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

Saleh, Dina; Alexander, William; Numano, Takamasa; Ahmed, Omnia Hosny Mohamed; Gunasekaran, Sivagami; Alexander, David B.; Abdelgied, Mohamed; El‐Gazzar, Ahmed; Takase, Hiroshi; Xu, Jiegou; Naiki‐Ito, Aya; Takahashi, Satoru; Hirose, Akihiko; Ohnishi, Makoto; Kanno, Jun; Tsuda, Hiroyuki

doi:10.1186/s12989-020-00382-y

Cited by 33 publications

(28 citation statements)

References 29 publications

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Section: Resultssupporting

confidence: 73%

“…Caution should be taken not to overstate the associations of the larger CNT/F as SWCNT have been shown to be potent inducers of chromosomal damage [10,114,117]. Also, MW #1 and #3 in this study induced significant effects complementing a recent pulmonary exposure study of a MWCNT 7.5 nm in diameter induced cancer [118]. Kuempel et al concluded in a review of CNT genotoxicity studies that there was not a straightforward relationship between length and genotoxicity, although most of the evaluated studies had CNT length of only a few microns or less [113].…”

Section: Hierarchical Clustering and Pca Of The Cellular Outcomesmentioning

confidence: 50%

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Physicochemical characterization and genotoxicity of the broad class of carbon nanotubes and nanofibers used or produced in U.S. facilities

et al. 2020

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Background Carbon nanotubes and nanofibers (CNT/F) have known toxicity but simultaneous comparative studies of the broad material class, especially those with a larger diameter, with computational analyses linking toxicity to their fundamental material characteristics was lacking. It was unclear if all CNT/F confer similar toxicity, in particular, genotoxicity. Nine CNT/F (MW #1–7 and CNF #1–2), commonly found in exposure assessment studies of U.S. facilities, were evaluated with reported diameters ranging from 6 to 150 nm. All materials were extensively characterized to include distributions of physical dimensions and prevalence of bundled agglomerates. Human bronchial epithelial cells were exposed to the nine CNT/F (0–24 μg/ml) to determine cell viability, inflammation, cellular oxidative stress, micronuclei formation, and DNA double-strand breakage. Computational modeling was used to understand various permutations of physicochemical characteristics and toxicity outcomes. Results Analyses of the CNT/F physicochemical characteristics illustrate that using detailed distributions of physical dimensions provided a more consistent grouping of CNT/F compared to using particle dimension means alone. In fact, analysis of binning of nominal tube physical dimensions alone produced a similar grouping as all characterization parameters together. All materials induced epithelial cell toxicity and micronuclei formation within the dose range tested. Cellular oxidative stress, DNA double strand breaks, and micronuclei formation consistently clustered together and with larger physical CNT/F dimensions and agglomerate characteristics but were distinct from inflammatory protein changes. Larger nominal tube diameters, greater lengths, and bundled agglomerate characteristics were associated with greater severity of effect. The portion of tubes with greater nominal length and larger diameters within a sample was not the majority in number, meaning a smaller percentage of tubes with these characteristics was sufficient to increase toxicity. Many of the traditional physicochemical characteristics including surface area, density, impurities, and dustiness did not cluster with the toxicity outcomes. Conclusion Distributions of physical dimensions provided more consistent grouping of CNT/F with respect to toxicity outcomes compared to means only. All CNT/F induced some level of genotoxicity in human epithelial cells. The severity of toxicity was dependent on the sample containing a proportion of tubes with greater nominal lengths and diameters.

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Section: Resultssupporting

confidence: 73%

Section: Hierarchical Clustering and Pca Of The Cellular Outcomesmentioning

confidence: 50%

Physicochemical characterization and genotoxicity of the broad class of carbon nanotubes and nanofibers used or produced in U.S. facilities

et al. 2020

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“…For short, thin and entangled MWCNT, the in vivo evidence on carcinogenicity is less clear. One study reported absence of carcinogenicity following intraperitoneal exposure to a high dose of a short and thin MWCNT (length~0.7 μm; diameter: 11.3 ± 3.9 nm) in rats [66], whereas pulmonary exposure to a thin and entangled MWCNT (agglomerate length 1.04 ± 0.71 μm; diameter: 7.4 ± 2.7 nm) caused lung cancer in rats [5].…”

