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Pulmonary fibrotic response to subchronic multi-walled carbon nanotube exposure.
Mercer-RR; Hubbs-AF; Scabilloni-JF; Wang-L; Battelli-LA; Castranova-V; Porter-DW
Toxicologist 2011 Mar; 120(Suppl 2):11
Multi-walled carbon nanotubes (MWCNTs) are manufactured carbon compounds with many commercial applications. To address the hypothesis that MWCNTs cause persistent pulmonary pathology, C57BL/6J mice were exposed by pharyngeal aspiration to 10, 20, 40 or 80 ug MWCNTs (mean dimensions of 3.9 um x 49 nm) or vehicle. Lungs were preserved at 1, 7, 28 and 56 days post exposure to analyze the distribution of lung burden. Morphometric measurement of Sirius Red staining was used to assess the connective tissue response. At day 1 post-exposure 62.0+/-2.5 and 9.9+/-2 percent of the lung burden (mean+/-SE, N=7) were in alveolar macrophages and alveolar tissue, respectively. The remainder of the lung burden (18.0+/-3.2) was in the airways. By 56 days post-exposure, 68.7+/-3.9, 7.5+/-1.9 and 22.0+/-5.1 percent of MWCNT were in alveolar macrophages, alveolar tissue and granulomatous lesions, respectively. No MWCNTs were found in the airways at 56 days. At 56 days post-exposure the average thickness of connective tissue in alveolar regions was 0.11+/-0.01, 0.12+/-.01, 0.12 +/-0.01, 0.16+/-0.01 and 0.19+/-0.01 um (mean+/-SE, N=6) for vehicle, 10, 20, 40 and 80 ug dose groups, respectively. The connective tissue in the alveolar region demonstrated a progressive increase in thickness over time in the 80 ug exposure group (0.11+/-0.01, 0.14 +/-0.01, 0.16+/-0.01 and 0.19+/-0.01 um for 1, 7, 28 and 56 day). The distribution of lung burden was predominately within alveolar macrophages with approximately 8% delivery to the alveolar tissue. Despite the relatively low fraction of the lung burden being delivered to the alveolar tissue (7.5% at day 56), the average thickness of connective tissue in the alveolar region was increased over vehicle control by 45% in the 40 ug and 72% in 80 ug exposure groups. These results demonstrate that MWCNT have the potential to produce a progressive, fibrotic response in the alveolar tissues of the lungs.
Airborne-particles; Air-contamination; Biological-effects; Cell-biology; Cellular-reactions; Cytotoxicity; Dose-response; Exposure-levels; Inhalation-studies; Lung; Lung-disorders; Lung-fibrosis; Lung-irritants; Microscopic-analysis; 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
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