140 A Framework for Grouping Inhaled Multi-Component Nanomaterials to Streamline Hazard Assessment

Abstract The GRACIOUS Framework (www.h2020gracious.eu) supports the grouping of nanomaterials to streamline hazard testing of nanomaterials. The GRACIOUS Framework includes a template to generate grouping hypotheses based upon use and life cycle stage (to inform exposure route), physicochemical properties (what they are), fate or toxicokinetics (where they go) and hazard (what they do). The gathering of evidence to test these hypotheses was supported by tailored Integrated Approaches to Testing and Assessment (IATAs). Subsequent NMBP-16 projects have developed the hypothesis template further for multicomponent nanomaterials. Modifications include additional information requirements to accommodate the complexity of composition (what they are) and enhanced properties, with an aim to incorporate the relationship of these to the mechanism of hazard. Furthermore, the template considers potential for the components to dissociate, disintegrate or dissolve, with different kinetics, leading to a complex exposure scenario both in lung lining fluid and inside cells. This knowledge informs the hazard assessment (whether hazard is driven by the intact multicomponent nanomaterial or various components) and whether interactions between the components may lead to antagonism, synergism or potentiation of response. Hazard assessment outcome can then inform Safe-by-Design modifications. The template has been adapted to formulate clear questions needed to test all aspects of the hypothesis, with these questions being used to formulate the IATA. Case studies of different multicomponent nanomaterials are being used to inform the design process, and demonstrate its usefulness. Funding acknowledgement European Commission Horizon 2020 for GRACIOUS, SUNSHINE, HARMLESS and DIAGONAL, Grant Agreement No. 760840, 952924, 953183 953152 respectively.