Inhalation Toxicity of Multiwall Carbon Nanotubes in Rats Exposed for 3 Months
Abstract
Carbon nanotubes (CNT) are of great commercial interest. Theoretically, during processing and handling of CNT and in abrasion processes on composites containing CNT, inhalable CNT particles might be set free. For hazard assessment, we performed a 90-day inhalation toxicity study with a multiwall CNT (MWCNT) material (Nanocyl NC 7000) according to Organisation for Economic Co-operation and Development test guideline 413. Wistar rats were head-nose exposed for 6 h/day, 5 days/week, 13 weeks, total 65 exposures, to MWCNT concentrations of 0 (control), 0.1, 0.5, or 2.5 mg/m(3). Highly respirable dust aerosols were produced with a proprietary brush generator which neither damaged the tube structure nor increased reactive oxygen species on the surface. Inhalation exposure to MWCNT produced no systemic toxicity. However, increased lung weights, pronounced multifocal granulomatous inflammation, diffuse histiocytic and neutrophilic inflammation, and intra-alveolar lipoproteinosis were observed in lung and lung-associated lymph nodes at 0.5 and 2.5 mg/m(3). These effects were accompanied by slight blood neutrophilia at 2.5 mg/m(3). Incidence and severity of the effects were concentration related. At 0.1 mg/m(3), there was still minimal granulomatous inflammation in the lung and in lung-associated lymph nodes; a no observed effect concentration was therefore not established in this study. The test substance has low dust-forming potential, as demonstrated by dustiness measurements, but nonetheless strict industrial hygiene measures must be taken during handling and processing. Toxicity and dustiness data such as these can be used to compare different MWCNT materials and to select the material with the lowest risk potential for a given application.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Carbon nanotubes were found not to be consistently toxic despite the fibre-pathogenicity paradigm's prediction.
“However, a specific class of nanoscale materials, carbon nanotubes (CNTs), was found not to be consistently toxic despite the fibre-pathogenicity paradigm’s prediction [17, 18].”
From Macrophages bend long fibres with flexural rigidity lower than 3 mN·nm2 to avoid frustrated phagocytosis (2026) · cites this paper as [18]
One reason for reduced CNT toxicity is that many CNT materials were tested in agglomerate state, and such granular agglomerates are not expected to show fibre-specific toxicity.
“One reason for reduced CNT toxicity was attributed to the fact that many CNT materials were toxicologically tested in agglomerate state as CNTs can already be synthesized as highly entangled agglomerates, can spontaneously re-agglomerate after dispersion, or, if thin and flexible, can self-tangle into granules. Such granular agglomerates are not expected to show fibre-specific toxicity.”
From Macrophages bend long fibres with flexural rigidity lower than 3 mN·nm2 to avoid frustrated phagocytosis (2026) · cites this paper as [18]
Cites
Helical microtubules of graphitic carbon
Iijima, S. (1991) · Nature · doi:10.1038/354056a0 · Cited by 43,126 · see citing works
Nonparametric Statistics for the Behavioral Sciences
Guitton, H., & Siegel, S. (1958) · Revue économique · doi:10.2307/3498751 · Cited by 35,281 · see citing works
A Multiple Comparison Procedure for Comparing Several Treatments with a Control
Dunnett, C. W. (1955) · Journal of the American Statistical Association · doi:10.1080/01621459.1955.10501294 · Cited by 5,930 · see citing works
Simultaneous Statistical Inference
Miller, R. G. (1981) · Springer series in statistics · doi:10.1007/978-1-4613-8122-8 · Cited by 5,608 · see citing works
Non-Parametric Statistics for the Behavioral Sciences.
