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Harmonised risk assessment for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals: A Food and feed Safety Perspective
Citation:
Dorne, J. AND P. Price. Harmonised risk assessment for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals: A Food and feed Safety Perspective. EuroTox 2018, Brussels, BELGIUM, September 02 - 05, 2018.
Impact/Purpose:
This presentation reports on the status and preliminary finding of an initiative by the European Union's European Food Safety Authority (EFSA). I am a reviewer of the document.
Description:
Over the last two years, the European Food Safety Authority (EFSA) has developed a guidance document on harmonised methodologies for the human health (HRA), animal health (ARA) and ecological risk assessment (ERA) of combined exposure to multiple chemicals (“chemical mixtures”). The guidance document is focused on the food and feed safety areas, however, its application can be broaden to other regulatory areas and across regulatory silos. Key challenges to harmonisation include the large number of chemicals involved, their associated exposure patterns, toxicological profiles in humans and species of veterinary and ecological relevance as well as the diversity of regulations and associated RA frameworks. First, a harmonised framework is proposed for HRA, ARA and ERA and is applied using the principles of tiering and stepwise approaches for problem formulation, exposure assessment, hazard assessment, risk characterisation and uncertainty analysis. The applications of tiering principles depend on the purpose of the RA, data availability, time and resources and range from qualitative, semi-quantitative to fully probabilistic approaches. The purpose of the RA, methodological approach used and analysis plan are defined during the problem formulation phase, which provides a decision point to undertake the RA using either a whole mixture (WMA) or a component-based approach (CBA). For the WMA, the mixture is most often assessed as a single compound. For the CBA, combined toxicity is assessed using the dose addition model. Under some circumstances, evidence for deviation from the dose addition assumption, particularly for synergistic effects, needs to be assessed using a weight of evidence approach. The results of this analysis allow the (semi)-quantification of the magnitude of an interaction through an extra uncertainty factor or a biologically-based model (e.g. toxicokinetic-toxicodynamic model) in the hazard assessment and the risk characterisation steps. For a given RA, once the relative risk has been determined, important caveats for interpretation need to be considered. For transparency of the RA process, reporting the results of a mixture RA is also of importance and a reporting template is proposed and illustrated for the HRA, ARA and ERA areas. Finally, future perspectives for mixture RA are discussed in the light of the integration of historical data and mechanistic alternatives to animal testing such as in silico and in vitro biologically-based tools and models. Open source platforms are also discussed as means to 1. Provide scientific tools directed towards the RA and regulatory community 2. Apply harmonised methodologies and 3. Train the current and next generation of risk assessors.
