MWCNT causes extensive damage to the ciliated epithelium of the trachea of rodents

Ohba, Teruya; Xu, Jiegou; Alexander, David B.; Yamada, Aki; Kanno, Jun; Hirose, Akihiko; Tsuda, Hiroyuki; Imaizumi, Yuji

doi:10.2131/jts.39.499

Cited by 6 publications

(5 citation statements)

References 18 publications

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“…Significant increases in absolute and relative lung weights were observed in both the male and female vehicle-treated groups compared to the untreated group. KP188, which is known to cause weak toxic effects in the lungs, has been used in several intratracheal instillation studies for dispersing test materials 15,16,[20][21][22][23][24] . The increase in the absolute and relative lung weights of the rats in the vehicle-treated groups was accompanied by a slight toxic effect due to repeated intratracheal instillation of the vehicle solution, KP188, as shown previously 16 .…”

Section: Macroscopic Pathological Examination Lung Burden and Organmentioning

confidence: 99%

Lung toxicity of a vapor-grown carbon fiber in comparison with a multi-walled carbon nanotube in F344 rats

Numano¹,

Sugiyama²,

Kawabe³

et al. 2021

J Toxicol Pathol

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Carbon fibers have excellent physicochemical and electrical properties. Vapor-grown carbon fibers are a type of carbon fibers that have a multi-walled carbon tube structure with a high aspect ratio. The representative vapor-grown carbon fiber, VGCF™-H, is extremely strong and stable and has superior thermal and electrical conductivity. Because some high-aspect-ratio multi-walled carbon nanotubes (MWCNTs) have been reported to have toxic and carcinogenic effects in the lungs of rodents, we performed a 13-week lung toxicity study using VGCF™-H in comparison with one of MWCNTs, MWNT-7, in rats. Male and female F344 rats were intratracheally administered VGCF™-H at doses of 0.2, 0.4, and 0.8 mg/kg bw or MWNT-7 at doses of 0.4 and 0.8 mg/kg bw once a week for 8 weeks and then up to week 13 without treatment. The lung burden was equivalent in the VGCF™-H and MWNT-7 groups; however, the lung weight had increased and the inflammatory and biochemical parameters in the broncho-alveolar lavage fluid and histopathological parameters, including inflammatory cell infiltration, alveolar type II cells proliferation, alveolar fibrosis, pleural fibrosis, lung mesothelium proliferation, and diaphragm fibrosis, were milder in the VGCF™-H group than in the MWNT-7 group. In addition, the proliferating cell nuclear antigen (PCNA)-positive index in the visceral and pleural mesothelium was significantly higher in the MWNT-7 group than in the controls, but not in the VGCF™-H group. Thus, the results of this study indicate that the lung and pleural toxicities of VGCF™-H were less than those of MWNT-7.

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Section: Macroscopic Pathological Examination Lung Burden and Organmentioning

confidence: 99%

Lung toxicity of a vapor-grown carbon fiber in comparison with a multi-walled carbon nanotube in F344 rats

Numano¹,

Sugiyama²,

Kawabe³

et al. 2021

J Toxicol Pathol

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“…Another study also analyzed the impact of CNT on ciliated tracheobronchial epithelium, as these cells play a role in the clearance of inhaled particles by ciliary transport [ 68 ]. These authors showed that MWCNT with a length of 3 and 8 μm damaged the ciliated epithelium in the trachea of rats (250 μg/ml in rat, corresponding to 75 μg/rat considering that rats were treated with 0.3 ml) and mouse tracheal epithelial cells in vitro (10 μg/ml) and suggested that these lesions can prevent the clearance of inhaled CNT in the lung and thus lead to a chronic inflammatory process.…”

Section: Indirect Effects Of Cnt On Fibroblastsmentioning

confidence: 99%

Mechanisms of lung fibrosis induced by carbon nanotubes: towards an Adverse Outcome Pathway (AOP)

