Comparative Assessment of In Vivo Toxicity Induced by Multiwalled Carbon Nanotubes and Nanofibers from US Facilities

Details

• Personal Author:
  Birch EM ; Bunker K ; Casuccio G ; Dahm, Matthew M. ; Erdely A ; Evans DE ; Eye T ; Fraser K ; Friend S ; Kodali VK ; Orandle MS ; Schubauer-Berigan, Mary K. ; Schwegler-Berry D ; Wu NQ ; Yanamala N
• Description:
  Pulmonary exposure to carbon nanotubes or nanofibers (CNT/F), known to induce inflammation, toxicity, or tumorigenesis, is a concern during production and dry powder handling. CNT/F represent a large class of materials and it is unclear if all confer similar toxicity. Our aim was to simultaneously test the pulmonary effects induced by CNT/F with variable physicochemical properties obtained from US facilities. Characterization was done for seven different multiwalled CNT and two CNF selected based on nominal diameter ranging from 10-150 nm. Cytotoxicity, inflammation, and histopathology was assessed in mice 1, 7, 28, and 84 d following oropharyngeal aspiration to 4 or 40 microg of each material. Utilized doses and material preparation for in vivo dosing were representative to ongoing occupational exposures. Lactate dehydrogenase (LDH) activity, a marker of cytotoxicity, was dose-dependently increased in bronchoalveolar lavage fluid (BALF) resolving toward baseline by 84 d in all groups. In materials with a diameter greater than or equal to 50 nm, LDH was persistently increased. Polymorphonuclear cell infiltration (%PMN), a marker of inflammation, was increased in all materials at 1 d post-exposure to 40 microg (<50 nm: 31.1%, >/= 50 nm: 37.1%). With exposure to materials less than 50 nm, PMN influx mostly resolved by 7 d while materials greater than or equal to 50 nm induced persistent inflammation (7 d: <50 nm: 10.5%, >/= 50 nm: 48.9%). For complement, inflammatory gene expression in lung tissue (e.g., Il1b, Il6, Ccl22, Cxcl2) and protein levels in BALF (e.g. Il1b, Il6, Il5, Ccl22, Cxcl1), were elevated to a greater extent in materials with a nominal tube diameter greater than or equal to 50 nm. In contrast, microscopic evaluation of lung sections at 84 d post-exposure indicated that histopathology does not appear distinguishable between CNT/F using diameter. In conclusion, general cytoxicity and inflammation exhibited a relationship with nominal diameter, with a threshold of sustained effects at approximately 50 nm and greater, that was dissimilar to histopathology. Ongoing research and modeling techniques will elucidate relationships between physicochemical characteristics and toxicities of various CNT/F. [Description provided by NIOSH]
• Subjects:
  Biomarkers Chemistry Cytotoxins Immune System Laboratories Lung Occupational Health Respiratory System Safety Toxicology
• Keywords:
  Carbon Nanofibers Carbon Nanotubes Cellular Reactions Chemical Properties CNF Cytotoxicity Dose Response Exposure Assessment Gene Expression Health Effects Histopathology Immune Reaction In Vivo Study Laboratory Animals Laboratory Testing Lung Cells Lung Tissue Multi-walled Carbon Nanotubes MWCNT Nanotechnology Nanotoxicology Particle Diameter Physical Properties Proteins Pulmonary Effects Toxic Effects

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Ohio ; OSHA Region 3 ; OSHA Region 5 ; OSHA Region 6 ; Pennsylvania ; Texas ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; DSHEFS - Division of Surveillance, Hazard Evaluations, and Field Studies ; DART - Division of Applied Research and Technology
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  162
• Issue:
  1
• NIOSHTIC Number:
  nn:20051244
• Citation:
  Toxicologist 2018 Mar; 162(1):407
• 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-512:06b10dcc4584c1f097dea57a52c9304a9a09dc8205b0991da213e1d1425beb6ba30677fa6f3d118d1bbfe4b0572e97eb543ce946fb0c8def8f68a13dacb3202c
• Download URL:
  https://stacks.cdc.gov/view/cdc/211310/cdc_211310_DS1.pdf
• File Type:
  [PDF - 839.69 KB ]