WEBVTT 1 00:00:00.296 --> 00:00:02.017 Safer Chemicals podcast. 2 00:00:02.737 --> 00:00:04.857 Sound science on harmful chemicals. 3 00:00:10.699 --> 00:00:15.140 All three partners are very well integrated with various European projects, 4 00:00:15.420 --> 00:00:21.642 which are aiming at developing the methodologies related to phasing out animal testing. 5 00:00:22.102 --> 00:00:23.163 So having them, 6 00:00:23.623 --> 00:00:27.484 it's like having almost European community working for us. 7 00:00:28.504 --> 00:00:30.886 We discussed a lot about pragmatic solutions, 8 00:00:30.886 --> 00:00:39.715 so we are not aiming to have the one and only most sophisticated model in the end that nobody can actually fill in this data because it's so over-complex. 9 00:00:40.075 --> 00:00:42.137 We are aiming at something very pragmatic. 10 00:00:42.758 --> 00:00:43.679 In today's episode, 11 00:00:43.819 --> 00:00:49.144 we're exploring how new approach methods are shaping the future of chemical hazard assessment and regulation, 12 00:00:49.384 --> 00:00:52.948 especially in light of growing commitments to replace animal testing. 13 00:00:54.240 --> 00:00:58.584 This shift away from animal testing has been making waves in the regulatory landscape for years. 14 00:00:59.325 --> 00:00:59.745 Recently, 15 00:00:59.985 --> 00:01:08.593 the European Chemicals Agency took a significant step by commissioning a project of 4.2 million euros aimed at developing advanced NAM-based tools. 16 00:01:09.634 --> 00:01:12.876 The project aims to improve the way we identify and assess hazards, 17 00:01:13.217 --> 00:01:16.900 particularly for complex chemicals like polymers and nanomaterials. 18 00:01:18.802 --> 00:01:21.504 This and other similar EU-level initiatives reflect a growing focus on combining scientific innovation with regulatory advancement, 19 00:01:26.889 --> 00:01:30.112 ultimately to ensure the safer use of chemicals across Europe. 20 00:01:31.673 --> 00:01:31.833 Now, 21 00:01:31.993 --> 00:01:37.798 today's discussions will be focusing on how ECHA and the research community can support and contribute to this work. 22 00:01:38.599 --> 00:01:42.963 I'm joined by Sylvia Escher from Fraunhofer Institute and coordinator of the project. 23 00:01:44.064 --> 00:01:46.126 Also with me is Tomasz Sobanski from ECHA, 24 00:01:46.346 --> 00:01:47.627 who will guide us through the goals, 25 00:01:47.707 --> 00:01:48.248 challenges, 26 00:01:48.956 --> 00:01:51.900 and we'll be also talking about potential impacts of this important work. 27 00:01:53.581 --> 00:01:53.722 Now, 28 00:01:53.862 --> 00:01:58.487 I know there's a workshop ongoing as we speak on laying the groundwork for this project. 29 00:01:58.507 --> 00:01:59.628 So first of all, 30 00:01:59.708 --> 00:02:03.533 I'd like to start by thanking you both for taking the time to join me here in the studio. 31 00:02:04.794 --> 00:02:06.416 Maybe if we then start with you, 32 00:02:06.536 --> 00:02:06.837 Sylvia, 33 00:02:06.937 --> 00:02:09.720 could you briefly introduce yourself and the consortium? 34 00:02:10.560 --> 00:02:10.820 Yeah, 35 00:02:10.820 --> 00:02:11.361 thanks a lot. 36 00:02:11.401 --> 00:02:12.542 So my name is Sylvia Escher. 37 00:02:12.562 --> 00:02:16.105 I'm working for Fraunhofer Institute for Toxicology and Experimental Medicine. 38 00:02:16.125 --> 00:02:21.209 And it's my pleasure to coordinate this project in which we teamed up with two other partners. 39 00:02:21.709 --> 00:02:22.169 One is 40 00:02:23.130 --> 00:02:23.971 Michabo Health 41 00:02:24.331 --> 00:02:27.774 Science from the UK led by Mark Weyand and the other partner is 42 00:02:28.314 --> 00:02:31.897 BASF Metabolome Solutions from Germany led by Henneke Kamp. 43 00:02:32.358 --> 00:02:33.198 And in this project, 44 00:02:33.198 --> 00:02:39.924 we are actually interested to promote the integration of new approach methods into risk assessment and therefore we are very glad 45 00:02:40.324 --> 00:02:43.546 to work together with ECHA on this exciting topic. 46 00:02:44.506 --> 00:02:49.129 And here we have all three different complementary expertises. 47 00:02:49.609 --> 00:02:50.710 So Mark and Henneke, 48 00:02:51.030 --> 00:02:56.813 they are mainly working on the integration of metabolome and transcriptome data, 49 00:02:56.893 --> 00:03:04.538 which means we are integrating data that tell us something about mechanisms leading to toxicological findings. 50 00:03:05.018 --> 00:03:07.880 And ETEM is also working on these transcriptome data, so 51 00:03:08.520 --> 00:03:09.401 gene changes, 52 00:03:09.601 --> 00:03:09.981 actually. 