Dataset Open Access
Bassan, Arianna; Ceriani, Lidia; Richardson, Jane; Livaniou, Anastasia; Ciacci, Andrea; Baldin, Rossella; Kovarich, Simona; Fioravanzo, Elena; Pavan, Manuela; Gibin, Davide; Di Piazza, Giulio; Pasinato, Luca; Cappé, Stefano; Verhagen, Hans; Robinson, Tobin; Dorne, Jean Lou
Background: EFSA's remit and chemical risk assessment of regulated products and contaminants
The European Food Safety Authority (EFSA) has the remit to provide scientific advice to risk managers and decision makers through risk assessment and risk communication on issues related to “food and feed safety, animal health and welfare, plant health, nutrition, and environmental issues”. Risk assessment has been defined as "a scientifically based process consisting of four steps: hazard identification, hazard characterisation, exposure assessment and risk characterisation" (EC, 2002).
In the food and feed safety area, hazard identification and hazard characterisation aim to determine safe levels of exposure for regulated products or contaminants as “reference values1” to protect human health, animal health, environmental-relevant species or the whole ecosystem. Such reference values for a given species are most often derived by using a “reference point2" determined from the critical toxicological study on which an uncertainty factor3 is applied.
Since its creation in 2002, the European Food safety Authority (EFSA) has produced risk assessments for more than 4,750 unique substances in over 1,800 Scientific Opinions, Statements and Conclusions through the work of its scientific Panels, Units and Scientific Committee.
For regulated products, these risk assessments have been performed by five scientific panels and four supporting units.
EFSA's chemical Hazards Database : OpenFoodTox
OpenFoodTox is a structured database summarising the outcomes of hazard identification and characterisation for the human health (all regulated products and contaminants), the animal health (feed additives, pesticides and contaminants) and the environment (feed additives and pesticides).
OpenFoodTox the substance characterisation, the links to EFSA’s related output, background European legislation, and a summary of the critical toxicological endpoints and reference values.
For each individual substance, the data model of OpenFoodTox has been designed using OECD Harmonised Template (OHTs) as a basis to collect and structure the data in a harmonised manner. OpenFoodTox provides open source data for the substance characterisation, EFSA outputs, reference points, reference values and genotoxicity. OpenFoodTox and can be searched under the following link using a microstrategy tool: http://www.efsa.europa.eu/en/microstrategy/openfoodtox
In order to disseminate OpenFoodTox to a wider community, two sets of data can be downloaded:
1. Five individual spreadsheets extracted from the EFSA microstrategy tool providing for all compounds: a. substance characterisation, b. EFSA outputs, c. reference points, d. reference values and, e. genotoxicity.
2. The full database.
OpenFoodTox contributes actively to EFSA’s 2020 Science Strategy (EFSA, 2016) and to the aim of widening EFSA’s evidence base and optimising access to its data as a valuable open source toxicological database that can be shared with all scientific advisory bodies and stakeholders with an interest in chemical risk assessment. In addition, OpenFoodTox has been submitted to the OECD’s Global Portal to Information on Chemical Substances (eChemPortal) so that individual substances can be searched as part of the national and international databases. Further description and associated references are described in the EFSA journal editorial (Dorne et al., 2017).
Using OpenFoodTox to develop innovative in silico models
Recently, in silico models using OpenFoodTox have been developed for ecological risk assessment (bees and rainbow trout) and human risk assessment using rat toxicological data (Como et al., 2017; Benefenati et al., 2017; Toporov et al., 2017, Toporov et al., 2018). These in silico models provide alternative means to animal experiments for the hazard identification and characterisation of chemicals, and are becoming of increasing interest in the risk assessment community to deliver the 3Rs (replacement, reduction, refinement) (Hartung, 2004; OECD, 2005) particularly since the banning of animal testing for the approval of cosmetics as consumer products (Regulation (EC) No. 1223/2009, Art.18(2)).
Data model based on the OECD harmonised templates (OHTs) for reporting toxicological data;
1 Reference Value : The estimated maximum dose (on a body mass basis) or the concentration of an agent to which an individual may be exposed over a specified period without appreciable risk. Reference values are established by applying an uncertainty factor to the reference point. Examples of reference values in human health include acceptable daily intake (ADI) for food and feed additives, and pesticides, tolerable upper intake levels (UL) for vitamins and minerals, and tolerable daily intake (TDI) for contaminants and food contact materials. For acute effects and operators, the acute reference dose (ARfD) and the acceptable operator exposure level (AOEL). In animal health and the ecological area, these include safe feed concentrations and the Predicted no effect concentration (PNEC) respectively (EFSA Scientific Committee, 2018).
2 Reference point : Defined point on an experimental dose–response relationship for the critical effect. This term is synonymous to Point of departure (USA). Reference points include the lowest or no observed adverse effect level (LOAEL/NOAEL) or benchmark dose lower confidence limit (BDML), used to derive a reference value or Margin of Exposure in human and animal health risk assessment. In the ecological area, these include lethal dose (LD50), effect concentration (EC5/ECx), no (adverse) effect concentration/dose (NOEC/NOAEC/NOAED), no (adverse) effect level (NEL/NOAEL), hazard concentration (HC5/HCx) derived from a Species Sensitivity Distributions (SSD) for the ecosystem (EFSA Scientific Committee,2018).
3 Uncertainty factor: Reductive factor by which an observed or estimated no observed adverse effect level or other reference point, such as the benchmark dose or benchmark dose lower confidence limit, is divided to arrive at a reference dose or standard that is considered safe or without appreciable risk (WHO, 2009).
Benfenati E, Como F, Marzo M, Gadaleta D, Toropov A and Toropova A, 2017. Developing innovative in silico models with EFSA's OpenFoodTox database. EFSA supporting publication 2017:EN-1206. 19 pp. https://doi.org/10.2903/sp.efsa.2017.EN-1206
Como F, Carnesecchi E, Volani S, Dorne JL, Richardson J, Bassan A, M. Pavan M, Benfenati E, 2017. Predicting acute contact toxicity of pesticides in honeybees (Apis mellifera) through a k-nearest neighbor model. Chemosphere 166 (2017) 438e444
Dorne JL, Richardson J, Kass G, Georgiadis N, Monguidi M, Pasinato L, Cappe S, Verhagen H and Robinson T, 2017. Editorial: OpenFoodTox: EFSA's open source toxicological database on chemical hazards in food and feed. EFSA Journal 2017;15(1):e15011, 3 pp. https://doi.org/10.2903/j.efsa.2017.e15011
EC, 2002. Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January 2002 laying down the general principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in matters of food safety. OJ L 31, 1.2.2002, p. 1–24.
EFSA Scientific Committee, Hardy A, Benford D, Halldorsson T, Jeger MJ, Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Silano V, Solecki R, Turck D, Younes M, Benfenati E, Castle L, Hougaard Bennekou S, Laskowski R, Leblanc JC, Kortenkamp A, Ragas A, Posthuma L, Svendsen C, Testai E, Tarazona J, Dujardin B, Kass GEN, Manini P, Dorne JL and Hogstrand C, 2018. Draft guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals. Public Consultation (26 June 2018). Available online: https://www.efsa.europa.eu/sites/default/files/consultation/consultation/180626-1-ax1.pdf
EFSA Strategy 2020, Trusted science for safe food: Protecting consumers' health with independent scientific advice on the food chain, EFSA 2016, doi: 10.2805/397609
Hartung T., Bremer S., Casati S., Coecke S., Corvi R., Fortaner S., Gribaldo L., Halder M., Hoffmann S., Roi A.J., Prieto P., Sabbioni E., Scott L., Worth A., Zuang V. (2004). A modular approach to the ECVAM principles on test validity. Altern. Lab. Anim. 32, 467-472
OECD. (2005). Guidance Document on the Validation and International Acceptance of New or Updated Test Methods for Hazard Assessment, Series on Testing and Assessment, No. 34. , Paris
Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products. OJ L 342, 22.12.2009, p. 59–209.
S-IN Soluzioni Informatiche, 2018a. Update and maintenance of the EFSA's Chemical Hazards Database. EFSA supporting publication 2018:EN-1265. 72 pp. https://doi.org/10.2903/sp.efsa.2018.EN-1265
S-IN Soluzioni-Informatiche; Report on "Data collection and data entry for EFSA's chemical hazards database NP/EFSA/EMRISK/2011/01". Supporting Publications 2013:EN-458. 140 pp. https://doi.org/10.2903/sp.efsa.2013.EN-458
S-IN Soluzioni Informatiche, 2018b. Update and maintenance of the EFSA's Chemical Hazards Database. EFSA supporting publication 2018:EN-1438. 60 pp. https://doi.org/10.2903/sp.efsa.2018.EN-1438
S-IN, Soluzioni Informatiche, 2014. Further development and update of EFSA's Chemical Hazards Database NP/EFSA/EMRISK/2012/01. EFSA supporting publication 2014:EN-654, 103 pp. https://doi.org/10.2903/sp.efsa.2014.EN-654
Toropov AA, Toropova AP, Marzo M, Dorne JL, Georgiadis N, Benfenati E, 2017.QSAR models for predicting acute toxicity of pesticides in rainbow trout using the CORAL software and EFSA's OpenFoodTox database. Environ Toxicol Pharmacol. 53:158-163
Toropova AP, Toropov AA, Marzo M, Escher SE, Dorne JL, Georgiadis N, Benfenati E, 2018. The application of new HARD-descriptor available from the CORAL software to building up NOAEL models. Food Chem Toxicol.112:544-550
WHO/IPCS (World Health Organization/International Programme on Chemical Safety), 2009. Principles and methods for the risk assessment of chemicals in food, Environmental Health Criteria 240, ISBN: 978 92 4 157240 8 Available online: http://www.who.int/foodsafety/publications/chemical-food/en/