated with inflammation according to previous studies. Further, additive interaction effects linked smoking and 3-HPMA levels. In the metabolite set enrichment analysis for diseases, the top two disease-associated metabolite pathways were systemic inflammation-related diseases including rheumatoid arthritis and systemic lupus erythematosus.

Conclusions
This global metabolomics study shows evidence that metabolite changes during welding fume exposure are closely associated with systemic inflammation. The altered metabolites detected may be potential health monitoring biomarkers for boilermakers, especially for inflammation-related disease prevention

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