Physicochemical predictors of Multi‐Walled Carbon Nanotube–induced pulmonary histopathology and toxicity one year after pulmonary deposition of 11 different Multi‐Walled Carbon Nanotubes in mice

Abstract

Multi-walled carbon nanotubes (MWCNT) are widely used nanomaterials that cause pulmonary toxicity upon inhalation. The physicochemical properties of MWCNT vary greatly, which makes general safety evaluation challenging to conduct. Identification of the toxicity-inducing physicochemical properties of MWCNT is therefore of great importance. We have evaluated histological changes in lung tissue 1 year after a single intratracheal instillation of 11 well-characterized MWCNT in female C57BL/6N BomTac mice. Genotoxicity in liver and spleen was evaluated by the comet assay. The dose of 54 μg MWCNT corresponds to three times the estimated dose accumulated during a work life at a NIOSH recommended exposure limit (0.001 mg/m ). Short and thin MWCNT were observed as agglomerates in lung tissue 1 year after exposure, whereas thicker and longer MWCNT were detected as single fibres, suggesting biopersistence of both types of MWCNT. The thin and entangled MWCNT induced varying degree of pulmonary inflammation, in terms of lymphocytic aggregates, granulomas and macrophage infiltration, whereas two thick and straight MWCNT did not. By multiple regression analysis, larger diameter and higher content of iron predicted less histopathological changes, whereas higher cobalt content significantly predicted more histopathological changes. No MWCNT-related fibrosis or tumours in the lungs or pleura was found. One thin and entangled MWCNT induced increased levels of DNA strand breaks in liver; however, no physicochemical properties could be related to genotoxicity. This study reveals physicochemical-dependent difference in MWCNT-induced long-term, pulmonary histopathological changes. Identification of diameter size and cobalt content as important for MWCNT toxicity provides clues for designing MWCNT, which cause reduced human health effects following pulmonary exposure.

The Advances in Biomedical Applications of Carbon Nanotubes

“…One of the main fields of studies on the toxicity of CNTs is an impact on the pulmonary system [165,166]. The CNTs belong to the big group of respirable materials, and they potentially can cause the inflammation of lung tissues.…”

NTP Technical Report on the Toxicity Studies of 1020 Long Multiwalled Carbon Nanotubes Administered by Inhalation to Sprague Dawley (Hsd:Sprague Dawley® SD®) Rats and B6C3F1/N Mice

“…Although the mechanism is not clear, several studies suggest that CNT may trigger the activation of the Nlrp3 inflammasome complex in macrophages and other phagocytic cells, resulting in caspase-1-mediated activation and release of pro-inflammatory cytokines 110; 119-121 . The ensuing pulmonary inflammatory response normally results in clearance of the foreign particles, tissue repair, and recovery; however, repeated exposure to a biopersistent CNT like L-MWNT-1020 can result in chronic inflammation and tissue damage 122 .…”

Models Contribution to the Understanding of Sarcoidosis Pathogenesis: “Are There Good Models of Sarcoidosis?”

“…After pulmonary exposure to MWCTs, a marked inflammatory response was present and associated with the development of granulomas and/or fibrosis [ 49 , 96 ]. Depending on the physicochemical properties of MWCTs, nanomaterial was detected one year later as black aggregates in macrophages or in granuloma [ 97 ]. Yanamala et al showed distinct and common inflammatory responses to various carbonaceous materials, including MWCTs [ 98 ].…”