Carbon nanotubes (CNT) are new members of carbon allotropes similar to fullerenes and graphite. Because of their unique electrical, mechanical and thermal properties, carbon nanotubes are being evaluated for novel applications in the electronics, aerospace and computer industries. Previously, we have observed that exposure of human bronchial epithelial cells to CNT induced iron-dependent oxidative stress, depletion of antioxidants, morphological changes, cytotoxicity, and apoptosis. In the current study, we investigated pulmonary toxicity of CNT in C57BL/6 mice after pharyngeal aspiration. End points were examined on days 1, 3, 7, 14, 28, and 60 post-exposure. We found that CNT caused dose-dependent formation of granulomatous bronchointerstitial pneumonia, fibrosis, and altered pulmonary function. Administration of CNT to C57BL/6 mice also resulted in a dose-dependent augmentation of inflammation biomarkers quantified by cell counts, total protein, lactate dehydrogenase (LDH) and gamma-glutamyltranspeptidase (GGT) activities in bronchoalveolar lavage (BAL) fluid samples. Markers of pulmonary cytotoxicity were associated with the development of inflammation, collagen accumulation, and pulmonary fibrosis. TGF-B was maximally increased in BAL fluid of mice 7 days after CNT exposure and correlated with morphometric evidence of collagen formation as well as pulmonary function changes. Mice exposed to an equal mass of ultrafine carbon black or fine crystalline silica exhibited less PMN recruitment and cytotoxicity than mice receiving CNT. Our data suggest that exposure to CNT leads to pulmonary toxicity involving inflammation and oxidative stress, which culminates in the development of multifocal granulomatous pneumonia and fibrosis.
Toxic-effects; Toxins; Thermal-properties; Electronics-industry; Aerospace-industry; Laboratory-animals; Animals; Animal-studies; Pulmonary-system-disorders; Exposure-levels; Exposure-assessment; Fibrosis; Biomarkers; Cytotoxicity; Cytotoxic-effects; Cytotoxins; Respiratory-system-disorders; Nanotechnology
The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana