title: Short-term inhalation of stainless steel welding fume causes sustained lung toxicity but no tumorigenesis in lung tumor susceptible A/J mice.
abstract: Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at-risk population for development of lung cancer. Our objective was to expose, by inhalation, lung tumor susceptible (A/J) and resistant C57BL/6J (B6) mice to stainless steel (SS) welding fume containing carcinogenic metals and characterize the lung-inflammatory and tumorigenic response. Male mice were exposed to air or gas metal arc (GMA)-SS welding fume at 40 mg/m(3)×3 h/day for 6 and 10 days. At 1, 4, 7, 10, 14, and 28 days after 10 days of exposure, bronchoalveolar lavage (BAL) was done. Lung cytotoxicity, permeability, inflammatory cytokines, and cell differentials were analyzed. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 78 weeks after 6 and 10 days of exposure. Inhalation of GMA-SS fume caused an early, sustained macrophage and lymphocyte response followed by a gradual neutrophil influx and the magnitudes of these differed between the mouse strains. Monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-α (TNF-α) were increased in both strains while the B6 also had increased interleukin-6 (IL-6) protein. BAL measures of cytotoxicity and damage were similar between the strains and significantly increased at all time points. Histopathology and tumorigenesis were unremarkable at 78 weeks. In conclusion, GMA-SS welding fume induced a significant and sustained inflammatory response in both mouse strains with no recovery by 28 days. Under our exposure conditions, GMA-SS exposure resulted in no significant tumor development in A/J mice.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Morgantown, WV 26505, USA. perdely@cdc.gov
authors.forename: Patti C
authors.initials: PC
authors.lastname: Zeidler-Erdely
authors.forename: Lori A
authors.initials: LA
authors.lastname: Battelli
authors.forename: Sam
authors.initials: S
authors.lastname: Stone
authors.forename: Bean T
authors.initials: BT
authors.lastname: Chen
authors.forename: David G
authors.initials: DG
authors.lastname: Frazer
authors.forename: Shih-Houng
authors.initials: SH
authors.lastname: Young
authors.forename: Aaron
authors.initials: A
authors.lastname: Erdely
authors.forename: Michael L
authors.initials: ML
authors.lastname: Kashon
authors.forename: Ronnee
authors.initials: R
authors.lastname: Andrews
authors.forename: James M
authors.initials: JM
authors.lastname: Antonini
mesh_terms: D000280:Administration, Inhalation; D000395:Air Pollutants, Occupational / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D015197:Carcinogenicity Tests; D016207:Cytokines / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics; D008214:Lymphocytes / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics; D010539:Permeability; D013193:Stainless Steel / Q000633:toxicity*; D018675:Toxicity Tests; D014896:Welding
chemical_list: D000395:Air Pollutants, Occupational; D016207:Cytokines; D018836:Inflammation Mediators; D013193:Stainless Steel