Objectives to describe evidence from human studies of welding fume associated responses predisposing to cancer.

Methods The process of evaluating potential carcinogenicity of occupational exposures entails comprehensive evaluation of in vitro and in vivo studies of cells, animals and human populations. With advancements in our ability to assess exposure-related health affects in humans, we can use molecular epidemiologic methods to study pre-clinical disruptions in homeostasis that can lead to cancer. Welding fumes were evaluated recently in IARC Monograph #118 (2017).

Results With respect to the key characteristics of human carcinogens, adequate data from in vitro and in vivo studies were available to evaluate if welding fumes: induce chronic inflammation; are immunosuppressive; are genotoxic; induce oxidative stress; alter cell proliferation, cell death, and nutrient supply; and modulate receptor-mediated effects. There is strong evidence that mild steel welding fumes, in addition to stainless steel, induce chronic inflammation and are immunosuppressive, and this was confirmed in molecular epidemiology studies of workers. We continued studies using metabolomic approaches in a repeated measures design and found welding fume exposure-related changes in blood in pathways related to disturbances in unsaturated fat metabolism, as in the signaling lipids Sphingosine 1-phosphate (S1P) and sphingasine 1-phosphate (SA1P). Global metabolomic profiling also revealed 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): compounds are all associated with inflammation.

Conclusion There is strong mechanistic evidence in humans for inflammatory and metabolic changes that promote carcinogenicity of welding fumes in humans.