The EuroMix toolbox of models and data to support chemical mixture risk assessment: Deliverable 6.4

A toolbox has been built to assess risks from combined exposure to multiple chemicals using probabilistic methods. The toolbox has more than 40 modules to address all areas of risk assessment, and includes a data repository with data collected in the EuroMix project. This paper gives an introduction to the toolbox and illustrates its use with examples from the EuroMix project. The toolbox can be used for hazard identification, hazard characterisation, exposure assessment and risk assessment, with special emphasis on the use of in vitro results. Examples shown for hazard identification are the selection of substances relevant for a specific adverse outcome based on adverse outcome pathways and QSAR models. Examples for hazard characterisation are the calculation of benchmark doses and relative potency factors with uncertainty estimates from dose response data, and the use of kinetic models to perform in vitro in vivo extrapolation. Examples for exposure assessment are assessing cumulative exposure at either the external or the internal level, where the latter option is needed in case dietary and non-dietary routes have to be aggregated. Finally, risk assessment is illustrated by graphical displays of the margin of exposure for single substances and cumulated, including uncertainties for the exposure and hazard characterisation estimates.