Abstract
BackgroundWelding fume has been categorized as "possibly carcinogenic" to humans. Our objectives were to characterize the lung response to carcinogenic and non-carcinogenic metal-containing welding fumes and to determine if these fumes caused increased lung tumorigenicity in A/J mice, a lung tumor susceptible strain. We exposed male A/J and C57BL/6J, a lung tumor resistant strain, by pharyngeal aspiration four times (once every 3 days) to 85 μg of gas metal arc-mild steel (GMA-MS), GMA-stainless steel (SS), or manual metal arc-SS (MMA-SS) fume, or to 25.5 μg soluble hexavalent chromium (S-Cr). Shams were exposed to saline vehicle. Bronchoalveolar lavage (BAL) was done at 2, 7, and 28 days post-exposure. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 48 and 78 weeks post-exposure.ResultsBAL revealed notable strain-dependent differences with regards to the degree and resolution of the inflammatory response after exposure to the fumes. At 48 weeks, carcinogenic metal-containing GMA-SS fume caused the greatest increase in tumor multiplicity and incidence, but this was not different from sham. By 78 weeks, tumor incidence in the GMA-SS group versus sham approached significance (p = 0.057). A significant increase in perivascular/peribronchial lymphoid infiltrates for the GMA-SS group versus sham and an increased persistence of this fume in lung cells compared to the other welding fumes was found.ConclusionThe increased persistence of GMA-SS fume in combination with its metal composition may trigger a chronic, but mild, inflammatory state in the lung possibly enhancing tumorigenesis in this susceptible mouse strain.
Highlights
Welding fume has been categorized as "possibly carcinogenic" to humans
Bronchoalveolar lavage (BAL) findings 2 days after exposure: gas metal arcmild steel (GMA-mild steel (MS)) and gas metal arc (GMA)-stainless steel (SS) GMA-MS welding fume caused a similar degree of lung cell death in both strains and no significant epithelial damage compared to the corresponding sham (Table 1)
The recovered BAL % polymorphonuclear leukocytes (PMN) was two-fold greater in the A/J compared to the C57BL/6J strain while lymphocytes were not elevated in response to this fume in either strain
Summary
Welding fume has been categorized as "possibly carcinogenic" to humans. Our objectives were to characterize the lung response to carcinogenic and non-carcinogenic metalcontaining welding fumes and to determine if these fumes caused increased lung tumorigenicity in A/J mice, a lung tumor susceptible strain. The International Agency for Research on Cancer has deemed welding fume a group 2B agent, defined as a mixture "possibly carcinogenic" to humans [1] This categorization of welding fume carcinogenicity, was based on limited evidence in humans and a lack of animal data. Debate exists over which type of welding may pose the greater risk Fumes from both non-carcinogenic metal-containing mild steel (MS) and carcinogenic metal-containing stainless steel (SS) welding wire have been shown to increase lung cancer risk in welders [6,7]. For these reasons, we initiated a multipart study to determine the carcinogenic potential of SS and MS welding fumes in an animal model
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