Effect of Crystalline Silica and Welding Fume on Lung-Associated Gene Changes in the Rat

Details

• Personal Author:
  Joseph P ; McKinney W ; Sager TM
• Description:
  A major source for the occupational diseases that result in significant morbidity and mortality is exposure to dust often containing toxic agents, such as silica and/or welding fumes. More than 424,000 workers in the U.S. and close to one million workers worldwide perform welding as part of their work duties. Because there is little information regarding the number or the health effects of workers who are exposed to both crystalline silica and welding fumes while carrying out work duties, this study was designed to assess the possible health effects on this unique population of workers. Male Fischer 344 rats weighing approximately 200 g were exposed to air or silica (15 mg/m3, 6 hours/day, 5 days). At 5- and 11-months post-silica exposure, rats received gas metal arc stainless steel welding fumes (20 mg/m3, 4 hours/day, 4 days/week for 4 weeks) by whole-body inhalation. At 1-day post welding fume exposure bronchoalveolar lavage was conducted to assess pulmonary toxicity. Lung expression gene changes were also assessed. The BAL results showed that both silica and welding fume exposures resulted in lung toxicity, at both post-exposure time points. The silica alone, welding fume alone, and the silica + welding fume exposure all resulted in a significant increase in neutrophil and macrophage infiltration at both 6-and 12-months post welding fume-exposure. For example, at 12-months post-exposure silica or welding fume exposure, alone, resulted in neutrophil infiltration of 250 and 625 times, respectively, compared to air controls. The exposure to silica + welding fume, however, caused neutrophil infiltration that was 1392 times higher compared to air controls. The induction of pulmonary inflammation in the exposed rats also caused a significant elevation in the measured cytokine levels, at both post-exposure timepoints. Although silica alone, welding fume alone, and the silica + welding fume exposures all caused this elevation, the elevation was most significant in the silica + welding fume exposure group at both 6- and 12-months post-exposure. Global gene expression changes in the lungs were also detected in all exposure groups, at both 6- and 12-months post-exposure. For example, silica exposure alone resulted in 750 significantly differentially expressed genes (SDEGs), while the welding fume alone group had 2255 SDEGs, and the silica + welding fume exposure had 1910 SDEGs, at 12-month post-exposure. The bioinformatic analysis at 12 months post-exposure showed the top 3 disease and function pathways in the welding fume and welding fume + silica exposure groups are respiratory system tumor, lung tumor, and lung cancer. Additionally, gene transcripts associated with lung cancer development were significantly expressed. Specifically, MMP7, MMP12, and FOLR4 (all genes associated with lung cancer development) have more than 3-fold higher expression rates in the welding fume + silica exposed lungs compare to the silica alone exposed lungs. Past studies have demonstrated that stainless steel welding fumes, which contain significant levels of nickel (Ni) and chromium (Cr), induce more lung injury and inflammation, and are retained in the lungs longer than mild steel welding fumes, which contains mostly iron. Previous studies have shown that Ni and Cr are key contributors to the development of lung cancer in stainless steel welders. Our study, assessing the pulmonary toxicity outcome to a mixed exposure of welding fume and crystalline silica concluded that the combined exposure caused a greater expression of disease/injury markers and functional pathways associated with lung cancer. Taken together, these results suggest a potentially enhanced effect of the silica + welding fume exposure on genes associated with lung tumor and lung cancer development. [Description provided by NIOSH]
• Subjects:
  Animals Blood Immune System Lung Lung Diseases Macrophages Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide Welding

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• Keywords:
  Animal Studies Crystalline Silica Gene Expression Immune Reaction Lung Cancer Lung Tissue Neutrophils Welding Fumes
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  192
• NIOSHTIC Number:
  nn:20067228
• Citation:
  Toxicologist 2023 Mar; 192(S1):466
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2023
• NORA Priority Area:
  Construction
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 62nd Annual Meeting & ToxExpo, March 19-23, 2023, Nashville, Tennessee
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:acd6fb4385500c75f32ffd94cf7b2d93504249e46448dc9a4ff490f2aa604dfbb25455e127ffde57e7ec4220451e10b9884676156afcd464984b6b791cc4a333
• Download URL:
  https://stacks.cdc.gov/view/cdc/231353/cdc_231353_DS1.pdf
• File Type:
  [PDF - 1.07 MB ]