53 00:03:10.522 --> 00:03:14.385 And we are also interested into learning more about the kinetics, 54 00:03:14.445 --> 00:03:15.826 which means the absorption, 55 00:03:15.926 --> 00:03:16.667 distribution, 56 00:03:16.767 --> 00:03:17.347 metabolism, 57 00:03:17.387 --> 00:03:20.430 and excretion of compounds into the human organism. 58 00:03:21.390 --> 00:03:21.871 Thanks for that, 59 00:03:21.911 --> 00:03:22.211 Sylvia. 60 00:03:22.311 --> 00:03:30.197 So it sounds like there's a really strong collaboration between your team and the partners from the UK and Germany that you mentioned, 61 00:03:30.237 --> 00:03:33.580 with kind of each group bringing a unique perspective to the table. 62 00:03:34.964 --> 00:03:39.746 It's interesting also that you're focusing on both the molecular data and the kinetics side of things. 63 00:03:39.806 --> 00:03:44.667 So understanding how these compounds are absorbed and processed in the body is definitely a big challenge, 64 00:03:45.167 --> 00:03:46.087 but a necessary one. 65 00:03:47.128 --> 00:03:53.689 Could you tell me a little bit more about the importance of collaboration and how you manage it between such a diverse set of partners? 66 00:03:54.770 --> 00:03:59.431 So basically what we set up is the so-called scientific framework contract, 67 00:03:59.811 --> 00:04:03.052 which basically set up the time that for the six years, 68 00:04:03.480 --> 00:04:15.085 we have the possibility to define small projects and through those projects we can tackle some specific issues which are of regulatory relevance or scientific relevance from our perspective. 69 00:04:15.505 --> 00:04:18.226 And then the consortium is meant to work on it. 70 00:04:18.246 --> 00:04:30.451 And actually the first three projects, which we already started December last year, are very good example of this kind of issues which are of high regulatory concern. 71 00:04:30.491 --> 00:04:31.852 From our perspective, 72 00:04:32.392 --> 00:04:39.538 we are very happy to have this consortium with our main contractors because they are not only great scientists, 73 00:04:39.618 --> 00:04:41.700 not only with complementary skills, 74 00:04:42.000 --> 00:04:49.306 but as well they are very nicely representing the European scientific society with whom we want to have a dialogue. 75 00:04:49.727 --> 00:05:00.115 So basically all three partners are very well integrated with various European projects which are aiming at developing the methodologies related to 76 00:05:01.116 --> 00:05:02.460 phasing out animal testing. 77 00:05:02.941 --> 00:05:03.984 So having them, 78 00:05:04.465 --> 00:05:08.315 it's like having almost European community working for us. 79 00:05:09.103 --> 00:05:09.323 I mean, 80 00:05:09.383 --> 00:05:12.384 you've got these experts who are deeply involved in European initiatives. 81 00:05:12.424 --> 00:05:19.407 So I guess that must give the project quite a solid foundation and also make sure that what you're doing is relevant not just to ECHA, 82 00:05:19.547 --> 00:05:21.628 but to the broader regulatory landscape, 83 00:05:21.628 --> 00:05:22.849 which I think is important. 84 00:05:23.809 --> 00:05:28.731 So what is the work involved so far and what are the first topics the project will be working on? 85 00:05:29.771 --> 00:05:32.292 We have three projects to work on. 86 00:05:32.673 --> 00:05:38.655 And the first topic is that we would like to develop a guidance document for omics sampling 87 00:05:39.996 --> 00:05:43.297 from in vivo animal studies and Mark is leading this activity. 88 00:05:43.758 --> 00:05:49.661 And the aim is to introduce possibility for measuring molecular biomarkers to a wide range of tox tests, 89 00:05:49.701 --> 00:05:52.162 which are already planned and requested by the regulator. 90 00:05:52.202 --> 00:05:55.324 So we are not aiming to do any extra animal studies, 91 00:05:55.364 --> 00:05:55.744 but we are, 92 00:05:55.724 --> 00:05:56.144 so to say, 93 00:05:56.525 --> 00:05:59.946 making the best out of already existing approaches. 94 00:06:00.387 --> 00:06:05.269 So this is also in the benefit of the reduction of animal testing. 95 00:06:06.170 --> 00:06:07.711 That guidance document you're working on, 96 00:06:07.911 --> 00:06:08.191 I guess, 97 00:06:08.251 --> 00:06:08.491 will be... 98 00:06:08.807 --> 00:06:11.109 very important for ensuring that researchers know, 99 00:06:11.949 --> 00:06:12.289 first of all, 100 00:06:12.309 --> 00:06:13.510 how to collect and then, 101 00:06:13.570 --> 00:06:13.991 second of all, 102 00:06:14.051 --> 00:06:15.912 handle these new types of molecular data. 103 00:06:16.392 --> 00:06:19.014 So it's really about making the current tests more efficient, 104 00:06:19.434 --> 00:06:20.175 more insightful, 105 00:06:21.095 --> 00:06:23.357 and without adding to the testing burden. 