Effects of pre-exposure dispersion status on nanoparticle distribution and fibrosis in the lung

Details

• Personal Author:
  Castranova, Vincent ; Holian A ; Mercer R ; Porter DW ; Sager TM ; Wolfarth M
• Description:
  An important aspect of nanoparticle toxicity is the deposition and translocation of the particles once they reach the lung. In the form of agglomerates deposition characteristics can change, as the agglomerates will have a greater aerodynamic diameter than singlet nanoparticles. We hypothesize that pre-exposure dispersion status of the nanoparticle will correlate with particle deposition and translocation within the lung. Specifically, we postulate that well dispersed (WD) particles will be more likely to move into the interstitial space of the lung, while poorly dispersed (PD) particles will primarily be taken up by the alveolar macrophages (AMs). To test our hypothesis, nano-sized NiO was suspended in four different dispersion media (PBS, dispersion medium (DM), Survanta, or Pluronics F-68). At each respective dose, WD and PD suspensions (sonicated at 25W continuous output, 20 min or 5 min, respectively) were created. Mice (male, C57BL/6J, 7 weeks old) were given 40 or 80 microg/mouse of nano-sized NiO in the different states of dispersion via pharyngeal aspiration. At 2 hours, 7, and 56 days post-exposure, lungs were collected and fixed by intratracheal perfusion. Lung sections were then viewed using a CytoViva microscope. At 2 hours post-exposure both PD and WD NiO structures were primarily distributed in the airspaces of the first few alveolar generations. However, the forms of distribution were quite different between PD and WD NiO at 7 and 56 day post-exposure. The majority of the PD particles were in large clumps in the airspaces. Many of the large clumps induced granulomatous nodules. The majority of WD NiO particles were in AMs or found within the interstitium. By 7 and continuing out to 56 days post-exposure, there was significant fibrotic development within the granulomatous nodules with PD NiO. However, granulomatous nodules and the associated fibrotic development were not observed with WD NiO particles. [Description provided by NIOSH]
• Subjects:
  Blood Cells, Cultured Fibrosis Laboratories Lung Lung Diseases Macrophages Occupational Health Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Alveolar Cells Cell Cultures Cellular Reactions Cellular Uptake Dispersion Dose Response Exposure Assessment Laboratory Animals Laboratory Techniques Laboratory Testing Lung Cells Lung Fibrosis Nanoparticles Nanotechnology Nickel Compounds Nickel Oxide Oxides Particle Aerodynamics Particle Diameter

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; Montana ; OSHA Region 3 ; OSHA Region 6 ; OSHA Region 8 ; 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:20047722
• Citation:
  Toxicologist 2016 Mar; 150(1):423
• CAS Registry Number:
  Nickel (CAS RN 7440-02-0) ; Nickel monoxide (CAS RN 1313-99-1)
• Federal Fiscal Year:
  2016
• 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-512:2f4af12d714a629303c82c8d77d7014f279243bb9a22a145393f1755c1e8154fa28ee6b44ace8b0f1da63f544cf8707830b3eb540ffd75e7fd0baea8dd1ea7b4
• Download URL:
  https://stacks.cdc.gov/view/cdc/202719/cdc_202719_DS1.pdf
• File Type:
  [PDF - 441.77 KB ]