Single-walled carbon nanotubes (SWCNT) and carbon nanofibers (CNF) are carbonaceous nanoparticles sharing fibrous morphology with a well-known, naturally occurring, toxic fiber, asbestos. Both short- and long-term outcomes of pulmonary exposure to asbestos, ranging from inflammation and fibrosis to mesothelioma and lung cancer, are well described. To date, no data are available describing longterm adverse effects of pulmonary exposure to SWCNT or CNF. Thus, a direct comparison of chronic effects of SWCNT, CNF and asbestos is of significant importance. Here, we assessed inflammatory, fibrogenic and genotoxic effects of SWCNT, CNF, and asbestos in C57BL/6J mice one year after a single pulmonary exposure by pharyngeal aspiration and inhalation. We provide evidence that up to one year after exposure, SWCNT, CNF and asbestos persist in the lung and regional lymphatics. All three particles induced chronic bronchopneumonia and lymphadenitis, accompanied by pulmonary fibrosis. While CNF and asbestos were found to promote the greatest degree of inflammation, followed by SWCNT, the latter was the most fibrogenic of all three types. SWCNT induced cytogenetic alterations including micronuclei and nuclear protrusions in vivo. Notably, SWCNT and CNF, but not asbestos, increased the incidence of K-ras oncogene mutations in lungs. No lung tumor incidence occurred after 1 year post exposure in any group. Inhalation exposure to SWCNT showed significantly greater inflammatory, fibrotic and genotoxic effects than bolus pharyngeal aspiration thus indicating that bolus exposure does not over-predict pulmonary response and appears useful for hazard determination. Overall, our data suggest that long-term pulmonary toxicity of particles with high aspect ratios - SWCNT, CNF and asbestos – is defined not only by their fibrous morphology but also by the chemical composition, specific surface area and type of exposure.
Toxicology; Exposure-levels; Nanotechnology; Toxins; Chemical-composition; Chemical-properties; Particulates; Cell-biology; Cell-function; Cellular-function; Animals; Laboratory-animals; Lung; Lung-function; Lung-tissue; Respiratory-system-disorders; Pulmonary-function; Pulmonary-disorders; Pulmonary-system; Pulmonary-system-disorders; Asbestos-fibers; Fibrous-bodies; Fibrosis; Cancer; Mesothelial-cells
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona