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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  MWCNT s 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.

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