Differential mouse pulmonary dose and time course responses to titanium dioxide nanospheres and nanobelts

Details

• Personal Author:
  Andrew M ; Battelli L ; Castranova, Vincent ; Friend S ; Funk K ; Hamilton R ; Holian A ; Hubbs A ; Li J ; Meng F ; Mercer R ; Porter DW ; Sriram K ; Wolfarth M ; Wu N ; Yang F
• Description:
  Three anatase titanium dioxide (TiO(2)) nanoparticles were prepared; nanospheres (NS), short nanobelts (NB1) and long nanobelts (NB2). These nanoparticles were used to investigate the effect of nanoparticle shape and length on lung toxicity. Mice were exposed (0-30 microg per mouse) by pharyngeal aspiration and pulmonary toxicity was assessed over a 112 day time course. Whole lung lavage data indicated that NB1- and NB2-exposed mice, but not NS-exposed mice, had significant dose- and time-dependent pulmonary inflammation and damage. Histopathological analyses at 112 days post-exposure determined no interstitial fibrosis in any NS-exposed mice, an increased incidence in 30 microg NB1-exposed mice, and significant interstitial fibrosis in 30 microg NB2-exposed mice. At 112 days post-exposure, lung burden of NS was decreased by 96.4% and NB2 by 80.5% from initial deposition levels. At 112 days post-exposure, enhanced dark field microscopy determined that alveolar macrophages were the dominant deposition site, but a fraction of NB1 and NB2 was observed in the alveolar interstitial spaces. For the 30 microg exposure groups at 112 days post-exposure, confocal microscopy and immunofluorescent staining demonstrated that retained NB2 but not NS were present in the interstitium subjacent to the terminal bronchiole near the normal location of the smallest lymphatic capillaries in the lung. These lymphatic capillaries play a critical role in particle clearance, and the accumulation of NB2, but not NS, suggests possible impaired lymphatic clearance by the high aspect ratio particles. In summary, our data indicate that TiO(2) nanoparticle shape alters pulmonary responses, with severity of responses being ranked as NS
• Subjects:
  Environmental Monitoring Hazardous Substances Laboratories Lung Lung Diseases Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Agents Author Keywords: Nanoparticles Dose-response Exposure-assessment Exposure-methods Histopathology Laboratory-animals Laboratory-testing Lung Lung-cells Lung-disorders Lung-function Lung-irritants Nanoparticles Nanotechnology Particulates Pulmonary-function Pulmonary-system Pulmonary-system-disorders Pulmonary Or Respiratory System Respiratory-system-disorders Respiratory Toxicology Toxic-dose Toxic-effects

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Montana ; OSHA Region 3 ; 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
• Pages in Document:
  179-193
• Volume:
  131
• Issue:
  1
• NIOSHTIC Number:
  nn:20041523
• Citation:
  Toxicol Sci 2013 Jan; 131(1):179-193
• Contact Point Address:
  Dale W. Porter, Ph.D., Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, M/S 2015, Morgantown, WV, 26505, USA
• Email:
  DPorter@cdc.gov
• CAS Registry Number:
  Titania (CAS RN 13463-67-7)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Toxicological Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9853b40ba20c5b43a7beec3e9d71dd8e254e4e6dda5436025eae68ced72944a0c2b4bf53475b8428f1145c8cf7d95127eee5f65b944ed648d7a5ff0df07a2e72
• Download URL:
  https://stacks.cdc.gov/view/cdc/194067/cdc_194067_DS1.pdf
• File Type:
  [PDF - 2.87 MB ]