Getting a grip on environmental persistence – Irene Bramke, AstraZeneca

What happens to the chemicals we use in everyday life once they enter the environment?

In this episode, I am joined by Dr. Irene Bramke, Senior Environmental Risk Assessor at AstraZeneca. 

Irene and I have a detailed discussion about persistence (how long it takes for chemicals to break down in the environment). With recent concerns around plastic pollution, PFAS 'forever chemicals', and broader sustainability goals, the persistence of chemicals in the environment has become one of the most urgent and pressing issues for policymakers and society.

Irene and I discuss the science behind persistence, and how it relates to the risks chemicals might pose to people and the environment. We also talk about recent regulatory developments in Europe, and how these are reshaping the future of chemicals management. 

Our conversation covers:

• Irene's background and career journey
• Grappling with complexity - insights from studying soils in an agrochemicals company
• Industry's participation in regulatory science - then vs now
• Issues of environmental relevance in laboratory biodegradation testing
• The evolving policy landscape for persistence
• Non-degradable chemicals and the legacy P/vP criteria
• In the eye of the beholder - the meaning of word 'persistent'
• Implications of new policies - the PMT/vPvM hazard classes
• A troubling outlook - data gaps, transformation products, and questionable impact assessments?
• Reflections on OECD simulation tests as tools for persistence assessments
• Insights from AstraZeneca's Ecopharmacovigilance programme
• The importance of data quality in monitoring efforts - the CREED approach
• Shifting regulatory paradigms - hazard assessment vs risk assessment, and the need for continuing dialogue
• Can we get better at assessing persistence? High-throughput and predictive methods

PBT/PMT assessment of active pharmaceutical ingredients - ScienceDirect

Environmental fate and effects assessment of human pharmaceuticals: lessons learnt from regulatory data | Environmental Sciences Europe

Overcoming challenges and advancing (bio)degradation guidelines: OECD TG309 revisited - ECETOC

AstraZeneca - EcoPharmacoVigilance Dashboard

Using environmental concentration exposure datasets in environmental assessments: The development of Criteria for Reporting and Evaluating Exposure Datasets (CREED): Integrated Environmental Assessment and Management

HOMEPAGE - imi-premier

Modernizing assessment of persistence and transformation products of chemicals – from new tools to implementation (23-October 24, 2025): Overview · HIFIS and Helmholtz Events (Indico)

Visit my website for more content and insights www.embarkchemical.com

Transcript

Chris 0:01

The issue of chemicals in the environment is a story about science, politics, and humanity's relationship with the planet. My name is Chris Hughes, independent scientist, and this is the Chemical Journeys Podcast. Join me as we uncover the story of chemicals in the environment through conversations with individuals working in this space. So, let's get started. Hello everyone and welcome to the Chemical Journeys Podcast. Today I'm speaking with Dr. Irene Bramke, who is a senior environmental risk assessor at AstraZeneca. Irene, thanks for joining me.

Irene 0:45

Thanks for having me, Chris. I will admit straight away that I'm slightly nervous because I'm, of course, familiar with your podcast and I've listened to past episodes, and I find myself in highly illustrious company here, so thank you for having me.

Chris 0:58

Oh no, not at all. You're obviously an expert in environmental fate and risk assessment of chemicals, and you've worked across multiple sectors as well. Whenever we've spoken at SETAC, I've always had really good conversations with you. We talk a lot about topics like persistence and the regulatory frameworks of chemicals. So I'm really glad that you've agreed to join me on the podcast. So perhaps it'd be good, first of all, if you could just tell the audience a little bit about your background and your career journey so far.

