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

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.

Keywords:

• Carbon nanotubes
• chromosome damage
• comet assay
• meta-analysis
• oxidative DNA damage
• mutations

View correction statement:

Erratum

Acknowledgements

The author thanks Drs. Eileen D Kuempel, National Institute for Occupational Safety and Health, Cincinnati, OH and Marie-Claude Jaurand, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche, Paris, France for fruitful comments to the manuscript.

Declaration of interest

The authors have sole responsibility for the writing and content of the paper. The authors have sole responsibility for the conceptualization and conduct of the study and the conclusions and recommendations contained therein. None of the authors has appeared during the past 5 years in any legal or regulatory proceedings related to the contents of the paper. The authors report no conflict of interest relevant to this review article. The author’s affiliation is as shown on the cover page.

This work was supported by the Danish Council of Independent Research (Medical Sciences, grant No. 6110-00103) and the Danish Centre for Nanosafety II.

Supplemental material

Supplemental material for this article is available online here.