Through an iterative process, working with stakeholders, GRACIOUS has generated a Framework to support the grouping and read-across of nanoforms, in order to streamline risk assessment, safe(r) by design approaches, identification of precautionary measures and testing strategies. (Stone et al 2020,
https://doi.org/10.1016/j.nantod.2020.100941(opens in new window)).
The Framework has been constructed as and open access software blueprint, allowing it to be incorporated into different risk assessment software. The blueprint is incorporated into risk assessment software via the SUN decision support system, and the GUIDEnano tool.
The Framework has also being written as a Guidance Document including worked examples to illustrate application of the Framework, Hints and Tips for each section to highlight important things for the user to consider and references to additional sources of information. A shorter 'Guidance in a nutshell' has also been generated as an induction to the GRACIOUS Framework. Both are published via Zenodo.
The project partners have used existing literature and databases to establish 40 pre-defined hypotheses incorporated in the Framework. These hypotheses cover different environmental compartments and different routes of exposure relevant to humans. Provision of limited basic information by the user allows identification of the most appropriate pre-defined hypothesis relevant to the nanoform(s) of interest and exposure route(s). The release of nanoforms (concentration and form) and exposure routes are determined via a series of decision trees that are supported by a release/ exposure library, providing data and information to support identification of relevant exposure scenarios and release pathways, and the consequent exposure concentrations.
For each hypothesis a tailored Integrated Approach to Testing and Assessment (IATA) has been developed. The IATAs are decision trees which guide the user through the most appropriate questions (decision nodes) to be addressed in order to identify the information and data needed to test the hypothesis. Each decision node is backed up by a tiered testing strategy of methods to allow acquisition of the most appropriate data where data gaps exist.
Completion of the IATA leads to population of a data matrix which collates all information for the proposed group members and benchmark materials for all decision nodes. This data matrix is required by ECHA for substance dossiers which utilise grouping and read-across.
A range of methods have been generated to quantitatively assess the similarity of nanoform using the data matrix. These methods have contributed to the generation of over 10 publications all submitted to generate a special issue of NanoImpact dedicated to the GRACIOUS similarity assessment work.
A range of internal and external case studies, including stakeholders from industry, regulators and academia were completed. These case studies assessed the whole Framework, IATAs and similarity assessment methods for both human and environmental applications of grouping and read-across. Feedback from these case studies was positive and allowed refinement of instructions included in the final Framework Guidance Document.