Irene 1:29

Oh dear, okay, you're taking me back. Right. Let me think. So I'm German originally, so I was born in the German Democratic Republic, so many years before the German reunification, and I had a primary and secondary school education very much rooted in science. I then did my first degree at Humboldt University in Berlin in the 1990s. And again, that curriculum was still very much structured to equip young graduates for any career in natural sciences. So it was very broad. There was a lot of chemistry and physics and maths, specifically in the first year of my degree, presumably to scare the softies that were just heading for biology away. But it didn't work. So I finished my degree and it included a year in research, which I did at the Max Planck Institute for Molecular Plant Physiology in Potsdam-Golm. And I caught the lab bug. So I loved working at the bench and conducting experiments, and I thought that that was going to be my career for ever after. I then had the opportunity to be an Erasmus Exchange student and went to Imperial College in London for six months and fell in love with the UK and decided that I really would like to come back and earn my PhD at a UK university. And I did that, and by 2003 I had achieved that and had also settled in the UK, so I decided to stay. And with a few detours in 2009, I then started as a postdoc on a postdoc position at Syngenta, so a pesticide company. Within a year, I managed to get myself a permanent position there, which was then my route into environmental risk assessment. My background until then was very much in genetics and plant physiology and microbiology and things like that. A tiny touch of medical research on the way somewhere, but really that industry position with the postdoc as an entry point, that was my life for the next 10 years, which I enjoyed very much. And then we, my family and I decided to relocate out of the UK and we're now living in the Netherlands, and then that then precipitated a need to find job positions elsewhere. I became a homeworker, and since February 2020, I've been working as an environmental risk assessor at AstraZeneca. And that's me in a nutshell.

Chris 3:57

Wow, that is really a very interesting course and a very international course. I guess it's quite common for people working in this field to live and work in many different countries. It's interesting as well that you you completed your PhD in 2003 and then you joined Syngenta as a postdoc in 2009. So you've obviously been through that kind of working as an academic for a number of years and then making a transition to industry. I hear that discussed a lot these days. Do you have any reflections about it?

Irene 4:27

Yeah, I've been actually reminiscing about that. I did, I picked up a little bit of a postdoc contract straight after my PhD, still at Royal Holloway University of London, which allowed me to write my PhD up and sort of stay in the laboratory research area. But I then found myself looking for the next opportunity. And I applied for a role as an application scientist in a startup company. They were called Genetics, and they were building picking robots for medical research. I remember this interview ever so well, and I was asked by the interviewer, why do you want to come? Why do you want to leave academia? And you know, being young and energetic, I said, in academia, all the wrong people get the wrong jobs for the wrong reasons. The interviewer was a bit taken aback, said that's very strong. But I had by then really reached a point where I felt academia wasn't for me. I wanted to working in an environment where there is a much more common sense of purpose in teams that are focused and goal-oriented, and there's a lot more direct reliance on each other and each other's mutual skills towards a specific goal. And that's exactly what I found when I then did that switch from the academic world into the industry environment.

Chris 5:47

That's really interesting. And I guess it sounds like you've not looked back.

Irene 5:51

No, I have not looked back. I uh and I haven't even looked back when I left the lab, surprisingly, right? So in my first job, I was still at the bench, still, you know, doing wet science, if you like. And even as the postdoc then at Syngenta, you know, I was still conducting experiments. But when I then was offered the permanent position there, you know, that there was very little then that still allowed me to be in the lab. And I was very nervous for a while, thinking I wouldn't know who I was if I wasn't working at the bench. But I've always sort of focused on what are my transferable skills? What is it that I am good at? What is it that I can do that helps, you know, a a smaller group of people to achieve their goals. So I haven't looked back, no.

Chris 6:35

No, that sounds it sounds like an evolution over time as well. I mean, some people say I was sick to death of the lab, and maybe for you the lab was kind of your having the tools and things at your disposal gave you that kind of confidence and that comfort, and you eventually grew beyond that.

Irene 6:52

Yes, definitely. And it it's helped me to shape my thinking and to be very analytical and ask lots of why questions and be open to surprises and understand that things are complex. If you come into environmental science from an entirely theoretical point of view, you might make the mistake of thinking certain things are easy or predictable or like in the textbook, and they're just not. That bit of my career has also given me a deep respect for the skill of people conducting the actual experiments. The reproducibility, the diligence, the note-keeping, the critical thinking, all of those things that sit behind that should never be underestimated.

Chris 7:35

Yes, no, that's very true. I'd like, if possible, we could then move now into your time with Syngenta. And when we were talking about this podcast and what we would talk about, we did sort of gravitate towards the topic of persistence, and you said it was a hobby of yours as well. So it'd be great if you could tell us a bit about your experience with that while you were at Syngenta and how it all evolved.

Irene 7:57

Yeah, it was an incredible journey and a super opportunity. So the postdoc role that I was offered was to investigate the difference between observed degradation of you know these substances in a laboratory environment versus a field environment. So this was the this was the time when the PBT criteria had come in and certain pesticides lost their uh their market, if you like, because they they just weren't sufficiently environmentally labile and people started building up really big concerns about environmental persistence. Um and it was also a time where the regulatory studies, so the OECD 307 studies specifically, you know, people had gathered a lot of experience with how can to conduct these studies, had learned a lot about how they need to treat the soils that they put into these test systems and all the things that can affect the success of such an experiment. Um, but were also conducting field studies and there was this discrepancy. And it was really the the motivation of the company at the time was to bring someone in who brings the molecular skills to start thinking about how how can we unravel this. And and you know, at that time in the industry, there was still a lot of sort of willingness and scope on behalf of companies to engage with the scientific progress on this and sort of contribute to that endeavor of furthering the science in that place. And I was then handed an amazing opportunity. There was it was a little slush fund of money, and I was told, what you know, what we would like you to do is run a two-day workshop, ring up some academics in the field, see if they want to come in, and we can, you know, sit down and ask ourselves what is it that we're missing when we're conducting these studies that allows, that hampers us in predicting how our compounds then behave in the environment. So I I yeah with great relish, I threw myself into that and organized that workshop. As a colleagues who who were risk assessors in the organization, metabolism chemists who were conducting soil studies, you know, at Jealott's Hill in the laboratories there and in collaboration with the contract research organizations. And then, you know, academics from slightly complementary angles in the soil science research. So who did we have? We had Gary Bending, who's now a professor of environmental microbiology at Warwick University, Thorunn Helgason, who's now at the University of Edinburgh at the time in York, Wilfred Otten, who's a soil physicist, actually, so really complementary angle to trying to understand this, but also Liz Shaw, who's a professor at Reading University. And I had all of these academic brains who've built their careers trying to tackle this fascinating topic of microbial diversity in soils and how that interlaces for degradation in a room where we're the why questions, but why is this happening? But how is this, does this work? And it's opened my eyes to, you know, the amazing environment that we're dealing with when we're conducting persistence assessments specifically in soil. So, you know, things like the incredible biodiversity in that, you know, 50,000 different species of bacteria, between 10 and 100 meters of fungal hyphae, so a network of mycelium and just a gram of soil. So you pick up a handful of soil and you've got a universe of life in there and metabolic capability. But also that a soil is more like a sponge than a solid, right? It has these pore systems in there, and with evapotranspiration, water moves in and out of these pores, which obviously does a lot for the bioavailability of any compounds that are in there, the accessibility for degradation. So I found all of that fascinating, and it's just sparked a lifelong interest for I used to call this to think like a microbe, because it's not a scale that we're necessarily as humans are used to thinking about, right? It's just dirt, but it isn't. So that's how I started getting interested in degradation behavior and all the factors that influence how a compound degrades at that time.

Chris 12:21

No, that's really fascinating. I think you touched on something there that when as scientists we're confronted with this all the time in our field, I think, in the environmental field, because we like to simplify everything down into concepts and just make straightforward predictions, like you say, but then you're constantly being hit in the face by the incredible complexity of the situation that you're analysing, like you said, and you know, soil is infinite in how we could look at it and analyse it and try to characterize it. You said quite a few really interesting points there that I'd love to explore with you. I think we could cover a lot of ground here, but you you mentioned there about industry having a willingness to contribute to scientific with the scientific enterprise in the ongoing development of of its work and uh I suppose with evolving regulations as well. Do you get a sense that that may have changed?

Irene 13:17

Yeah, it has definitely changed. Yes. So I think there was a lot of optimism of being able to, you know, like I said, contribute to the science, and then a lot of disappointment when the only direction of travel with the interpretation of the science and the outcomes of studies was towards greater and greater conservatism. And it's it sort of turned that that spirit of curiosity and and endeavor to understand the complexity of it all to a looking for the gap, right? So we can't pass this risk assessment. Risk assessment, what can we do? What refinement options do we have, right? So it's a different way of um thinking about the wider problem. And I think we've lost something. As a as a as a stakeholder landscape, we've lost something along the ways, right? And we all have our roles to play in this in this interesting triangle between scientists and industry, scientists and the regulatory authorities, and academic scientists. And you know, it's such a it's such a wide range of of scientific endeavor that is possible there. I any attempts of excluding part of that landscape from the conversation just baffles me. I don't understand, you know, there's so much room to play. And while we all need to remember what our role is in this stakeholder landscape, you know, as a scientist, we're all scientists, we just wear different hats. And it's important to remember in the conversations with each other who we are and what we represent in this landscape, but not to engage with all the brilliant scientific minds that we have in all three corners of this. I just it intrigues me where this is coming from.

