Acute In Vitro and In Vivo Toxicity of a Commercial Grade Boron Nitride Nanotube Mixture

Details

• Personal Author:
  Barger M ; Bishop L ; Chen BT ; Erdely AD ; Eye T ; Friend S ; Jordan KC ; Kodali VK ; Porter DW ; Roach KA ; Roberts, Jennifer R. ; Schwegler-Berry D ; Shoeb M ; Stefaniak, Aleksandr B. ; Whitney RR ; Wolfarth MG
• Description:
  Boron nitride nanotubes (BNNTs) are an emerging engineered nanomaterial attracting significant attention due to superior electrical, chemical and thermal properties. Currently, the toxicity profile of this material is largely unknown. Commercial grade BNNTs are composed of a mixture (BNNT-M) of approximately 50-60% BNNTs, and approximately 40-50% impurities of boron and hexagonal boron nitride. We performed acute in vitro and in vivo studies with commercial grade BNNT-M, dispersed by sonication in vehicle, in comparison to the extensively studied multiwalled carbon nanotube-7 (MWCNT-7). THP-1 wild-type and NLRP3-deficient human monocytic cells were exposed to 0-100 ug/ml and C57BL/6 J male mice were treated with 40 ug of BNNT-M for in vitro and in vivo studies, respectively. In vitro, BNNT-M induced a dose-dependent increase in cytotoxicity and oxidative stress. This was confirmed in vivo following acute exposure increase in bronchoalveolar lavage levels of lactate dehydrogenase, pulmonary polymorphonuclear cell influx, loss in mitochondrial membrane potential and augmented levels of 4-hydroxynonenal. Uptake of this material caused lysosomal destabilization, pyroptosis and inflammasome activation, corroborated by an increase in cathepsin B, caspase 1, increased protein levels of IL-1beta and IL-18 both in vitro and in vivo. Attenuation of these effects in NLRP3-deficient THP-1 cells confirmed NLRP3-dependent inflammasome activation by BNNT-M. BNNT-M induced a similar profile of inflammatory pulmonary protein production when compared to MWCNT-7. Functionally, pretreatment with BNNT-M caused suppression in bacterial uptake by THP-1 cells, an effect that was mirrored in challenged alveolar macrophages collected from exposed mice and attenuated with NLRP3 deficiency. Analysis of cytokines secreted by LPS-challenged alveolar macrophages collected after in vivo exposure to dispersions of BNNT-M showed a differential macrophage response. The observed results demonstrated acute inflammation and toxicity in vitro and in vivo following exposure to sonicated BNNT-M was in part due to NLRP3 inflammasome activation. [Description provided by NIOSH]
• Subjects:
  Cytotoxins Immune System Laboratories Occupational Health Safety
• Keywords:
  Author Keywords: Boron Nitride Nanotubes Boron Nitride Cytotoxicity Immune Reaction Inflammation In Vitro Studies In Vivo Studies Laboratory Animals Lysosomal Damage MWCNT-7 NALP3 Inflammasome Nanomaterials Nanotechnology Nanotubes Oxidative Stress Phagocytosis Pyroptosis

  More +
• ISSN:
  1743-5390
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Virginia ; 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:
  11
• Issue:
  8
• NIOSHTIC Number:
  nn:20050625
• Citation:
  Nanotoxicology 2017 Oct; 11(8):1040-1058
• Contact Point Address:
  Aaron Erdely, NIOSH/HELD/PPRB, 1095 Willowdale Rd, MS-2015, Morgantown, WV 26505-2888
• Email:
  efi4@cdc.gov
• CAS Registry Number:
  Boron nitride (CAS RN 10043-11-5)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Nanotoxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3531efdad516cf18f5957d3148e52d37fbcac44fb3f865f20f57f04d1ab17980e19aca56dcd58c2dbc3a737a62558de351f894f6f111b6b30ebf16555916f1ca
• Download URL:
  https://stacks.cdc.gov/view/cdc/210897/cdc_210897_DS1.pdf
• File Type:
  [PDF - 3.61 MB ]