Lung Response to Crystalline Silica and Coal Dust Exposure in Rats

Details

• Personal Author:
  Joseph, Pius ; McKinney, Walter G. ; Beck, Timothy W. ; Sager, Tina M.
• Description:
  Background and Purpose: The passage of the Federal Coal Mine Health and Safety Act (Coal Act) in 1969, along with the establishment of the Coal Workers Health Surveillance Program (CWHSP) managed by the National Institute for Occupational Safety and Health (NIOSH) in association with the Mine Safety and Health Administration (MSHA), significantly reduced the incidence of coal workers pneumoconiosis (CWP) in the U.S. Nevertheless, since the early 2000s, this trend has reversed with a notable increase in CWP cases, particularly in the central Appalachian states of Virginia, Kentucky, and West Virginia. However, the etiological factor(s) contributing to this resurgence remain unclear. While crystalline silica has been proposed as a potential contributor to the re-emergence of CWP cases, there is currently insufficient experimental evidence to confirm its definitive role in the resurgence. Methods: The potential role of crystalline silica in the re-emergence of CWP has been investigated using a rat whole-body inhalation-exposure and lung toxicity model. All experiments were done in an AAALAC International approved animal facility (NIOSH, Morgantown, WV) following a protocol approved by the CDC-Morgantown Animal Care and Use Committee. Aerosols containing crystalline silica (Min-U-Sil 5) or coal dust (Keystone Mineral Black 325BA) were generated using a custom-built automated system and rats exposed in a whole-body inhalation chamber. The particle size distribution in the aerosol samples was assessed with a micro-orifice uniform deposit impactor (MOUDI).Approximately 3-month-old male Fischer 344 rats (n=6/ group) were divided into four exposure groups: 1. Filtered-air control (6 hours/day, 5 days/week for week 1 followed by filtered air again for 6 hours/day, 4 days/week for 3, 6, or 12 months); 2. Min-U-Sil 5 silica (15 mg/m3, 6 hours/day, 5 days during week 1 followed by filtered air for 6 hours/day, 4 days/week for 3, 6, or 12 months); 3. Coal dust (filtered air for 6 hours/day, 5 days during week 1 followed by coal dust, 10 mg/m3, 6 hours/day, 4 days/week for 3, 6, or 12 months); 4. Min-U-Sil 5 + coal dust (Min-U-Sil 15 mg/m3, 6 hours/day, 5 days during week 1, followed by coal dust, 10 mg/m3, 6 hours/day, 4 days/week for 3, 6, or 12 months). The silica content in the coal dust sample used in the study was 5.4%. Rats were euthanized at the end of the 3rd, 6th, or 12th month, after the first exposure, and bronchoalveolar lavage (BAL) was conducted in the right lung. The BAL samples collected were analyzed to determine the number of total cells, alveolar macrophages, and polymorphonuclear leukocytes. Simultaneously, the diaphragmatic and cardiac lobes of the left lung collected were fixed in formaldehyde, embedded in paraffin, sectioned at a thickness of 5 µm, stained with hematoxylin and eosin or Mason's trichrome stain, and examined for histological changes by a pathologist. Results: The mass median aerodynamic diameter of the crystalline silica and coal dust particles in the aerosol samples generated was 1.6 µm geometric standard deviation (sigmag) 1.6 and 1.36 µm (sigmag 2.3), respectively. The body weights of the rats exposed to coal dust alone or a combination of coal dust and silica were lower compared to the corresponding controls in the 3- and 6-months groups, with reductions of approximately 5% for coal dust and about 10% for the combination of crystalline silica followed by coal dust. Exposure to crystalline silica alone did not result in any significant difference in body weight, compared with the control group at any of the time intervals. Results from bronchoalveolar lavage (BAL) analysis and lung histology indicated progression of lung toxicity in the aerosol- exposed rats, compared to the time-matched, air-only exposed control group. Notably, at the 3- and 6-month intervals, the lung response was more pronounced in rats exposed to both crystalline silica and coal dust aerosols than in those exposed to the individual agents. For instance, histological changes indicative of lung fibrosis were detectable as early as 3-months post-exposure in only the rats exposed to both types of aerosols. Additionally, hyperplasia of the bronchus-associated lymphoid tissue (BALT) was observed exclusively in the rats exposed to the combination of crystalline silica and coal dust aerosols. Conclusions: Taken together, the results suggest that exposure to a combination of crystalline silica and coal dust induces a more pronounced pulmonary response in rats, as indicated by the BAL parameters of pulmonary toxicity and lung histology, compared to exposure to either agent individually. These findings highlight the potential role of crystalline silica exposure in the re-emergence of CWP in the U.S. Description provided by NIOSH
• Subjects:
  • Coal
  • Coal Mining
  • Lung
  • Mining
  • Occupational Health
  • Pneumoconiosis
  • Rats
  • Respiratory System
  • Safety
  • Silicon Dioxide
• Keywords:
  • Crystalline silica; Coal dust; Coal workers pneumoconiosis; Black lung disease; Inhalation; Laboratory animals; Toxicology
• Source:
  Toxicologist 2025 Mar; 204(S1):574
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Pennsylvania ; Philadelphia Region OSHA ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; PMRD - Pittsburgh Mining Research Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  2 pdf pages
• Volume:
  204
• NIOSHTIC Number:
  nn:20071588
• CAS Registry Number:
  • Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2025
• NORA Priority Area:
  Mining
• Peer Reviewed:
  False
• Download URL:
  https://stacks.cdc.gov/view/cdc/259363/cdc_259363_DS1.pdf
• File Type:
  [PDF - 261.58 KB]
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d3ae7164055306b76693fca1587f44beccbb9bcc382fb1725dd51f4d09b073871ae1343468cbe8246872bee935a14e318d757fb040728071cd0dbc921be8d7e5