Assessment of Pristine Carbon Nanotubes Toxicity in Rodent Models
Abstract
:1. Introduction
2. Toxicological Aspects
3. Pulmotoxicity
4. Hepatotoxicity
5. Nephrotoxicity
6. Dermal Toxicity
7. Cardiovascular Toxicity
8. Neurotoxicity
9. Prospects on Standardized In Vivo Testing
10. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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---|---|---|---|---|---|---|---|
Hojo et al., 2022 [32] | MWCNTs | Length 5.11 µm, width 84.7 nm | Fisher 344 rats | Intratracheal instillation | 0, 0.125, and 0.5 mg/kg | Every 4 weeks for over 2 years | Dose- and time-dependent inflammatory, fibrotic, and hyperplastic lesions. In the high-dose group, significantly increased incidences of lung carcinomas, lung adenomas, and pleural mesotheliomas. |
Fujita et al., 2022 [57] | MWCNTs | Diameter 9.5 nm, length 1.5 μm, | Crl:CD rats | Intratracheal instillation | 0.25, 0.5 and 1.0 mg/kg | 1, 3, 7, 30, 90, and 180 days | BALF cells, total protein, lactate dehydrogenase, and pro-inflammatory cytokines showed that MWCNTs induced pneumonia. |
Numano et al., 2021 [69] | MWCNTs | Diameter 75 nm, length 9 μm | Fisher 344/DuCrlCrlj rats | Intratracheal instillation | 0.2, 0.4 and 0.8 mg/kg | 6 weeks | Increased lung weight, inflammation in the lungs, fibrosis of the visceral and parietal pleura. |
Seidel et al., 2021 [63] | MWCNTs | Diameter 67 and 12 nm, length 4 and 0.4 μm, purity > 95% | Sprague Dawley rats | Nose-only inhalation | 0.5 and 1.5 mg/m3 | 4 weeks | Induction of pneumonia, dose-dependent increase in the number of genes and proteins with differential expression. |
Kim et al., 2020 [74] | MWCNTs | Diameter 5–10 nm, length > 1 µm | Sprague Dawley rats | Nose-only inhalation | 0, 0.257, 1.439 and 4.253 mg/m3 | 1, 7, and 28 days | Increase in lung inflammation parameters in BALF. |
Lim et al., 2020 [61] | MWCNTs | Diameter 56.0–61.0 nm, length 4.08–4.88µm | B6C3F1 mice | Pharyngeal aspiration | 40 µg/mouse | 1, 7, and 28 days | Induction of high levels of leukotriene B4 and prostaglandin E2, acute inflammation in the lungs at low doses. |
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References | Materials | Materials Properties | Animals | Routes of Administration | Doses/ Concentrations | Exposure Times | Toxicity Effects |
---|---|---|---|---|---|---|---|
Kim et al., 2015 [74] | MWCNTs | Diameter 12.5 ± 2.5 nm, purity > 95% | C57BL/6J mice | Intratracheal instillation | 0.1 mg/mouse | 1 year | Mice developed nonalcoholic steatohepatitis-like phenotype, characterized by inflammation, hepatic steatosis, and fibrosis. |
Lin et al., 2013 [83] | SWCNTs | Diameter 0.8–1.2 nm, length of several microns | Wistar rats | Intratracheal instillation | 7.5, 15, and 22.5 mg/kg | 15 days | Rise in extract concentrations of choline and phosphocholine, together with decreased lipids and lipoproteins, which indicated a disruption of membrane fluidity caused by lipid peroxidation. |
Folkman et al., 2009 [68] | SWCNTs | Diameter 0.9–1.7 nm, lengths < 1 µm | Fisher 344 rats | Intragastric administration | 0.064 and 0.64 mg/kg | Rats were sacrificed at 9 weeks of age | SWCNT increased the levels of 8-oxodG in liver, which is likely to be caused by genotoxicity. |
