Time Course of Pulmonary Responses to Inhalation of Crystalline Silica in the Rat Model: Evidence for a Threshold Burden Beyond Which Silicosis Progresses Without Further Exposure

Details

• Personal Author:
  Castranova, Vincent ; Hubbs, Ann F. ; Millecchia L ; Porter DW ; Willard P
• Description:
  Exposure to crystalline silica has been associated with pulmonary disease in sand blasters, rock drillers, miners, tunnelers, granite workers, etc. However, the molecular and cellular events which trigger the shift from an exposed state to a pathologic condition remain to be elucidated. This study investigated the relationship between silica-induced pulmonary responses (lung damage, inflammation and fibrosis) and nitric oxide production in rats exposed by inhalation to crystalline silica (15 mg/m3, 6 hr/day, 5 days/week, for 116 exposure days). In addition, recovery (a decrease) or progression (an increase) of pulmonary pathology was evaluated in rats exposed to silica for 20, 40 or 60 days and sacrificed either immediately or 36 days after exposure. Markers of pulmonary inflammation and damage were significantly elevated by 5-16 days of exposure and were maintained at this relatively stable new set point through 40 days of exposure. Exposure beyond 40 days was associated with an explosive increase in inflammation and damage. Only during this explosive inflammatory phase was the development of granulomas and fibrosis in the lung parenchyma and the bronchus-associated lymphoid tissue (BALT) observed. No recovery of pulmonary inflammation and damage was noted in rats exposed for 20 days and sacrificed 36 days after the cessation of exposure. In contrast, after 40 or 60 days of silica exposure, inflammation, damage and granulomas progressed during the 36 day period of non-exposure. Nitric oxide (NO) products in the bronchoalveolar lavage fluid exhibited a time course which preceded fibrosis and was similar to that for inflammation and damage, i.e., a significant but stable elevation from 5-40 days of exposure followed by an explosive increase thereafter. As with inflammation and damage, during the 36 day period of non-exposure NO production did not recover after a 20 day exposure and progressed after a 40 day exposure. Immunohistochemical analysis of pulmonary inducible NO synthase (iNOS) and nitrotyrosine identified elevated iNOS and NO-induced damage in alveolar macrophage and type II cells which co-localized with areas of silica deposition, phospholipidosis, and granulomatous lesions. Progression of iNOS staining after cessation of exposure was evident in alveolar macrophages and BALT. The results suggest that there is a threshold burden of silica beyond which disease progresses without further exposure, and that NO production appears to be associated both temporally and spatially with the pathogenic response to silica exposure. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Animals Dust Laboratories Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide

  More +
• Keywords:
  Animal-studies Dust-exposure Dust-particles Dusts Exposure-levels Inhalation-studies Laboratory-animals Lung-disease Lung-disorders Lung-irritants Organic-dusts Pulmonary-system-disorders Respirable-dust Respiratory-system-disorders Silica-dusts Silicates Statistical-analysis

  More +
• ISSN:
  0025-7818
• Document Type:
  Text
• Genre:
  Proceedings ; Abstract
• Place as Subject:
  California ; Ohio ; OSHA Region 3 ; OSHA Region 5 ; OSHA Region 9 ; 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:
  93
• NIOSHTIC Number:
  nn:20027144
• Citation:
  Med Lav 2002 Oct; 93(Suppl):S39
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2003
• Peer Reviewed:
  False
• Source Full Name:
  La Medicina del Lavoro. 3rd International Symposium on Silica, Silicosis, Cancer and Other Diseases, S. Margherita Ligure, 21-25 October 2002
• Supplement:
  Suppl
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c5914da66a9b83f1f87fff3e7c199eadaa4bac406c49aa422d901c84accf369da51af6e58c7f114823f447a642c73770690c4c6f5fafa7601f58da421e603a69
• Download URL:
  https://stacks.cdc.gov/view/cdc/197477/cdc_197477_DS1.pdf
• File Type:
  [PDF - 323.47 KB ]