Mouse Pulmonary Dose- and Time Course-Responses Induced by Exposure to Nitrogen-Doped Multi-Walled Carbon Nanotubes

Details

• Personal Author:
  Andrew M ; Battelli L ; Castranova, Vincent ; Chen BT ; Cruz-Silva R ; Endo M ; Orandle M ; Porter DW ; Terrones M ; Tsuruoka S ; Wolfarth MG ; Wu N
• Description:
  Multi-walled carbon nanotubes (MWCNT) can be modified by doping them with other elements. These modifications change the intrinsic properties of MWCNT and may also alter their bioactivity. In this study, we compared the in vivo bioactivity of nitrogen doped multiwalled carbon nanotubes (NDMWCNT) to pristine MWCNT to test the hypothesis that nitrogen doping would alter their bioactivity. First, characterization of the MWCNT and NDMWCNT was conducted. High resolution TEM confirmed the multilayer structure of MWCNT with an average layer distance of 0.36 nm, which was not altered by nitrogen doping. TEM analyses indicated the nanomaterials had similar widths (NDMWCNT=53 nm, MWCNT=49 nm) and lengths (NDMWCNT=4.73 microm, MWCNT=3.86 microm). Comparison of MWCNT and NDMWCNT XPS spectra demonstrated presence of a N1S peak, while FTIR spectra indicated the presence of N-H bonding only in the NDMWCNT sample. For in vivo studies, male C57BL/6J mice received a single dose of either dispersion medium (DM: vehicle control), 2.5, 10, or 40 microg/mouse of NDMWCNT, or 40 microg/mouse of MWCNT. Animals were euthanized at 1 and 7 days post-exposure for whole lung lavage (WLL) studies. NDMWCNT caused time- and dose-dependent pulmonary inflammation. However, on an equivalent mass basis, it is less than that caused by MWCNT. Activation of the NLRP3 inflammasome was assessed in mice exposed to 40 microg MWCNT or NDMWCNT by measuring cathepsin activity and cytokine production in acellular WLL fluid at 1 day post-exposure. In comparison to DM-exposed mice, cathepsin activity, as well as IL-1beta and IL-18, was significantly increased in MWCNT- and NDMWCNT-exposed mice. Comparison of MWCNT- to NDMWCT-exposed mice showed that cathepsin activity, IL-1beta and IL-18 were significantly higher in MWCNTexposed mice. At 56 days post-exposure, histopathological analyses determined lung fibrosis in MWCNT-exposed mice was greater than that determined for NDMWCNT-exposed mice. These data indicate that nitrogen doping of MWCNT decreases their bioactivity, and that lower activation of the NLRP3 inflammasome by NDMWCNT relative to MWCNT may be responsible. [Description provided by NIOSH]
• Subjects:
  Immune System Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety Toxicology
• Keywords:
  Dose Response Immune Reaction Lung Fibrosis Multi-walled Carbon Nanotubes MWCNT Nanotoxicology
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; OSHA Region 6 ; Pennsylvania ; Texas ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  162
• Issue:
  1
• NIOSHTIC Number:
  nn:20051257
• Citation:
  Toxicologist 2018 Mar; 162(1):419
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 57th Annual Meeting and ToxExpo, March 11-15, 2018, San Antonio, Texas
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:204353117b6736511fcd341a48ef0658b382c070982410d1051c30011c3356b5d0d45dd0f5177ab972dbc7eacd722a8b428699c872f099ebbc9545c5e2f25069
• Download URL:
  https://stacks.cdc.gov/view/cdc/211319/cdc_211319_DS1.pdf
• File Type:
  [PDF - 832.97 KB ]