In Vivo Lung Toxicity Associated with Boron Nitride Nanotubes with Different Purities

Details

• Personal Author:
  Barger M ; Bowers L ; Dénommée S ; Erdely AD ; Jakubinek MB ; Kim K ; Kodali V ; Leonard, Stephen S. ; Porter DW ; Roach KA ; Roberts, Jennifer R. ; Wolfarth MG ; Xin X
• Description:
  Boron nitride nanotubes (BNNTs), a newly emerging nanomaterial with enhanced physicochemical properties, are increasingly incorporated into industrially relevant applications. Currently, commercial production of BNNTs is synthesized with 30-60 % residual compounds and impurities. The goal of this study was to assess the lung toxicity associated with in vivo exposure to BNNTs with various purities. Three BNNT samples with a gradient of purity were provided by the National Research Council, Canada, to assess lung toxicity in vivo: a low purity as-produced sample with approx. 50% BNNT (BNLP), an intermediate purity sample (BNMP), and a highly purified sample with >90% BNNT (BNHP). Hexagonal boron nitride (h-BN, <100 nm in diameter) was used as a control material for one of the by-products during synthesis affecting the purity of the BNNT material. All BNNT samples tested were shown to be agglomerated bundles of BNNTs (approx. 3 to 5 walls/tube) with boron and h-BN as the primary impurities. Sample purity was confirmed by electron microscopy (EM). The BNNT samples prepared in dispersion medium (DM) were 0.5-1.5 microm in length and 5-30 nm in diameter. Male C57BL/6 mice were exposed by oropharyngeal aspiration to 4 or 40 microg of sample/mouse dispersed in DM or DM alone on day 0. Animals were euthanized at 4 h, 1 d, 7 d, 1 m, and 3 m post-exposure and lung lavage was performed to evaluate lung injury and inflammation. At 4 h post-exposure, lactate dehydrogenase (LDH) activity and neutrophils influx, indicators of lung injury and inflammation, were significantly increased by high dose of BNMP and BNHP. At 1 d and 7 d post-exposure, the effects were greatest in the high dose of all three tested BNNT samples, with BNHP>BNMP>BNLP, and persisted in the BNHP group up to 1 m post-exposure. Irritant response, indicated by eosinophils increase, was observed in the high dose of BNNT groups at 1 d and 7 d post-exposure, with BNHP>BNMP>BNLP. Lung lymphocytes continued to increase in the BNHP group up to 1 m post-exposure. The results indicated that the tested BNNT samples induced acute toxicity and inflammation only at high concentration and the effects were more pronounced with increasing purity. The reference material used to represent one of the by-products of synthesis, h-BN, did not show significant lung toxicity, suggesting lung effects where present may be due primarily to BNNTs. [Description provided by NIOSH]
• Subjects:
  Blood Environmental Exposure Hazardous Substances Immune System Laboratories Lung Lung Diseases Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Boron Nitride Chemical Synthesis Dispersion Dose Response Exposure Assessment Exposure Levels Immune Reaction In Vivo Study Laboratory Animals Laboratory Testing Lung Disorders Lymphocytes Nanomaterials Nanotoxicology Nanotubes Neutrophils Particle Diameter Particle Size Sample Preparation Toxic Effects Toxic Materials

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; 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:
  174
• Issue:
  1
• NIOSHTIC Number:
  nn:20058970
• Citation:
  Toxicologist 2020 Mar; 174(1):277
• CAS Registry Number:
  Boron nitride (CAS RN 10043-11-5)
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 59th Annual Meeting and ToxExpo, March 15-19, 2020, Anaheim, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d80aef4785d478177d923724a1dcb758ba5a9d6d7d5fef70de31f9242c2ce62f25d47e16911a3a23422269dd707bea39a205df6c07ae41103c056c9b9bc95503
• Download URL:
  https://stacks.cdc.gov/view/cdc/223315/cdc_223315_DS1.pdf
• File Type:
  [PDF - 524.33 KB ]