JRC Project Browser

TA4.HLO2 - To develop improved frameworks, systems, and tools for the safety assessment of chemicals (including nanomaterials) to scientifically underpin the EU legislative process and contribute to international harmonisation

The Systems Toxicology (ST) Action provides scientific support to EU policies and legislation that ensure the safe use of chemicals in the EU and worldwide for the protection of the consumer, worker and the environment. In particular, the ST Action strives to develop the safety assessment science that underpins regulatory decisions about chemicals while reducing our reliance on animal testing. In this regard the Action addresses a number of objectives related to the development, integration, evaluation, validation and demonstration of modern toxicological methods based on theoretical, experimental (in vitro) and computational approaches to predict adverse effects in humans and the environment. The ST Action also covers the activities of the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) established by Directive 2010/63/EU on the protection of animals used for scientific purposes. The key responsibilities of the EURL ECVAM are to (1) guide and participate in the development of alternative methods, (2) conduct and coordinate validation studies, (3) facilitate regulatory acceptance and (4) promote the use of alternative methods by end-users.
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. The Directive on the protection of animals used for scientific purposes (2010/63/EU), the Regulation on cosmetic products (EC 1223/2009), and the Regulation concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH, EC 1907/2006) are prominent examples of legislation that require replacing animal testing wherever possible. The development of suitable in vitro methods provides one viable means for achieving the goal of replacement, reduction and refinement of animal testing (3Rs principle); and the validation of such methods, i.e. the demonstration that the methods work reliably and predict the toxicological response in question correctly, paves the way to regulatory acceptance.
Besides being costly, lengthy and ethically questionable, traditional risk assessment methods applying animal testing are based on purely phenomenological observations. However, there is enough scientific knowledge to build a new safety assessment paradigm based on understanding rather than simple observation. Thus the basic premise behind the scientific approach of the ST Action is that to be ultimately predictive of adverse effects in humans and the environment that a chemical may cause requires a thorough understanding of its toxicological mode-of-action within the exposed organism. The mode-of-action is described by sequence of biochemical or biological events at different levels of biological organisation (e.g. cell, tissue, organ, organism, and even population) that lead to an adverse effect. The thinking is that although in the most detailed sense the action of every chemical is somewhat unique, in more general terms chemicals can be classified and grouped together based on their common mode-of-action. This mode-of-action driven approach to toxicology will pave the way for using combinations of alternative methods to profile the toxicokinetic and toxicodynamic profile of chemicals thereby facilitating hazard identification, mechanistic based read-across and ultimately the prediction of derived no-effect levels necessary for quantitative risk assessment. Moreover, this will also provide a scientific basis for the assessment of combined exposure to multiple chemicals which is more relevant to the real life situation that the traditional approach to assess chemicals individually.

In order to fulfil its objectives, the ST Action is networking and collaborating with major EU and International stakeholders. The ST Action is a main contributor to the private-public research initiative SEURAT-1 (Safety Evaluation Replacing Animal Testing) co-funded by Cosmetics Europe and the European Commission under the FP7 Health programme. The Action is also a collaboration partner within the US interagency Tox 21 initiative and participates in many international activities related to safety assessment and standardisation of assessment approaches at the OECD and WHO, especially in the context of the International Programme on Chemical Safety (IPCS). The ST Action serves EU policies on safety of food and consumer products, including cross-cutting issues such as endocrine disruption, combined exposure, nanomaterials, alternative methods, as well as sectoral policies such as REACH, CLP and Biocidal Products Regulations.

In 2013, the ST Action will focus on (i) development, evaluation and application of assessment science concepts and tools to support EU policies on chemicals and consumer products, (ii) optimisation, standardisation and validation of in vitro methods suitable for regulatory safety assessment, (iii) improvement of the biological models used, including evaluation of the suitability of the model for human safety assessment, (iv) implementation of in vitro assays in high throughput screening for the classification of a high number of tested materials based on their organelle and cellular effects, and (v) development of data and knowledge base to facilitate efficient exchange of information across the entire research community and use this as a tool for building safety assessment strategies. A significant proportion of these innovation, validation and communication activities will support the role of EURL ECVAM.
The ST Action will continue activities focussed on a common strategy towards a mode-of-action based safety assessment of chemicals using alternative methods, both in vitro and in silico. This will also be applied for the EURL ECVAM testing strategies. A general evaluation of alternative methods currently used within the EU and further development of EURL ECVAM strategies for alternative testing are described under Objective 1.Objectives 2 and 3 are focussing on further development of safety assessment strategies including quantitative predictions based on in vitro testing and theoretical prediction models where most deliverables are related to indirect actions. The processes directly connected to the operation of EURL ECVAM are described in Objectives 5 and 6, including the standardisation and harmonisation of alternative methods in an international regulatory context. Objective 7 is related to the provision of informatics tools necessary for a successful implementation and harmonised use of alternative methods in chemicals safety assessment. This objective can directly serve activities carried out under Objectives 1-3, 5 and 6 and strongly and directly contributes to several international initiatives in the context of OECD and WHO and in close collaboration with US EPA.

The different activities on endocrine disrupting chemicals (EDCs) described under Objective 4 give strong support to the EU Community Strategy on EDCs, thereby providing an example of how research activities under ST Objectives 2, 3 and 7 can be directly exploited to support EU policies within one specific field of concern. The activities under objective 4 are partly financed through Administrative Agreements with DG ENV. Direct support to DG ENV is provided also under Objective 8 on the complex task to predict adverse effects originating from combined exposure to chemicals and chemical mixtures.