Acute toxicity of boron nitride nanotubes in-vitro and in-vivo

Details

• Personal Author:
  Barger M ; Erdely A ; Eye T ; Kodali V ; Porter, Dale ; Roach K ; Roberts J ; Schwegler-Berry D ; Smith K ; Wolfarth M
• Description:
  Boron nitride nanotubes (BNNTs) are an emerging engineered nanomaterial that has attracted significant attention due to its superior electrical, chemical, and thermal properties. As the number of applications grow, occupational exposures will likely increase. Since its toxicity is largely unknown, we performed acute in-vitro and in-vivo exposure studies with 13-23 nm diameter x 0.6-1.6 microm length BNNTs. THP-1 wild-type and NLRP3 knockout human monocytic cells were exposed to 0-100 microg/ml and male C57BL/6 mice were exposed by pharyngeal aspiration to 4 or 40 microg BNNTs and sacrificed 4 and 24 h post-exposure. The multi-walled carbon nanotube-7 (MWCNT-7) served as a particle control. In-vitro, BNNT induced a dose-dependent increase in cytotoxicity. This was confirmed in vivo by increased bronchoalveolar lavage levels of lactate dehydrogenase, a measure of lung cytotoxicity. In vitro, lysosomal destabilization, likely a result of particle uptake, was evident by acridine orange staining. Subsequent NLRP3 inflammasome activation was demonstrated by a dose dependent increase in IL-1beta protein as well as cathepsin B and caspase 1 activity. Toxicity, and IL-1beta production were attenuated in exposed NLRP3 knockout THP-1 cells. In-vivo, elevated pulmonary IL-1beta confirmed in vitro findings. Consistent with suspected BNNT-induced inflammation, pulmonary neutrophil influx and inflammatory markers (Il6, Ccl2, Ccl22, Cxcl2) increased in a dose-dependent manner. In general, toxicity induced by BNNTs was less in comparison to MWCNT-7. Taken together, these results demonstrate that BNNTs induce inflammation in vitro and in vivo in part due to NLRP3 inflammasome activation and sub-chronic in vivo studies are warranted. [Description provided by NIOSH]
• Subjects:
  Biomarkers Cells, Cultured Chemistry Cytotoxins Electricity Environmental Exposure Hazardous Substances Immune System Laboratories Lung Occupational Exposure Occupational Health Respiratory System Safety Toxicology

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• Keywords:
  Acute Exposure Author Keywords: Emerging Nanomaterials Biological-effects Boron Compounds Boron Nitride Cell Cultures Cellular Reactions Chemical Properties Cytotoxicity Dose Response Electrical Properties Emerging Technology Exposure Assessment Exposure Levels Health-hazards Humans Immune Reaction In Vitro Study In Vivo Study Laboratory Animals Laboratory Testing Lung Irritants Multi-walled Carbon Nanotubes MWCNT Nanomaterials Nanoparticles Nanotechnology Nanotoxicology Nanotubes Neutrophils Proteins Thermal Properties Ultrafine-particulates

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• Publisher:
  International Nanotoxicology Congress
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Massachusetts ; OSHA Region 1 ; 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
• NIOSHTIC Number:
  nn:20048175
• Citation:
  nanoTOX 2016, Proceedings of the 8th International Nanotoxicology Congress, June 1-4, 2016, Boston, Massachusetts. Boston: MA: International Nanotoxicology Congress, 2016 Jun; :162
• CAS Registry Number:
  Boron nitride (CAS RN 10043-11-5) ; Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  nanoTOX 2016, Proceedings of the 8th International Nanotoxicology Congress, June 1-4, 2016, Boston, Massachusetts
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c1ef0c2bc58335492a607808221ef3a5cb38f62951e9af473700c1ec69948f7bde3c4df1ddc65e2632374f4b7ed3a96a185fe9724d741d2c00b08ed6e9b7b9f8
• Download URL:
  https://stacks.cdc.gov/view/cdc/202996/cdc_202996_DS1.pdf
• File Type:
  [PDF - 379.22 KB ]