Pulmonary Toxicity of Intratracheally Instilled Multiwall Carbon Nanotubes in Male Fischer 344 Rats

Abstract

In order to assess pulmonary toxicity of multiwall carbon nanotubes (MWCNT), male F344 rats were intratracheally instilled with MWCNT suspension at a dose of 40 or 160 μg/head or α-quartz particles as a positive control at a dose of 160 μg/head and sacrificed for lung histopathology and bronchoalveolar lavage (BAL) fluid analyses on Day 1, 7, 28 or 91 after instillation. Well-dispersed MWCNT brought about dose- or time-dependent changes in lung weight, total proteins, albumin, lactate dehydrogenase and alkaline phosphatase in the BAL fluid, and pulmonary lesions including inflammation, Type II cell hyperplasia, microgranulomas and fibrosis. Phagocytosed and free forms of MWCNT were found in both bronchiolar and alveolar spaces. MWCNT deposition in the bronchus-associated lymphoid tissue gradually increased after instillation. Persistent infiltration of macrophages, transient infiltration of inflammatory cells primarily composed of neutrophils, microgranulomas associated with macrophages engulfing MWCNT, Type II cell hyperplasia and fibrosis with alveolar wall thickening as well as number of multinucleated alveolar macrophages increased dose-dependently. The MWCNT-induced lesions were more potent on Day 91 than the α-quartz-induced ones at an equal mass dose. The present results for intratracheally instilled MWCNT were extrapolated to potential inhalation exposure of humans to MWCNT at workplaces based on several assumptions.