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Pulmonary Response to Crystalline Silica and Coal Dust Exposure in Rats

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    Background and Purpose: Passage of the Federal Coal Mine Health and Safety Act (Coal Act) in 1969 together 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), has greatly reduced the caseload of coal workers pneumoconiosis (CWP) in the U.S. Since the early 2000s, however, the trend has reversed. A significant rise in the incidence of CWP has been reported in the U.S., especially in the central Appalachian states of Virginia, Kentucky, and West Virginia. Yet the etiological factor(s) responsible for the re-emergence of CWP remains elusive. Crystalline silica has been suggested as a potential contributor to the re-emergence of CWP. However, experimental evidence supporting a definite role for crystalline silica in the re-emergence of CWP in the U.S. is lacking. Methods: The potential role of crystalline silica in the reemergence of CWP has been investigated by a rat whole-body inhalation-exposure and lung toxicity model. All experiments were done in an Association for Assessment and Accreditation of Laboratory Animal Care 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 by a custom-built automated system. Particle size distribution in the aerosol samples was determined using 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 during week 1 followed by 6 hours/day, 4 days/ week for 3 or 6 months); 2. Min-U-Sil 5 (15 mg/m3, 6 hours/day, 5 days during week 1 followed by filtered air for 6 hours/day, 4 days/week for 3 or 6 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 or 6 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 or 6 months). Rats were euthanized at the end of the 3rd or 6th month, after the first exposure, and bronchoalveolar lavage (BAL) was performed to determine the pulmonary response to exposure(s). Results: Mass median aerodynamic diameter of the crystalline silica and coal dust particles in the aerosol samples generated was 1.6 µm [geometric standard deviation (sg) 1.6] and 1.36 µm (sg 2.3), respectively. At both the time points analyzed, the body weights of the rats belonging to the aerosol exposure groups were less compared to those of the corresponding controls (approx. 5% for coal dust alone and approx. 10% for crystalline silica followed by coal dust). Exposure to crystalline silica alone resulted in no apparent difference in body weight. Quantification and differential analysis of the bronchoalveolar lavage (BAL) cells revealed significant differences in the aerosol(s)-exposed rats versus time-matched controls. The total number of BAL cells, the number of BAL macrophages (AM), and BAL polymorphonuclear leukocytes (PMN) was higher in rats exposed to the aerosols, either individually or in combination, than the controls. Moreover, at the 3 months interval, these increases were significantly higher (p<0.05) in rats exposed to both crystalline silica and coal dust aerosols than the rats exposed to the individual agents. Conclusions: Taken together, the results suggest that exposure to a combination of crystalline silica and coal dust leads to a greater pulmonary response in rats, especially the inflammatory response, compared to exposure to either agent individually. The data underscores the potential role of exposure to crystalline silica in the re-emergence of CWP in the U.S. [Description provided by NIOSH]
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  • ISSN:
    1096-6080
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  • Location:
  • Volume:
    198
  • NIOSHTIC Number:
    nn:20069348
  • Citation:
    Toxicologist 2024 Mar; 198(S1):447
  • CAS Registry Number:
  • Federal Fiscal Year:
    2024
  • NORA Priority Area:
  • Peer Reviewed:
    False
  • Source Full Name:
    The Toxicologist. Society of Toxicology 63rd Annual Meeting & ToxExpo, March 10-14, 2024, Salt Lake City, Utah
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  • Main Document Checksum:
    urn:sha-512:9786d6a6173e6fc00b568303aef2ef0c409bbd83a360a21b1275fcc71b312e8a617d5a8c5c5e0b5d5c5d6a941804fc392a3945b6d76b7491b02ccf93086eee68
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    Filetype[PDF - 540.16 KB ]
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