Our research includes a series of case studies on systemic toxicity evaluation. These case studies are applied safety assessments of certain chemicals, based on non-animal new approach methodologies (NAMs) and show performance of new generation risk assessments (NGRA). They aim to practically implement, test and refine our scientific workflow. For instance, in systemic toxicity, this workflow uses the approaches that we develop in the toxicodynamic and toxicokinetic projects, and strategically combines them. This workflow allows concluding on the safety of a chemical by using a set of NAMs which are based on the level of exposure to a certain chemical and on the data availability for the chemical which we want to evaluate and its analogues. These approaches are the thresholds of toxicological concerns (TTC), internal TTC, chemical and biological read across, and ab initio approaches. When NAMs data are not available, for the chemicals of interest, we generate them e.g., skin penetration, or transcriptomics data. Our case studies series aims at benefiting to the whole safety assessment community and as such is opened to partnerships, including regulatory advisory bodies.