106 00:06:24.498 --> 00:06:24.758 Yes. 107 00:06:25.098 --> 00:06:25.739 So basically, 108 00:06:25.919 --> 00:06:27.700 the guidance is to allow 109 00:06:28.240 --> 00:06:30.722 CROs, so the contract research organisations, 110 00:06:30.762 --> 00:06:34.284 which are normally the place when you are conducting the animal studies, 111 00:06:34.945 --> 00:06:35.886 or any other studies, 112 00:06:35.946 --> 00:06:37.747 because actually we are not only limited to 113 00:06:38.259 --> 00:06:48.366 in vivo studies we are as well aiming and introducing those measurements to the other regulatory testing also in vitro. 114 00:06:49.207 --> 00:06:59.054 And basically the idea is to give them clear instruction how they should collect and preserve the samples to make them suitable for different type of omics analysis, 115 00:06:59.094 --> 00:07:01.676 so to generate properly the molecular data, 116 00:07:01.776 --> 00:07:05.399 because that's the starting point for any further discussion 117 00:07:05.903 --> 00:07:08.405 on how you can use them in the regulatory context. 118 00:07:09.666 --> 00:07:10.547 That makes a lot of sense. 119 00:07:10.627 --> 00:07:19.555 So the idea of giving organisations kind of clear instructions on how to handle and store samples for omics analysis really speaks to the kind of practical side of this work. 120 00:07:19.996 --> 00:07:21.397 So it's not just about the science, 121 00:07:21.417 --> 00:07:23.959 but actually really making sure that people on the ground, 122 00:07:23.999 --> 00:07:25.120 those running the tests, 123 00:07:25.561 --> 00:07:29.244 can actually then implement these methods in a way that regulators can also use. 124 00:07:29.984 --> 00:07:30.185 Now, 125 00:07:30.385 --> 00:07:32.567 you mentioned the three first projects, but 126 00:07:32.647 --> 00:07:32.767 I suppose there's also some kind of prioritisation going on and you're looking at certain focus areas that you think will have high impact. 127 00:07:41.374 --> 00:07:44.296 In terms of what areas research should be focusing on, 128 00:07:45.137 --> 00:07:51.141 can you talk a little bit more about these projects and any future ones that you've already considered as being of high relevance? 129 00:07:52.602 --> 00:07:53.223 First of all, 130 00:07:53.543 --> 00:07:58.527 all of those three topics were the topics which we already discussed last year during our NAM workshop. 131 00:07:59.199 --> 00:07:59.900 If you remember, 132 00:07:59.920 --> 00:08:08.125 we had those discussions of how to demonstrate that what we can already achieve with different new approach methodologies already now without changing anything. 133 00:08:08.485 --> 00:08:18.912 And we identify that basically there are certain elements which we have to cover to have this more successful demonstration of those methodologies, 134 00:08:18.972 --> 00:08:24.916 which is exactly the ability to generate this omics data from the normal regulatory testing. 135 00:08:24.956 --> 00:08:27.638 This is what we already discussed about the omics sampling project. 136 00:08:27.918 --> 00:08:28.719 The second 137 00:08:28.879 --> 00:08:31.481 is about using molecular data. 138 00:08:31.521 --> 00:08:32.181 So applying, 139 00:08:32.281 --> 00:08:42.228 basically utilising those data in read-across and category buildings because read-across is the most common adaptation used by our registrants. 140 00:08:42.468 --> 00:08:53.795 At the same time it is the which is most often failed by us during the compliance check because basically there is no strong... 141 00:08:54.624 --> 00:08:58.287 basis for building the hypothesis for those read acrosses. 142 00:08:58.327 --> 00:09:03.992 So we want to really use this molecular data to strengthen those hypotheses. 143 00:09:04.272 --> 00:09:13.040 And the third one is about toxicokinetics and especially the role of the toxicokinetics in doing in vitro to in vivo extrapolation. 144 00:09:13.080 --> 00:09:21.307 So then how you can extrapolate the results from the in vitro test to the in vivo situation that you know it can inform the hazards for the general population or for environment later on. 145 00:09:25.628 --> 00:09:27.029 Just for the benefit of our listeners, 146 00:09:27.589 --> 00:09:29.889 can you explain briefly read-across adaptations? 147 00:09:29.929 --> 00:09:31.410 So what does that involve exactly? 148 00:09:35.631 --> 00:09:45.193 So read-across means that you want to avoid animal testing and you use existing data from other compounds to predict the toxicity of a compound that you don't yet know. 149 00:09:45.834 --> 00:09:50.515 So you predict or infer its toxicological properties. 