Pulmonary inflammation, epithelial hyperplasia, and lymph node translocation after multi-walled carbon nanotube inhalation.
Multi-walled carbon nanotubes (MWCNTs) are engineered nanotubes with multiple fullerene carbon walls, a high aspect ratio, and rapidly increasing industrial uses. To investigate the toxicity of inhaled MWCNTs, mice were exposed 5 hours/day to 10 mg/m3 MWCNTs (Mitsui, MWNT-7, count mode aerodynamic diameter 420 nm) for 4, 8 or 12 days and sacrificed 24 h post-exposures. Histopathologic sections of lung and tracheobronchial lymph nodes were examined at all time points and sections of nose (4 levels) were examined after the 12 day exposure. In lung, the principal changes were 1) inflammation centered around the bronchioloalveolar junction, 2) vasculitis, and 3) bronchiolar epithelial hypertrophy and hyperplasia. These were seen in all exposed mice (n=8, 6 and 6 at 4, 8 and 12 days, respectively). Peribronchiolar inflammation was principally histiocytic and neutrophilic with occasional giant cells. In many macrophages, cytopathologic changes included 1) MWCNT penetration of the cytoplasmic membrane, 2) MWCNT penetration of nuclei, and 3) karyolysis. Vascular changes were present in all exposed mice but manifestations varied and included medial hypertrophy and contraction, mural neutrophil infiltrates, and rare mural MWCNTs. Bronchiolar hypertrophy and hyperplasia were present after 4 days and persisted. After 12 days of exposure, all mice had foci of peribronchiolar fibrosis and bronchiolar epithelial mucous metaplasia. Pleural MWCNTs were seen in two mice. In lungs of air exposed controls (n=8, 6 and 6 at 4, 8 and 12 days, respectively), vasculitis and bronchiolar changes were absent; a single focus of inflammation was seen in one mouse. MWCNT translocation to the tracheobronchial lymph node progressed with time and localized to the deep paracortex, the normal location of T lymphocytes and dendritic cells. In the nose, neutrophilic rhinitis and hyaline droplet formation were consistent changes. These findings suggest that chronic inhalation toxicity studies are needed.
Aerosols; Animals; Animal-studies; Cell-biology; Cell-damage; Cytotoxic-effects; Cytotoxicity; Engineering-controls; Exposure-levels; Fumes; Inhalation-studies; Laboratory-animals; Lung; Lung-disease; Lung-disorders; Lung-function; Lung-irritants; Nanotechnology; Particle-aerodynamics; Particulates; Particulate-sampling-methods; Pulmonary-disorders; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Qualitative-analysis; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Tissue-disorders; Toxic-effects; Toxic-vapors; Vapors
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC