Assisting toxicological risk assessments of chemicals with VHP4Safety

The Virtual Human Platform for Safety Assessment (VHP4Safety) is a project from the Dutch national science agenda with the ultimate goal of providing solutions to perform precision safety assessments solely based on human data, without the use of laboratory animals. The aim is to improve the prediction of potential harmful effects of chemicals, including pharmaceuticals, based on the integration of data on human physiology, chemical characteristics and perturbations of biological processes. The project works on the development of a cloud-based infrastructure that integrates in silico models combined with databases and new approach methodologies for in vitro evaluations, to perform chemical risk assessments relevant to humans. Within the VHP4Safety project, various in silico models are developed to predict the toxicokinetics and toxicodynamics of chemicals and pharmaceuticals and their effect on human physiology. For example, PBPK models and metabolism predictions are developed to provide insights into the toxicokinetics, linking external exposure and internal concentrations in specific organs. In the platform, the Adverse Outcome Pathway (AOP), a risk assessment framework that captures mechanistic information of toxicological processes, linked by measurable endpoints that progress toward an adverse outcome, is a key element. Furthermore, QSAR models, MIE predictions and quantitative AOPs provide insights into toxicodynamics. A central idea of the VHP4Safety project is the integration of in silico models, in vitro data and biological knowledge, for providing safety estimates and a thorough understanding of potential risks. Another objective of the platform is to manage access to existing clinical and in vitro data from external resources, including patient, biomonitoring and epidemiological data, as well as experimental data generated in the project. To integrate the large variety of data and models in a virtual infrastructure, core data management concepts such as Data Management Plans and FAIR principles are applied where possible, providing all essential information on the data life cycle and metadata, linked to ontologies and persistent identifiers for optimal integration and use in computational workflows. The aim of this poster is to share the progress within VHP4Safety with the Toxicology community and to have open discussions on the implemented approaches in modelling, experimental analysis, integration, and communication, which we will initiate by formulating questions for the audience. This way, we will be able to create a more inclusive community and optimise future developments within the project for application in risk assessments. The same poster was also shown at the NUTRIM Symposium in November 2022. Poster presented at International Congress of Toxicology (ICT) 2022, Maastricht (2022).