150 00:09:50.895 --> 00:09:52.396 And now with the new approach methods, 151 00:09:52.396 --> 00:10:00.123 we have the opportunity to also support this reading across by showing some evidence on a shared mode of action. 152 00:10:00.203 --> 00:10:04.867 And here we need the new approach methods because they are generating this mechanistic understanding. 153 00:10:05.267 --> 00:10:05.668 And this is, 154 00:10:05.648 --> 00:10:06.028 so to say, 155 00:10:06.128 --> 00:10:09.351 our chance to really get this read across better. 156 00:10:09.431 --> 00:10:11.693 And also with the kinetics in the third project, 157 00:10:11.693 --> 00:10:13.915 we can also not only show a shared mode of action, 158 00:10:14.315 --> 00:10:17.158 but we can also show shared kinetic properties. 159 00:10:17.158 --> 00:10:18.339 So the compound is actually 160 00:10:19.028 --> 00:10:22.210 Having the same bioavailability or show a similar trend 161 00:10:23.005 --> 00:10:25.186 when it's absorbed and then you have taken it in, 162 00:10:25.266 --> 00:10:28.848 like you have already ingested it or you have inhaled it, 163 00:10:30.048 --> 00:10:33.530 it was on your skin and somehow it penetrates into your organism. 164 00:10:34.571 --> 00:10:35.471 Thanks for breaking that down, 165 00:10:35.531 --> 00:10:35.791 Sylvia. 166 00:10:35.831 --> 00:10:37.132 So essentially, 167 00:10:37.472 --> 00:10:42.974 Read Across lets you predict the effects of one chemical based on data from another similar one, 168 00:10:43.015 --> 00:10:43.235 right? 169 00:10:43.735 --> 00:10:47.977 And these new methods are helping you add more confidence to those predictions, 170 00:10:48.445 --> 00:10:51.187 by understanding the biological mechanisms that are involved. 171 00:10:51.187 --> 00:10:52.888 So that's quite a big step forward. 172 00:10:53.328 --> 00:10:54.429 You mentioned the NAM, 173 00:10:54.649 --> 00:10:58.532 or new approach methodologies workshop that we organised here at ECHA last year. 174 00:10:58.552 --> 00:11:06.397 And I think one thing that came out clearly from there is that there are challenges and we may well be quite far actually from the ultimate goal of fully, 175 00:11:06.777 --> 00:11:06.998 I mean, 176 00:11:07.098 --> 00:11:08.519 fully replacing animal tests. 177 00:11:08.539 --> 00:11:11.020 So let's focus on the challenges for a while. 178 00:11:11.040 --> 00:11:13.822 So especially in terms of the work of the consortium, 179 00:11:14.343 --> 00:11:17.705 what do you expect to be the main challenges for the projects that you've identified? 180 00:11:18.889 --> 00:11:19.949 So in the first phase, 181 00:11:20.650 --> 00:11:22.771 actually the work that we are doing in this first year, 182 00:11:22.831 --> 00:11:28.053 we are relying mainly on existing data and later on we can also define more experimental data. 183 00:11:28.533 --> 00:11:38.177 But here we are facing the situation that not all data are standardised and it's a kind of issue that we have to work on this to make them comparable. 184 00:11:38.617 --> 00:11:46.100 And also the quality and validity of these assays needs to be assessed to be integrated in the end into a concept to integrate them into risk assessment. 185 00:11:46.140 --> 00:11:47.841 That's one challenge that we are facing. 186 00:11:48.573 --> 00:11:52.877 I can imagine that the lack of standardised data would be a real hurdle. 187 00:11:53.877 --> 00:11:55.439 I guess without consistency, 188 00:11:56.580 --> 00:11:58.821 how can you make accurate comparisons or conclusions? 189 00:11:59.502 --> 00:12:08.950 So I think it's clear that tackling this from the start is probably going to be crucial in making sure these methods can be trusted and then ultimately used more widely. 190 00:12:09.430 --> 00:12:17.597 I think the other challenge is that many of those approaches were applied primarily for pharmaceuticals. 191 00:12:19.698 --> 00:12:22.479 The compounds which are meant to be bioactive, 192 00:12:22.899 --> 00:12:30.382 which are meant to be bioavailable because basically they need to do some certain work in the organism. 193 00:12:31.703 --> 00:12:42.307 While now we are extrapolating those approaches to industrial chemicals which were not designed having in mind any interaction with human body or any organism. 194 00:12:42.727 --> 00:12:46.128 So we will face some difficulties in how to test them, 195 00:12:46.408 --> 00:12:47.369 how to dissolve them. 196 00:12:48.053 --> 00:12:49.694 To which extent they are bioavailable. 197 00:12:50.714 --> 00:13:01.959 And then we will need to cover this complexity and try to come up with the solution which can be understood by our registrants and by the contract lab research organisations to perform those. 