Specific Challenge:

Risk assessment is often largely based on the toxicological profile of the material in question. The reason is that the costs related to hazard assessment are usually not in balance with the costs for exposure monitoring, let alone risk containment or risk mitigation. However with the very big number of new material likely to enter production and use, the usually short period between development and marketing and the increase in societal risk aversion, the classical toxicological testing paradigm so far focusing on in vivo testing is gradually but steadily shifting towards in-vitro and in-silico testing approaches. This is particularly true in the field of nanosafety where, in front of potentially thousands of different nanomaterials, economic constraints make it essential to develop and establish robust, fast and yet reliable and realistic methods that should be applied in figuring out "nanomaterials of concern".

Significant progresses have been made in assessing nanomaterial hazard. Yet, knowledge gaps remain on long-term effects (low doses, chronic exposure), both for human health and the environment. Questions also arise on the adequacy of the models used in existing in-vitro and in-silico testing and on the relevance of the exposure conditions (e.g. linked to the current understanding of the nanomaterial-biomolecule-cell interface) to correctly assess and predict real-life hazards. It is also necessary to prepare the ground for the next challenge, defining hazard profiles based on in-silico testing alone.

Scope:

With a view to intelligent testing strategies (ITS) for nanomaterials, it is of high priority to develop and adopt realistic and advanced in vitro tests which have the potential to substantially improve the relevance of in-vitro approaches. Current in-vitro experiments mostly rely on established immortalized single cell lines, which often do not reflect the in-vivo situation. Therefore, new or advanced models, such as co-culture models, 3D cultures or primary cell models should be developed for relevant endpoints lacking, or having inadequate, in-vitro models. Transport through biological barriers could also be addressed, for instance with the objective of assessing the true internal dose of the materials to which living organisms are being exposed, as well as disease models or models with impaired barriers.

Low-level chronic exposure is a likely scenario as many ENMs will probably exist at very low concentrations in the environment and potentially be persistent. Thus, assays and models with low chronic exposure, elucidating toxicokinetics, different mechanisms of action and adverse outcome pathways, as well as specific disease models, should be developed and assessed against appropriate animal studies and could include for instance effects on kinetics, growth, reproduction, metabolism, and behaviour. Research could also focus on long-term, ecologically relevant, effects in realistic environmental concentrations of ENMs.

The transformations in biological or environmental matrices have been demonstrated as having potentially significant effect on the ENM tests results. Therefore, dosing with realistic exposure levels and conditions should be an integral part of the developments, taking into consideration the dynamic and complex nature of environmentally induced transformations with realistic external and internal forms and levels of exposure.

For validation purposes and to ensure that the experimental results can form a solid and meaningful basis for grouping, read-across, and modelling purposes, the testing should be performed on sets of well-defined and characterised libraries of nanomaterials and, when possible, on nanomaterials for which high-quality in-vivo data are already existing (to minimize animal testing).

Activities are expected to focus on Technology Readiness Levels 4 to 6.

This topic is part of the open data pilot.

This topic is particularly suitable for international cooperation.

The Commission considers that proposals requesting a contribution from the EU between EUR 10 and 13 million would allow this specific challenge to be addressed appropriately. Nonetheless, this does not preclude submission and selection of proposals requesting other amounts.

No more than one action will be funded.

Expected Impact:

• The research approach should be innovative and represent a significant advance beyond the current state-of-the-art. Research should focus on provision of solutions to the long-term challenge of nanosafety and nanoregulation;
• New models and assays for use in in-vitro and in-silico testing improving prediction of chronic effects in a broad array of representative organisms and changes in ecosystem function;
• Improved predictive power of in-vitro and in-silico approaches for in vivo systems to support acceptance in a regulatory framework;
• Developed test guidelines for further standardisation, and ring testing (including guidance on design of the ring testing).