Pulmonary effects of single-walled carbon nanotubes: inhalation vs aspiration.
Kisin-E; Murray-AR; Hubbs-AF; Mercer-RR; Keohavong-P; Sussman-N; Chen-BT; Deye-G; Castranova-V; Baron-PA; Kagan-VE; Shvedova-AA
Toxicologist 2009 Mar; 108(1):459
Health effects and occupational risk of exposures associated with manufacturing and application of nanoparticles are critical points for the safe and sustainable development of nanotechnology. The toxic effects of nanoscale materials have not been fully characterized and the limited in vivo studies indicate the urgent necessity for further toxicological assessments of nanomaterials. Some argue that pharyngeal aspiration - a single exposure to a bolus of SWCNT - is an artificial exposure where the single large dose contributes to the pulmonary response. Moreover, aspiration studies reported thus far have been relatively high dose exposures, which may not be relevant to chronic lower dose seen in occupational settings. Inhalation of SWCNT more closely mimics occupational and environmental venues than the above mentioned administrations providing more dispersed SWCNT structures while bolus effects are avoided. By applying a new technique to aerosolize SWCNT, we obtained stable and uniform SWCNT dispersions with a concentration of 5 mg/m3 and a count mode aerodynamic diameter of 240 nm for the inhalation experiments. In the current study, we utilized non-purified SWCNT containing up to 17.7% of iron for both inhalation (5 mg/m3, 5 hrs/day for 4 days) and aspiration (varying doses of 5- 20 ug/mouse) exposures. Pathological events in both exposure routes were realized through qualitatively similar synergized interactions of early inflammatory response and oxidative stress culminating in the development of multifocal granulomatous pneumonia and interstitial fibrosis. Quantitatively, SWCNT inhalation was more effective than aspiration in causing inflammatory response, oxidative stress, collagen deposition and fibrosis as well as mutations of K-ras gene locus in the lung of C57BL/6 mice.
Aerosol-particles; Biological-effects; Biological-factors; Cellular-reactions; Cell-biology; Cytology; Exposure-assessment; Exposure-levels; Exposure-methods; Genotoxic-effects; Irritants; Inhalation-studies; Laboratory-animals; Lung-cells; Lung-disorders; Lung-irritants; Microscopic-analysis; Microscopy; Oxidative-metabolism; Oxidative-processes; Particle-aerodynamics; Particulates; Qualitative-analysis; Respiratory-irritants; Respiratory-system-disorders; Risk-factors; Statistical-analysis; Toxic-effects; Nanotechnology
The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland
University of Pittsburgh at Pittsburgh