198 00:13:01.959 --> 00:13:09.022 So I think that this is an extension of the standardisation because this is the standardisation of the quite complex solution, 199 00:13:09.102 --> 00:13:11.523 how to approach the technical difficulties. 200 00:13:11.983 --> 00:13:13.044 That's a really important point. 201 00:13:13.064 --> 00:13:14.384 So unlike pharmaceuticals, 202 00:13:14.584 --> 00:13:16.385 many industrial chemicals weren't designed 203 00:13:16.845 --> 00:13:20.267 with the expectation that they interact with the body in a specific way. 204 00:13:20.327 --> 00:13:23.109 So you're not just dealing with scientific complexity, 205 00:13:23.209 --> 00:13:27.091 but also with kind of practical challenges around how to even test them. 206 00:13:28.091 --> 00:13:30.453 It's almost like you're building the plane while flying it, 207 00:13:30.513 --> 00:13:31.873 which is never a good idea. 208 00:13:32.314 --> 00:13:33.534 And I think to add to that, 209 00:13:33.594 --> 00:13:36.576 I think today we discussed a lot about pragmatic solutions. 210 00:13:36.576 --> 00:13:45.401 So we are not aiming to have the one and only most sophisticated model in the end that nobody can actually fill in this data because it's so over complex. 211 00:13:45.741 --> 00:13:47.803 We are aiming at something very pragmatic. 212 00:13:47.823 --> 00:13:49.524 We want to make this alive. 213 00:13:49.965 --> 00:13:50.565 And therefore, 214 00:13:51.106 --> 00:13:51.366 we are, 215 00:13:51.366 --> 00:13:51.746 so to say, 216 00:13:51.826 --> 00:13:55.950 coming with something which is soluble also by applicants. 217 00:13:56.690 --> 00:13:57.070 Exactly. 218 00:13:57.111 --> 00:14:03.816 It seems like you're aiming for something that strikes a kind of balance between being first and foremost scientifically robust, 219 00:14:04.276 --> 00:14:04.857 but then also, 220 00:14:05.197 --> 00:14:05.417 you know, 221 00:14:05.518 --> 00:14:07.459 importantly doable in the real world. 222 00:14:08.260 --> 00:14:14.325 How do you ensure that the solutions you're developing are both scientifically valid and practical for regulatory use? 223 00:14:15.365 --> 00:14:21.590 We've seen already some attempts to integrate those data into the read-across attempts, 224 00:14:21.590 --> 00:14:30.097 so basically to justify that substance which is used as a source of the information is indeed very similar to the substance for which you want to cover, 225 00:14:31.598 --> 00:14:34.060 you want to generate this toxicological information. 226 00:14:34.080 --> 00:14:39.605 So this is probably the first most obvious application of those technologies. 227 00:14:40.325 --> 00:14:43.427 Although we have to remember that even this is not so straightforward, 228 00:14:43.467 --> 00:14:44.628 because what we are trying to do, 229 00:14:44.628 --> 00:14:46.409 we are trying to use molecular data. 230 00:14:46.790 --> 00:14:55.436 So data which are measured at the quite basic level of biological organisation and associated with the adverse outcome, 231 00:14:55.436 --> 00:14:58.338 which is at the end of the biological process. 232 00:14:58.678 --> 00:15:04.042 So there is a lot of steps in between which we have to tackle and we need to come up with a pragmatic solution, 233 00:15:04.362 --> 00:15:05.643 not overcomplicating it, 234 00:15:05.783 --> 00:15:08.905 but making it as well accessible for our registrants. 235 00:15:09.621 --> 00:15:09.841 Right. 236 00:15:10.222 --> 00:15:12.523 And regulatory acceptance is key here. 237 00:15:12.563 --> 00:15:14.565 So even if you've got the science nailed down, 238 00:15:15.525 --> 00:15:19.248 it doesn't really matter if it doesn't fit within the strict framework of regulations. 239 00:15:20.029 --> 00:15:24.232 But starting with read-across as an entry point for these new methods seems like a logical place. 240 00:15:24.952 --> 00:15:29.435 Could you talk a bit about how you're working towards regulatory acceptance for these methods, 241 00:15:29.475 --> 00:15:31.437 particularly when it comes to read-across? 242 00:15:32.208 --> 00:15:32.488 Yeah, 243 00:15:32.488 --> 00:15:40.632 I agree fully that read across is probably the obvious thing to do because also we can compare new approach methods to anchoring in vivo animal data, 244 00:15:40.712 --> 00:15:43.814 so traditional data that we always used for risk assessment. 245 00:15:44.194 --> 00:15:47.816 So that's a kind of nice way to learn also about, 246 00:15:48.396 --> 00:15:52.819 to gain some more confidence about these new approach methods and how they are performing. 247 00:15:52.859 --> 00:15:55.060 So that's a very nice way to learn it. 248 00:15:55.516 --> 00:16:01.782 And then I think the next midterm achievement will be that we can probably use it for screening and prioritisation of compounds. 249 00:16:02.143 --> 00:16:07.067 So just identifying those compounds that are a little bit more hazardous and those that are non-hazardous. 250 00:16:07.128 --> 00:16:08.649 And this is a challenge on its own, 251 00:16:09.009 --> 00:16:10.010 but we are working on that. 252 00:16:10.491 --> 00:16:15.256 And I think the long-term goal is still the refinement and reduction of animal testing. 253 00:16:15.676 --> 00:16:19.660 And here this is something that we all would like to achieve. 254 00:16:20.104 --> 00:16:25.207 But I think here we have a lot of more steps to do and we will probably not solve this in the next six years, 255 00:16:25.267 --> 00:16:25.627 I think. 256 00:16:25.907 --> 00:16:26.207 As well, 257 00:16:26.207 --> 00:16:33.011 a very critical element for the regulatory acceptance is actually exposing our risk assessors, 258 00:16:33.091 --> 00:16:33.732 our experts, 259 00:16:33.912 --> 00:16:35.392 to this kind of data. 260 00:16:36.033 --> 00:16:37.273 In the scientific literature, 261 00:16:37.293 --> 00:16:39.395 there is a lot of evidence and a lot of discussions, 262 00:16:39.435 --> 00:16:43.737 but actually almost none of this evidence was phasing out when, 263 00:16:44.017 --> 00:16:44.557 for example, 264 00:16:44.798 --> 00:16:48.319 Risk Assessment Committee is deciding about classifying substances. 265 00:16:48.880 --> 00:16:48.1000 So what we are aiming at is that by now introducing those molecular measurements as routine techniques within the toxicity testing, 266 00:16:57.706 --> 00:17:02.129 we will by nature start to expose our experts to this data more often. 267 00:17:02.469 --> 00:17:06.712 So they will be able to build their own confidence and their own understanding how it can work. 268 00:17:07.473 --> 00:17:17.760 And then it will be much easier in the future to change the system because people will already have some experience in using this data in the practical decision-making. 269 00:17:20.470 --> 00:17:21.211 That's a great point. 270 00:17:21.311 --> 00:17:24.734 Getting risk assessors familiar with these new types of data is so important. 271 00:17:24.734 --> 00:17:28.697 It sounds like by integrating omics data into routine testing, 272 00:17:29.238 --> 00:17:30.779 you're not only advancing the science, 273 00:17:30.879 --> 00:17:32.501 but also easing its way, 274 00:17:32.901 --> 00:17:33.381 one could say, 275 00:17:33.441 --> 00:17:38.346 into regulatory acceptance by making it a part of the everyday decision-making process. 276 00:17:39.006 --> 00:17:44.411 Could you talk a little bit about the kind of cooperation between other EU institutions and how this feeds into your work? 277 00:17:45.011 --> 00:17:45.452 Of course. 278 00:17:46.192 --> 00:17:46.452 Silvia, 279 00:17:46.472 --> 00:17:47.033 would you like to start? 280 00:17:47.033 --> 00:17:47.333 Yeah, 281 00:17:47.353 --> 00:17:47.994 I'd like to start. 282 00:17:48.054 --> 00:17:50.536 So at the moment there are several initiatives around. 283 00:17:50.596 --> 00:17:54.420 So we have the huge cluster of three European projects, 284 00:17:54.440 --> 00:17:55.621 which is called ASPIS. 285 00:17:56.162 --> 00:18:02.007 And here we are working on the integration of new approach methods for different endpoints like systemic toxicity. 286 00:18:02.147 --> 00:18:03.188 So when you have, 287 00:18:03.188 --> 00:18:03.589 so to say, 288 00:18:03.589 --> 00:18:07.753 an exposure to a compound over a long time and it causes some type of toxicity, 289 00:18:07.853 --> 00:18:08.674 that's our question. 290 00:18:09.134 --> 00:18:10.736 And we want to develop an... 291 00:18:12.356 --> 00:18:15.059 it's called integrated approaches to testing and assessment. 292 00:18:15.059 --> 00:18:18.161 So we want to develop an in vitro and in silico testing battery. 293 00:18:18.261 --> 00:18:25.426 So we want to use cell lines and cell models to infer toxicological properties in the end, 294 00:18:25.566 --> 00:18:26.807 probably also to predict them. 295 00:18:27.568 --> 00:18:31.831 And we integrate them together because not only one cell line can tell us everything, 296 00:18:32.191 --> 00:18:35.594 but you have to have different bits and pieces to make this happen. 297 00:18:35.874 --> 00:18:37.896 So this is one huge activity. 298 00:18:38.336 --> 00:18:41.237 And here we are already working together with three different projects. 299 00:18:41.237 --> 00:18:43.138 And then we have the PARC consortium. 300 00:18:43.198 --> 00:18:45.919 This is another huge European initiative. 301 00:18:45.939 --> 00:18:51.102 And here we are working on an international level together with authorities and academia and we have different types of toxicological properties that we want to work on. 302 00:18:55.703 --> 00:18:56.684 But it's the same idea. 303 00:18:56.704 --> 00:19:01.806 We also want to use NAM data to do risk assessment in the end 304 00:19:01.886 --> 00:19:04.027 and also these two are already collaborating. 305 00:19:04.107 --> 00:19:05.788 And then we also have EFSA. 306 00:19:06.408 --> 00:19:15.814 And EFSA has also funded some interesting projects about how to best use NAMs for food and feed safety. 307 00:19:16.475 --> 00:19:19.237 And we are also working on the same types of questions. 308 00:19:19.257 --> 00:19:21.118 So what is the minimal scope? 309 00:19:21.258 --> 00:19:25.861 What do we have to do as a minimal type of testing to come to a conclusion? 310 00:19:26.302 --> 00:19:28.803 And is this safe enough in the end? 311 00:19:29.724 --> 00:19:30.905 And maybe as well to add, 312 00:19:31.365 --> 00:19:31.825 of course, 313 00:19:32.426 --> 00:19:33.266 being realistic, 314 00:19:33.346 --> 00:19:35.288 we will never reach the full 315 00:19:35.288 --> 00:19:35.688 100% percent alignment between different agencies or different member states simply because our legal frameworks are working slightly different, that there is slightly different logic behind the system and slightly different need. However what we already identified last year and what we are now working quite hard with EFSA is to really agree what 316 00:19:55.746 --> 00:20:01.792 are the commonalities for example how and there are commonalities for example how we are characterising hazard is common, 317 00:20:02.312 --> 00:20:04.554 regardless whether we are talking about biocides, 318 00:20:04.614 --> 00:20:06.056 pesticides or REACH chemicals, 319 00:20:06.076 --> 00:20:09.239 we need to characterise hazard and we are doing it more or less in the same way. 320 00:20:10.199 --> 00:20:21.089 We are already aligning our views on how it should be done in the future and in addition we are already looking for how we can use our initiatives to combine them, 321 00:20:21.690 --> 00:20:24.212 to use the synergies. And just to give you an example, 322 00:20:25.814 --> 00:20:28.296 EFSA was working for many years to develop 323 00:20:28.480 --> 00:20:29.962 toxicokinetics platforms, 324 00:20:30.142 --> 00:20:36.748 toxicokinetic solutions and different models because they're needed in many different applications. 325 00:20:37.109 --> 00:20:39.551 We've been not so active with toxicokinetics, 326 00:20:39.852 --> 00:20:42.995 but now we have as well very concrete needs regarding the toxicokinetics. 327 00:20:42.995 --> 00:20:48.160 So we basically now will use the EFSA platform to develop REACH specific solutions. 328 00:20:49.208 --> 00:20:49.828 And the same, 329 00:20:50.409 --> 00:20:52.630 we started this initiative about the sampling, 330 00:20:52.650 --> 00:20:56.151 so the guidance of best practices for sampling for omics, 331 00:20:56.251 --> 00:21:01.593 and then now we are as well introducing it to the test guideline development programme to endorse it. 332 00:21:02.034 --> 00:21:02.314 And then 333 00:21:02.694 --> 00:21:05.475 EFSA will as well directly benefit from that, 334 00:21:05.495 --> 00:21:16.060 and they are already investigating how they can already request certain extension of the traditional study to use it directly in their decision-making system. 335 00:21:16.640 --> 00:21:16.760 So... 336 00:21:17.060 --> 00:21:21.964 we are already identifying those synergies and we are trying to really work together towards this. 337 00:21:23.005 --> 00:21:26.007 I think there's another example where you can collaborate a lot. 338 00:21:26.147 --> 00:21:27.989 So I think also on data sharing, 339 00:21:28.009 --> 00:21:36.055 I think you started collaboration and it would be really brilliant if we could share all the available data on a European level, 340 00:21:36.115 --> 00:21:36.996 not only in IUCLID, 341 00:21:37.036 --> 00:21:42.260 but in a really standardised database to develop better models for risk assessment. 342 00:21:42.812 --> 00:21:55.198 And then of course there is another dimension because whenever we are talking about regulatory hazard and risk assessment we have to remember the OECD level which means basically you know mutual acceptance of data. 343 00:21:55.258 --> 00:21:59.780 This is the concept that if you will do the toxicity testing in any of the 344 00:22:00.400 --> 00:22:04.662 OECD member states it will be accepted in others in the same regulatory context. 