Development of an Integrated Approach to Testing and Assessment for grouping High Aspect Ratio Nanomaterials within The EU Project GRACIOUS

The pathogenicity of asbestos fibres towards the mesothelium, resulting in tumour formation, is inexorably linked to the physiochemical characteristics of the fibres, namely high aspect ratio and biopersistence. In recent years concerns have been raised that new forms of high aspect ratio nanomaterials (HARN) will pose a similar hazard to the lung and pleural mesothelium in light of their structural similarities to pathogenic asbestos fibres. However as the number, type and variation of HARN developed for a wide range of diverse applications expands, testing every unique HARN for potential adverse effects has become virtually impossible, due to the financial, time and ethical considerations.

The GRACIOUS Framework aims to support the practical application of grouping to nanomaterials or nanoforms (NFs), in order to facilitate a streamlined risk assessment and management process and reduce the burden of toxicity testing of individual NF. Grouping decisions will be underpinned by scientifically justified hypotheses, which identify descriptors relevant to grouping of different NFs for a specific purpose.

With respect to High Aspect Ratio Nanomaterials (HARN), a grouping hypothesis based upon the structure-activity relationship governing asbestos carcinogenicity has been developed. The GRACIOUS hypothesis for grouping of HARN is substantiated by an Integrated Approach to Testing and Assessment (IATA) which guides relevant information gathering and experimental testing designed to provide the necessary evidence to support the grouping decision. The HARN IATA is based on the critical descriptors related to the key pathogenic events in asbestos-induced mesothelioma development, from initial insult to tumour formation. Implemented in tiers of increasing specificity and complexity, the IATA will reduce, refine and replace the need for animal testing by promoting the use of modelling, in vitro and cell-free tests in the initial tiers to screen potentially harmful HARN enabling practical risk analysis without extensive testing.
By moving away from case-by-case risk assessment, the GRACIOUS framework aims to prevent, in future, devastating occupational epidemics, such as asbestos-induced mesothelioma, by improving the efficiency of risk analysis and decision making, enabling safer design, production and use of new forms of HARN.