NanoInformaTIX aims to create a comprehensive, sustainable, multi-scale modelling framework for exposure and (eco)-toxicity of Engineered Nanomaterials (ENM) to facilitate cost-effective risk assessment, less reliant on animal testing, and to support the design of safer materials and products. Our approach integrates several relevant EU/US databases with validated nanoinformatics models covering: Materials, Exposure, Physiologically-Based Pharmacokinetics (PBPK), Quantitative-Structure-Activity Relations (QSAR) and Systems Biology modelling and in vitro/in vivo extrapolation to support the prediction of biological effects and exposure of ENM at various stages of their life cycle and product development. NanoInformaTIX will address grouping and read-across for risk assessment and safer product design. NanoInformaTIX will use existing curated data from several completed EU/US projects and from peer-reviewed literature to develop, extend the models and will also consider emerging data from ongoing projects for model validation following the OECD validation principles. This will take the NanoInformaTIX models from TLR4 to TLR6. The NanoInformaTIX modelling framework will be a web-based platform with a user-friendly interface tailored to the needs of different stakeholders (industry, regulators, academia and the civil society). To obtain optimal confidence in the use of the NanoInformaTIX modelling and database framework, all models will be described clearly using agreed standards terminology and implemented on harmonized standard operating protocols based on Good Modelling/Software Design practices. Their applicability domain will be clearly documented and referenced for full transparency and detailed user guidance for each will be provided. NanoInformaTIX will achieve considerable impact by providing the much -needed validated accessible data management modelling framework to predict human and environmental risks, to support the design of sustainable ENM and products.