Bioactivity of Boron Nitride Nanotube Preparations That Differ in Purity In Vitro and In Vivo

Details

• Personal Author:
  Barger M ; Erdely A ; Eye T ; Kodali V ; Leonard, Stephanie ; Porter, Dale ; Roach K ; Roberts J ; Stefaniak, Aleksandr B. ; Wolfarth M ; Xin X
• Description:
  Boron nitride nanotubes (BNNTs), due to their wide band gap and thermal and chemical stability, are expected to be incorporated into a myriad of industrial applications. Currently, commercial production of BNNTs occurs through different processes including a pressurized vapor/high temperature process (PVTH) or an induction thermal plasma process (plasma), both resulting in 30-60 % residual compounds and impurities. In the current work, we evaluated the pulmonary and systemic toxicity arising due to acute exposure of BNNTs from the plasma process. Four BNNTs with a gradient of purity (from 50% to 90% tubes) were used to assess toxicity and evaluate bioactivity. Hexagonal boron nitride (less than 100 nm in diameter) was used as a reference material. All BNNTs tested were agglomerated bundles of few multi-walled tubes (approximately 3 to 5 walls/tube). Electron microscopy (EM) confirmed a visible decrease in impurities and an increase in tubular structures across the gradient samples. In vitro and in vivo experiments were performed following sonication of BNNTs in dispersion media (DM). Preliminary EM sizing showed that the BNNTs dispersed in DM had a length of approximately 0.5 - 1.5 microm and a diameter of approximately 5 - 30 nm. Electron paramagnetic resonance measurements showed no change in surface hydroxyl radicals among the BNNTs with various purities. In vitro, the toxicity was evaluated in human monocyte cells (THP-1) wild-type and NLRP3-deficient cells at a concentration range of 0-100 microg/ml. At the high doses, there was a small but statistically significant increase in lactate dehydrogenase (LDH) released in the highest purity BNNT exposures. This increase in toxicity was attenuated in NLRP3-deficient cells. In vivo toxicity was evaluated in male C57BL/6 mice exposed by oropharyngeal aspiration to 4 or 40 microg of BNNT sample/mouse. Animals were euthanized 1 and 7 d post-exposure and lung lavage was performed to evaluate lung injury and inflammation. At day 1 there was a significant influx in neutrophils, a marker for lung inflammation, as well as an increase in LDH activity in particle-exposed groups. The response was highest in animals exposed to the high dose of the highest purity BNNT mixture. Inflammation and injury began to resolve by 7 d. The results indicate that BNNTs made by plasma process induce acute toxicity and inflammation only at high concentrations and ongoing studies will evaluate histopathological changes and clearance up to 3 mo post-exposure. [Description provided by NIOSH]
• Subjects:
  Biomarkers Cells, Cultured Environmental Exposure Hazardous Substances Immune System Laboratories Lung Lung Diseases Occupational Exposure Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety Toxicology

  More +
• Keywords:
  Acute Exposure Acute Toxicity Bioactivation Biological Systems Boron Nitride Cell Cultures Cell Culture Techniques Cellular Effects Cellular Reactions Dispersion Dose Response Exposure Assessment Exposure Levels Humans Immune Reaction In Vitro Study In Vivo Study Laboratory Animals Laboratory Testing Lung Disorders Nanotechnology Nanotoxicology Nanotubes Neutrophils Particle Diameter Particle Size Pulmonary Effects Toxic Effects

  More +
• 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
• Volume:
  168
• Issue:
  1
• NIOSHTIC Number:
  nn:20055039
• Citation:
  Toxicologist 2019 Mar; 168(1):291
• CAS Registry Number:
  Boron nitride (CAS RN 10043-11-5)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 58th Annual Meeting and ToxExpo, March 10-14, 2019, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9cf9208d90408e79860e10eb42b0b06d326e41fa8c18c8153028f6797e5b0cef59e3131e503a87f6091d1b8b6d429e7bbf526cf32cdd652fc2e2da5a5701c3fd
• Download URL:
  https://stacks.cdc.gov/view/cdc/217433/cdc_217433_DS1.pdf
• File Type:
  [PDF - 867.43 KB ]