Lung toxicity following a dose-response in vivo study of dispersed boron nitride nanotubes

Details

• Personal Author:
  Barger M ; Erdely A ; Kodali V ; Porter DW ; Roach KA ; Roberts, Jennifer R. ; Schwegler-Berry D ; Stefaniak, Aleksandr B. ; Wolfarth M
• Description:
  Boron nitride nanotubes (BNNT) are multi-walled nanotubes composed of hexagonal B-N bonds and are an emerging nanomaterial for which markets are rapidly expanding. Although not rigid in nature, the high aspect ratio (HAR) raises concern for potential toxicity that may be associated with lung exposure. The goal of the study was to assess lung toxicity using an in vivo dose-response time course model. The BNNT in this study were originally manufactured to be 5 nm wide and up to 200 microm long. Dispersion by sonication in ethanol, drying, and suspension in physiological dispersion medium (DM) yielded byproducts with surface area approximately 180 m2/g and size distribution on average of 13-23 nm in diameter x 0.6-1.6 microm in length lowering the original HAR by up to 99.9%. Male C57BL/6J mice received 4 or 40 microg of dispersed BNNT or DM by oropharyngeal aspiration. Bronchoalveolar lavage (BAL) was performed and blood collected at 4 hour, 1 day, 7 day, 1 month, and 2 month post-exposure. Lung lymph nodes (LN) and spleens were also harvested. Lung injury (BAL lactate dehydrogenase) was significantly elevated in the dispersed high-dose BNNT group up to 1 month post-exposure with resolution by 2 month. BAL neutrophils and eosinophils, a measure of inflammation and irritant response, were elevated in the high-dose group up to 7 day post-exposure, peaking at 1 and 7 day, respectively. BAL lymphocytes were significantly elevated at 1 and 7 day post-exposure and, to a lesser degree, at 2 month due primarily to increased CD4+ and CD8+ T cells. LN lymphocytes were also significantly increased in the high dose group at 7 day. No significant alterations were observed in spleenocytes cell populations. The low dose did not result in significant changes in any parameters measured. In summary, the products of the dispersed BNNT sample used in this study caused acute pulmonary inflammation and lung injury only at the highest exposure, which peaked by 7 day post-exposure and showed resolution over time (2 month). Further studies are needed to determine if physicochemical properties, such as length and impurities, will impact toxicity profiles of BNNT and byproducts resulting from dispersion. [Description provided by NIOSH]
• Subjects:
  Blood Chemistry Environmental Exposure Immune System Laboratories Lung Lung Diseases Lymphatic System Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Boron Compounds Boron Nitride Cell Alteration Cellular Effects Cellular Reactions Chemical Properties Dispersion Dose Response Exposure Assessment Exposure Levels Immune Reaction Immune System In Vivo Study Laboratory Animals Laboratory Testing Lung Disorders Lung Irritants Lymph Nodes Lymphocytes Nanomaterials Nanotechnology Nanotoxicology Nanotubes Neutrophils Particle Diameter Particle Size Physical Properties Pulmonary Effects Splenic Tissue

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; RHD - Respiratory Health Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  79-80
• Volume:
  156
• Issue:
  1
• NIOSHTIC Number:
  nn:20049389
• Citation:
  Toxicologist 2017 Mar; 156(1):79-80
• CAS Registry Number:
  Boron nitride (CAS RN 10043-11-5)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Healthcare and Social Assistance ; Services
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 56th Annual Meeting and ToxExpo, March 12-16, 2017, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e6d9c589d8453e94d8b470ff4990d8aa8d8b93706a6aa31c7a8d16fc17e53508de2a3f8dc3976d8d29a68d17c014eab62ceb06e74d4c6c8848051316e74e91d9
• Download URL:
  https://stacks.cdc.gov/view/cdc/203849/cdc_203849_DS1.pdf
• File Type:
  [PDF - 965.57 KB ]