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Reconnecting exposure, toxicokinetics and toxicity in food safety : OpenFoodTox and TKplate for human health, animal health and ecological risk assessment

Abstract : In food safety, sound risk characterisation requires the integration of external dose (oral exposure), internal dose (toxicokinetics (TK) and toxicodynamic (TD) data. Here, a workflow allowing such integration is presented and illustrated with examples from the human health, animal health and ecological area. Since its creation in 2002, the European Food Safety Authority (EFSA) has performed risk assessments for more than 5000 chemicals. An open source database: OpenFoodTox, designed using OECD harmonised templates, and providing summary toxicological data used by EFSA for setting safe levels (reference points and reference values) of food and feed chemicals in humans, animals and the environment has been recently published. OpenFoodTox is available in a. EFSA's Data Warehouse as a microstrategy tool, b. EFSA's knowledge junction for full download, c. The OECD e-chem portal. Since 2014, EFSA has funded collaborative research to develop generic TK and PB-TK models in the R freeware available on an open source modelling platform: TK Plate, to support integration of exposure, TK and TD parameters under different situations (data poor, data rich). Several models have been developed including TK and PB-TK models in humans, farm and companion animals (pig, chicken, cat, sheep), fish (zebra fish, rainbow trout, fathead minnow) and Dynamic Energy Budget (DEB) models for terrestrial and aquatic organisms. The first prototype of TKPlate has been designed for human TK and PB-PK models using the US-EPA ‘httk’ package and includes variability distributions for human metabolism. Future developments of OpenFoodTox 2.0 and TK Plate include: 1. Data collection for physico-chemical properties, TK, biodegradation and bioaccumulation data, exposure data, 2. Integration of QSAR tools to predict TK and TD properties, 3. Integration of all models in TKplate for all species, 4. Development of a guidance document to illustrate the global use of TK and metabolism data in chemical risk assessment with case studies (e.g. regulated products and contaminants). In conclusion, the importance of international cooperation is emphasised, in particular between national, international scientific advisory bodies and academic institutions as the corner stone for the translation of 21st century toxicology into harmonised methodologies and tools and for the training of the next generation of risk assessors.
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Jean-Lou Dorne, Billy Amzal, Nadia Quignot, W. Wiecek, Camille Bechaux, et al.. Reconnecting exposure, toxicokinetics and toxicity in food safety : OpenFoodTox and TKplate for human health, animal health and ecological risk assessment. 54. Congress of the European Societies of Toxicology (EUROTOX 2018), Sep 2018, Bruxelles, Belgium. pp.S29, ⟨10.1016/j.toxlet.2018.06.1128⟩. ⟨ineris-03224935⟩



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