On September 21, 2018, the Organization for Economic Cooperation and Development (OECD) announced four new case studies on integrated approaches for testing and assessment (IATA), including a Case Study on Grouping and Read-Across for Nanomaterials — Genotoxicity of Nano-TiO2. The European Union (EU) Joint Research Center (JRC) developed the case study for the genotoxicity of nano-titanium dioxide (TiO2) for illustrating the practical use of IATA. The case study applies the workflow for grouping and read-across proposed in the European Chemicals Agency’s (ECHA) Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) guidance update for nanomaterials and explores the extent to which ECHA’s Read-Across Assessment Framework (RAAF) is applicable to nanoforms for identifying sources of uncertainty associated with the read-across. According to the case study, the purpose of the read-across exercise was to determine the genotoxic hazard potential of two nano-TiO2 target substances based on the in vitro comet assay results from other TiO2 nanoforms. Overall, the case study shows the practical application of the ECHA guidance for grouping and read-across of nanomaterials, which was slightly adapted for the case study. Furthermore, the case study states, it demonstrates the usefulness of cheminformatics techniques to support the grouping hypothesis by identifying the differences between nanoforms and by supporting the weight of evidence. JRC successfully applied the ECHA RAAF for evaluating the confidence in the read-across argumentation of nanomaterials. According to the case study, some nanospecific issues were identified for further specification of the RAAF for nanomaterials, in particular the concept of similarity, which cannot be based only on structural similarity for nanomaterials.
OECD states that the objective of the IATA Case Studies Project is to increase experience with the use of IATA by developing case studies that constitute examples of predictions fit for regulatory use. The aim is to create common understanding of using novel methodologies and the generation of considerations/guidance stemming from these case studies. OECD published the following three case studies with the case study on nano-TiO2:
- Case Study on the Use of Integrated Approaches for Testing and Assessment (IATA) for Estrogenicity of the Substituted Phenols;
- A Case Study on the Use of Integrated Approaches for Testing and Assessment for Sub-Chronic Repeated-Dose Toxicity of Simple Aryl Alcohol Alkyl Carboxylic Esters: Read-Across.
OECD also published a considerations document summarizing the learnings and lessons of the review experience of the case studies, Report on Considerations from Case Studies on Integrated Approaches for Testing and Assessment (IATA) — Third Review Cycle (2017).