Size‐ and shape‐dependent pleural translocation, deposition, fibrogenesis, and mesothelial proliferation by multiwalled carbon nanotubes

Abstract

Multiwalled carbon nanotubes (MWCNT) have a fibrous structure similar to asbestos, raising concern that MWCNT exposure may lead to asbestos-like diseases. Previously we showed that MWCNT translocated from the lung alveoli into the pleural cavity and caused mesothelial proliferation and fibrosis in the visceral pleura. Multiwalled carbon nanotubes were not found in the parietal pleura, the initial site of development of asbestos-caused pleural diseases in humans, probably due to the short exposure period of the study. In the present study, we extended the exposure period to 24 weeks to determine whether the size and shape of MWCNT impact on deposition and lesion development in the pleura and lung. Two different MWCNTs were chosen for this study: a larger sized needle-like MWCNT (MWCNT-L; l = 8 μm, d = 150 nm), and a smaller sized MWCNT (MWCNT-S; l = 3 μm, d = 15 nm), which forms cotton candy-like aggregates. Both MWCNT-L and MWCNT-S suspensions were administered to the rat lung once every 2 weeks for 24 weeks by transtracheal intrapulmonary spraying. It was found that MWCNT-L, but not MWCNT-S, translocated into the pleural cavity, deposited in the parietal pleura, and induced fibrosis and patchy parietal mesothelial proliferation lesions. In addition, MWCNT-L induced stronger inflammatory reactions including increased inflammatory cell number and cytokine/chemokine levels in the pleural cavity lavage than MWCNT-S. In contrast, MWCNT-S induced stronger inflammation and higher 8-hydroxydeoxyguanosine level in the lung tissue than MWCNT-L. These results suggest that MWCNT-L has higher risk of causing asbestos-like pleural lesions relevant to mesothelioma development.

Carcinogenic potential of high aspect ratio carbon nanomaterials

“…long, needle-like MWCNTs (length 8 μm, diameter 150 nm), but not small, tangled MWCNTs (length 3 μm, diameter 15 nm) can translocate into the pleural mesothelium and induce inflammation and hyperplasia. 55 This study supports the growing hypothesis that tangled nanotubes behave like granular particles with few free single CNTs available to induce mesothelioma.…”

Systemic and immunotoxicity of pristine and PEGylated multi-walled carbon nanotubes in an intravenous 28 days repeated dose toxicity study

“…The reason for this is that the longer MWCNTs allow for higher residential time in tissues and organs and induce stronger inflammation than shorter MWCNTs. 41,42 In our present study, we hypothesized that the tube length of MWCNTs and functionalized surface play a role in the immune effects of MWCNTs. The length of p-MWCNTs became short in the process of functionalization, and treatment of mice with the longer MWCNTs caused significant immune response, while no detectable defects were evident after treatment with the shorter MWCNTs.…”

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

“…Inflammation following inhalation or intratracheal instillation of MWCNTs has been shown by some studies (Ryman-Rasmussen et al 2009; Xu et al 2012; Xu et al 2014). Acute pleural mononuclear cell aggregates were found following inhalation of 30 mg/m 3 of MWCNTs (6 hr in 1 day; examined up to 14 wk post-exposure); however, cell aggregates returned to control levels 6 weeks post-exposure (Ryman-Rasmussen et al 2009).…”

“…When F344 rats were exposed by transtracheal spraying to a larger sized needle-like MWCNT (MWCNT-L) and a smaller sized MWCNT (MWCNT-S) that forms cotton-like aggregates over a period of 24 weeks, the MWCNT-L, but not the MWCNT-S, translocated into the pleural cavity, deposited in the parietal pleura, and was found in pleural lavage (Xu et al 2014). …”