The large scale manufacture of multi-walled carbon nanotubes (MWCNT) suggests occupational exposures may occur. In order to investigate the pulmonary toxicity of MWCNT, male C57BL6/J mice (6 weeks old) were exposed to aerosolized MWCNT (10 mg/m3, 5 hours per day; mass mode aerodynamic diameter 1.3 um, count mode aerodynamic diameter 0.4 um) for 2, 4, and 8 days. All mice were sacrificed at one day 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. Air-exposed controls had 0.2 +/- 0.1 (x 103) PMNs/mouse. MWCNT exposure increased PMNs levels to 153.7 +/- 26.6 and 125.2 +/- 26.2 (x 103) PMNs/mouse after 2 and 4 days exposure, respectively. After 8 days exposure, PMNs increased further to 1,151.7 +/- 124.2 (x 103) PMNs/mouse. In air-exposed controls, BAL fluid LDH activity was 58 +/- 3 (units/l), and MWCNT exposure induced significant increases to 131 +/- 6, 159 +/- 9, and 252 +/- 10 (units/l) after 2, 4 and 8 days exposure, respectively. Air-exposed control BAL fluid albumin was 0.13 +/- 0.01 (mg/ml), and MWCNT exposure induced significant increases to 0.19 +/- 0.01, 0.28 +/- 0.02, and 0.37 +/- 0.02 (mg/ml) after 2, 4 and 8 days exposure, respectively. Histopathological evaluation of lungs after 4 and 8 days of exposure confirmed pulmonary inflammation. After 8 days of MWCNT exposure, some mice had histopathological evidence of fibrosis at sites of MWCNT deposition. In summary, these data indicate that exposure to aerosolized MWCNTs results in dose-dependent increases in pulmonary inflammation and damage, suggesting that aerosolized MWCNT may pose an occupational health hazard. However, additional dose-response and time course studies are necessary to fully evaluate the potential health risks posed by exposure to aerosolized MWCNT.
Airborne-particles; Aerosol-particles; Biological-effects; Biological-factors; Blood-cells; Blood-stream; 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; Particle-aerodynamics; Particulates; Pulmonary-function; Pulmonary-disorders; Pulmonary-system-disorders; Respiratory-irritants; Respiratory-hypersensitivity; Risk-factors; Statistical-analysis; Tissue-culture; Toxic-effects; Nanotechnology
The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland