Toxicity evaluations of various carbon nanomaterials

Our plain-English summary of Toxicity evaluations of various carbon nanomaterials, by M. Uo, T. Akasaka, F. Watari, et al (Dental Materials Journal, 2011).

The study

• Authors: M. Uo, T. Akasaka, F. Watari, Y. Sato, K. Tohji
• Journal: Dental Materials Journal
• Published: 2011;30(3):245-63
• Type of article: Review
• Cited by: 36 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

After the discovery of fullerene and carbon nanotubes, various carbon nanomaterials were discovered or synthesized. The carbon nanomaterials have remarkable properties, different from bulk materials with the same chemical composition, and are therefore useful for industrial applications. However, the toxicity of nanomaterials may also differ from that of the bulk materials; this difference poses a concern. The physical similarity of nanomaterials to asbestos has led to evaluations for toxicity by many researchers using various methods. In this review, we compile and compare the toxicity evaluations of each carbon nanomaterial.

In plain English

This article was a review. The authors compiled and compared published toxicity tests of carbon nanomaterials, including fullerene (C60) and single-walled and multi-walled carbon nanotubes (SWCNTs, MWCNTs). The tests used cells, animals, microbes and plant cells. Nanotubes are suspected of asbestos-like toxicity because of their shape. One reviewed study reported that MWCNTs instilled into rats' airways remained in the lungs after 60 days and caused inflammation, fibrotic reactions and granulomas, similar to chrysotile. Another found that long, but not short, MWCNTs and amosite fibers injected into the abdominal cavity of mice caused inflammation and granulomas there. A third gave MWCNTs and crocidolite by intraperitoneal injection to p53 heterozygous mice, described as sensitive to asbestos; MWCNTs induced mesothelioma earlier than crocidolite. Results in cell tests varied with factors such as purity, clumping and the test method used. The authors noted that experimental doses often exceeded actual exposures. They concluded that the exact toxicity is difficult to specify, that nanotube toxicity should be discussed separately from that of asbestos, and that these materials should be handled like other hazardous materials under the precautionary principle.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of published toxicity studies of carbon nanomaterials
• Who was studied: Published toxicity reports on fullerene (C60), SWCNTs, MWCNTs and other carbon nanomaterials (carbon nanocapsules, carbon nanofibers, carbon nanohorns). The reports used cell cultures, animals (including rats, mice, fish and Drosophila), bacteria and plant cells. The number of such reports increased from 2005 onward.
• Exposure: Carbon nanomaterials given by several routes: intratracheal instillation, inhalation, intraperitoneal or intravenous injection, oral dosing, and addition to cell cultures. Several reviewed studies compared MWCNTs or SWCNTs with chrysotile, amosite or crocidolite asbestos.
• Main results:
  • A reviewed study (Muller et al.) reported that in rats, MWCNTs instilled into the airways remained in the lungs after 60 days and induced inflammation, fibrotic reactions and granulomas. The tissue reaction and cytotoxicity were similar to those of chrysotile.
  • A reviewed study (Poland et al.) injected fibers into the peritoneal (abdominal) cavity of mice. Long fibers of MWCNTs and amosite induced inflammation and granulomas in the abdominal cavity, but short fibers did not.
  • A reviewed study (Takagi et al.) gave MWCNTs and crocidolite by intraperitoneal injection to p53 heterozygous mice, which the article describes as sensitive to asbestos. MWCNTs induced mesothelioma earlier than crocidolite.
  • A reviewed study (Soto et al.) reported that macrophages showed similar EC50 values for MWCNTs, asbestos (chrysotile) and carbon black. Human lung epithelial cells (A549) showed a low EC50 for MWCNTs compared with asbestos and carbon black.
  • A reviewed study (Wick et al.) reported that suspended SWCNT bundles were less cytotoxic than clumped (agglomerated) SWCNTs and asbestos. The authors inferred that clumping strongly affects SWCNT cytotoxicity.
  • A reviewed study (Wörle-Knirsch et al.) found that SWCNTs decreased A549 cell viability by up to 40% when measured with the MTT assay, but no decrease was seen with the WST-1 assay. The authors took this to mean that apparent toxicity depended on the assay method.
  • From the MWCNT cytotoxicity studies, the authors inferred that cytotoxicity was strongly affected by tube size, purity and surface condition.
  • In a reviewed rat study of polyalkylsulfonated C60, oral dosing caused no lethal damage. The median lethal dose (LD50) for intraperitoneal dosing was estimated at 600 mg/kg.
  • A reviewed study (Lam et al.) reported that SWCNTs induced dose-dependent epithelioid granulomas and interstitial inflammation that were stronger than those induced by quartz.
  • Typical inhaled amounts under routine working conditions were reported as less than 1 µg/kg/day for SWCNTs and several µg/kg/day for MWCNTs. Rats exposed to 2.5 mg/m3 of CNTs for 90 days were estimated to inhale more than 1000 µg at maximum.
• The authors' conclusion: The authors concluded that different methods gave different results and that the exact toxicity of carbon nanomaterials is difficult to specify. They held that nanotube toxicity should be discussed carefully and separately from that of asbestos, because nanotubes are more flexible and chemically different. Because toxicity has been neither shown nor disproven, they concluded the materials should be handled like other hazardous materials under the precautionary principle.
• Limitations the authors state:
  • In the reviewed studies that suggested toxicity, the experimental exposure conditions often produced a higher load than actual exposures.
  • Real exposure differs from the experimental routes used in many reviewed studies, such as instillation into the airways or injection into the abdomen.
  • MWCNTs clump more readily than asbestos, so clumped granules may form after instillation or injection into animals.

Topics

Medical terms in this study, explained in our Lexicon: Discovery.

Related studies

• Cytotoxicity assessment of some carbon nanotubes and related carbon nanoparticle aggregates and the implications for anthropogenic carbon nanotube aggregates in the environment — L.E. Murr, K.M. Garza, et al. (2005)
• A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials — V.C. Sanchez, P. Weston, et al. (2011)
• Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons — A.A. Shvedova, N. Yanamala, et al. (2014)
• Cytotoxic effects of aggregated nanomaterials — K. Soto, K.M. Garza, et al. (2007)
• Toxicity of nanomaterials — S. Sharifi, S. Behzadi, et al. (2012)
• Cell entry of one-dimensional nanomaterials occurs by tip recognition and rotation — X. Shi, A. von dem Bussche, et al. (2011)

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