Comparison of early vs late pulmonary toxicity in crystalline silica exposed rats

Details

• Personal Author:
  Chen T-h ; Joseph P ; McKinney W ; Orandle M ; Roberts J ; Umbright C
• Description:
  Occupational exposure to respirable crystalline silica can result in silicosis in addition to other adverse health effects. Currently, we investigated and compared the early vs. late pulmonary toxicity induced by inhalation exposure of rats to crystalline silica. In addition, differential expression of specific genes involved in known mechanisms of silicosis viz. inflammation and fibrosis, were determined in the principal target organ of silica toxicity (lung) and a surrogate tissue (blood) in the rats. Rats were exposed by inhalation to air (control) or respirable crystalline silica (Min-U-Sil 5 Silica) at a concentration of 15 mg/m3, for 6 hours per day for 5 days. The rats, following exposure, were maintained under standard animal housing conditions either for 1- or 9-months and euthanized. Silica-induced pulmonary toxicity was determined on the basis of lung histology, and bronchoalveolar lavage (BAL) parameters of toxicity (lactate dehydrogenase activity, number of alveolar macrophages and polymorphonuclear leukocytes, and generation of reactive oxygen species). Differential expressions of specific genes involved in inflammation and fibrosis were determined in the lungs and blood using PCR arrays. Mild inflammation was the only histological change detected in the rat lungs at the 1-month post-exposure period whereas type II pneumocyte hyperplasia and fibrosis were detected in the lungs at the 9-months post-exposure period. Similarly, compared to the early time period, more significant changes in all BAL parameters of toxicity were noticed in the rats at the late post-exposure period. Differential expression of several genes associated with inflammatory response and fibrosis were detected in the lungs and blood of all of the silica exposed rats. However, both the number of significantly differentially expressed genes and the changes in gene expression were greater at the 9-month post-exposure period compared with the 1-month period. Collectively, these results, demonstrated the critical role of post-exposure time interval in the progression of silica-induced pulmonary toxicity in rats. [Description provided by NIOSH]
• Subjects:
  Blood Cytotoxins Environmental Monitoring Enzymes Fibrosis Genetics Histology Immune System Inhalation Exposure Laboratories Lung Lung Diseases Macrophages Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide Toxicology

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• Keywords:
  Alveolar Cells Analytical-processes Biological-effects Cytotoxic Effects Enzyme-activity Exposure-assessment Exposure-levels Gene Expression Genes Immune-reaction Inhalants Laboratory-animals Laboratory-testing Leukocytes Lung Fibrosis Pulmonary-system-disorders Reactive Oxygen Species ROS Silica-dusts Target Organs

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; OSHA Region 3 ; OSHA Region 6 ; 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:
  150
• Issue:
  1
• NIOSHTIC Number:
  nn:20047666
• Citation:
  Toxicologist 2016 Mar; 150(1):216
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 55th Annual Meeting and ToxExpo, March 13-17, 2016, New Orleans, Louisiana
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:eebbdd813660bb7eb4b0dcb02cf58d5f8f91ff2936134508df00453ac6493ece23f91ba16ec19744d7a35955aad44fd7be46aa80adfb6af16b9ca08ce6eca4a8
• Download URL:
  https://stacks.cdc.gov/view/cdc/202674/cdc_202674_DS1.pdf
• File Type:
  [PDF - 441.98 KB ]