title: Additional histopathologic examination of the lungs from a 3-month inhalation toxicity study with multiwall carbon nanotubes in rats.
abstract: For hazard assessment of multiwalled carbon nanotubes (MWCNTs), a 90-day inhalation toxicity study has been performed with Nanocyl NC 7000 in accordance with OECD 413 test guideline. MWCNTs produced no systemic toxicity. However, increased lung weights, multifocal granulomatous inflammation, diffuse histiocytic and neutrophilic infiltrates, and intra-alveolar lipoproteinosis were observed in lung and lung-associated lymph nodes at 0.5 and 2.5mg/m(3). Additional investigations of the lungs were performed, including special stains for examination of connective tissue, and electron microscopy was performed to determine the location of the MWCNTs. The alveolar walls revealed no increase of collagen fibers, whereas within the microgranulomas a slight increase of collagen fibers was observed. The pleura did not reveal any increase in collagen fibers. Only a slight increase in reticulin fibers in the alveolar walls in animals of the 0.5 and 2.5mg/m(3) concentration group was noted. In the 0.1mg/m(3) group, the only animal revealing minimal granulomas exhibited a minimal increase in collagen within the granuloma. No increase in reticulin was observed. Electron microscopy demonstrated entangled MWCNTs within alveolar macrophages. Occasionally electron dense particles/detritus were observed within membrane-bound vesicles (interpreted as phagosomes), which could represent degraded MWCNTs. If so, MWCNTs were degradable by alveolar macrophages and not persistent within the lung. Inhalation of MWCNTs caused granulomatous inflammation within the lung parenchyma but not the pleura in any of the concentration groups. Thus, there are some similarities to effects caused by inhaled asbestos, but the hallmark effects, namely pleural inflammation and/or fibrosis leading to mesotheliomas, are absent.
authors.affiliation: Experimental Toxicology and Ecology, BASF SE, Ludwigshafen, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Treumann
authors.forename: Lan
authors.initials: L
authors.lastname: Ma-Hock
authors.forename: Sibylle
authors.initials: S
authors.lastname: Gröters
authors.forename: Robert
authors.initials: R
authors.lastname: Landsiedel
authors.forename: Bennard
authors.initials: B
authors.lastname: van Ravenzwaay
mesh_terms: D000336:Aerosols; D000393:Air Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015769:Granuloma, Respiratory Tract / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D017408:Guidelines as Topic; D019570:Inhalation Exposure; D008074:Lipoproteins / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure*; D016676:Macrophages, Alveolar / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000633:toxicity*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010316:Particle Size; D051381:Rats; D012155:Reticulin / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D014018:Tissue Distribution; D059550:Toxicity Tests, Subchronic / Q000379:methods; D014463:Ultrasonography
chemical_list: D000336:Aerosols; D000393:Air Pollutants; D008074:Lipoproteins; D037742:Nanotubes, Carbon; D012155:Reticulin
keywords: 90-day inhalation study; MWCNT; asbestos; fibrosis; lung; pleura