Toxicity Evaluation Following Pulmonary Exposure to an As-Manufactured Dispersed Boron Nitride Nanotube (BNNT) Material In Vivo

Details

• Personal Author:
  Barger M ; Bowers L ; Dunn, Kevin H. ; Dunn, Kevin L. ; Erdely A ; Friend S ; Glassford, Eric ; Kashon M ; Kodali V ; Leonard, Stephen S. ; Porter DW ; Roach KA ; Roberts, Jennifer R. ; Stefaniak, Aleksandr B. ; Wolfarth M ; Xin X
• Description:
  Boron nitride nanotubes (BNNT) are multi-walled nanotubes composed of hexagonal B[sbnd]N bonds and possess many unique physical and chemical properties, creating a rapidly expanding market for this newly emerging nanomaterial which is still primarily in the research and development stage. The shape and high aspect ratio give rise to concern for the potential toxicity that may be associated with pulmonary exposure, especially in an occupational setting. The goal of this study was to assess lung toxicity using an in vivo time course model. The sample was manufactured to be 5 nm wide and up to 200 um long, with approximately 50% purity covalently bound with hexagonal boron nitride (hBN) in the sample. Following preparation for in vivo studies, sonication of the material disrupted the longer tubes in the complex and the size distribution in dispersion medium (DM) of the structures was 13-23 nm in diameter and 0.6-1.6 um in length. Male C57BL/6 J mice were exposed to 4 or 40 ug of BNNT or DM (vehicle control) by a single oropharyngeal aspiration. Pulmonary and systemic toxicity were investigated at 4 h, 1 d, 7 d, 1 mo and 2 mo post-exposure. Bronchoalveolar lavage (BAL) studies determined pulmonary inflammation (neutrophil influx) and cytotoxicity (lactate dehydrogenase activity) occurred at early time points and peaked at 7 d post-exposure in the high dose group. Histopathological analysis showed a minimal level of inflammatory cell infiltration in the high dose group with resolution over time and no fibrosis, and lung clearance analysis showed approximately 50% of the material cleared over the time course. The expression of inflammatory- and acute phase response-associated genes in the lung and liver were significantly increased by the high dose at 4 h and 1 d post-exposure. The increases in lung gene expression of Cxcl2, Ccl2, Il6, Ccl22, Ccl11, and Spp1 were significant up to 2 mo but decreased with time. The low dose exposure did not result in significant changes in any toxicological parameters measured. In summary, the BNNT-hBN sample used in this study caused acute pulmonary inflammation and injury at the higher dose, which peaked by 7 d post-exposure and showed resolution over time. Further studies are needed to determine if physicochemical properties and purity will impact the toxicity profile of BNNT and to investigate the underlying mechanisms of BNNT toxicity. [Description provided by NIOSH]
• Subjects:
  Immune System Laboratories Lung Occupational Health Particulate Matter Pathology Respiratory System Safety Toxicology
• Keywords:
  Author Keywords: Boron Nitride Nanotubes Boron Nitride Exposure Assessment Immune Reaction Inflammation In Vivo In Vivo Study Laboratory Animals Lung Irritants Nanotechnology Nanotoxicology Nanotubes Neutrophils Particle Size Pulmonary Effects Pulmonary Toxicity

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• ISSN:
  2452-0748
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; RHD - Respiratory Health Division ; DFSE - Division of Field Studies and Engineering
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  19
• NIOSHTIC Number:
  nn:20060356
• Citation:
  NanoImpact 2020 Jul; 19:100235
• Contact Point Address:
  J.R. Roberts, CDC/NIOSH/HELD/ACIB, 1095 Willowdale Rd., MS4020/L3407, Morgantown, WV
• Email:
  jur6@cdc.gov
• CAS Registry Number:
  Boron nitride (CAS RN 10043-11-5)
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Manufacturing ; Services
• Peer Reviewed:
  True
• Source Full Name:
  NanoImpact
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:cd2efcc33eaf6921d9dd9644103aca62d20d5542c1b7f67f5e756b6a2985deab635992aeec1ad9bf970c76e6b9a4f57ae945410bb066be34ecbfca1b8ad73960
• Download URL:
  https://stacks.cdc.gov/view/cdc/224294/cdc_224294_DS1.pdf
• File Type:
  [PDF - 4.32 MB ]