345 00:22:04.682 --> 00:22:08.404 So basically if we really want to move forward this 346 00:22:09.752 --> 00:22:10.872 animal-free approaches, 347 00:22:10.992 --> 00:22:14.674 we need to do it as well at the OECD level together with our partners from US, 348 00:22:14.734 --> 00:22:15.094 Canada, 349 00:22:15.194 --> 00:22:15.534 Japan. 350 00:22:16.014 --> 00:22:25.757 Because otherwise we will end up with different solutions in different jurisdictions and again registrants will be very confused what to follow, 351 00:22:25.817 --> 00:22:26.457 how to do it. 352 00:22:26.997 --> 00:22:36.020 And so that's another very important layer of collaboration and even here majority of those projects have as well the OECD components already. 353 00:22:36.040 --> 00:22:36.940 So we want to fit 354 00:22:37.572 --> 00:22:41.795 outcomes from those collaborations into the OECD discussions which we're having at the moment. 355 00:22:42.395 --> 00:22:43.476 That's really encouraging to hear. 356 00:22:43.536 --> 00:22:50.221 So the fact that these efforts are being mirrored across these different projects and organisations shows how widespread the commitment is. 357 00:22:51.101 --> 00:22:55.424 The collaboration between agencies like the European Food Safety Authority and us at ECHA, 358 00:22:55.825 --> 00:22:57.706 and even on a broader international scale, 359 00:22:58.006 --> 00:23:01.649 I guess is key to making sure these new methods aren't just developed in silos, 360 00:23:01.709 --> 00:23:04.711 but can then be applied across the board and globally, 361 00:23:05.491 --> 00:23:06.132 on a global level. 362 00:23:06.792 --> 00:23:07.352 Before we end, 363 00:23:07.372 --> 00:23:08.353 in one sentence, 364 00:23:08.433 --> 00:23:11.754 what would you say will be different after the consortium has carried out its work? 365 00:23:11.874 --> 00:23:12.935 What will concretely change? 366 00:23:13.495 --> 00:23:14.535 In one sentence? 367 00:23:14.655 --> 00:23:14.956 Okay. 368 00:23:15.196 --> 00:23:15.336 Well, 369 00:23:15.336 --> 00:23:16.636 it doesn't have to be one sentence, 370 00:23:16.676 --> 00:23:17.917 but as shortly as possible. 371 00:23:17.957 --> 00:23:18.637 What's the vision, 372 00:23:18.737 --> 00:23:19.177 basically, 373 00:23:19.197 --> 00:23:20.138 for when the work is over? 374 00:23:21.018 --> 00:23:21.138 Yeah, 375 00:23:21.158 --> 00:23:29.982 the vision is that we gain more confidence in the new approach methods and we also work on concrete steps to implement them in regulatory risk assessment. 376 00:23:30.002 --> 00:23:34.444 And I think this is a fruitful way to do this in this close cooperation between 377 00:23:34.928 --> 00:23:36.008 industrial partners, 378 00:23:36.108 --> 00:23:38.189 academia partners and authority. 379 00:23:39.069 --> 00:23:39.209 Yeah. 380 00:23:39.969 --> 00:23:40.390 And for me, 381 00:23:40.470 --> 00:23:41.850 I think what I see, 382 00:23:41.930 --> 00:23:48.832 what can happen by the end of the six years is that we will really build the foundation for the new system. 383 00:23:48.952 --> 00:23:50.372 It will be not yet new system. 384 00:23:50.412 --> 00:23:53.113 It will be not even the beginning of the new system, 385 00:23:53.153 --> 00:23:56.974 but we will have a strong fundament to start thinking about the new system. 386 00:23:59.375 --> 00:24:01.195 And that brings us to the end of our episode. 387 00:24:01.456 --> 00:24:02.936 It's been a pleasure having you 388 00:24:03.136 --> 00:24:03.596 all here. 389 00:24:03.697 --> 00:24:04.557 Very heavy stuff, 390 00:24:04.657 --> 00:24:05.518 but very interesting, 391 00:24:05.538 --> 00:24:05.918 I'm sure, 392 00:24:05.938 --> 00:24:08.200 especially to our scientific audiences. 393 00:24:09.341 --> 00:24:09.842 To conclude, 394 00:24:09.842 --> 00:24:10.062 I'd say that it's clear that the work being done by this consortium through this project could very well help lay the groundwork for a future where new approach methodologies are both widely accepted and actually implemented then in regulatory settings. 395 00:24:23.753 --> 00:24:24.113 Of course, 396 00:24:24.153 --> 00:24:28.437 then hopefully reducing animal testing and enhancing safety assessments. 397 00:24:29.277 --> 00:24:30.879 So as Sylvia and Tomasz highlighted, 398 00:24:31.179 --> 00:24:32.140 while we're not there yet, 399 00:24:32.440 --> 00:24:37.426 the foundation that is being built is vital and a key part in this whole picture. 400 00:24:38.327 --> 00:24:40.790 Thanks again to both of you for sharing your expertise. 401 00:24:40.930 --> 00:24:42.552 And thank you to you for listening. 402 00:24:44.374 --> 00:24:46.076 Safer Chemicals Podcast. 403 00:24:46.797 --> 00:24:48.920 Sound science on harmful chemicals.