Weight of evidence analysis for assessing the genotoxic potential of carbon nanotubes

Our plain-English summary of Weight of evidence analysis for assessing the genotoxic potential of carbon nanotubes, by P. Møller, N.R. Jacobsen (Critical Reviews in Toxicology, 2017).

The study

• Authors: P. Møller, N.R. Jacobsen
• Journal: Critical Reviews in Toxicology
• Published: 2017;47(10):867-884
• Type of article: Review
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Carbon nanotube (CNT) is a nanomaterial that has received interest because of its high-tensile strength and low weight. Although CNTs differ substantially in physico-chemical properties, they share high aspect ratio which resembles that of asbestos and other fibers causing lung cancer and mesothelioma. One type of multi-walled CNTs (i.e. MWCNT-7) has been classified as possibly carcinogenic to humans by IARC (Group 2B) based on experimental animal data, whereas other types of MWCNTs and single-walled CNTs (SWCNT) could not be classified due to lack of data from epidemiologic studies and insufficient mechanistic evidence. Damage to DNA is considered to be a key mechanistic step in the development of fiber-induced cancer. Thus, the genotoxic potential can be a cornerstone in the evaluation of hazards of CNTs. The present study used a weight of evidence (WoE) analysis to evaluate the genotoxicity of different types of CNTs. Genotoxicity endpoints close to cancer (mutations and chromosome aberrations) and animal models had highest weight in the WoE analysis. Eight CNT materials out of 130, which had been assessed in several studies, were evaluated in the WoE analysis. The results demonstrated that MWCNT-7 has strongest WoE for a genotoxic hazard among the MWCNTs. Two types of SWCNTs have a similar WoE for genotoxicity as MWCNT-7. Several reference materials from the Joint Research Centre have less WoE for genotoxicity. The WoE analysis demonstrates a difference in genotoxicity for CNTs, but further research is required to unravel the physico-chemical characteristics that govern the differences in genotoxic hazard.

In plain English

This review examined research on whether carbon nanotubes damage DNA (genotoxicity). It did not itself assess asbestos genotoxicity or risk; asbestos appeared as background and in earlier studies' comparison groups. The authors noted that carbon nanotubes resemble the shape of asbestos and other fibers causing lung cancer and mesothelioma. The authors found 111 eligible publications covering 89 multi-walled and 41 single-walled nanotube types. Eight materials entered a weight of evidence analysis that gave most weight to animal studies, mutations and chromosome aberrations. In the category-based analysis, MWCNT-7, the single-walled CNI material and Sigma 636797 had the strongest weight of evidence of genotoxicity; the others were mixed. The effect-size analysis did not convincingly show differences between materials, and the high Sigma 636797 score was described as skewed. After excluding low-precision, high-effect studies, pooled cell-culture micronucleus results gave similar group-level effects for multi-walled and single-walled nanotubes. The authors concluded that the results indicated a strong likelihood of genotoxicity for MWCNT-7 and CNI, with other materials inconclusive. They noted that few materials were included and CNI was tested in one laboratory.

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: a systematic narrative review of published studies combined with a weight of evidence analysis and a meta-analysis
• Who was studied: 111 eligible publications on genotoxicity of carbon nanotubes, covering 89 types of multi-walled carbon nanotubes (MWCNTs) and 41 types of single-walled carbon nanotubes (SWCNTs). Eight materials were included in the weight of evidence analysis. The publications were identified mainly through PubMed, plus a Google search.
• Exposure: Pristine carbon nanotubes. The eight materials in the weight of evidence analysis were five MWCNTs (MWCNT-7, NM400, NM401, NM402, NM403) and three SWCNTs (CNI, EliCarb, Sigma 636797). They were tested in animals (mainly lungs) and in cell cultures. Asbestos was not part of the weight of evidence analysis. It appears only in the background and as comparison groups in earlier animal studies listed in Table 1.
• Main results:
  • In the qualitative weight of evidence analysis of eight materials, MWCNT-7, CNI and Sigma 636797 had the strongest weight of evidence of genotoxicity. The remaining materials fell into the mixed-results group.
  • The qualitative analysis did not show a clear difference between multi-walled and single-walled nanotubes as groups.
  • The quantitative (effect-size) weight of evidence analysis did not convincingly demonstrate a difference in genotoxic potential between the materials. The high weighted score for Sigma 636797 was described as skewed, with a wide 95% confidence interval.
  • In the meta-analysis of micronucleus results in cultured cells, the authors used a restricted dataset that excluded two studies with low precision and high effect size from the other MWCNTs group. In that dataset, all MWCNTs (28 results) had a standardized mean difference of 0.60 (95% CI 0.27 to 0.93).
  • In the same restricted micronucleus meta-analysis, two studies with low precision and high effect size were excluded from the Sigma 636797 and other SWCNTs groups. All SWCNTs (13 results) had a standardized mean difference of 0.73 (95% CI 0.17 to 1.29). The authors described this restricted analysis as showing a similar effect to MWCNTs at group level.
  • The authors reported substantial heterogeneity between studies in some subgroups of the micronucleus meta-analysis. They stated that more studies are needed before individual products can meaningfully be distinguished.
  • The micronucleus meta-analysis did not convincingly separate the most genotoxic MWCNT (MWCNT-7) and SWCNT (CNI) from other types. The authors suggested the micronucleus assay may not be suitable for grading the overall genotoxic potential of carbon nanotubes.
• The authors' conclusion: The authors concluded that the combined qualitative and quantitative analyses indicate a strong likelihood of genotoxicity for MWCNT-7 and CNI. They also concluded that other carbon nanotubes remain inconclusive, and that physico-chemical characteristics cannot presently be used to predict genotoxic potential.
• Limitations the authors state:
  • The final weight of evidence analysis included relatively few carbon nanotube materials.
  • The three single-walled materials analysed are no longer available.
  • The CNI material was tested in only one laboratory, and its results should be reproduced elsewhere.
  • Only pristine (not functionalized) carbon nanotubes were included.
  • With only eight materials, the dataset was too small to measure links between physico-chemical characteristics and genotoxicity.
  • The authors used expert judgment in certain cases, especially for oxidative DNA damage measurements.

Topics

Medical terms in this study, explained in our Lexicon: Tensile Strength, Aspect Ratio (Length-to-diameter ratio), Lung Cancer, Mesothelioma, Carcinogenic, IARC, Genotoxicity.

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