Deliverable 8.3: EuroMix handbook for mixture risk assessment

The EuroMix handbook for mixture risk assessment describes the methodology and tools for assessing risks of combined exposures to multiple substances developed by the EuroMix project. The handbook is consistent with and expands upon the recent documents on mixture risk assessment published by OECD and EFSA. The aim is to provide a practical handbook for harmonised application of the EuroMix outcome under consideration of EFSA and OECD guidance and not to repeat the basic principles and information provided in the documents from OECD and EFSA.

The handbook contains concise descriptions of the methodology and tools developed in the EuroMix project. Annexes in the handbook provide detailed information, useful templates and illustrative examples. The mixture risk assessment can be performed using the web‐based EuroMix toolbox. The handbook refers to the toolbox but the aim of the handbook is not to provide a step‐by‐step manual for the toolbox. 

The EuroMix methodology focuses on component‐based mixture risk assessment where substances are grouped based on toxicological considerations. Toxicity and exposure information for each substance in the assessment group is used for estimation of the combined risk using the dose addition hypothesis and relative potency factors (RPFs). The exposure assessment of mixtures is based on probabilistic methodology considering the individual consumption and concentration data allowing estimation of different percentiles of exposure to the mixture. The focus is on dietary exposure but other exposure routes are also described.

The EuroMix methodology is very flexible, enabling assessment of both data‐rich and data‐poor substances. The handbook and EuroMix toolbox can also be applied for substances grouped based on other than toxicological considerations, e.g. structure or exposure considerations.

The handbook starts by introducing the EuroMix toolbox. Thereafter, the handbook describes the EuroMix methodology and tools for the key elements in the framework for mixture risk assessment: problem formulation, hazard assessment, exposure assessment and risk characterisation. Finally, general issues of tiering approaches and uncertainty analysis are described.