As JRC representative and member of the international advisory panel in EURION, we asked Dr Sharon Munn about the vision of JRC on the current status of EDC legislation in the EC.
Why is there need for a cluster such as EURION?
The current toolbox of methods and approaches to identify endocrine disruptors is not complete. We hope that the eight projects, which constitute the EURION cluster, will go a long way to filling that gap. For example, a number of the projects focus on the thyroid system, which we know can be disrupted in many different ways and for which it is expected we will need a suite of reliable methods to support regulatory decision making. Other projects cover different aspects of the endocrine system but nevertheless all the projects have a lot of challenges in common, such as how to best capture and interpret ‘omics data, approaches to validation, selecting common chemicals to better compare or combine data across projects and developing AOP networks, to name but a few. Working together through activities at the cluster level will allow ideas to be shared, synergies to be found and solutions to emerge.
Why do you think it is important that EURION develops AOPs?
AOPs are a great way to capture mechanistic information and describe the mode of action of a chemical, showing how its initial interaction at cellular level can progress to an adverse effect. Considering the criteria for identification of an endocrine disruptor requires that a biologically plausible link between endocrine activity and adverse effect can be demonstrated (i.e. an endocrine mode of action). The AOP is the perfect framework to demonstrate such link.
AOPs can be built based on existing knowledge and the EURION projects will generate information on endocrine-pathways that can be used to further substantiate and fill some gaps in our knowledge. The ultimate aim is to create networks of AOPs covering the many different ways in which the different endocrine systems can be perturbed. This is why it is so important to work together across the cluster to identify measurable key events which may be common to a number of AOPs relevant to different organs, as these may be the ones for which the development of methods will be most useful.
It’s important to emphasise that the AOPs developed under EURION should follow the available OECD guidance and be entered into the AOP Knowledge Base .
What could the IATAs developed in EURION bring?
It is envisaged that a combination of methods will be required to build evidence that a substance has endocrine disrupting properties by linking endocrine activity to an adverse effect. This need fits well to the concept of Integrated Approaches to Testing and Assessment (IATA) which are flexible approaches for chemical safety assessment based on the integration and translation of the data derived from multiple methods and sources of information, including new approach methodologies. IATAs may be based on methods that measure or predict key events in the AOPs or AOP networks developed within the EURION cluster.
EURION partners should aim to describe how their test methods would fit within an IATA in order to illustrate the utility of the methods within a regulatory context. EURION should serve as a pillar for developing AOPs and IATAs on endocrine-related outcomes.
An overview of the IATA concepts and available guidance has recently been published by OECD and the OECD’s Working Party on Hazard Assessment has an ongoing project to develop and share experience on IATAs through case studies. EURION partners could consider developing a case study for submission to the OECD.
Could you elaborate on how the recent fitness check of EU legislation
on endocrine disruptors could help EURION to move forward?
The fitness check of EU legislation on endocrine disruptors (recently published together with the Commission Communication on a Chemicals Strategy for Sustainability ), highlights the need to review and strengthen information requirements within legislation on endocrine disruptors and reaffirms the need for the further development and validation of methods for their identification.
What can the JRC bring to EURION?
The JRC has a long experience in the validation and regulatory acceptance of test methods at OECD level as well as detailed knowledge of the EU regulatory landscape on the safety assessment of chemical substances. Our specific sphere of interest is in the development of new approach methodologies preferably using human cell-based test systems, which reduce reliance on animals, such as high throughput screening and high content imaging methods (some of which we implement in our own laboratories), along with computational methods. So, we are well placed to help partners in developing their methods in a way which will facilitate their validation and translation into regulatory practice (by defining aspects to be taken into consideration for ‘in-house validation’, regulatory need and acceptance, development of clear SOPs, working according to GIVIMP principles, etc).