Global metabolomic profiling reveals an association of metal fume exposure and plasma unsaturated fatty acids

PLoS One. 2013 Oct 15;8(10):e77413. doi: 10.1371/journal.pone.0077413. eCollection 2013.

Abstract

Background: Welding-associated air pollutants negatively affect the health of exposed workers; however, their molecular mechanisms in causing disease remain largely unclear. Few studies have systematically investigated the systemic toxic effects of welding fumes on humans.

Objectives: To explore the effects of welding fumes on the plasma metabolome, and to identify biomarkers for risk assessment of welding fume exposure.

Methods: The two-stage, self-controlled exploratory study included 11 boilermakers from a 2011 discovery panel and 8 boilermakers from a 2012 validation panel. Plasma samples were collected pre- and post-welding fume exposure and analyzed by chromatography/mass spectrometry.

Results: Eicosapentaenoic or docosapentaenoic acid metabolic changes post-welding were significantly associated with particulate (PM2.5) exposure (p<0.05). The combined analysis by linear mixed-effects model showed that exposure was associated with a statistically significant decline in metabolite change of eicosapentaenoic acid [β(95% CI) = -0.013(-0.022 ≈ -0.004); p = 0.005], docosapentaenoic acid n3 [β(95% CI) = -0.010(-0.018 ≈ -0.002); p = 0.017], and docosapentaenoic acid n6 [β(95% CI) = -0.007(-0.013 ≈ -0.001); p = 0.021]. Pathway analysis identified an association of the unsaturated fatty acid pathway with exposure (p Study-2011 = 0.025; p Study-2012 = 0.021; p Combined = 0.009). The functional network built by these fatty acids and their interactive genes contained significant enrichment of genes associated with various diseases, including neoplasms, cardiovascular diseases, and lipid metabolism disorders.

Conclusions: High-dose exposure of metal welding fumes decreases unsaturated fatty acids with an exposure-response relationship. This alteration in fatty acids is a potential biological mediator and biomarker for exposure-related health disorders.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cohort Studies
  • Fatty Acids, Unsaturated / blood*
  • Gene Regulatory Networks / drug effects
  • Humans
  • Male
  • Metabolomics*
  • Metals / chemistry*
  • Metals / toxicity*
  • Middle Aged
  • Occupational Exposure / adverse effects*
  • Volatilization
  • Welding

Substances

  • Fatty Acids, Unsaturated
  • Metals