Stuart, A., & Siegel, S. (1957) · Economica · doi:10.2307/2551606 · Cited by 3,388 · see citing works
Large-scale synthesis of carbon nanotubes
Ebbesen, T. W., & Ajayan, P. M. (1992) · Nature · doi:10.1038/358220a0 · Cited by 3,141 · see citing works
New Tables for Multiple Comparisons with a Control
Dunnett, C. W. (1964) · Biometrics · doi:10.2307/2528490 · Cited by 3,126 · see citing works
Lam, C.-W. (2003) · Toxicological Sciences · doi:10.1093/toxsci/kfg243 · Cited by 1,992 · see citing works
Comparative Pulmonary Toxicity Assessment of Single-wall Carbon Nanotubes in Rats
Warheit, D. B. (2003) · Toxicological Sciences · doi:10.1093/toxsci/kfg228 · Cited by 1,519 · see citing works
Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice
Shvedova, A. A., Kisin, E. R., Mercer, R., Murray, A. R., Johnson, V. J., Potapovich, A. I., Tyurina, Y. Y., Gorelik, O., Arepalli, S., Schwegler-Berry, D., et al. (2005) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00084.2005 · Cited by 1,312 · see citing works
Lam, C., James, J. T., McCluskey, R., Arepalli, S., & Hunter, R. L. (2006) · Critical Reviews in Toxicology · doi:10.1080/10408440600570233 · Cited by 1,237 · see citing works
Respiratory toxicity of multi-wall carbon nanotubes
Muller, J., Huaux, F., Moreau, N., Misson, P., Heilier, J.-F., Delos, M., Arras, M., Fonseca, A., Nagy, J. B., & Lison, D. (2005) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2005.01.008 · Cited by 1,123 · see citing works
Salmela, L., Puglisi, S. J., & Mäkinen, V. (2016) · Lecture notes in computer science · doi:10.1007/978-3-319-44543-4 · Cited by 924 · see citing works
Advances toward bioapplications of carbon nanotubes
Lin, Y., Taylor, S., Li, H., et al. (2004) · Journal of Materials Chemistry · doi:10.1039/b314481j · Cited by 869 · see citing works
Shvedova, A. A., Kisin, E. R., Murray, A. R., Johnson, V. J., Gorelik, O., Arepalli, S., Hubbs, A. F., Mercer, R. R., Keohavong, P., Sussman, N., et al. (2008) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.90287.2008 · Cited by 643 · see citing works
Statistical Inference Based on Ranks
Hora, S. C., & Hettmansperger, T. P. (1986) · Technometrics · doi:10.2307/1270456 · Cited by 621 · see citing works
Pulmonary and Systemic Immune Response to Inhaled Multiwalled Carbon Nanotubes
Mitchell, L., Gao, J., Wal, R. L. V., Gigliotti, A. P., Burchiel, S. W., & McDonald, J. D. (2007) · Toxicological Sciences · doi:10.1093/toxsci/kfm196 · Cited by 433 · see citing works
Cardiovascular Effects of Pulmonary Exposure to Single-Wall Carbon Nanotubes
Li, Z., Hulderman, T., Salmen, R., Chapman, R. S., Leonard, S. S., Young, S., Shvedova, A. A., Luster, M. I., & Simeonova, P. P. (2006) · Environmental Health Perspectives · doi:10.1289/ehp.9688 · Cited by 413 · see citing works
Clastogenic and aneugenic effects of multi-wall carbon nanotubes in epithelial cells
Muller, J., Decordier, I., Hoet, P. H., Lombaert, N., Thomassen, L., Huaux, F., Lison, D., & Kirsch-Volders, M. (2008) · Carcinogenesis · doi:10.1093/carcin/bgm243 · Cited by 298 · see citing works
Animal model of human disease.
Lofland, H. B. (1975) · PubMed · Cited by 289 · see citing works
Helical microtubes of graphitic carbon
Wang, Y., Fang, D., Soh, A. K., et al. (2007) · Acta Mechanica Sinica · Cited by 237 · see citing works
Elder, A. C. P., Gelein, R. M., Finkelstein, J. N., Driscoll, K. E., Harkema, J. R., & Oberdörster, G. (2005) · Toxicological Sciences · doi:10.1093/toxsci/kfi327 · Cited by 214 · see citing works
Ma‐Hock, L., Burkhardt, S., Strauss, V., Gamer, A. O., Wiench, K., van Ravenzwaay, B., & Landsiedel, R. (2008) · Inhalation Toxicology · doi:10.1080/08958370802361057 · Cited by 197 · see citing works
Self-citationPHYSIOLOGICAL TESTING OF CARBON NANOTUBES: ARE THEY ASBESTOS-LIKE?
Huczko, A., Lange, H., Całko, E., Grubek-Jaworska, H., & Droszcz, P. (2001) · Fullerene Science and Technology · doi:10.1081/fst-100102973 · Cited by 159 · see citing works
Long-Term Retention and Clearance of Particles Inhaled by Mammalian Species
Snipes, M. B. (1989) · Critical Reviews in Toxicology · doi:10.3109/10408448909017909 · Cited by 155 · see citing works
The comparison of a fibrogenic and two nonfibrogenic dusts by bronchoalveolar lavage
Lindenschmidt, R. C., Driscoll, K. E., Perkins, M. A., Higgins, J. M., Maurer, J. K., & Belfiore, K. A. (1990) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(90)90026-q · Cited by 123 · see citing works
Progression of Lung Inflammation and Damage in Rats After Cessation of Silica Inhalation
Porter, D. W. (2004) · Toxicological Sciences · doi:10.1093/toxsci/kfh110 · Cited by 121 · see citing works
In vitro genotoxic effects of different combinations of cobalt and metallic carbide particles
Boeck, M. D., Lombaert, N., Backer, S. D., et al. (2003) · Mutagenesis · doi:10.1093/mutage/18.2.177 · Cited by 80 · see citing works
Generation and Characterization of Test Atmospheres with Nanomaterials
Ma‐Hock, L., Gamer, A. O., Landsiedel, R., Leibold, E., Frechen, T., Sens, B., Linsenbühler, M., & van Ravenzwaay, B. (2007) · Inhalation Toxicology · doi:10.1080/08958370701479190 · Cited by 76 · see citing works
Self-citationKaufmann, W. S. H., Bader, R., Ernst, H., et al. (2009) · Experimental and Toxicologic Pathology · doi:10.1016/j.etp.2009.01.001 · Cited by 62 · see citing works
The ultrastructure of acute silicosis.
Hoffmann, E. O., Lamberty, J., Pizzolato, P., et al. (1973) · PubMed · Cited by 37 · see citing works
Heppleston, A. G. (1975) · PubMed · Cited by 30 · see citing works
Smart nanotubes for biomedical and biotechnological applications
Kohli, P., & Martin, C. R. (2003) · Drug News & Perspectives · doi:10.1358/dnp.2003.16.9.829338 · Cited by 25 · see citing works
Warheit, D. B., Hansen, J. F., & Hartsky, M. A. (1991) · The Anatomical Record · doi:10.1002/ar.1092310112 · Cited by 10 · see citing works
Large Scale Production of VGCF
Lake, M. L. (2001) · Springer eBooks · doi:10.1007/978-94-010-0777-1_12 · Cited by 9 · see citing works
A review of upper respiratory tract inhalation pathology
McInnes, E. F., & Miller, R. A. (2007) · Comparative Clinical Pathology · doi:10.1007/s00580-007-0699-6 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Application of short-term inhalation studies to assess the inhalation toxicity of nanomaterials
Landsiedel, R., Ma-Hock, L., Hofmann, T., Wiemann, M., Strauss, V., Treumann, S., Wohlleben, W., Gröters, S., Wiench, K., & van Ravenzwaay, B. (2014) · Particle and Fibre Toxicology · doi:10.1186/1743-8977-11-16 · Cited by 169 · see citing works
Self-citationManufactured nanomaterials: categorization and approaches to hazard assessment
Gebel, T., Foth, H., Damm, G., Freyberger, A., Kramer, P.-J., Lilienblum, W., Röhl, C., Schupp, T., Weiss, C., Wollin, K.-M., et al. (2014) · Archives of Toxicology · doi:10.1007/s00204-014-1383-7 · Cited by 137 · see citing works
Thickness of Multiwalled Carbon Nanotubes Affects Their Lung Toxicity
Fenoglio, I., Aldieri, E., Gazzano, E., Cesano, F., Colonna, M., Scarano, D., Mazzucco, G., Attanasio, A., Yakoub, Y., Lison, D., et al. (2012) · Chemical Research in Toxicology · doi:10.1021/tx200255h · Cited by 128 · see citing works
The asbestos-carbon nanotube analogy: An update
Kane, A. B., Hurt, R. H., & Gao, H. (2018) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2018.06.027 · Cited by 106 · see citing works
Hazard Assessments of Manufactured Nanomaterials
Morimoto, Y., Kobayashi, N., Shinohara, N., Myojo, T., Tanaka, I., & Nakanishi, J. (2010) · Journal of Occupational Health · doi:10.1539/joh.r10003 · Cited by 83 · see citing works
The Significance and Insignificance of Carbon Nanotube-Induced Inflammation
Boyles, M., Stoehr, L., Schlinkert, P., Himly, M., & Duschl, A. (2014) · Fibers · doi:10.3390/fib2010045 · Cited by 22 · see citing works
Pauluhn, J. (2017) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2017.03.023 · Cited by 11 · see citing works
Broßell, D., Meyer-Plath, A., Gräb, O., Heunisch, E., Kämpf, K., Haase, A., & Wiemann, M. (2026) · Particle and Fibre Toxicology · doi:10.1186/s12989-026-00666-9 · Cited by 2 · see citing works
- Authors
- Ma-Hock, L., Treumann, S., Strauss, V., Brill, S., Luizi, F., Mertler, M., Wiench, K., Gamer, A. O., van Ravenzwaay, B., & Landsiedel, R.
- Affiliations
- BASF (Germany) (DE)
- Nanocyl (Belgium) (BE)
- Venue
- Toxicological Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-07-07
- Volume
- 112
- Issue
- 2
- Pages
- 468-481
- ISSN
- 1096-0929 (ISSN-L)
- 1096-6080
- OpenAlex
- W2126207677
- Cited by
- 448
- References
- 36
- Citations by year
- 2026: 3 · 2025: 15 · 2024: 9 · 2023: 21 · 2022: 10 · 2021: 19 · 2020: 15 · 2019: 19 · 2018: 22 · 2017: 31 · 2016: 30 · 2015: 50 · 2014: 42 · 2013: 44 · 2012: 45
- FWCI
- 23.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Graphene and Nanomaterials Applications
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- multi-walled carbon nanotubes, inhalation toxicity, granulomatous inflammation, lung-associated lymph nodes, neutrophilia, respiratory inflammation, NOEC, occupational exposure, carbon nanotube composites, hazard assessment
- MeSH terms
- Aerosols, Animals, Larynx, Lung, Lymph Nodes, Microscopy, Electron, Scanning, Nasal Cavity, Trachea, Reactive Oxygen Species, Inhalation Exposure, Nanotubes, Carbon, Microscopy, Electron, Transmission, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review