Characterization of lung toxicity following pulmonary exposure to graphene nanoparticles in different oxidized forms

Details

• Personal Author:
  Bishop L ; Castranova, Vincent ; Chaudhuri IS ; Erdely A ; Eye T ; Farris BY ; Kodali V ; Kyrlidis A ; Leonard, Stephen S. ; McLoughlin CE ; Mercer RR ; Porter DW ; Roach KA ; Roberts, Jennifer R. ; Sager T ; Schwegler-Berry D ; Stefaniak, Aleksandr B. ; Wolfarth M ; Yanamala NV
• Description:
  As the manufacturing of graphene nanoparticles (GNP) increases, there is concern for the health effects that due to lung exposure in workers. This study evaluated lung toxicity of different oxidized forms of GNP: non-oxidized graphite nanoplates (Gr), an oxidized intermediate (GO), and the reduced form of GO (rGO), with multi-walled carbon nanotubes (MWCNT, Mitsui-7) as a particle control. Male C57BL/6J mice received 4 or 40 microg of Gr, GO, rGO, MWCNT, or dispersion medium (DM) by oropharyngeal aspiration. Bronchoalveolar lavage (BAL) was performed at 4 hr, 1 d, 7 d, 1 m, and 2 m post-exposure. In separate mice, lungs were preserved for pathology and RNA analysis. Lung injury was elevated in MWCNT and rGO at 40 microg when compared to all groups at all times, with the greatest increase in the MWCNT group at 1 and 7 d, and in the rGO group at 1 and 2 m. Gr and GO at 40 microg, and MWCNT at 4 microg increased injury at early time points only. Alveolar macrophages (AM) in BAL were elevated in all 40 microg groups at 7 d, with the greatest increase in the rGO animals at 7 d and 1 m. This response persisted for the rGO and MWCNT 40 microg groups up to 2 m. BAL neutrophils were increased in all 40 microg groups up to 7 d, and persisted in the MWCNT and rGO groups up to 2 m. 4 microg doses of rGO and MWCNT also caused increased neutrophils at early time points. Acutely, all 40 microg exposures increased relative mRNA expression of Cxcl2, Ccl2, Il6, and Ccl22. The effects persisted 1 m in the Gr and GO 40 microg dose and MWCNT 4 microg dose, and 2 m for rGO and MWCNT 40 microg groups. Histopathology showed fibrosis at 7 d in MWCNT and rGO 40 microg groups scored as minimal, which persisted throughout the time course, and mild type II epithelial hyperplasia and inflammation, which resolved over time. Gr and GO caused transient inflammation/injury, whereas rGO caused comparable toxicity to MWCNT. Differences in toxicity may be due to chemistry, shape, and/or density of materials, with a higher volume load per mass delivered for the low density particles, MWCNT and rGO. [Description provided by NIOSH]
• Subjects:
  Blood Environmental Exposure Fibrosis Hazardous Substances Immune System Laboratories Lung Lung Diseases Macrophages Occupational Health Particulate Matter Pathology Respiratory System Respiratory Tract Diseases Safety Toxicology

  More +
• Keywords:
  Alveolar Cells Dispersion Dose Response Exposure Assessment Exposure Levels Gene Expression Graphene Histopathology Immune Reaction Inhalation Laboratory Animals Laboratory Testing Lung Fibrosis Lung Function Multi-walled Carbon Nanotubes MWCNT Nanoparticles Nanoplates Nanotechnology Neutrophils Oxidation Oxides Particle Size Pulmonary Effects Pulmonary System Ribonucleic Acids RNA Toxic Effects Toxic Materials

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; Massachusetts ; OSHA Region 1 ; OSHA Region 3 ; OSHA Region 6 ; 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:
  150
• Issue:
  1
• NIOSHTIC Number:
  nn:20047823
• Citation:
  Toxicologist 2016 Mar; 150(1):586
• CAS Registry Number:
  Graphene (CAS RN 1034343-98-0)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 55th Annual Meeting and ToxExpo, March 13-17, 2016, New Orleans, Louisiana
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:061ebf495093900bd18e99b7d52709591d31a87ae0652bd05228a17638281441cab8fe2cbdbd65814b70ae772e567aac94b953b7a61a006b32b04d2359a1acc0
• Download URL:
  https://stacks.cdc.gov/view/cdc/202791/cdc_202791_DS1.pdf
• File Type:
  [PDF - 443.12 KB ]