Single-walled carbon nanotubes induce oxidative stress and inflammation in skin.
Murray AR; Kisin E; Kommineni C; Kagan VE; Castranova V; Shvedova AA
Toxicologist 2007 Mar; 96(1):291
Single-walled carbon nanotubes (SWCNT) are a novel material with unique electronic and mechanical properties. 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 (HiPco). The SWCNT produced by this method usually contain significant amounts of iron that may act as a catalyst of oxidative stress. The skin is a prime target for SWCNT toxicity as topical exposure can result during technologic processing and use. We hypothesized that SWCNT are toxic to the skin and the toxicity is dependent on their content of iron. The major toxicity mechanisms include induction of an inflammatory response, and oxidative stress exacerbated by iron. To test this hypothesis, the effects of SWCNT were assessed in vitro and in vivo. Exposure of human keratinocytes (HaCaT) revealed cytotoxicity in cells exposed to SWCNT; partially-purified SWCNT (0.25 weight % iron) exerted lower toxicity than unpurified SWCNT (40 weight % iron). Murine epidermal cells (JB6 P+) revealed a significant dose-dependent activation of AP-1 following exposure to unpurified SWCNT while partially-purified SWCNT did not activate AP-1. NF-kappa B was dose-dependently activated by both unpurified and partially-purified SWCNT. In vivo experiments evaluated the skin of SKH-1 mice following 5 days of unpurified SWCNT exposure (2, 4, or 8 mg/kg). Depletion of glutathione, increased myeloperoxidase activity, and an increase in IL-6 levels were observed following exposure to unpurified SWCNT. Histological evaluation of the skin following SWCNT exposure revealed an increased number of mast cells and polymorphonuclear leukocytes around hair follicles of the mouse skin. These data indicate that dermal exposure to SWCNT, particularly unpurified SWCNT, can result in inflammation, oxidative stress and dermal toxicity during occupational exposures.
Physical-reactions; Risk-analysis; Risk-factors; Dose-response; Chemical-analysis; Chemical-composition; Chemical-hypersensitivity; Chemical-reactions; Work-environment; Animal-studies; Skin-absorption; Skin-diseases; Skin-exposure; Skin-irritants; Skin-disorders; Skin-sensitivity; Dermatitis; Dermatosis; Oxidative-metabolism; Oxidative-processes; Cell-biology; Cell-damage; Cellular-reactions; Nanotechnology
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina