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ALTERNATIVE will develop an innovative platform able to detect the cardiotoxicity of chemicals and their bio-transformation products. The novel platform will enable regulators and industry to identify, quantify and prevent cardiotoxic co-exposures to industrial chemicals and pharmaceuticals in a cost-effective way. ALTERNATIVE will particularly focus on cardiotoxic effects on older people, which is of high relevance in view of the ageing EU population and the high spread of cardiovascular diseases. The platform will consist of a three-dimensional tissue engineering in-vitro model mimicking the human cardiac tissue, coupled with a reliable, high-throughput monitoring system based on multi-omics analyses, and integrated into a Machine Learning (ML) risk assessment tool. In addition, ALTERNATIVE will modify the tissue model to reproduce the aged myocardial tissue and elucidate the adverse effects of chemicals on older people. ALTERNATIVE?s proof-of-concept validation will be performed on well-known mixtures of pollutants, affecting different environmental compartments, and selected via epidemiological, toxicological and modelling expertise. ALTERNATIVE will also provide systematic reviews of high-quality epidemiological studies to support integrated in vitro and in silico data, giving a more robust basis for regulatory decisions. The ALTERNATIVE platform will be an innovative tool for complying with the current regulation associated with the assessment of chemical compounds. It will be a new instrument to evaluate unpredictable toxicity due to synergistic effects of different chemicals, additionally worsened by the human ageing process. By introducing an in vitro cardiac system and ML models, ALTERNATIVE will provide a platform able to refine, reduce and replace the need for animal testing, providing close-to-real scenario information on toxicity and achieving a significant reduction of the associated direct and indirect costs