Yang et al., 2008 [87] | SWCNTs | Diameter 10–30 nm, length 2–3 μm, purity > 95% | CD-ICR mice | Tail-vein injections | 40, 200 μg/mouse and 1.0 mg/mouse | 3 months | Low hepatotoxicity compared to functionalized SWCNTs. |
Kasai et al., 2016 [70] | MWCNTs | Diameter 95.5–109.6 nm, length 5.8–5.9 μm. | Fisher 344 rats | Whole-body inhalation | 0, 0.02, 0.2, and 2 mg/m3 | 6 h/day, 5 days/week for 104 weeks | Lung carcinomas were significantly increased in animals exposed to MWCNTs, however, there was no development of pleural mesothelioma. |
Folkman et al., 2009 [68] | SWCNTs | Diameter 0.9–1.7 nm, length < 1 µm | Fisher 344 rats | Intragastric administration | 0.064 and 0.64 mg/kg | Rats were sacrificed at 9 weeks of age | Increased levels of 8-oxodG in the liver, which are likely to be caused by genotoxicity. |
Ryman-Rasmussen et al., 2009 [65] | MWCNTs | Diameter 10–50 nm, length 0.5–50 μm | C57BL6 mice | Nose-only inhalation | 1 and 30 mg/m3 | 1 day, 2 weeks, 6 weeks, or 14 weeks | Increase in subpleural fibrosis. |
Mitchell et al., 2007 [66] | MWCNTs | Diameter 10–20 nm, length 5–15 μm, purity > 95% | C57BL/6 mice | Whole-body inhalation | 0.3, 1 and 5 mg/m3 | 7 and 14 days | Inflammation and histopathological changes in the lungs were not observed. |
Shvedova et al., 2005 [62] | SWCNTs | Diameter 1– 4 nm, surface area 1040 m2/g | C57BL/6 mice | Pharyngeal aspiration | 0, 10.0, 20.0 and 40.0 μg/mouse | 1, 3, 7, 28, and 60 days | There was acute inflammation and, over time, pulmonary fibrosis. |
Lam et al., 2004 [59] | CNTs | - | B6C3F mice | Intratracheal instillation | 0.1 and 0.5 mg/mouse | 7 and 90 days | Mortality occurred in mice that received 0.5 mg of CNTs. |
Warheit et al., 2003 [60] | SWCNTs | Diameter 1.4 nm, length > 1 μm | Crl:CD(SD)IGS BR rats | Intratracheal instillation | 1 and 5 mg/kg | 24 h, 1 week, 1 month, and 3 months | Initial mortality in 15% of rats, there were transient inflammation and multifocal granulomas, irrespective of the dose. |
References | Materials | Materials Properties | Animals | Routes of Administration | Doses/ Concentrations | Exposure Times | Toxicity Effects |
---|---|---|---|---|---|---|---|
Zamani et al., 2021 [91] | MWCNTs | Diameter 10 and 100 nm, length 140–180 μm | Wistar rats | Inhalation | 5 mg/m3 | 2 weeks | Mitochondrial damage in kidney cells, including renal tubular cells. |
Awogbindin et al., 2021 [92] | MWCNTs | Diameter 15–30 nm, length 15–20 μm, purity > 95% | Wistar rats | Intravenous administration | 1 mg/kg | 15 days | Severe disseminated congestion and infiltration of inflammatory cells in the kidneys. |
Guzmán-Mendoza et al., 2020 [93] | CNTs | Diameter 20–40 nm, length 30 μm | BALB/c mice | Tail-vein injections | 2 mg/kg | 1, 14, 29, and 60 days | Pristine CNTs have the highest toxicity due to accumulation in the kidneys and the lungs even at 60 days; moreover, they produced lung damage, tumor growth, hepatotoxicity, renal failure, and could possibly induce heart failure. |
Tang et al., 2012 [94] | MWCNTs | Diameter 10–20 nm, length 5–50 μm, purity > 95% | Kunming mice | Tail-vein injections | 100 mg/mouse | 1 day, 3 days, and 1 year | There were no differences in vivo in inflammatory responses, the coagulation system, hemograms, or vital kidney functions. |
Jain et al., 2011 [89] | MWCNTs | Diameter 100–500 nm, length < 500 nm | Swiss albino mice | Tail-vein injections | 10 mg/kg | 7 and 28 days | No apparent nephrotoxicity. |
