Pulmonary toxicity of two different multi-walled carbon nanotubes in rat: Comparison between intratracheal instillation and inhalation exposure

Gaté, Laurent; Knudsen, Kristina Bram; Seidel, Carole; Berthing, Trine; Chézeau, Laëtitia; Jacobsen, Nicklas Raun; Valentino, Sarah; Wallin, Håkan; Bau, Sébastien; Wolff, Henrik; Sébillaud, Sylvie; Lorcin, Mylène; Grossmann, Stéphane; Viton, Stéphane; Nunge, Hervé; Darné, Christian; Vogel, Ulla; Cosnier, Frédéric

doi:10.1016/j.taap.2019.05.001

Cited by 52 publications

(65 citation statements)

References 55 publications

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“…Note, that similar structures were observed both in vivo and in vitro after exposure to crystalline quartz (DQ12), a well-known occupational hazard causing pulmonary alveolar proteinosis (PAP) 13 , but not for all carbon nanotubes (CNTs) 27,28 .…”

Section: Passivation Of Nanomaterialsmentioning

confidence: 75%

From the Roundabout of Molecular Events to Nanomaterial-Induced Chronic Inflammation Prediction

Majaron

Kokot

Sebastijanović

et al. 2020

Preprint

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Many chronic diseases manifest in prolonged inflammation and often ignored dysregulated lipid metabolism. When associated with inhalation of nanomaterials, limited information is available on the relevant molecular events and their causal connections. This prevents reliable prediction of outcomes by efficient testing strategies. To unravel how acute nanomaterial exposure leads to chronic conditions, we employed advanced microscopy and omics in vitro and in vivo together with in silico modelling.For selected metal-oxide nanomaterials, we show that lung epithelial cells survive the exposure by excreting internalized nanomaterials and passivating them on the surface, employing elevated lipid synthesis. Macrophages, on the contrary, lose their integrity whilst degrading the passivized bio-nano agglomerates, releasing the nanomaterials, which are taken up again by the epithelial cells. Constant proinflammatory signalling recruits new phagocytes that feed the vicious cycle of events, resulting in a long-lasting response to a single exposure. The proposed mechanism explains the nanomaterialassociated in vivo chronic outcomes and allows its prediction based on in vitro measurements. Similar mechanisms may trigger other chronic diseases affecting millions of lives worldwide.

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Section: Passivation Of Nanomaterialsmentioning

confidence: 75%

From the Roundabout of Molecular Events to Nanomaterial-Induced Chronic Inflammation Prediction

Majaron

Kokot

Sebastijanović

et al. 2020

Preprint

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“…This means that for the same amount of material, the surface area of MWCNT-B is approximately 20-fold higher than the surface area of MWCNT-A. Since surface area is considered to be an important factor in MWCNT toxicity in the lung [29], the greater surface area of MWCNT-B may have played a role in the lung carcinogenicity of MWCNT-B.…”

Section: Discussionmentioning

confidence: 99%

Comparative carcinogenicity study of a thick, straight-type and a thin, tangled-type multi-walled carbon nanotube administered by intra-tracheal instillation in the rat