Section: Discussionmentioning

confidence: 99%

“…The increased production of MWCNT has raised concern for workers health. When inhaled, MWCNT are biopersistent in the lung and, similarly to asbestos, have been shown to induce chronic inflammation, fibrosis and cancer in rats following chronic inhalation [3][4][5][6]. Notably, one long MWCNT (MWCNT-7) was classified as possibly carcinogenic to humans by IARC [7], based on animal data [6,8,9].…”

Section: Introductionmentioning

confidence: 99%

In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT

et al. 2021

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Background Multi-walled carbon nanotubes (MWCNT) have received attention due to extraordinary properties, resulting in concerns for occupational health and safety. Costs and ethical concerns of animal testing drive a need for in vitro models with predictive power in respiratory toxicity. The aim of this study was to assess pro-inflammatory response (Interleukin-8 expression, IL-8) and genotoxicity (DNA strand breaks) caused by MWCNT with different physicochemical properties in different pulmonary cell models and correlate these to previously published in vivo data. Seven MWCNT were selected; two long/thick (NRCWE-006/Mitsui-7 and NM-401), two short/thin (NM-400 and NM-403), a pristine (NRCWE-040) and two surface modified; hydroxylated (NRCWE-041) and carboxylated (NRCWE-042). Carbon black Printex90 (CB) was included as benchmark material. Human alveolar epithelial cells (A549) and monocyte-derived macrophages (THP-1a) were exposed to nanomaterials (NM) in submerged conditions, and two materials (NM-400 and NM-401) in co-cultures of A549/THP-1a and lung fibroblasts (WI-38) in an air-liquid interface (ALI) system. Effective doses were quantified by thermo-gravimetric-mass spectrometry analysis (TGA-MS). To compare genotoxicity in vitro and in vivo, we developed a scoring system based on a categorization of effects into standard deviation (SD) units (< 1, 1, 2, 3 or 4 standard deviation increases) for the increasing genotoxicity. Results Effective doses were shown to be 25 to 53%, and 21 to 57% of the doses administered to A549 and THP-1a, respectively. In submerged conditions (A549 and THP-1a cells), all NM induced dose-dependent IL-8 expression. NM-401 and NRCWE-006 caused the strongest pro-inflammatory response. In the ALI-exposed co-culture, only NM-401 caused increased IL-8 expression, and no DNA strand breaks were observed. Strong correlations were found between in vitro and in vivo inflammation when doses were normalized by surface area (also proxy for diameter and length). Significantly increased DNA damage was found for all MWCNT in THP-1a cells, and for short MWCNT in A549 cells. A concordance in genotoxicity of 83% was obtained between THP-1a cells and broncho-alveolar lavaged (BAL) cells. Conclusion This study shows correlations of pro-inflammatory potential in A549 and THP-1a cells with neutrophil influx in mice, and concordance in genotoxic response between THP-1a cells and BAL cells, for seven MWCNT.

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“…However, entangled nanotubes administered into the peritoneal cavity did not induce carcinogenesis. 150 …”

Section: Physicochemical Characteristics Of Carbon Nanotubes That Limit Their Application In Vaccinesmentioning

confidence: 99%

Advances and Perspectives in the Use of Carbon Nanotubes in Vaccine Development

Lima¹,

Diaz²,

Justo³

et al. 2021

IJN

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Advances in nanobiotechnology have allowed the utilization of nanotechnology through nanovaccines. Nanovaccines are powerful tools for enhancing the immunogenicity of a specific antigen and exhibit advantages over other adjuvant approaches, with features such as expanded stability, prolonged release, decreased immunotoxicity, and immunogenic selectivity. We introduce recent advances in carbon nanotubes (CNTs) to induce either a carrier effect as a nanoplatform or an immunostimulatory effect. Several studies of CNT-based nanovaccines revealed that due to the ability of CNTs to carry immunogenic molecules, they can act as nonclassical vaccines, a quality not possessed by vaccines with traditional formulations. Therefore, adapting and modifying the physicochemical properties of CNTs for use in vaccines may additionally enhance their efficacy in inducing a T cell-based immune response. Accordingly, the purpose of this study is to renew and awaken interest in and knowledge of the safe use of CNTs as adjuvants and carriers in vaccines.

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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

Cited by 33 publications

References 29 publications

Physicochemical characterization and genotoxicity of the broad class of carbon nanotubes and nanofibers used or produced in U.S. facilities

Physicochemical characterization and genotoxicity of the broad class of carbon nanotubes and nanofibers used or produced in U.S. facilities

In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT

Advances and Perspectives in the Use of Carbon Nanotubes in Vaccine Development

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