The carcinogenic effect of various multi-walled carbon nanotubes (MWCNTs) after intraperitoneal injection in rats
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BACKGROUND: Biological effects of tailor-made multi-walled carbon nanotubes (MWCNTs) without functionalization were investigated in vivo in a two-year carcinogenicity study. In the past, intraperitoneal carcinogenicity studies in rats using biopersistent granular dusts had always been negative, whereas a number of such studies with different asbestos fibers had shown tumor induction. The aim of this study was to identify possible carcinogenic effects of MWCNTs. We compared induced tumors with asbestos-induced mesotheliomas and evaluated their relevance for humans by immunohistochemical methods. METHODS: A total of 500 male Wistar rats (50 per group) were treated once by intraperitoneal injection with 10⁹ or 5 × 10⁹ WHO carbon nanotubes of one of four different MWCNTs suspended in artificial lung medium, which was also used as negative control. Amosite asbestos (10⁸ WHO fibers) served as positive control. Morbid rats were sacrificed and necropsy comprising all organs was performed. Histopathological classification of tumors and, additionally, immunohistochemistry were conducted for podoplanin, pan-cytokeratin, and vimentin to compare induced tumors with malignant mesotheliomas occurring in humans. RESULTS: Treatments induced tumors in all dose groups, but incidences and times to tumor differed between groups. Most tumors were histologically and immunohistochemically classified as malignant mesotheliomas, revealing a predominantly superficial spread on the serosal surface of the abdominal cavity. Furthermore, most tumors showed invasion of peritoneal organs, especially the diaphragm. All tested MWCNT types caused mesotheliomas. We observed highest frequencies and earliest appearances after treatment with the rather straight MWCNT types A and B. In the MWCNT C groups, first appearances of morbid mesothelioma-bearing rats were only slightly later. Later during the two-year study, we found mesotheliomas also in rats treated with MWCNT D - the most curved type of nanotubes. Malignant mesotheliomas induced by intraperitoneal injection of different MWCNTs and of asbestos were histopathologically and immunohistochemically similar, also compared with mesotheliomas in man, suggesting similar pathogenesis. CONCLUSION: We showed a carcinogenic effect for all tested MWCNTs. Besides aspect ratio, curvature seems to be an important parameter influencing the carcinogenicity of MWCNTs.
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This rigidity range is similar to the bounds of the critical rigidity value of 7 mN∙nm2 for MWCNTs, deduced from Rittinghausen et al. [25].
“In addition, this rigidity range is similar to the bounds of the critical rigidity value of 7”
From Macrophages bend long fibres with flexural rigidity lower than 3 mN·nm2 to avoid frustrated phagocytosis (2026) · cites this paper as [25]
Intraperitoneal injection of different MWCNT materials in rodents for 24 months showed fibre-specific toxicity for critical fibres with different geometric mean diameters except the thinnest (37 nm).
“Intraperitoneal injection of suspensions of different MWCNT materials in rodents that were kept for 24 months showed fibre-specific toxicity for critical fibres exhibiting different geometric mean diameters except thinnest with a diameter of 37”
From Macrophages bend long fibres with flexural rigidity lower than 3 mN·nm2 to avoid frustrated phagocytosis (2026) · cites this paper as [25]
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- Authors
- Rittinghausen, S., Hackbarth, A., Creutzenberg, O., Ernst, H., Heinrich, U., Leonhardt, A., & Schaudien, D.
- Affiliations
- Fraunhofer Institute for Toxicology and Experimental Medicine (DE)
- Leibniz Institute for Solid State and Materials Research (DE)
- Corresponding author
- Rittinghausen, Susanne
- Venue
- Particle and Fibre Toxicology
- Published
- 2014-11-20
- Volume
- 11
- Issue
- 1
- Pages
- 59-59
- ISSN
- 1743-8977 (ISSN-L)
- PMC
- PMC4243371
- OpenAlex
- W2152314477
- Cited by
- 193
- References
- 61
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 16 · 2023: 15 · 2022: 16 · 2021: 21 · 2020: 25 · 2019: 17 · 2018: 24 · 2017: 22 · 2016: 13 · 2015: 11
- FWCI
- 12.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Particle and Fibre Toxicology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion, other-oa)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- Funders
- Bundesministerium für Bildung und Forschung (03X0109A)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Physical Sciences › Engineering › Biomedical Engineering › Graphene and Nanomaterials Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- multi-walled carbon nanotubes, carcinogenicity, malignant mesothelioma, intraperitoneal injection, asbestos, amosite, nanotube curvature, aspect ratio, podoplanin, pancytokeratin, vimentin, rats, nanotube toxicity
- MeSH terms
- Abdominal Neoplasms, Animals, Carcinogens, Dose-Response Relationship, Drug, Immunohistochemistry, Injections, Intraperitoneal, Male, Mesothelioma, Microscopy, Electron, Scanning, Neoplasm Invasiveness, Neoplasm Proteins, Particle Size, Serous Membrane, Carcinogenicity Tests, Survival Analysis, Rats, Wistar, Nanotubes, Carbon
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