Chris 15:12

Yes, yes. You know, this topic's come up a few times also on the podcast in terms of discussions around conflicts of interest and what do, sort of, do about that, but also this disengagement or this kind of demotivation on industry's part that they think it's kind of hopeless to try to engage on this because you know, thoughts are going to be dismissed or evidence is going to be thrown out. I think you're right. I've picked up those kind of signals as well, and maybe we'll get into some real examples of that when we talk about persistence because it has gone through quite an evolution itself, the whole framework and how it's used over the last 20 years. I wanted to ask you if you could go back to looking at the soils and looking at that discrepancy between lab and field. One thing that strikes me is that it's lucky in a way that in the plant protection sector you do such thorough evaluations of the active ingredients because then you were able to conduct experiments both in the lab and in the field and actually get sight of you know that there was a discrepancy there which would lead you to take pause with making decisions, say, purely based on lab data. And one thing that comes out to me is that we'd often do those kinds of experiments with other sorts of chemistries. So, what can we learn from plant protection products in this area?

Irene 16:31

Yeah, what I think lots of things were learned on the way and looking into that, right? Contributions from parts of that diversity in a natural soil which are lost in a laboratory study. So if you think about photosynthetic organisms sitting directly on the soil surface with some chemistries, they really form an important subgroup that contributes to the breakdown of plant protection products. Well, they're not in the regulatory studies, those studies are conducted in the dark, right? That's number one. Also, fungi have already mentioned the mycelial networks in soils and the contribution of fungi to that. There's, you know, there's huge diversity in soil uh fungal organisms and the metabolic capability that they have again isn't fully understood. But if you think about a laboratory study, those soils are taken out of their natural context. They're dried down to a certain extent because the guidance prescribes there must be sieved down to you know two millimeters sieves in an attempt of making these studies reproducible, but at the same time destroying organisms that under natural conditions would potentially contribute to that degradation. I've already also mentioned the pore structure. So soil pores, they're not there by accident. It is fungi, for instance, that actually terraform that microenvironment. And again, after you've sieved that soil, you know, that's just not the case anymore, right? So a lot of things are now known about that difference between the environment that a compound incurs if you put it into a regulatory study as opposed to under use conditions. And what it has led to is an understanding about the range of the variability of the breakdown half-lives that we're seeing. And it's puzzled a lot of people. There's a school of thought that says it's an inherent property of the compound, its persistence. And that just doesn't gel with then the observation in the real world that half-lives can differ by orders of magnitude. And that scares people, and it's obviously very difficult to square that circle when it then comes to making regulatory decisions. And I appreciate that. But I think as scientists, we are grown up enough by now that we have tools that can embrace that variability, rather than saying, Yeah, Chris, I'm always thinking if something degrades sometimes in some conditions, in some experiments, under field conditions, and in others it doesn't. I think that tells you something. And what it but in my view, it doesn't tell you that that compound is inherently persistent.

Chris 19:12

Yeah, yeah. Well, yeah, it's obviously got the potential to degrade because there it is, right before your eyes. And I guess that goes back to the point around conservatism of approaches and you know using a precautionary lens on decision making. You know, I've heard it before that it's about what proportion of situations you're protecting with your policy situation, and that was one of the reasons put forward for devaluing the use of sewage treatment plant simulation test data to evaluate substances because not all wastewater in Europe is connected up to wastewater treatment plants, for instance, they're using septic tanks or other things. You know, so that minority situation was then part of the argument to make a broader policy decision. So I guess this gets to the point that with a lot of this, it is policy-driven and values-driven rather than necessarily objectively science-driven.

