The NanoMILE project is conceived and led by an international elite of scientists from the EU and US with the aim to establish a fundamental understanding of the mechanisms of nanomaterial interactions with living systems and the environment, and uniquely to do so across the entire life cycle of nanomaterials and in a wide range of target species. Identification of critical properties (physico-chemical descriptors) that confer the ability to induce harm in biological systems is key to allowing these features to be avoided in nanomaterial production (“safety by design”). Major shortfalls in the risk analysis process for nanomaterials are the fundamental lack of data on exposure levels and the environmental fate and transformation of nanomaterials, key issues that this proposal will address, including through the development of novel modelling approaches. A major deliverable of the project will be a framework for classification of nanomaterials according to their impacts, whether biological or environmental, by linking nanomaterial-biomolecule interactions across scales (sub-cellular to ecosystem) and establishing the specific biochemical mechanisms of interference (toxicity pathway).