Comparative inflammatory lung response in A/J and C57BL/6J mice exposed to stainless steel welding fume.
Zeidler-Erdely-PC; Young-S; Roberts-JR; Reynolds-SH; Antonini-JM
Toxicologist 2006 Mar; 90(1):216
Several epidemiology studies suggest that inhalation of welding fume (WF) increases lung cancer risk in welders. Stainless steel WF in particular contains both chromium and nickel, two known human carcinogens. However, controlled animal studies are undoubtedly needed to conclusively link WF exposure to increased lung cancer risk. Thus, we initiated a multipart study to compare the inflammatory and tumorigenic responses to WF in a lung tumor susceptible (A/J) and resistant (C57BL/6J) mouse strain. Mice were exposed by pharyngeal aspiration to a total of four doses, one every three days, of 5mg/kg manual metal arc-stainless steel WF (MMA-SS), 1.5 mg/kg soluble chromium (S-Cr), or saline vehicle. Bronchoalveolar lavage (BAL) was performed postmortem at one and four weeks after the final dose. Indices of lung cytotoxicity (lactate dehydrogenase release) and air-blood barrier damage (albumin) were measured in the acellular BAL fluid. The cellular BAL fraction was used to assess inflammation via polymorphonuclear leukocyte (PMN) infiltration. One week post-exposure, MMA-SS WF caused a slightly greater lung cytotoxicity compared to S-Cr, which was more pronounced in A/J versus the C57BL/6J mice. MMA-SS WF, but not S-Cr, caused greater airblood barrier damage in A/J versus C57BL/6J mice. PMN infiltration was significantly elevated compared to control in both mouse strains one-week post-exposure to MMA-SS WF. S-Cr elicited a significant PMN response in A/J mice only at one week post-exposure. By four weeks post-exposure to MMA-SS WF or S-Cr, lung injury in both mouse strains returned to control. PMN infiltration decreased, but remained elevated in both strains exposed to MMA-SS WF, with the A/J mice showing greater inflammation. In conclusion, exposure to MMA-SS WF or S-Cr elicited greater lung injury and inflammation at one versus four weeks in both mouse strains. The A/J strain showed increased susceptibility to lung injury and inflammation compared to the C57BL/6J mice following exposure to MMA-SS WF or S-Cr.
Chromium-compounds; Welding; Welding-industry; Welders-lung; Fumes; Fumigants; Bacterial-infections; Laboratory-animals; Animals; Animal-studies; Pulmonary-system-disorders; Lung-irritants; Lung-disorders; Bacteria; Metals; Stainless-steel; Exposure-levels; Exposure-assessment
Work Environment and Workforce: Mixed Exposures
The Toxicologist. Society of Toxicology 45th Annual Meeting and ToxExpo, March 5-9, 2006, San Diego, California