2015

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Several experimental studies have shown that carbon nanotubes (CNT) can induce respiratory effects, including lung fibrosis. The cellular and molecular events through which these effects develop are, however, not clearly elucidated. The purpose of the present review was to analyze the key events involved in the lung fibrotic reaction induced by CNT and to assess their relationships. We thus address current knowledge and gaps with a view to draft an Adverse Outcome Pathway (AOP) concerning the fibrotic potential of CNT.As for many inhaled particles, CNT can indirectly activate fibroblasts through the release of pro-inflammatory (IL-1β) and pro-fibrotic (PDGF and TGF-β) mediators by inflammatory cells (macrophages and epithelial cells) via the induction of oxidative stress, inflammasome or NF-kB. We also highlight here direct effects of CNT on fibroblasts, which appear as a new mode of toxicity relatively specific for CNT. Direct effects of CNT on fibroblasts include the induction of fibroblast proliferation, differentiation and collagen production via ERK 1/2 or Smad signaling. We also point out the physico-chemical properties of CNT important for their toxicity and the relationship between in vitro and in vivo effects. This knowledge provides evidence to draft an AOP for the fibrogenic activity of CNT, which allows developing simple in vitro models contributing to predict the CNT effects in lung fibrosis, and risk assessment tools for regulatory decision.

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“…The choice of vehicle depends on both the toxicity of the vehicle and the solubility/dispersibility of the test agent in the vehicle. For example, polyoxyethylene-polyoxypropylene copolymers such as Pluronic F-68 (discontinued) and KP188 have been used for dispersal of hydrophobic carbon nanotubes and potassium octatitanate fibers 10,[20][21][22] . KP188 is used as the vehicle; however, it is water-soluble and not bio-persistent in the lung.…”

Section: Discussionmentioning

confidence: 99%

Effects of administering different vehicles via single intratracheal instillation on responses in the lung and pleural cavity of Crl:CD(SD) rats

Numano¹,

Morioka²,

Higuchi³

et al. 2020

J Toxicol Pathol

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Intratracheal instillation is the introduction of a substance directly into the trachea. Intratracheal instillation has been used to investigate the lung toxicity of several chemicals and requires the suspension or dissolution of test material in a vehicle for even dispersal throughout the lung. Importantly, the toxicities of vehicles used in intratracheal instillation studies are generally considered to be insignificant. Hence, evaluating the influence of different vehicles on the lung due to intratracheal instillation is crucial. We examined the toxic effects of pure water, saline, phosphate buffered saline (PBS), 0.5% Kolliphor ® P188 (KP188), 0.1% Tween 20 in saline, and 1.0% BSA in PBS. These vehicles were administered to male Crl:CD(SD) rats by a single intratracheal instillation. On day 3, broncho-alveolar lavage fluid (BALF) from the right lung was collected and processed for cell counting and biochemical analysis, while the left lung was used for histopathological examination. Accumulation of alveolar macrophages was observed in all vehicletreated groups but was minimal in the group administered saline, somewhat higher in the groups administered pure water, PBS, 0.1% Tween 20, and 1% BSA, and notably higher in the group administered 0.5% KP188. The results from BALF analysis indicated that intratracheal instillation of 0.5% KP188 also induced alveolar damage. Additionally, administering pure water did not appear to cause tissue damage. Eosinophil infiltration in the interstitial regions was histopathologically observed. Altogether, the results of this study are helpful for the selection of appropriate vehicles for use in intratracheal instillation studies.

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MWCNT causes extensive damage to the ciliated epithelium of the trachea of rodents

Abstract: -The ciliated tracheobronchial epithelium plays an important role in the excretion ofIn vitro -

Cited by 6 publications

References 18 publications

Lung toxicity of a vapor-grown carbon fiber in comparison with a multi-walled carbon nanotube in F344 rats

Lung toxicity of a vapor-grown carbon fiber in comparison with a multi-walled carbon nanotube in F344 rats

Mechanisms of lung fibrosis induced by carbon nanotubes: towards an Adverse Outcome Pathway (AOP)

Effects of administering different vehicles via single intratracheal instillation on responses in the lung and pleural cavity of Crl:CD(SD) rats

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