The vision of the ONTOX consortium is to provide a functional and sustainable solution for advancing human risk assessment of chemicals without the use of animals in line with the principles of 21st century toxicity testing and next generation risk assessment. Specifically, ONTOX will deliver a generic strategy to create innovative new approach methodologies (NAMs) in order to predict systemic repeated dose toxicity effects that, upon combination with tailored exposure assessment, will enable human risk assessment. This strategy can be applied to any type of chemical and systemic repeated dose toxicity effect. However, for proof-of-concept purposes, focus will be put on 6 specific NAMs addressing adversities in the liver (steatosis and cholestasis), kidneys (tubular necrosis and crystallopathy) and developing brain (neural tube closure and cognitive function defects) induced by a variety of chemicals, including from the pharmaceutical, cosmetics, food and biocide sectors. The 6 NAMs will each consist of a computational system based on cutting-edge artificial intelligence (AI) and will be primarily fed by available biological/mechanistic, toxicological/epidemiological, physico-chemical and kinetic data. Data will be consecutively integrated in physiological maps, quantitative adverse outcome pathway networks and ontology frameworks. Data gaps, as identified by AI, will be filled by targeted state-of-the-art in vitro and in silico testing. The 6 NAMs will be evaluated and applied in collaboration with industrial and regulatory stakeholders in order to maximise end-user acceptance and regulatory confidence. This is anticipated to expedite implementation in risk assessment practice and to facilitate commercialisation. ONTOX will have a deep and long-lasting impact at many levels, in particular by consolidating Europe’s world-leading position regarding the development, exploitation, regulation and application of animal-free methods for human risk assessment of chemicals.

Drug safety assessment is a knowledge-intensive process that demands advancement in data handling methods and tools for facilitating data sharing, mining, analysis and predictive modelling. This need is not restricted to any specific type of data and real advancement requires integrating information of different types and from different sources (e.g. publicly available biomedical knowledge, proprietary preclinical and clinical data, evidence from post-marketing studies) for addressing drug safety assessment from a holistic perspective. The eTRANSAFE project will address these needs by developing a powerful data integration infrastructure (Knowledge Hub) and a collection of computational tools (exploitation modules) for making optimal use of these data. The proposed system will be a flexible and expandable framework, built on previous experience and applying state-of-the-art methods and technologies for providing the most advanced solutions for data sharing, interoperability and exploitation. An experienced honest broker will guarantee the confidentiality of any proprietary data. The project will develop in silico tools for data mining, visualisation, and prediction of potential toxicity, with specific attention to the assessment of the preclinical to clinical predictivity and the discovery of safety biomarkers. The CDISC-SEND format will be supported, facilitating the preparation of regulatory-compliant documentation. This infrastructure will be underpinned by development of open standards and guidelines recognised by regulatory agencies and international organisations. The eTRANSAFE consortium brings together 13 organizations that mobilize an unprecedented capacity and resources, uniquely placed to leverage the experience of eTOX and other EU projects and initiatives. The project partners are six prestigious academic institutions, six highly skilled small-medium enterprises (SME) and one European infrastructure (ELIXIR), bringing in this way a perfect balance.