References | Materials | Materials Properties | Animals | Routes of Administration | Doses/Concentrations | Exposure Times | Toxicity Effects |
---|---|---|---|---|---|---|---|
Ema et al., 2011 [96] | MWCNTs and SWCNTs | Diameter 1.8, 3, 44, and 60 nm | Kbl:NZW rabbits, Slc:Hartley guinea pigs | Topical administration | 5 mg/mouse, 10 mg/mouse | 1, 24, 48 and 72 h | One MWCNT caused very slight erythema at 24 h, but not at 72 h, after patch removal in the dermal irritation experiments, very weak acute irritant to the skin and eyes. |
Murray et al., 2009 [100] | SWCNTs | - | SKH-1 Hairless mice | Topical administration | 40 g/mouse, 80 g/mouse, or 160 g/mouse | 5 days | SWCNTs induced free radical generation, oxidative stress, and inflammation, thus causing dermal toxicity. |
References | Materials | Materials Properties | Animals | Routes of Administration | Doses/Concentrations | Exposure Times | Toxicity Effects |
---|---|---|---|---|---|---|---|
Chen et al., 2015 [104] | MWCNTs | Diameter < 8 nm, length 0.5–2 μm | Wistar-Kyoto rats | Intratracheal instillation | 600 μg/kg | 7 and 30 days | MCWNTs caused subchronic toxicity, especially the sustained inflammation of the pulmonary and cardiovascular system. |
Legramante et al., 2009 [105] | SWCNTs | Diameter 1.2–1.6 nm, length 2–5 nm, and surface area 300 m2/g | Wystar-Kyoto rats | Intratracheal instillation | 1 μg/g | 24 h, 2 weeks, 24 weeks. | SWCNTs may alter the TFIIB-related factor, thus affecting the autonomic cardiovascular control regulation. |
Li et al., 2007 [106] | SWNCTs | Diameter 1–4 nm, surface area 1040 m2/g | C57BL/6 mice | Intrapharyngeal instillation | 10 and 40 µg/mouse | 7, 28, and 60 days | SWCNTs induced activation of heme oxygenase-1, damage to mtDNA, and acceleration of the formation of atherosclerotic plaques. |
References | Materials | Materials Properties | Animals | Routes of Administration | Doses/Concentrations | Exposure Times | Toxicity Effects |
---|---|---|---|---|---|---|---|
Samiei et al., 2020 [114] | MWCNTs | Diameter 10 and 100 nm, length 0.14–1.7 and 0.16–1.8 μm | Wistar rats | Inhalation | 5 mg/m3 | 2 weeks | MWCNTs induce damage in varying degrees on the mitochondrial respiratory chain and increase mitochondrial ROS formation in different parts of rat brains. |
Aragon et al., 2017 [111] | MWCNTs | - | C57BL6 mice | Oropharyngeal aspiration | 10 and 40 μg/mouse | 4 h | Acute pulmonary exposure to MWCNTs causes neuroinflammatory responses that are dependent on the disruption of BBB integrity. |
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Witkowska, M.; Florek, E.; Mrówczyński, R. Assessment of Pristine Carbon Nanotubes Toxicity in Rodent Models. Int. J. Mol. Sci. 2022, 23, 15343. https://doi.org/10.3390/ijms232315343
Witkowska M, Florek E, Mrówczyński R. Assessment of Pristine Carbon Nanotubes Toxicity in Rodent Models. International Journal of Molecular Sciences. 2022; 23(23):15343. https://doi.org/10.3390/ijms232315343
Chicago/Turabian StyleWitkowska, Marta, Ewa Florek, and Radosław Mrówczyński. 2022. "Assessment of Pristine Carbon Nanotubes Toxicity in Rodent Models" International Journal of Molecular Sciences 23, no. 23: 15343. https://doi.org/10.3390/ijms232315343