Grouping of multi-walled carbon nanotubes to read-across genotoxicity: A case study to evaluate the applicability of regulatory guidance

Multi-walled carbon nanotubes (MWCNTs) consist of multiple layers of graphene sheets in a tubular shape. Depending on the synthesis and purification method, MWCNTs may differ in size, shape, rigidity and other properties. Previous research has shown that physicochemical properties can influence the translocation and toxicity of MWCNTs. Extensive in vitro and in vivo testing may be required to characterise the hazard of various physical forms of MWCNTs. Grouping of MWCNTs to read-across data for toxicological endpoints could efficiently contribute to reduce and focus MWCNT testing. This paper describes a case study to explore and illustrate read-across of genotoxicity data by following the “Recommendations for nanomaterials applicable to the Guidance on QSARs and Grouping” developed by the European Chemicals Agency (ECHA). The grouping hypothesis was supported by the use of chemoinformatics techniques such as hierarchical clustering and principal components analysis. The uncertainties of the present case study were evaluated using the Read-Across Assessment Framework (RAAF) developed by ECHA. While the aim of this study was not to conduct a hazard assessment, the study data chosen for illustrative purposes suggest that the MWCNTs analogues selected are not genotoxic. No (major) differences between the analogues were observed which could be attributed to differences in physicochemical properties such as length, diameter or rigidity/straightness. Such properties, however, may have an impact on other hazard endpoints such as carcinogenicity. This study shows the practical application of the ECHA framework for grouping of nanomaterials (NMs) as well as use of the ECHA RAAF for NMs, and how this can be supported by chemoinformatics techniques. Some adaptations to the workflow are suggested for a more practical and straightforward narrative in the reporting. © 2018 Elsevier B.V.