et al. 2020

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Background Multi-walled carbon nanotubes can be divided into two general subtypes: tangled and straight. MWCNT-N (60 nm in diameter) and MWCNT-7 (80–90 nm in diameter) are straight-type MWCNTs, and similarly to asbestos, both are carcinogenic to the lung and pleura when administered to rats via the airway. Injection of straight-type MWCNTs into the peritoneal cavity also induces the development of mesothelioma, however, injection of tangled-type MWCNTs into the peritoneal cavity does not induce carcinogenesis. To investigate these effects in the lung we conducted a 2-year comparative study of the potential carcinogenicities of a straight-type MWCNT, MWCNT-A (approximately 150 nm in diameter), and a tangled-type MWCNT, MWCNT-B (7.4 nm in diameter) after administration into the rat lung. Crocidolite asbestos was used as the reference material, and rats administered vehicle were used as the controls. Test materials were administered by intra-Tracheal Intra-Pulmonary Spraying (TIPS) once a week over a 7 week period (8 administrations from day 1 to day 50), followed by a 2-year observation period without further treatment. Rats were administered total doses of 0.5 or 1.0 mg MWCNT-A and MWCNT-B or 1.0 mg asbestos. Results There was no difference in survival between any of the groups. The rats administered MWCNT-A or asbestos did not have a significant increase in bronchiolo-alveolar hyperplasia or tumors in the lung. However, the rats administered MWCNT-B did have significantly elevated incidences of bronchiolo-alveolar hyperplasia and tumors in the lung: the incidence of bronchiolo-alveolar hyperplasia was 0/20, 6/20, and 9/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively, and the incidence of adenoma and adenocarcinoma combined was 1/19, 5/20, and 7/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively. Malignant pleural mesothelioma was not induced in any of the groups. Conclusions The results of this initial study indicate that tangled-type MWCNT-B is carcinogenic to the rat lung when administered via the airway, and that straight-type MWCNT-A did not have higher carcinogenic potential in the rat lung than tangled-type MWCNT-B.

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“…Several laboratories are using this set-up with an inhalation tower around which the contention tubes are setup. In those systems, the airflow containing the inhaled compound is highly controlled and the aerosol metrology is carried out thoroughly (Buckley et al, 2017;Gate et al, 2019;Lucci et al, 2019). These articles point out the fact that all parameters deserve to be closely monitored: particles size distribution and concentration, airflow within the chamber, animal position and breath rate.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Design of an Inhalation Chamber and Metrology Assessment to Study Tungsten Aerosol Neurotoxic Effects

Macé

Ibanez

Gélain

et al. 2021

Aerosol Air Qual. Res.

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In order to study the impact of exposure to tungsten aerosol on brain toxicity, we designed a strategy to control the generation of tungsten aerosol with mass concentrations within the magnitude of the average occupational exposure limit value (5 to 10 mg.m-3).Due to such extreme density of tungsten particles, the challenge was to perform relevant measurements of aerosol characteristics needed for upper airways and lung deposition calculations. We mixed tungsten bead powder of coarse diameter with the powder of interest in well-defined mass proportions. We used a cyclone at the exit of a RBG 1000 generator (PALAS) to remove the coarse particles from the aerosol of interest. Measurements of aerosols produced in the inhalation chamber were carried out using several instruments paired with sample lines arranged symmetrically: a low pressure impactor DLPI-30 lpm Dekati® with a basic sampling on filter holder; a DLPI with an APS (Aerodynamic Particle Sizer) 3321 TSI® ; an EEPS (Engine Exhaust Particle Sizer) 3090 TSI® with an APS. The DLPI and the filter holder always provided very close measurements in terms of mass concentrations. The mass median aerodynamic diameter (Da) was 1.77 and 1.89 µm as determined by the DLPI and the APS with the Stokes correction, respectively. The count median diameter in electrical mobility determined by EEPS was 0.17 µm. The results obtained show very good agreement between the measurements carried out with the DLPI, APS and EEPS. The methodology developed for the analysis of the EEPS results confirms that the measurements of the electrical mobility diameter made with this instrument is within a range of aerodynamic sizes never explored and for which the instrument was not initially designed. CFD simulations of the airflows and aerosol dispersion in the chamber allowed to ensure that the aerosol inhaled by the animals is homogeneous and representative.

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Pulmonary toxicity of two different multi-walled carbon nanotubes in rat: Comparison between intratracheal instillation and inhalation exposure

Cited by 52 publications

References 55 publications

From the Roundabout of Molecular Events to Nanomaterial-Induced Chronic Inflammation Prediction

From the Roundabout of Molecular Events to Nanomaterial-Induced Chronic Inflammation Prediction

Comparative carcinogenicity study of a thick, straight-type and a thin, tangled-type multi-walled carbon nanotube administered by intra-tracheal instillation in the rat

Design of an Inhalation Chamber and Metrology Assessment to Study Tungsten Aerosol Neurotoxic Effects

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