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Genotoxicity and inflammatory potential of stainless steel welding fume particles: an in vitro study on standard vs Cr(VI)-reduced flux-cored wires and the role of released metals.

ABSTRACT: Welders are daily exposed to various levels of welding fumes containing several metals. This exposure can lead to an increased risk for different health effects which serves as a driving force to develop new methods that generate less toxic fumes. The aim of this study was to explore the role of released metals for welding particle-induced toxicity and to test the hypothesis that a reduction of Cr(VI) in welding fumes results in less toxicity by comparing the welding fume particles of optimized Cr(VI)-reduced flux-cored wires (FCWs) to standard FCWs. The welding particles were thoroughly characterized, and toxicity (cell viability, DNA damage and inflammation) was assessed following exposure to welding particles as well as their released metal fraction using cultured human bronchial epithelial cells (HBEC-3kt, 5-100 µg/mL) and human monocyte-derived macrophages (THP-1, 10-50 µg/mL). The results showed that all Cr was released as Cr(VI) for welding particles generated using standard FCWs whereas only minor levels (< 3% of total Cr) were released from the newly developed FCWs. Furthermore, the new FCWs were considerably less cytotoxic and did not cause any DNA damage in the doses tested. For the standard FCWs, the Cr(VI) released in cell media seemed to explain a large part of the cytotoxicity and DNA damage. In contrast, all particles caused rather similar inflammatory effects suggesting different underlying mechanisms. Taken together, this study suggests a potential benefit of substituting standard FCWs with Cr(VI)-reduced wires to achieve less toxic welding fumes and thus reduced risks for welders.

SUBMITTER: McCarrick S

PROVIDER: S-EPMC8380239 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at risk population for the development of lung cancer. Recently, we found that exposure to welding fume caused an acutely greater and prolonged lung inflammatory response in lung tumor susceptible A/J versus resistant C57BL/6J (B6) mice and a trend for increased tumor incidence after stainless steel (SS) fume exposure. Here, our objective was to examine potential strain-dependent differences in the regulation and resolution of the lung inflammatory response induced by carcinogenic (Cr and Ni abundant) or non-carcinogenic (iron abundant) metal-containing welding fumes at the transcriptome level. METHODS: Mice were exposed four times by pharyngeal aspiration to 5 mg/kg iron abundant gas metal arc-mild steel (GMA-MS), Cr and Ni abundant GMA-SS fume or vehicle and were euthanized 4 and 16 weeks after the last exposure. Whole lung microarray using Illumina Mouse Ref-8 expression beadchips was done. RESULTS: Overall, we found that tumor susceptibility was associated with a more marked transcriptional response to both GMA-MS and -SS welding fumes. Also, Ingenuity Pathway Analysis revealed that gene regulation and expression in the top molecular networks differed between the strains at both time points post-exposure. Interestingly, a common finding between the strains was that GMA-MS fume exposure altered behavioral gene networks. In contrast, GMA-SS fume exposure chronically upregulated chemotactic and immunomodulatory genes such as CCL3, CCL4, CXCL2, and MMP12 in the A/J strain. In the GMA-SS-exposed B6 mouse, genes that initially downregulated cellular movement, hematological system development/function and immune response were involved at both time points post-exposure. However, at 16 weeks, a transcriptional switch to an upregulation for neutrophil chemotactic genes was found and included genes such as S100A8, S100A9 and MMP9. CONCLUSIONS: Collectively, our results demonstrate that lung tumor susceptibility may predispose the A/J strain to a prolonged dysregulation of immunomodulatory genes, thereby delaying the recovery from welding fume-induced lung inflammation. Additionally, our results provide unique insight into strain- and welding fume-dependent genetic factors involved in the lung response to welding fume.

Project description:The welding of shear stud connectors to structural steel in construction requires a prolonged stooped posture that exposes ironworkers to biomechanical and welding fume hazards. In this study, biomechanical and welding fume exposures during stud welding using conventional methods were compared to exposures associated with use of a prototype system that allowed participants to weld from an upright position. The effect of base material (i.e. bare structural beam versus galvanized decking) on welding fume concentration (particle number and mass), particle size distribution, and particle composition was also explored. Thirty participants completed a series of stud welding simulations in a local apprenticeship training facility. Use of the upright system was associated with substantial reductions in trunk inclination and the activity levels of several muscle groups. Inhalable mass concentrations of welding fume (averaged over ~18 min) when using conventional methods were high (18.2 mg m(-3) for bare beam; 65.7 mg m(-3) for through deck), with estimated mass concentrations of iron (7.8 mg m(-3) for bare beam; 15.8 mg m(-3) for through deck), zinc (0.2 mg m(-3) for bare beam; 15.8 mg m(-3) for through deck), and manganese (0.9 mg m(-3) for bare beam; 1.5 mg m(-3) for through deck) often exceeding the American Conference of Governmental Industrial Hygienists Threshold Limit Values (TLVs). Number and mass concentrations were substantially reduced when using the upright system, although the total inhalable mass concentration remained above the TLV when welding through decking. The average diameters of the welding fume particles for both bare beam (31±17 nm) through deck conditions (34±34 nm) and the chemical composition of the particles indicated the presence of metallic nanoparticles. Stud welding exposes ironworkers to potentially high levels of biomechanical loading (primarily to the low back) and welding fume. The upright system used in this study improved exposure levels during stud welding simulations, but further development is needed before field deployment is possible.

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Genotoxicity and inflammatory potential of stainless steel welding fume particles: an in vitro study on standard vs Cr(VI)-reduced flux-cored wires and the role of released metals.

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