EFSA's OpenFoodTox: An open source toxicological database on chemicals in food and feed and its future developments.

Since its creation in 2002, the European Food Safety Authority (EFSA) has produced risk assessments for over 5000 substances in >2000 Scientific Opinions, Statements and Conclusions through the work of its Scientific Panels, Units and Scientific Committee. OpenFoodTox is an open source toxicological database, available both for download and data visualisation which provides data for all substances evaluated by EFSA including substance characterisation, links to EFSA's outputs, applicable legislations regulations, and a summary of hazard identification and hazard characterisation data for human health, animal health and ecological assessments. The database has been structured using OECD harmonised templates for reporting chemical test summaries (OHTs) to facilitate data sharing with stakeholders with an interest in chemical risk assessment, such as sister agencies, international scientific advisory bodies, and others. This manuscript provides a description of OpenFoodTox including data model, content and tools to download and search the database. Examples of applications of OpenFoodTox in chemical risk assessment are discussed including new quantitative structure-activity relationship (QSAR) models, integration into tools (OECD QSAR Toolbox and AMBIT-2.0), assessment of environmental footprints and testing of threshold of toxicological concern (TTC) values for food related compounds. Finally, future developments for OpenFoodTox 2.0 include the integration of new properties, such as physico-chemical properties, exposure data, toxicokinetic information; and the future integration within in silico modelling platforms such as QSAR models and physiologically-based kinetic models. Such structured in vivo, in vitro and in silico hazard data provide different lines of evidence which can be assembled, weighed and integrated using harmonised Weight of Evidence approaches to support the use of New Approach Methodologies (NAMs) in chemical risk assessment and the reduction of animal testing.

Potential emerging chemical risks in the food chain associated with substances registered under REACH.

A screening procedure for the identification of potential emerging chemical risks in the food and feed chain developed in a previous EFSA-sponsored pilot study was applied to 15021 substances registered under the REACH Regulation at the time of evaluation. Eligible substances were selected from this dataset by excluding (a) intermediates handled under strictly controlled conditions, (b) substances lacking crucial input data and (c) compounds considered to be outside the applicability domain of the models used. Selection of eligible substances resulted in a considerable reduction to 2336 substances. These substances were assessed and scored for environmental release (tonnage and use information from REACH registration dossiers), biodegradation (predictions from BIOWIN models 3, 5 and 6 evaluated in a battery approach), bioaccumulation in food/feed (ACC-HUMANsteady modelling) and chronic human health hazards (classification according to the CLP Regulation for carcinogenicity, mutagenicity, reproductive toxicity and repeated dose toxicity as well as IARC classification for carcinogenicity). Prioritisation based on the scores assigned and additional data curation steps identified 212 substances that are considered potential emerging risks in the food chain. Overall, 53% of these substances were prioritised due to chronic hazards identified in REACH registrations dossiers only (i.e. hazards not identified in classifications from other sources). Bioaccumulation in food and feed predicted on the basis of ACC-HUMANsteady modelling identified many substances that are not considered bioaccumulative in aquatic or terrestrial organisms based on screening criteria of the relevant ECHA guidance documents. Furthermore, 52% of the priority substances have not yet been assessed for their presence in food/feed by EU regulatory agencies. This finding and illustrative examples suggest that the screening procedure identified substances that have the potential to be emerging chemical risks in the food chain. Future research should investigate whether they actually represent emerging chemical risks as defined in EFSA's mandate.

Development of a novel scoring system for identifying emerging chemical risks in the food chain.

The European Food Safety Authority (EFSA) is responsible for risk assessment of all aspects of food safety, including the establishment of procedures aimed at the identification of emerging risks to food safety. Here, a scoring system was developed for identifying chemicals registered under the European REACH Regulation that could be of potential concern in the food chain using the following parameters: (i) environmental release based on maximum aggregated tonnages and environmental release categories; (ii) biodegradation in the environment; (iii) bioaccumulation and in vivo and in vitro toxicity. The screening approach was tested on 100 data-rich chemicals registered under the REACH Regulation at aggregated volumes of at least 1000 tonnes per annum. The results show that substance-specific data generated under the REACH Regulation can be used to identify potential emerging risks in the food chain. After application of the screening procedure, priority chemicals can be identified as potentially emerging risk chemicals through the integration of exposure, environmental fate and toxicity. The default approach is to generate a single total score for each substance using a predefined weighting scenario. However, it is also possible to use a pivot table approach to combine the individual scores in different ways that reflect user-defined priorities, which enables a very flexible, iterative definition of screening criteria. Possible applications of the approaches are discussed using illustrative examples. Either approach can then be followed by in-depth evaluation of priority substances to ensure the identification of substances that present a real emerging chemical risk in the food chain.

Parallel measurements of drug actions on Erythrocytes by dielectrophoresis, using a three-dimensional electrode design.

A type of well-based assay that uses a laminated three-dimensional electrode design to characterise the effects of different drugs on red blood cells using dielectrophoresis is presented. The capability of the system to determine the effects of chemical agents on the electrophysiology of red blood cells is demonstrated using saponin and valinomycin as two examples of drugs that can penetrate the cell membrane and therefore change the dielectric properties of the cell. Light intensity changes are measured in the well over a period of time at various frequencies and the dielectric properties of the cells determined using an ellipsoidal multi-shell model. It is shown that the laminated electrode permits a high degree of automation and thus a high number of parallel experiments, which reduces both the time and effort needed to examine differences between populations of red blood cells. The technique is directly compatible with the industry-standard 1536 well-plate analysis technique.