Oxidative Stress and Inflammatory Response in Dermal Toxicity of Single-Walled Carbon Nanotubes

Details

• Personal Author:
  Castranova, Vincent ; Kagan VE ; Kisin E ; Kommineni C ; Leonard, Stephen S. ; Murray AR ; Shvedova AA ; Young SH
• Description:
  Single-walled carbon nanotubes (SWCNT) represent a novel material with unique electronic and mechanical properties. The extremely small size (approximately 1 nm diameter) renders their chemical and physical properties unique. A variety of different techniques are available for the production of SWCNT; however, the most common is via the disproportionation of gaseous carbon molecules supported on catalytic iron particles (high-pressure CO conversion, HiPCO). The physical nature of SWCNT may lead to dermal penetration following deposition on exposed skin. This dermal deposition provides a route of exposure which is important to consider when evaluating SWCNT toxicity. The dermal effects of SWCNT are largely unknown. We hypothesize that SWCNT may be toxic to the skin. We further hypothesize that SWCNT toxicity may be dependent upon the metal (particularly iron) content of SWCNT via the metal's ability to interact with the skin, initiate oxidative stress, and induce redox-sensitive transcription factors thereby affecting/leading to inflammation. To test this hypothesis, the effects of SWCNT were assessed both in vitro and in vivo using EpiDerm FT engineered skin, murine epidermal cells (JB6 P+), and immune-competent hairless SKH-1 mice. Engineered skin exposed to SWCNT showed increased epidermal thickness and accumulation and activation of dermal fibroblasts which resulted in increased collagen as well as release of pro-inflammatory cytokines. Exposure of JB6 P+ cells to unpurified SWCNT (30% iron) resulted in the production of ESR detectable hydroxyl radicals and caused a significant dose-dependent activation of AP-1. No significant changes in AP-1 activation were detected when partially purified SWCNT (0.23% iron) were introduced to the cells. However, NFkB was activated in a dose-dependent fashion by exposure to both unpurified and partially purified SWCNT. Topical exposure of SKH-1 mice (5 days, with daily doses of 40 ug/mouse, 80 ug/mouse, or 160 ug/mouse) to unpurified SWCNT caused oxidative stress, depletion of glutathione, oxidation of protein thiols and carbonyls, elevated myeloperoxidase activity, an increase of dermal cell numbers, and skin thickening resulting from the accumulation of polymorphonuclear leukocytes (PMNs) and mast cells. Altogether, these data indicated that topical exposure to unpurified SWCNT, nduced free radical generation, oxidative stress, and inflammation, thus causing dermal toxicity. [Description provided by NIOSH]
• Subjects:
  Animals Chemistry Dermatitis Hypersensitivity Laboratories Occupational Health Oxidants Risk Assessment Risk Factors Safety Skin Skin Absorption Skin Diseases Workplace

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• Keywords:
  Animal-studies Author Keywords: Single-walled Nanotubes Cell-biology Cell-damage Cellular-reactions Chemical-analysis Chemical-composition Chemical-hypersensitivity Chemical-reactions Dermatosis Dose-response Electron Spin Resonance Glutathione Laboratory-animals Laboratory-testing Nanotechnology Oxidative-metabolism Oxidative-processes Oxidative Stress Physical-reactions Risk-analysis Risk-factors Skin-absorption Skin-diseases Skin-disorders Skin-exposure Skin-irritants Skin-sensitivity Work-environment

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• ISSN:
  0300-483X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  161-171
• Volume:
  257
• Issue:
  3
• NIOSHTIC Number:
  nn:20035029
• Citation:
  Toxicology 2009 Mar; 257(3):161-171
• Contact Point Address:
  A.R. Murray & A.A. Shvedova, Health Effects Laboratory Division, Pathology and Physiology Research Branch, NIOSH, M/L 2015, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  zsk1@cdc.gov
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0)
• Federal Fiscal Year:
  2009
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Toxicology
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e11d8430a6303d00de75a07e12b72b8d086ebcfd91208f13dfc5f4f8bd0452622e1deb29810479a84e2f530bc83909aa918dcbad1857e8524edb574257445239
• Download URL:
  https://stacks.cdc.gov/view/cdc/187022/cdc_187022_DS1.pdf
• File Type:
  [PDF - 1.05 MB ]