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, 8 and 12 days. All mice were sacrificed at one day post-exposure. Whole lung lavage (WLL) was conducted and polymorphonuclear leukocytes (PMNs) were assessed to index pulmonary inflammation. WLL fluid assays included lactate dehydrogenase (LDH) activity as a measure of cytotoxicity, albumin as a marker of the lung air-blood barrier integrity, as well as various cytokines. MWCNT lung burden ranged from 6.6 +/- 0.5 ug/lung (2 days exposure) to 30.6 +/- 1.2 ug/lung (12 days exposure). MWCNT-exposure induced increases in PMN levels from 152 +/- 27 (x 103) PMNs/mouse (2 days exposure) to 1,893 +/- 462 (x 103) PMNs/mouse (12 days exposure). MWCNT-exposure increased WLL fluid albumin from 0.18 +/- 0.01 mg/ml (2 days exposure) to 0.41 +/- 0.04 mg/ml (12 days exposure), while WLL fluid LDH increased from 131 +/- 6 units/L (2 days exposure) to 286 +/- 35 units/L (12 days exposure). MWCNT exposure caused increased interleukin-6 (IL-6), chemokine ligands 1 and 2 (CXCL1, CCL2), and granulocyte macrophage colony stimulating factor (GM-CSF) levels relative to air-exposed controls. 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.
Aerosol-particles; Airborne-particles; Air-contamination; Biological-effects; Cell-biology; Cellular-reactions; Cytotoxic-effects; Cytotoxicity; Dose-response; Exposure-levels; Inhalation-studies; Laboratory-animals; Laboratory-testing; Lung; Lung-disease; Lung-disorders; Lung-function; Lung-irritants; Nanotechnology; Physiological-effects; Pulmonary-system-disorders; Quantitative-analysis; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Statistical-analysis; Toxic-effects
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC