Chemical safety assessment has traditionally been based on animal testing but the EU has been promoting for many years the replacement, reduction, and refinement of animal testing. Further it is also considered that traditional risk assessment approaches are insufficient to adequately predict the potential risk associated with any given substance, especially when considering normal life low-dose exposure. Therefore new prediction models are needed in a new intelligent and more efficient safety assessment, based on in vitro testing in combination with computational modelling.
The Directive on the protection of animals used for scientific purposes (2010/63), the Regulation on cosmetic products (1223/2009), REACH (2007/2006) and Classification, Labelling and Packaging (CLP) (1272/2008) are examples of EU legislation that require, or strongly encourage, the replacement of animal testing. The EU policies on endocrine disruptors, combination effects of chemicals and nanomaterials are all examples of areas of concern where traditional risk assessment is coming to an end.
New integrated methods based on in-depth biological knowledge are needed. Therefore the JRC develops and tests new animal-free methods, alternatives to animal-based tests, to be applied in an integrated safety assessment of chemicals, and also provides informatics tools and databases to support this approach.
One of the activities is to support the implementation of EU chemicals policy (including the safety assessment of industrial chemicals, chemicals in consumer products, pesticides and biocides). In support of regulatory decision making, the JRC develops, evaluates and applies alternative (non-animal) methodologies for human health safety assessment.
EURL ECVAM, the European Union Reference Laboratory for Alternatives to Animal Testing
The JRC is host to the EU’s principal organisation for the scientific validation of alternative methods to animal testing – EURL ECVAM, the European Union Reference Laboratory for Alternatives to Animal Testing, formally established in 2011.
EURL ECVAM's mandate and activities (as outlined in Directive 2010/63/EC on the protection of animals used for scientific purposes) cover the entire life cycle of alternative methods, i.e. from development over validation to regulatory acceptance, international recognition and proper scientific use.
EURL ECVAM is actively involved in the search for test methods which replace, reduce or refine (the 'Three Rs') the use of laboratory animals in the test process. Methods developed by research laboratories are submitted to EURL ECVAM whose assessment of the robustness, reliability and predictive capacity of the methods is based on independent peer review of validation study reports. More information...
Improved safety assessment of chemicals without relying on animal testing
Recent advances in toxicological science, bioinformatics, and systems biology have provided means to transform toxicology into a predictive science.
Animal models are approximate models for human toxic responses: using their knowledge about physical, chemical and biological processes, the JRC teams adopt a hypothesis-driven, multi-disciplinary approach integrating in vitro methods with computational based methodologies (in silico) together with 'omics' approaches (e.g. proteomics, genomics and metabonomics: promising approaches to study impact of toxicants on expression of genes, proteins and cellular metabolites). This is aimed at identifying potential toxicants on the basis on an understanding of their mechanisms of biological action. These methods, sometimes referred to as “non-testing methods”, can be used to reduce our reliance on experimental testing, and in particular animal testing. In practice, these methods are used in Integrated Testing Strategies (ITS), along with experimental data generated by alternative (non-animal) tests, such as in vitro tests and high throughput screening.
An ITS is a "smart" decision making model where different intermediate effects are considered based on the mode-of-action of a chemical introduced into the biological system, rather than looking at adverse outcomes in animals at high dose exposure levels, which is the traditional way of performing toxicity testing. Computational toxicology also includes biokinetic modelling, such as in vivo/in vitro extrapolation, prediction of internal doses related to exposure through different routes of exposure to better understand the systemic distribution of the toxicant in the organism.
Automated high throughput approaches are also being developed to both reduce the time it takes to assess the toxicity of a chemical, speed up validation and enable categorization of chemicals based on their mode-of-action. This New Testing and Assessment Paradigm could provide more efficient and cost-effective ways to test chemicals not only to ensure the highest levels of safety, but also to reduce our reliance on animal testing and support innovation and competitiveness for many EU industrial sectors
Activities and facilities
Read more on JRC's main fields of activity and facilities related to new approaches in safety assessment of chemicals:
TSAR (Tracking System for Alternative Test Methods Review, Validation and Approval in the context of the EU regulations on chemicals) is a tool to provide a transparent view on the status of alternative methods as they progress from purely scientific protocols submitted for pre-validation, to being actively used in a regulatory context. Read more...
JRC (Q)SAR Model Database. Quantitative Structure-Activity Relationship (QSAR) models can be used to obtain information on the properties and activities of substances from chemical structure alone, and can thus be used to fill data gaps in the safety assessment of chemicals. The JRC QSAR Model Inventory is an inventory of information on the validity of (Q)SAR models that have been submitted to the JRC. Read more...
The Chemical Lists Information System (CheLIST) provides a means of identifying whether a chemical (or chemical group) has been tested in a range of research projects (including EU-funded and JRC projects), and also whether the chemical of interest is regulated (listed under a specific regulatory inventory). Read more...
The DataBase service on ALternative Methods, DB-ALM provides an overall picture on the state-of-the-art of alternative methods in use in all stages of development (including EU Integrated Project results), validation or regulatory acceptance for a given topic area. Read more...
EURL ECVAM Search Guide Read more...
Alternatives to animal testing of chemicals under REACH legislation
The EU Regulation on chemicals and their safe use - REACH (Registration, Evaluation, Authorisation and Restriction of Chemical substances) - which came into force in 2007 has implications for the testing methods used for evaluating the effects of chemical substances. To minimise the number of animal tests required in implementing the REACH Regulation, provision has been made to provide a number of possibilities for adapting the testing requirements, and to use existing data and alternative assessment approaches instead.
The Regulation gives greater responsibility to industry to manage the risks from chemicals and to provide safety information on the substances to allow safe handling; it also calls for the progressive substitution of the most dangerous chemicals where possible.
One of the main tasks of the JRC's EURL ECVAM is to validate alternative methods that can replace, reduce and refine the use of animals in scientific testing. The work carried out by EURL ECVAM is essential in reducing the volume of animal experiments in the EU.
Every three years ECHA, the key European institution for the implementation of the EU's chemicals legislation, reports to the European Commission on the use of methods to generate information which has been used instead of tests on animals. The 2011 report had shown that many companies already used alternatives to animal testing. ECHA’s second report, issued in June 2014, highlights that in 2010-2013 REACH registrants have widely used alternative methods to generate information required by REACH to ensure the safe use of chemicals. Read more...
Alternative tests methods and cosmetics
The safety of cosmetic and personal care products is covered by the EU law, which obliges manufacturers to utilise the best science and latest available research data to substantiate the safety of their cosmetic products before they are placed on the market. The Cosmetics Directive provides the regulatory framework for the phasing out of animal testing for cosmetics purposes. The same provisions are contained in the Cosmetics Regulation, which replaced the Cosmetics Directive as of 11 July 2013.
The testing ban on finished cosmetic products applies since 11 September 2004; the testing ban on ingredients or combination of ingredients applies since 11 March 2009. The marketing ban applies since 11 March 2009 for all human health effects with the exception of repeated-dose toxicity, reproductive toxicity and toxicokinetics. For these specific health effects the marketing ban applies since 11 March 2013, irrespective of the availability of alternative non-animal tests. More on the ban on animal testing …
A report from the former ECVAM was the basis for the timetable for phasing out the animal tests relating to cosmetics as required under the Cosmetics Directive: ECVAM Technical report on the Status of Alternative Methods for Cosmetics Testing (2008 – 2009).
EURL ECVAM regularly publishes Reports providing an update on the development, validation and regulatory acceptance of alternative methods/approaches. Read more…
Alternative test methods & Biologicals/Vaccines
Traditionally, laboratory animals have played a major role in quality control of vaccines. Still, many laboratory animals used in Europe are required for testing the safety and potency of batches of vaccines for veterinary and human application. The former ECVAM has been involved as sponsor, coordinator and participating laboratory in a number of pre-validation and validation studies on alternative methods for the quality control of human vaccines and veterinary vaccines.
Activities in this field are now carried on by EURL ECVAM. Read more...
April 2013: EURL ECVAM contributed to the recently adopted VICH guideline on "Harmonization od criteria to waive the target animal batch safety testing for inactivated vaccines for veterinary use"
Test method regulation
The JRC develops standardised methods for determining the intrinsic properties of chemicals. Good knowledge of these properties helps identify and assess any potential dangers and provide information needed for risk assessment. Having standardised Test Methods for chemicals at the EU level is also important for ensuring the internal market and free trade inside the EU. The legally binding EU standardised Test Methods to determine the hazardous properties of chemicals are written into the Test Methods Regulation (TMR, Commission Regulation (EC) No 440/2008 of 30 May 2008). Test methods are regularly updated or new methods introduced as required.
The technical work to prepare new or updated methods is undertaken by the JRC's IHCP, through consultation meetings with the EU National Co-ordinators and competent authorities, national experts for each area of concern as well as participation in relevant working groups/meetings of OECD and other international organisations.
Joint initiative on alternative approaches to animal testing
A joint initiative from the European Commission, European trade associations from seven industry sectors and individual companies in 2005 led to the creation of the European Partnership for Alternative Approaches to Animal Testing (EPAA). Its purpose is to promote the development and implementation of new methods to replace, reduce, refine (the '3 Rs') animal testing with modern alternative approaches.
The JRC is involved in various international collaboration initiatives in the context of the Organisation for Economic Cooperation and Development (OECD), the World Health Organisation (WHO) and with US governmental organisations (Tox21).
The JRC is also a main contributor to the FP7 research initiative SEURAT-1, the largest EU project ever on alternative methods focussing on the replacement of in vivo repeated dose systemic toxicity testing. SEURAT-1 is co-funded by the European Commission and Cosmetics Europe. Read more...
A recent example is the collaboration with US EPA, IPSC/WHO, OECD and other international organisations in the development of AOP WIKI, an IT tool for crowdsourcing information about Adverse Outcome Pathways (AOP). More on AOP and AOP Wiki…