Scientific paper ready for submission describing the PB-PK/D model approach

Biological materials (serum samples and/or leucocytes) from subjects with known exposure to the selected chemicals in the mixture (task 7.2) will be analysed for biomarkers of effects as selected based on the studies in WP3 and WP4 focussing on hepatic, developmental or endocrine endpoints. The exact identification of the biomarkers of effects need to await reporting of the results from the in vivo and in vitro study but might include clinical chemistry endpoints, RNA array profiling data, DNA and/or protein adducts or other biochemical markers associated with the effects observed. Based on the biomarkers selected appropriate laboratories performing these analyses will be selected based on experiences and methods available. Inter-individual variability in the biomarkers of effect will be studied. The PB-PK models and Adverse Outcomes Pathways developed in Acropolis and further refined in WP3 – WP6 will be used to model the effects of exposures to the chemicals in the mixture as selected in WP2. Human variability in such biomarkers will be estimated by population Monte-Carlo simulations. The results will be described in a scientific paper (deliverable 7.3 (M45))