All nanomaterials have a fundamental dimension less than 100 nanometers. However, agglomerates of nanomaterials, micrometers in diameter, are the more common form of the material. This is particularly evident in prior studies of the pulmonary toxicity of single walled carbon nanotubes (SWCNT) where large granulomatous lesions encased by epithelioid macrophages were produced by large agglomerates of SWCNT (approximately 15 um diameter). In this study, a highly dispersed preparation of SWCNT with a mean geometric diameter of 1.1 Ám was given by pharyngeal aspiration to C57BL/6 mice in order to determine the pulmonary toxicity. Lung responses were studied by lavage and morphometry of lung sections at 1 hour, 1 day, 7 days and 1 month after a single SWCNT exposure of 10 ug/mouse. A PBS aspiration group served as the negative control. Examination of lung sections and lavage cell differential demonstrated an early, transient neutrophilic, inflammatory phase which rapidly resolved and was similar to that observed with large agglomerates. However, no granulomatous lesions or epithelioid macrophages were detected. Electron microscopy demonstrated a highly dispersed, interstitial distribution of SWCNT deposits by 1 day. The deposits were generally less than 1 Ám. Alveolar macrophage phagocytosis of SWCNT was minimal at all times. Morphometric measurement of the Sirius red staining in sections was used to assess the connective tissue response. The average thickness of Sirius red stained connective tissue in alveolar regions, excluding alveoli adjacent to CNT deposits, was 0.10+/-0.02, 0.10+/-0.03, 0.09+/-0.02, 0.51+/-0.05 and 1.10+/-0.35 Ám (mean+/-SE N=6)for PBS, 1 hour, 1 day, 7 days and 1 month groups, respectively. The results demonstrate that dispersed SWCNT are rapidly incorporated into the alveolar interstitium and produce a generalized fibrotic response. Alveolar macrophage clearance is not a significant component of the lung response.
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina