112 Introduction Electric arc welding joins pieces of metal that are rendered liquid by heat. Arc temperatures above 4000°C heat the base metal pieces to be joined and the consumable elec- trode wire that is continuously fed into the weld. he vapor- ized metals, derived primarily from the wire, react with air and form the fume, which consists of a complex mixture of metal oxides. Depending on the welding process employed, the electrode coating, shielding gases, luxes, base metal, and paint or surface coatings may comprise the welding fume (Antonini, 2003). Among the numerous types of welding processes, gas metal arc (GMA) welding is commonly used in the workplace. GMA welding with stainless steel (SS) wire produces fumes that contain carcinogenic metals such as Cr and Ni, which are primarily in an insoluble form. As a result, the potential carcinogenic nature of SS welding fume has emerged as a chief health concern for weld- ers; this concern remains one of the most important unanswered questions in welding fume-related toxico- logical research. he harmful health efects of welding are well documented and epidemiological evidence RESEARCH ARTICLE Short-term inhalation of stainless steel welding fume causes sustained lung toxicity but no tumorigenesis in lung tumor susceptible A/J mice Patti C. Zeidler-Erdely 1 , Lori A. Battelli 1 , Sam Stone 1 , Bean T. Chen 1 , David G. Frazer 1 , Shih-Houng Young 1 , Aaron Erdely 1 , Michael L. Kashon 1 , Ronnee Andrews 2 , and James M. Antonini 1 1 Health Efects Laboratory Division, National Institute for Occupational Safety and Health, Health Efects Laboratory Division, Morgantown, WV, USA, and 2 Division of Applied Research and Technology, National Institute for Occupational Safety and Health, Cincinnati, OH, USA 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. Keywords: welding, chromium, lung cancer, strain A mice, bronchoalveolar lavage Address for Correspondence: Patti C. Zeidler-Erdely, PhD, National Institute for Occupational Safety and Health, Health Efects Laboratory Division, 1095 Willowdale Road (M/S L2015), Morgantown, WV 26505, Tel: 304-285-5881; Fax: 304-285-5938. E-mail: perdely@cdc.gov (Received 23 June 2010; revised 10 December 2010; accepted 13 December 2010) Inhalation Toxicology, 2011; 23(2): 112–120 © 2011 Informa Healthcare USA, Inc. ISSN 0895-8378 print/ISSN 1091-7691 online DOI: 10.3109/08958378.2010.548838 Inhalation Toxicology Downloaded from informahealthcare.com by CDC Center for Disease Control on 02/10/11 For personal use only.