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Responses of lung parenchyma to carbon nanotubes.

Mercer-RR; Scabilloni-J; Kisin-K; Gorelik-O; Arepalli-S; Murray-AR; Castranova-V; Shvedova-AA
Toxicologist 2005 Mar; 84(Suppl 1):213
An increasing number of applications have been and are being developed for new carbon allotropes such as carbon nanotubes (CNT). Pharyngeal aspiration by C57BL/6 mice was used to determine the pulmonary toxicity of CNT. Morphometry of paraffin sections from fixed lung tissue was used to determine the size of deposited CNT and the size of granulomatous lesions produced in response to the aspiration. Measurement of the Sirius red staining in sections was used to assess the connective tissue response. Lung responses were studied at 1 day, 7 days, 1 month and 2 months after a single CNT exposure of 0, 10, 20 or 40 microg/mouse. Examination of lung sections 1 day after aspiration, demonstrated that deposition of the CNT mass was generally in the first or second alveolar ducts proximal to the terminal bronchiole with an average diameter of 15.2 +/- 0.6 microm (mean +/- SE, n=12). At 1 day, CNT deposits were infiltrated with alveolar macrophages. At 7 days significant connective tissue accumulation was apparent within the CNT deposits. At 1 and 2 months, the granulomatous masses were encased in cuboidal epithelial cells. At 2 months, the granulomatous lesions accounted for 0, 0.7 +/- 0.1, 2.4 +/- 0.2 and 4.6 +/- 0.6 % of the alveolar parenchyma at doses of 0, 10, 20 and 40 microg/mouse, respectively. In addition to the granulomatous lesions there were also changes in the alveolar walls. For instance, the average thickness of Sirius red stained connective tissue in alveolar regions, excluding the granulomatous areas, was 0.10 +/- .03, 0.20 +/- .09, 0.3 +/- 0.09 and 0.5 +/- 0.1 microm at doses of 0, 10, 20 and 40 microg/mouse, respectively. The results demonstrate that CNT produce a rapid response in the alveolar region with both focal granulomatous lesions and a more generalized fibrotic response that is dose dependent.
Laboratory-animals; Animals; Animal-studies; Toxins; Toxic-effects; Pulmonary-system-disorders; Lung-tissue; Exposure-levels; Exposure-assessment; Respiratory-system-disorders; Nanotechnology
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The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana