Transcription

• Speaker #0

  Safer Chemicals Podcast. Sound science on harmful chemicals. Hello and welcome to this episode of the Safer Chemicals Podcast. I'm Adam, working here at the Communications Unit at ECHA, and I'm also your host today. Now, Europe wants to phase out animal testing for chemical safety assessments, but how do you actually move from ambition to actual implementation? That's what we're going to be looking at in this episode. We'll talk about what the Commission's roadmap sets out to do, what new approach methodologies can already deliver, where the main scientific and regulatory hurdles remain, and how ECHA is helping to build the structures needed for the transition. And I'm very pleased to say that today we're joined by Tomasz Zabanski from ECHA, who comes to this conversation straight from the first meeting of ECHA's Collaborative Platform on Alternatives to Animal Testing. So Tomasz, this is a very timely day to speak with you about how the roadmap can move from this kind of policy ambition to practical regulatory progress. So thank you very much for taking the time to join and welcome.

• Speaker #1

  Thank you. Yes, I'm happy to be here with you.

• Speaker #0

  So Tomasz, before we bring in the wider perspectives, maybe we should start with the basics. When we talk about these new approach methodologies or NAMs, what do we actually mean? What kind of methods are we talking about?

• Speaker #1

  Yes, new approach methodologies are a broad set of scientific methods. and approaches used to generate information on hazardous properties of the chemicals without relying on traditional observations in animal experiments.

• Speaker #0

  But then really for a layperson, are we talking about computer modeling? What are the actual kind of methods that you use? Yes,

• Speaker #1

  so indeed, some methods are computer models, which are allowing us first to predict certain properties and as well integrate different data streams together. There are as well in vitro methods when you are using the cell-based assays to measure some biological responses at cellular or tissue level. There are as well those methods which are allowing you to predict how substance will behave in the organism. So how it is absorbed and then distributed within the organism. We call those methods like toxicokinetics, Brody or ADMI.

• Speaker #0

  Well, why are these methods then becoming so important now? chemical safety assessment particularly?

• Speaker #1

  I think we need to look at NAMs from the broader perspective, not only from the animal replacement perspective, but why they are key. They are allowing you to get out from the traditional reliance on traditional toxicology when we've been observing how animals are reacting to the different chemical treatments. From one side, it's very pragmatic and very efficient because basically you are observing Thank you. what's going on. But this does not allow you to extrapolate from those observations and learn what was the reason, what was the cause for those adversities. And so if you want to make more informed decisions, move faster, you need to better understand what is behind the adverse outcomes. And this is what NAMS allows.

• Speaker #0

  So I guess it would be fair to say that NAMS are not kind of one single method, but a broad set of approaches that can help us assess chemical safety. in new ways that we don't necessarily even know yet are out there. And I think this discussion is especially timely because of the commission's roadmap that was just published earlier this month on phasing out animal testing for chemical safety assessments. Now, from your perspective, what is the roadmap trying to actually achieve? Is it mainly about reducing animal testing or is it also about changing, as you hinted already, how chemical safety assessment may work in the future?

• Speaker #1

  You know, for the simpler endpoints, when we've been measuring some direct effects of chemicals, the process of replacement was relatively straightforward. Like skin irritation, you measure how different chemicals might irritate your skin. That was almost, we called it one-to-one replacements. Now, when you are shifting to more complex endpoints, this is not anymore about taking out one element of the system and putting the new one, which is animal-free. This requires hole. redesigning the whole structure, how we are regulating chemicals. And this redesign needs some policy choices and policy tools. And that's why roadmap is very important, because it gives us those directions, policy ambitions, policy directions, and some tools how we can implement it in the future.

• Speaker #0

  So how should listeners kind of understand the ambition here? Is this something that can happen quickly? I'm guessing I know the answer to this already. Or are we talking about a transition with kind of short, medium and longer term steps?

• Speaker #1

  Yes, I think in the roadmap you have provisions with the different timelines. There are certain things and easy fixes which we can do almost immediately and they call it short-term actions or short-term basket. Then for those there is a common kind of belief at least at the commission level that those things can move relatively forward and it's more a matter of implementing it in the legal system. So almost all elements scientifically are in place.

• Speaker #0

  And can you give some examples? Yes. Just a couple of what those short-term… wins would be?

• Speaker #1

  For example, one of our proposals is to replace acute oral toxicity test which is normally the test done on rodents with QSAR predictions for that.

• Speaker #0

  Okay, and QSAR is the...

• Speaker #1

  QSAR is the computer model which based on the structure of the substance can predict the toxic outcome. For this particular case it is predicting the acute oral toxicity potential. So basically, whether the substance will be acutely toxic or not.

• Speaker #0

  Okay, thank you. And then the medium term, long term?

• Speaker #1

  Medium term, there are a few things which we believe scientifically almost all elements are in place, but there are still some fine tuning needed. Some test needs to be better validated. Maybe we need as well to develop a bit more robust methodology. For example, toxicokinetics. This is one of our proposals, which is considered to be midterm because we not yet ready for immediate implementation, there is still some homework which needs to be done.

• Speaker #0

  Sounds like a complex workload, but good that things are happening. Now, to set the policy context, we actually contacted the European Commission, asking them why this roadmap matters and what successful implementation could look like. So let's listen to a soundbite from Georg Streck from DG Grow.

• Speaker #2

  The roadmap towards phasing out animal testing for chemical safety assessment. contains 22 policy actions and more than 30 recommendations for specific human health or environmental endpoints. The Commission will now start to establish the organizational structures that are mentioned in the roadmap, for example, the roadmap steering team. The roadmap identifies options for animal testing that can be replaced in the short term. These should be implemented in the coming years. I would consider it as a great success if in two or three years you would have consensus among regulators in the EU, but hopefully also beyond the EU, what are the important elements of such a new regulatory risk assessment?

• Speaker #0

  So the roadmap is now moving from kind of policy direction again into implementation and identifying kind of the regulatory needs, looking at where animal testing can be replaced sooner and also preparing for deeper changes in how safety assessment work. is done in the longer term. Now, what does this mean for ECA in practice?

• Speaker #1

  For us in practice, roadmap gives clearer direction in which commission would like us to go. Not only us, but as well other important players. And this is quite important because already in ECA strategy for 2024-2028, we had very strong actions on the promotion of alternatives. Those were mainly our initiatives, those things which we believed are useful and important and needed. So now we can better link what we believe is needed to what Commission believes is necessary. Most probably will help us to gain coherence with other players in the direction in which we are going, and as well will help us prioritize our own activity.

• Speaker #0

  Okay, so on a kind of strategic level, I see that, and now also the direction setting. But then kind of in the day-to-day, so what does ECA need to do to help? kind of make non-animal approaches more usable in real regulatory decisions? What kind of role do we play there?

• Speaker #1

  We are contributing in three different areas. First of all, by communicating what we believe is important and what are the biggest stoppers for moving towards alternatives. So this is the first, just kind of informing and inspiring the research where we believe there is still more long-term research needed. So this is the first thing. We can as well facilitate and discuss how certain solutions could be implemented in practice in the different regulatory applications. So this is the second part. And then as well sharing the guidance and the best practices with member states, with registrants, both at the OECD level and on the different…

• Speaker #0

  I'm glad that you mentioned the OECD level because this is not just an EU operation. This has a lot of impact also internationally.

• Speaker #1

  Since few years already our strategy was that whenever we decided that something is worth to develop As soon as we feel we are ready, we wanted to bring it to OECD. Of course, OECD's QSAR toolbox was the first, this kind of development, which we are already doing since almost the beginning of ECA since 2008. There is no something like European hazard assessment. The main players in the chemical market are international players, which are not only present on the European market, but as well in the other markets. So this harmonization of the approaches, how we want to move forward with hazard. and risk assessment is very important.

• Speaker #0

  Well, maybe we move then a bit more towards the kind of the one important question, obviously, which is what does this all look like for companies, you know, who need to generate and submit the safety data that is then used by regulators? We did actually ask CEFIC what, from an industry perspective, would help to accelerate the regulatory uptake of non-animal approaches. So we have Katja Lakas from CEFIC with a soundbite. So I'll play that now.

• Speaker #3

  From an industry perspective, the biggest accelerator is not simply more data. It's about prioritizing the right non-animal methods. So we need more data. We need methods that are fit for real regulatory decisions, that are designed to replace the animal testing over time, not just add another layer to today's requirements. When it comes to the more complex endpoints, these one-to-one replacements are clearly not realistic. So where we need here is a more tiered and integrated approach and make sure that we have the stronger exposure and toxicokinetic information available. That means clear readiness and acceptance criteria, early dialogue with regulators, and space to learn from practical use. These are the essential requirements. So if new methods are only added on top of the existing requirements, we risk slowing innovation instead of accelerating the phase out of animal testing.

• Speaker #0

  So, Thomas, from ECHA's side, what can realistically be clarified in the short term for industry and others? And what depends on longer term changes to the full kind of regulatory framework behind?

• Speaker #1

  I don't know if you remember in our first NAMM workshop, we came up with this three-step proposal how to phase out animal testing when our first step was really analyzing the critical gaps, what is stopping us from moving forward. Second step was, okay, what we can do already now to gain experience, to build confidence. And then based on those two, how we can redesign the overall system. And now I think regarding the step one, we've been already quite good in indicating. many of those critical gaps, and they are frequently reported on our report, you know, these key areas of regulatory challenges, and when you have a very extensive chapter on alternatives to animal testing.

• Speaker #0

  We just published, if I'm not wrong, the 2026 update.

• Speaker #1

  Yes, new update. And now I agree with Katia on the thing that the next step now is that we indicated already what we believe are the most critical. things to cover, but we've not yet been very explicit on how we would like to see those gaps be covered. So we have to be more explicit on the criteria. What we would like to see as an evidence on the table to comfortably conclude that, okay, this is not the gap anymore. And this is, I guess, one of the first priority for us to be more explicit what we want to see in the system for the future.

• Speaker #0

  Right. And this, I guess, in turn translates then into the guidance that you were talking about earlier so that the people doing the tests are able to adequately meet these needs.

• Speaker #1

  Not always. It's only the guidance because sometimes there is still some research needed and we need to set up like objective success criteria.

• Speaker #0

  Right.

• Speaker #1

  And to do it before the solution just to be able to then objectively conclude whether we reach the objectives and we cover the gap or not. Once we will cover the gap. Once we conclude that this works well, then is the time for the guidance to inform registrants, okay, how now you can use this new evidence in your regulatory applications. So the guidance comes later as an outcome.

• Speaker #0

  Now, you mentioned research there and getting the right research. Who does this research? Are we able to commission studies at ECHO? Is it other players? Who does the work, the actual scientific research to help with this?

• Speaker #1

  They are. different scientific consortia which are taking this on board and the best example is the park. So this is this partnership between member states, academia and us, when we are trying to, in this collaboration between regulators and scientists, try to solve this. Then there is as well a lot of private funding from the industry associations, other initiatives at the European level, like this Horizon 2020 or Horizon Europe. I think we at ECHA, as an agency who is responsible for implementing different laws, We are not necessarily those which should drive the research and development, but we have a responsibility, and this is already well recognized, to indicate where are the needs, especially from the implementation point of view, where are still the needs to do more. We can inspire the projects and make sure that they have a good regulatory focus.

• Speaker #0

  Right. Okay. Thank you. Very much appreciate the concrete examples. I think they help shed a lot of light as to how many players are involved and how much work there is and who is actually taking it on. So thanks for that. When people hear about phasing out animal testing, it can sound like something that sits, you know, very far in the future. But ECHA, as you've indicated already, is already kind of working with several tools and approaches that can help reduce or replace animal testing or support regulatory conclusions. So what are the kind of most tangible examples that you can give? on progress that Eke can point to today. I think you've hinted to some already.

• Speaker #1

  Yes, and this is maybe as well a very good moment to say that actually we have as well some funding possibilities. We have the NAM framework contract, which allows us to invest in some specific NAM generation, which is more filling the gap between research and implementation. And as well, we have a framework contract for scientific services. QSAR toolbox is another example that this constant development of the toolbox is as well financed from our resources. The other concrete example is we are basically doing the feasibility test study on enhanced fish embryo tests. So basically test which is using fish embryos and after relatively short exposure with combined with transcriptomics measurements. So we are measuring how... fish embryos are response to the toxicants at the transcript level to predict chronic effects, which normally you would see after a few weeks of chronic exposure on the adult fish.

• Speaker #0

  One aspect is the collaboration also that you've hinted here. So maybe we could move a little bit towards that. You mentioned already Cefek and other players. I mean, collaboration is essential, both in Europe and internationally also, as we've touched upon. One example is this European Partnership for Alternative Approaches to Animal Testing, EPAA. We asked Gavin Maxwell, who is the chair, I believe, of the platform, why this kind of cross-sector collaboration matters if Europe wants to move from promising methods to methods that regulators can then actually trust. So let's listen to Gavin.

• Speaker #4

  The European Partnership for Alternative Approaches to Animal Testing is a collaboration between the European Commission and industry stakeholders to replace, reduce and refine animal use for meeting regulatory requirements. ECHA is a very active partner within EPA, contributing to many of our scientific projects and hosting our annual NAM user forum. EPA is focused on supporting the Commission roadmaps through helping identify research methods that could address unmet regulatory requirements, building confidence in non-animal approaches through facilitating scientific dialogue between regulators, industry safety assessors and NAM experts. and enabling the transition to a new global regulatory paradigm that uses NAMs to strengthen human health and environmental protection. I'm hopeful that the collaborative platform and alternatives to animal testing continues to provide this space to open up conversations and how we can build confidence in animal-free safety signs for regulatory decision making.

• Speaker #0

  Now, that point about confidence building from Gavin, I think, is really important. So it's not only about kind of individual methods. It's also about creating these conditions so that regulators, companies and other actors can understand when and how these methods can be used. And that actually brings us to one of the most concrete implementation tools in this area. So the new collaborative platform on alternatives to animal testing that ECHA is hosting. So, Tomás, you're joining us just after the first meeting of this new platform. Maybe we start with why. Does ECHA need a dedicated platform to begin with?

• Speaker #1

  So to some extent, we've been doing all those dialogue before already, like with EPA, like Gavin mentioned, we had this long lasting collaboration. But what we've been missing a bit in all this landscape was direct platform, which allows us to have this dialogue as well with our member states, with those experts which are contributing to those decisions. And it was quite clear when we started to work on the roadmap that they would like to be heard, that would like to actively contribute, because at the end, those are the people which are dealing with practical cases. They are deciding on risk management measures, on hazard outcomes, and so on. So we need to have them on board. And that was a bit missing. And the main idea behind the platform is to bring them on board on those discussions. maintaining still connection to other important key stakeholders we have still ngos and industry but we want to focus here from on member states as well and just to add you know the building confidence and dialogue is not only important for eca stakeholders we need to as well align with other agencies in europe we need to align internationally at this ocd level but it's really very complex interaction between many different players and many different levels and So how to make sure that all contributing actors, they have their place, they have their say, and we are not redoing those things in parallel.

• Speaker #0

  Okay, so how do you think that this platform can then kind of help move the discussion from general support for NAMs to these specific regulatory use cases? What concretely can the platform do there?

• Speaker #1

  At least at the beginning to gain momentum, to build confidence and to have this feel of achievement. We are starting with things which we've been already investing as ECA and as other stakeholders like EPA, SEFIC, already for quite many years. We believe that many of those elements are already ready. We want to bring those elements and discuss how it can work in the rich context, in the biocide context, in the water drinking directly context, how we can use them directly in our different regulatory processes. And we want to discuss it together with our colleagues from the member states. with the input from industry and NGOs to gain this consensus, because then at the end, all the changes in the legal frameworks needs to happen with approval of those players. And so it's better to build first consensus rather than have never-ending discussions during the policy discussions later on.

• Speaker #0

  Now, you've had the first meeting. So I'm curious as to, you know, any outcomes from this one that you could already share. Have you... I would understand that the first meeting is always about roles and next steps and so on, and how do we set up the governance and these kinds of things. But is there anything that you've come up with as a plan other than what you just mentioned?

• Speaker #1

  So first of all, before the meeting, after the nomination process was concluded, we asked all the nominated members, please give us your ideas about the work items. And basically, based on this discussion, we ended up with four main working topics for the first two years. in silico methods and QSARs, refinement of the in vitro toxicokinetic battery in the context of rich information requirements, but then we can as well use it for other things. And the third one is use of OMICS for reader cross-and-grouping applications is the first step, just to make it more concrete. And then the fourth one is use of NAMs for nanomaterials and other advanced materials.

• Speaker #0

  Okay, good, thank you. Well... Moving on to the next stakeholder group who are also very active and very needed in this work. So civil society obviously has an important role in how this transition to NAMS happens. Maybe we start with the animal welfare perspective. So we have Julia Baines from PETA and let's play her soundbite.

• Speaker #5

  We really value and welcome the roadmap, which makes it clear that the future of chemical safety assessment is based on non-animal approaches. But the question now is one of delivery. And that's because progress will be measured by what changes in practice. And that's whether non-animal approaches become the default and if the system evolves to support them. Because without these types of changes to regulations, tests on animals will continue. And that's also why initiatives like ECHA's collaborative platform on alternatives to animal testing is so important, as it brings regulators, industry and NGOs together to help build confidence. So we now look to ECHA to act swiftly and decisively in leading the way to build trust in these methods across the agency and beyond.

• Speaker #0

  There is also the question how to make that transition while keeping the chemical safety decisions protective. So we also asked HEAL, this is the Health and Environment Alliance, for an environmental health perspective. So this is Sandra Jen from HEAL.

• Speaker #6

  At HEAL, we see the implementation of the Commission Roadmap as a crucial opportunity, both to reduce the dependency on animal testing and to strengthen regulatory management of chemicals in the EU. It's important to stress the core principle of the roadmap, that non-animal approaches must deliver a level of protection equivalent to that of currently established methods. So in line with this core principle, the protection of health and the environment must always be given priority. Therefore, we support the... cautious transition to new approach methods, or in short, NAMs. These methods are not yet available to fully replace animal tests for the regulatory identification and risk management of the most serious hazards, such as carcinogenicity, reproduction toxicity, and endocrine disrupting properties. But several promising tools like grouping and read-across are already available to help reducing animal testing. So let's start making the most of them as well.

• Speaker #0

  So we've heard now two civil society expectations, faster and more visible progress away from animal testing and still a cautious transition that maintains strong protection for health and the environment. Tomasz, how can ECA help bring these expectations together in a practical regulatory setting?

• Speaker #1

  Excellent question. And I think if you want to have the alternatives to be default option, you need to first set up what are the performance expectations, how you can make sure. that the predictions are as good as the experimental data from animal tests. This is very important because we don't want to compromise on level of protection. So the first step is to agree how we will judge the performance of the method against the existing data. We need to make sure that at least half of the substance can work, right? Because otherwise there is no sense to propose as a default option something which can only work for 10 or 5. percent of cases right then it will create problem for everybody for us for registrants create many confusions and the most important is to be explicit where it can work and when it cannot this is what we are referring as this domain of applicability for those tests now

• Speaker #0

  we've talked about the ambition the tools that already exist and the role of collaboration how important that is but i think it's also important not to make this sound simpler than it actually is Several of the contributors we've had today have pointed to confidence, acceptance criteria and protection standards, as we've just discussed. What are the kind of biggest misconceptions about how quickly animal tests can be phased out?

• Speaker #1

  To some extent, it really depends on your regulatory case and your regulatory scenario. I think those which are more enthusiastic and believe it can move faster are the people where... from the sector where the exposure context is very well known. They know exactly how the substance is used, what are the concentrations you are exposed to, and basically then it's enough to measure that at this concentration levels which you are exposed to, you don't see any signs. Even at the basic molecular level, you don't see any signs of toxicological response. And then you can believe that you can conclude on safety. The problem is that... A sector like industrial chemicals is a relatively open sector. It means the way how you can use chemicals. If you are putting something on the consumer market, you are losing control how it will be used. And probably you know that people are very innovative in the way how they can use chemicals. And they can use it in a completely uncontrolled and not necessarily predicted way. Plus, we have to keep in mind that there is co-exposure, that the fact that you predict that if you are using shampoo, are getting this This exposure from the substance does not mean that the same substance is not in the furnitures which we are using every day in your office. They are not in your textiles. They are not somewhere else.

• Speaker #0

  So the level of exposure can be actually quite a lot higher.

• Speaker #1

  Exactly. Chemicals which we believe they are inert and that we shouldn't have any exposure, we found those chemicals in the bloodstream of the general population everywhere. So for that, we need to as well be able to characterize the hazard without this exposure. context component. So we would like to know whether certain chemicals are intrinsically dangerous because we don't want to put into the general, expose general population to the things which are carcinogens, which are mutagens, which can, you know, affect our reproduction, health and so on, right? So we need to characterize those things before putting chemicals in the market. And this is the biggest challenge. And this is the biggest misunderstanding between those different stakeholders groups and ABDs. Because to change that, we need to... rethink how we will do this hazard identification and characterization. And this is not easy.

• Speaker #0

  Actually, this idea that you're exposed to potentially the same chemical through different settings or different products leads to this cocktail effect as well. Is this something that new approach methodologies can somehow help deal with? The fact that combinations of chemicals and their levels of exposure and building kind of scenarios as to how that affects people in the environment? Is this something that's considered?

• Speaker #1

  Yes, and this is one of the promises of the NAMs, which did not yet materialize, but I believe it is one of the important tools which can help us break through some of the limitations which we have today.

• Speaker #0

  Because in the classical toxicological testing, the outcome of the test is the knowledge that chemical X in test Y cannot give you response Z. And that's it. It's very difficult to extrapolate this knowledge to anything else. You don't know what will happen if you will change the composition. You don't know what will happen if you add a new component. With NAMS, it's a bit different. because we start to measure the biological responses on the molecular levels, we can think about it like specific fingerprints for the different type of toxicity caused by different kind of, let's call them library chemicals. And then we can deconvolute. If you have a very complex toxicological response from the mixture effect, you can try to decompose this for those individual fingerprints. And then you can try to understand what was the contributing factors to that. So I think in the future, once we will learn to build those library of those fingerprints, it will be much easier to identify which type of components were responsible for this toxic outcome. And it will be much easier to deconvolute those complex responses to those individual contributing factors.

• Speaker #1

  Now, before we close, let me briefly summarize what we've covered today. So the roadmap gives Europe a clearer direction for moving away from animal testing and chemical safety assessment. But as we've heard, implementation will depend on practical and credible steps. Identifying where non-animal approaches can already be used, building confidence where more evidence is still needed, adapting regulatory practice over time, and keeping the protection of health and the environment at the forefront of this work. Now, ECHA's role is to help make this transition workable in real regulatory settings together with the Commission, member states, industry, researchers and civil society. The Collaborative Platform on Alternatives to Animal Testing is one way to support this by bringing together regulatory needs, scientific developments and stakeholder expectations. And ECHA's role is to help turn that ambition into regulatory reality. Tomás, thank you so much for joining us today after a... busy two days and for sharing your insights on this.

• Speaker #0

  Thank you for having me.

• Speaker #1

  And to our listeners, thank you for listening. Science is becoming increasingly important in ECHA's work. And if you want to learn more about our scientific priorities and activities, visit the science section of our website at eccha.europa.eu forward slash science. To stay up to date with the latest developments, you can also subscribe to our news. Safer Chemicals podcast. Sound Science on Harmful Chemicals.