EFSA’s Chemical Hazards Database OpenFoodTox: EFSA’s Chemical Hazards Database Jean Lou Dorne Senior Scientific Officer Scientific Committee and Emerging Risks Unit Datathon 15/06/2018

Four pillars of risk assessment Hazard identification and characterisation Exposure assessment Levels in food, feed, water, environmental media, dietary exposure, food consumption, relevant food groups, time trends Deterministic vs probabilistic ADME, acute/sub-chronic/chronic toxicity, human data, genotox, reprotox, mode of action, NOECs (ecological) NOELs, LOAELs (animal, human) mathematical modelling (BMD), Health based guidance (TDI…) OpenFoodTox The risk-characterization step integrates exposure to a chemical in a given population with toxicological effects on which a health-based guidance value is based, and concludes with the likelihood of adverse effects. Risk characterisation Relate exposure to environmental standards (ecological), margin of safety (animal) Margin of Exposure for genotoxic carcinogens (Human)

-Why EFSA’s Chemical Hazards Database ?- Catalogue of EFSA’s chemical risk assessment since its creation -Contaminants (Human and Animal health) -Vitamins and minerals (Human health) (NDA), -Food additives and Nutrient Sources, Food contact materials, Flavourings and processing aids ,enzymes (Human Health) -Feed Additives (Human and Animal Health, Ecotoxicology) -Pesticides (Human and Animal health, Ecotoxicology) Easy Reference and Crisis One reference Database on Chemical Hazards: Search easily and efficiently Crisis: Quick and Easy access to all EFSA’s Hazard Data International Harmonisation International efforts to Harmonise Templates for Hazard Data (ECHA/OECD) Data Model based on templates compatible with IUCLID/ ECHA-OECD QSAR toolbox

-Qualitative map of the data model- Chemical components Substances EFSA documents Hazard identification/ Characterisation Endpoint Study (e.g., critical studies) Human health (including genotoxicity) Animal health (target and non-target species) Eco-toxicological data Hazard Characterisation/Risk Characterisation Health-based guidance value (threshold effects) Margin of exposure (MOE) values (non-threshold effects) Exposure (for MOE)

-Overview of the Data Model - Chemical Information Information on chemical nomenclature (EU nomenclature, IUPAC, CAS... ), trade name, chemical group/panel (i.e. pesticide), chemical use (i.e fungicide), chemical structure (i.e triazoles, organophosphates….). Document descriptors Information on EFSA’s opinion for the specific chemical or group of chemicals. Info from EFSA ‘s RAW system (question number, mandate, number), link to the document Toxicity Endpoint/ Hazard identification Information on critical toxicity study using OECD picklists when possible (species, dose, target organ…) Critical study to demonstrate genotoxicity status Providing essential information of critical genotoxicity study when assessed Hazard /Risk characterisation Information for health based guidance values (ADI/TDI), margin of exposures, safety factors…

Relationships among data Toxicity data: Endpoint Study (e.g., critical studies) Human health(including genotoxicity on positive substances) Animal health (target and non-target animals) Ecotoxicity Hazard/Risk characterisation (ADI, TDI, MOE, MOS) Toxicity data (NOAEL, effects, toxicity) Bibliographic details (publication date, titles, authors) Chemical identification (substance and components) Chemical components Substances Hazard characterisation/ Risk characterisation Health-based guidance value (threshold effects) Margin of exposure (non-threshold effects) Margin of safety Environmental standards Documents

CONTENT Microstrategy Tool: https://dwh.efsa.europa.eu/bi/asp/Main.aspx?rwtrep=400 Full Download Knowledge junction: https://zenodo.org/record/344883#.WyOM4vlubIU 1,650 Scientific outputs (metadata + DOI) 4,400 Substances (chemical identifiers including SMILES) 12,000 risk assessment summaries 10,000 Toxicological endpoint studies 140 Positive genotoxicity studies

Main title

Openfoodtox and in silico tools Future Mixture RA EFSA Openfoodtox and in silico tools Case studies to develop in silico tools QSAR model on pesticide Toxicity in bees (OpenFoodTox, US-EPA, DEMETRA DB) : Classifier QSAR model to predict LC50 in rainbow trout (OpenFoodTox) : Continuous model -Physico-chem properties, structure, toxicity : R2 >0.75 QSAR model to predict NOAEL in rats (OpenFoodTox, Fraunhofer) : Continuous model Scientific report Summer 2017 QSAR model to predict NOAEL for liver toxicity in rats (OpenFoodTox, Fraunhofer) : Continuous model

Main title

Main title

Main title

THe Future of Openfoodtox Sep 2018-2022 Collect new properties Physico-chemical properties, TK data, bioaccumulation etc Summary exposure estimates Intermediate effects (mechanistic data) New templates (OECD harmonised Templates) Design template for WoE, biological relevance and uncertainty Update TK template Link OpenFoodTox with QSAR platforms e.g VEGA Published EFSA values and Predicted values

Many Thanks Questions ?