Characterization of acute in vitro and in vivo toxicity of boron nitride nanotube and byproducts following dispersion

Details

• Personal Author:
  Barger M ; Erdely AD ; Eye T ; Friend S ; Kodali VK ; Michael WG ; Porter, Dale ; Roach KA ; Roberts, Jennifer R. ; Schwegler-Berry D ; Shoeb M
• Description:
  Boron nitride nanotubes (BNNTs) are an emerging engineered nanomaterial attracting significant attention due to superior electrical, chemical, and thermal properties. Despite promising potential, the toxicity profile of this material is largely unknown. We performed acute in vitro and in vivo studies with BNNT byproduct mixture containing BNNT with boron, amorphous boron nitride and hexagonal boron nitride impurities. The dispersion procedure (sonication in ethanol, drying, and suspension in physiological dispersion medium (DM)) resulted in a byproduct mixture containing tubes with 13-23 nm diameter x 0.6-1.6 microm length.THP-1 wild-type and NLRP3 knockout human monocytic cells were exposed to 0-100 microg/ml. The in vitro findings were confirmed in vivo by exposing male C57BL/6 mice with 40 microg of BNNT for 24 h by oropharyngeal aspiration. The single dose administered reflects a relatively high exposure scenario to measure a maximal response based on studies of multiwalled carbon nanotubes (MWCNT). MWCNT-7 served as a particle control. In vitro, the test mixture induced a dose-dependent increase in cytotoxicity and oxidative stress. This was confirmed in vivo by acute increased bronchoalveolar lavage levels of lactate dehydrogenase, pulmonary neutrophil influx, loss in mitochondrial membrane potential and augmented levels of 4-hydroxynonenal. Uptake of this material caused lysosomal destabilization and inflammasome activation, corroborated by an increase in cathepsin B, caspase 1, and increased protein levels of IL-1â both in vitro and in vivo. Effects were attenuated in exposed NLRP3 knockout THP-1 cells, demonstrating inflammasome activation. Functionally, pretreatment with the byproduct mixture caused an acute suppression in bacterial uptake by THP-1 cells, an effect that was mirrored in challenged alveolar macrophages. Analysis of cytokines secreted by LPS-challenged alveolar macrophages collected after in vivo exposure to dispersions of BNNT or MWCNT-7 showed both materials caused a similar shift in macrophage phenotype. The observed results, which likely reflect a high exposure scenario, demonstrated acute inflammation, and toxicity in vitro and in vivo in part due to NLRP3 inflammasome activation. [Description provided by NIOSH]
• Subjects:
  Blood Cytotoxins Environmental Exposure Hazardous Substances Laboratories Lung Macrophages Occupational Health Particulate Matter Respiratory System Safety Toxicology

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• Keywords:
  Acute Toxicity Alveolar Cells Boron Compounds Boron Nitride Cellular Effects Cellular Reactions Cellular Uptake Cytokines Cytotoxic Effects Cytotoxicity Dispersion Dose Response Exposure Assessment Exposure Levels In Vitro Study In Vivo Study Laboratory Animals Laboratory Testing Metabolic Activation Multi-walled Carbon Nanotubes MWCNT Nanomaterials Nanotechnology Nanotoxicology Nanotubes Neutrophils Oxidative Stress Particle Diameter Particle Size Pulmonary Effects

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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
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  76
• Volume:
  156
• Issue:
  1
• NIOSHTIC Number:
  nn:20049385
• Citation:
  Toxicologist 2017 Mar; 156(1):76
• CAS Registry Number:
  Boron nitride (CAS RN 10043-11-5) ; Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Manufacturing
• 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-512:519f02f5471a9fbef689f1bffb4a336550914bd20e9a7fd7207628f9ca6d3279ea4827093c312d9ad5b0f4ab0c9c4ec0c436db7b31004ba0990dc6d8df04d33a
• Download URL:
  https://stacks.cdc.gov/view/cdc/203845/cdc_203845_DS1.pdf
• File Type:
  [PDF - 950.58 KB ]