WP1 – Characterization of hepatic 3D spheroids
WP1 aims to investigate the 3D organoid model`s morphology structure and physiology during compound exposure. To address this, state-of-the-art image- and OMICS techniques and chemical analysis will be used.
WP2 – Chronic exposure of spheroids
WP 2 aims to evaluate the hepatic 3D spheroids suitability for chronic toxicity screening.
WP3 – Biotransformation of chemicals using 3D spheroids
The aim of WP3 is to evaluate the 3D spheroids’ potential as a complementary bioassay in the BC assessment of slowly biotransformed compounds.
WP4 – Multi-compartment co-culturing of hepatic spheroids and other cell types
WP4 aims to refine and implement a multi-compartment co-culturing test system that may account for complex biological scenarios similar to in vivo.
WP5 – In vitro to in vivo (IVIVE) modelling
WP5 aims to apply computational PBTK and fish plasma models (FPM) with reverse dosimetry to better estimate the IVIVE using the hepatic spheroid model.
WP6 – Quasi-experimental modelling
This WP aims to identify in silico methods, such as difference-in-differences, regression discontinuity design, instrumental variables and matching that are appropriate for estimating true mechanistic interactions appropriate for the data obtained in WP1-4. These methods will then be used to compare causal linkage within experimental in vitro bioassays and finally towards in vivo.