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Pulmonary toxicity of multi-walled carbon nanotubes.

Wolfarth-MG; Porter-DW; Hubbs-AF; Leonard-S; Battelli-L; Andrew-M; Castranova-V
Toxicologist 2009 Mar; 108(1):457
Occupational exposures may occur due to the large scale manufacture of multiwalled carbon nanotubes (MWCNT). Because the toxicity of carbon nanotubes can be influenced by the presence of metal contaminants, bulk MWCNT were examined for their metal content. These analyses determined MWCNT had 0.78% metal contamination, with Fe (0.32%) being a major constitutent. Acellular electron spin resonance studies determined that MWCNT do not generate ROS, despite the presence of trace iron in the MWCNT. In order to investigate the pulmonary toxicity of MWCNT, male C57BL6/J mice (6 weeks old) were exposed by pharyngeal aspiration to MWCNT (0-40 mu g/mouse) and mice were sacrificed at 1,7, 28 and 56 days post-exposure. In bronchoalveolar lavage (BAL) studies, polymorphonuclear leukocytes (PMNs) were assessed to index pulmonary inflammation, BAL fluid lactate dehydrogenase (LDH) activity was measured as a marker of cytotoxicity, and BAL fluid albumin was determined as a marker of the lung airblood barrier integrity. MWCNT exposure induced dose- and time-dependent changes, with maximum changes occurring at 7 days post-exposure for all three BAL markers. At 7 days post-exposure, mice exposed to 40 mu g/mouse MWCNT had increased BAL PMNs (724-fold), BAL fluid LDH activity (2.6-fold) and BAL fluid albumin (2.4-fold) versus vehicle-exposed controls. At 56 days post-exposure, mice exposed to 40 mu g/mouse MWCNT still had increased BAL PMNs (22.3- fold), BAL fluid LDH activity (1.9-fold) and BAL fluid albumin (1.6-fold) versus vehicle-exposed controls. Thus, relative to 7 days post-exposure, these BAL markers had decreased, but were still significantly elevated above vehicle-exposed controls at 56 days post-exposure. At 28 and 56 days post-exposure, histopathology confirmed persistent interstitial inflammation and indicated fibrosis. In summary, these data indicate that exposure to MWCNT results in dose- and time-dependent changes in pulmonary inflammation and damage, suggesting that MWCNT may pose an occupational health hazard.
Airborne-particles; Aerosol-particles; Biological-effects; Biological-factors; Cell-morphology; Cellular-reactions; Cell-biology; Cytology; Exposure-assessment; Exposure-levels; Exposure-methods; Inhalation-studies; Irritants; Laboratory-animals; Lung-cells; Lung-irritants; Occupational-exposure; Microscopic-analysis; Metal-compounds; Metal-fumes; Metal-industry; Metal-industry-workers; Metal-oxides; Metal-workers; Metallic-fumes; Particle-aerodynamics; Particulates; Pulmonary-function; Pulmonary-disorders; Pulmonary-system-disorders; Respiratory-irritants; Respiratory-hypersensitivity; Risk-factors; Statistical-analysis; Tissue-culture; Toxic-effects; Nanotechnology
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The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland