Effect of Age on Crystalline Silica-Induced Pulmonary Toxicity in Rats

Details

• Personal Author:
  Joseph P ; McKinney W ; Sager TM
• Description:
  Background and Purpose: Millions of workers are exposed to crystalline silica in the United States. Silica exposure at levels above the OSHA PEL (50 µg/m3) is known to contribute to potentially fatal pulmonary diseases such as silicosis, cancer, and chronic obstructive pulmonary disease. The age composition of workers is changing in the U.S. and worldwide and it is anticipated that many workers will continue to work at older ages. It is currently unknown what relationship, if any, the age of the worker has on his/her response to occupational exposure to silica. Furthermore, it is critical to determine the mechanisms underlying the potential modification of the silica-induced lung toxicity by age. The objective of the proposed study, therefore, was to determine the effect of age on the pulmonary toxicity induced by crystalline silica exposure by employing a rat lung toxicity model. Methods: All experiments in this study 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. To conduct these studies, two age groups of male F344 rats were used. The first group of animals (6 months old at the time of exposure) was designated as the young age group. This age group of rats simulate workers who are approximately 18 to 20 years old. The second group of rats (18 months old at the time of exposure) was designated as the old age group. This age group of rats simulate workers who are between the ages of 45 to 50 years. The young and old age groups of rats were exposed to either air (control) or Min-U-Sil 5 crystalline silica (15 mg/m3, 6 hours/day, 5 days) in a whole-body inhalation system. At two post-exposure time periods (1-day and 6-months) the animals were euthanized with an intraperitoneal injection of ≥100 mg sodium pentobarbital/kg b.w. followed by exsanguination by severing the descending abdominal aorta. Immediately following euthanasia, a tracheal cannula was inserted, the right lobes were tied off and the left lung lobe underwent bronchoalveolar lavage (BAL). The BAL fluid and the cells collected were employed to assess the pulmonary response to silica exposure. Lactate dehydrogenase (LDH) activity was determined in the BAL fluid to assess lung injury. Using the BAL cells from the lavage samples, cell counts and differentials were conducted to assess pulmonary inflammation. To determine the generation of reactive oxygen species (ROS) by the BAL phagocytes, a luminol-dependent chemiluminescence assay was performed. Results: silica exposure resulted in an increase in the BAL fluid LDH activity, suggesting the induction of lung injury. In the young-aged animals, LDH activity was higher in silica treated animals compared to controls, at both 1-day and 6-month post-exposure. However, this elevation in LDH activity was not significantly different (p>0.05) from control at both time points. The increase in LDH activity was significantly (p<0.05) higher in the silica exposed groups compared to air exposed groups in the old-aged animals at both 1-day and 6-month post-exposure. At 6-months post-exposure in the old-aged animals LDH activity was 2.6-fold higher in the silica exposed animals compared to age-matched controls. Furthermore, the results also show increases in BAL cell ROS generation between animals treated with silica and controls. Specifically, in both the young-aged and old-aged animals, ROS generation was significantly (p<0.05) higher in silica treated animals compared to controls, at both 1-day and 6-month post-exposure. However, at 6-months post-exposure ROS generation was 2.4-fold higher in the silica exposed old-aged animals compared to the silica exposed young-aged animals. Additionally, silica inhalation resulted in a significant increase in neutrophil infiltration at both 1-day and 6-months post-exposure for both the young-aged and old-aged rats. At 1-day and 6-months post-exposure, in the young animals, silica exposure caused a 150-fold and 124-fold increase in neutrophil infiltration respectively, compared to the controls. On the other hand, at 1-day post-exposure in the old animals, silica caused a 271-fold increase in neutrophil infiltration while at 6- months post-exposure in the old animals, silica caused a 243-fold increase in the infiltration of neutrophils compared to the corresponding controls. Thus, the neutrophil infiltration in the silica exposed older rats was approximately 2-fold higher, compared to their younger counterparts. Conclusions: Inhalation exposure to crystalline silica results in pulmonary toxicity in the rats, regardless of their age. However, our results reflect that advanced exposure age leads to an enhanced pulmonary response to crystalline silica exposure in the rats. In the lungs of the older animals, silica exposure facilitates significantly higher neutrophil infiltration, LDH activity, and oxidant generation compared to young animals exposed to crystallin silica. In conclusion, our results support the hypothesis that enhanced age exacerbates the pulmonary response to crystalline silica inhalation exposure. [Description provided by NIOSH]
• Subjects:
  Age Factors Aging Laboratories Lung Occupational Health Respiratory System Safety Silicon Dioxide
• Keywords:
  Age Factors Crystalline Silica Inhalation Laboratory Animals Pulmonary Effects
• 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:
  198
• NIOSHTIC Number:
  nn:20069349
• Citation:
  Toxicologist 2024 Mar; 198(S1):487
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Mining
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 63rd Annual Meeting & ToxExpo, March 10-14, 2024, Salt Lake City, Utah
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4761d74e46b301459043bd7faf4d33923f5441636eb3bdc5a2f605f35921c8a609144401b208ccb557b6eb4930e3d7145b020c6675c33051f03e2e707cc7ee7c
• Download URL:
  https://stacks.cdc.gov/view/cdc/207846/cdc_207846_DS1.pdf
• File Type:
  [PDF - 519.91 KB ]