The vision of OBERON was to contribute to the improvement of current tiered approaches by building an integrated testing strategy (ITS) to detect endocrine disruptors (EDs) related metabolic disorders by developing, improving and validating a battery of test systems. To increase our understanding of the biological complexity and predict the effects of chemical substances on human health, OBERON was based on the concept of an integrated approach for testing and assessment (IATA). OBERON combined experimental methods (in vitro e.g. on human cells, organs or tissue, and in vivo i.e. in zebrafish at different stages), high throughput omics technologies (metabolomics, lipidomics and transcriptomics) with epidemiology and human biomonitoring studies and advanced computational models (in silico and systems biology) on functional endpoints related to metabolism. Such interdisciplinary framework intended to help at deciphering EDs based on mechanistic understanding of toxicity by providing and making available more effective alternative test methods for human health that were in line with regulatory needs.
TEAM was mainly involved in the work package 4.
The main objective of this WP was to provide predictive computational methods for endocrine disruptor compounds.
Advanced computational models will be established to predict the ED potential of compounds based on the physicochemical properties of the substances (QSAR).
Toxicokinetic models for the integration of human biomarker data and meaningful extrapolation of in vitro assay results. PBPK models give access to cellular doses in in vitro and in vivo systems are essential for integration of human biomarker data and meaningful extrapolation of in vitro assay results.
Codaccioni, M., Bois, F., Brochot, C., 2019. Placental transfer of xenobiotics in pregnancy physiologically-based pharmacokinetic models: Structure and data. Computational Toxicology 12, 100111.
Audouze, K., Sarigiannis, D., Alonso-Magdalena, P., Brochot, C., Casas, M., Vrijheid, M., Babin, P.J., Karakitsios, S., Coumoul, X., Barouki, R., 2020. Integrative Strategy of Testing Systems for Identification of Endocrine Disruptors Inducing Metabolic Disorders-An Introduction to the OBERON Project. International Journal of Molecular Sciences 21.
Codaccioni, M., Brochot, C., 2020. Assessing the impacts on fetal dosimetry of the modelling of the placental transfers of xenobiotics in a pregnancy physiologically based pharmacokinetic model. Toxicology and Applied Pharmacology 409.