Inhaled carbon nanotubes reach the subpleural tissue in mice

Abstract

Summary Carbon nanotubes have fibre-like shape1 and stimulate inflammation at the surface of the peritoneum when injected into the abdominal cavity of mice2, raising concerns that inhaled nanotubes3 may cause pleural fibrosis and/or mesothelioma4. Here we show that multi-walled carbon nanotubes reach the sub-pleura in mice after a single inhalation exposure of 30 mg/m3 for 6 hours. Nanotubes were embedded in the sub-pleural wall and within sub-pleural macrophages. Mononuclear cell aggregates on the pleural surface increased in number and size after 1 day and nanotube-containing macrophages were observed within these foci. Sub-pleural fibrosis increased after 2 and 6 weeks following inhalation. None of these effects were seen in mice that inhaled carbon black nanoparticles or a lower dose of nanotubes (1 mg/m3). This work advances a growing literature on pulmonary toxicology of nanotubes5 and suggests that minimizing inhalation of nanotubes during handling is prudent until further long term assessments are conducted.

Single-walled carbon nanotube-induced mitotic disruption

“…Although the MWCNT exposure studies have been criticized due to the high dose and the route of exposure, the studies raise concerns about the potential of cancer due to occupational and environmental exposures to particles that may have physical properties similar to asbestos fibers. Further evidence of the similarity of carbon nanotubes to asbestos was demonstrated in two recent publications showing migration of MWCNT to the subpleural tissue and entrance into the intrapleural space in a manner similar to asbestos [78,79].…”

Length-Dependent Retention of Carbon Nanotubes in the Pleural Space of Mice Initiates Sustained Inflammation and Progressive Fibrosis on the Parietal Pleura

“…Therefore, it is the diameter (not the length) of fibers that affects transit through the lungs, allowing high-aspect ratio particles like CNTs, which may have a diameter in the nanometer range but a length extending to tens of micrometers, to deposit in the distal regions of the lung. 17 Indeed, the distal deposition of CNTs was shown by Ryman-Rasmussen et al, 39 who reported the presence of CNTs in the subpleural tissue of the lung after a single inhalation exposure in mice. Translocation of particles and fibers from the distal lung to the pleural space is not well understood.…”

Repeated exposure to carbon nanotube-based aerosols does not affect the functional properties of a 3D human epithelial airway model

“…Furthermore, in a recent study, rats exposed repeatedly to a 5 mg/m 3 MWCNT aerosol showed fibrotic response that was found to develop and persist up to 336 days (d) after exposure . Although it represents a severe overload study, Ryman-Rasmussen et al also reported increased pleural mononuclear cell accumulation and sub-pleural fibrosis up to 6 weeks after single inhalation exposure of 30 mg/m 3 for 6 h in mice (Ryman-Rasmussen et al, 2009). In another in vivo inhalation study, mice were exposed repeatedly for 19 days to 1970 ng/d (corresponding to 1000 d of a human exposure), 197 ng/d (100 d human exposure) and 19.7 ng/d (10 d) MWCNTs, with a post-incubation time up to 84 days (Erdely et al, 2013).…”