Irene 20:14

Yes, and I appreciate that. And I need to always remind myself that you know policy decisions are aiming at not always at the same thing, right? So there are compounds that are ultra persistent, you know, something that a mentor in my past used to call brick dust, right? So things that really do not have any liability to environmental breakdown processes. But we need to, and we and we have ways of conceptualizing that and diagnose what those particularly concerning compounds are. But that is a long cry from a persistence criteria under REACH or CLP, right? So there are compounds being caught under that label of persistent or very persistent that actually do have a certain capacity to be broken down in the environment. When it comes to really understanding risk and identifying the compounds that we ought to be worrying about, a catch all like that isn't very helpful. Okay. And I think it's an important distinction to make to say this is a sustainability issue. We're building up trouble here for generations to come. These compounds are ultra persistent, they're going to not ever go away once we've put them into the environment, as opposed to we're trying to understand what the level of risk is under these specific use conditions. It's a different story. Some of the concern, the rising concern and that very lively, robust dialogue that we're having in this landscape at the moment, I see those as growing pains. I think I would like to think that as a species, you know, we're growing up and we're realizing we're making a hell of a mess and we should be better than that. Right. And it comes then when it comes to inventing new compounds and developing new compounds, it's a could we, should we question. Right. Just because we can do it and we can pass risk assessments and we have a good use case for the substance. Perhaps there are reasons why we shouldn't do that. Right? But it's a different it can't be one size fits all. It's a different consideration. And when it comes to understanding risk, treating something that has reasonable potential to be broken down in the environment needs to be looked at with that information in mind and not say leans toward the precaution and say, oh, this is just terrible and we shouldn't have it. And whatever use it has is no longer interesting.

Chris 22:44

Yes. It's amazing, I think, that here we are in 2025. We've been arguing about persistence and in particular the new hazard class of PMT and vPvM, the persistent and mobile chemicals. We've been arguing about that for uh seven years now, and we have new criteria in place which use the same frameworks, the same persistence assessment framework. And it does baffle me that we didn't really seem to probe that point around that persistence is not a binary thing. It's not a you are or you aren't persistent, it's a scale. It's about the duration that something hangs around. And yes, we had criteria in the regulation for persistence, but they were developed for this PBT framework for persistent bioaccumulative and toxic chemicals, and they were developed in concert with the criteria for bioaccumulation to address a specific concern which related to those kinds of chemistries. So it seems like the the dialogue, all the discourse around those new hazard classes, all the discussion around PFAS and whatnot as well, didn't make the connection that there's a difference between the criteria that we use in regulation for persistence and then this new concern of effectively non-degradable chemicals. And we needed to make that distinction, I think. You know, unfortunately, we also had very persistent criteria, which you know makes it sound pretty damn tough, even though it's only 50% more tough than the persistent chemicals. And the problem is you speak to different people, you say the word persistence of different people, it means a different thing. Like to the people experienced with policy, you know, the criteria kind of etched into our minds. But if you speak to people working on contaminated land, it means something completely different. And if you speak to a member of the public or a policymaker, it might be something totally different again. So yeah, uh, it feels like a missed opportunity to me.

Irene 24:40

If I couldn't agree with you more, and what you said about you know the the word meaning different things to different people, it does amazing me that it's actually become a dirty word. Persistence per se doesn't necessarily have to be a bad thing. If you talk to a soil scientist, they will tell you that soil organic matter, you know, there are some fractions that are incredibly persistent over millennia. And that that's a good thing because it locks away more carbon than is in the atmosphere and in current vegetation. So, you know, if if that soil organic matter wasn't persistent over millennia, we couldn't do agriculture and we would have a much greater global warming problem on our hands than we have now. So it always pays to take a step back and think about what is it that I mean when I make a certain statement and how is it understood by someone who comes from an adjacent field of science or perhaps isn't a scientist at all.

Chris 25:41

Yes, yeah, because we've had a wild few years in terms of the implementation of new policies and whatnot. To some extent, I think a lot of the decisions have already been taken and we almost have to live with the consequences now. So I'm thinking about these new criteria that have been introduced. We're now in this process of implementing those through the generation of new data and carrying out assessments, but I think it'll be a while before we see what the ultimate outcomes of that are.

Irene 26:06

Yes. And as you know, together with other environmental risk assessors and led by Gemma Janer, we've published last year a paper that actually tries to make a case that perhaps not all chemicals need to be tested for a hazard classification. That perhaps pharmaceutical compounds, for instance, present a special case because our use rates are dependent on regulatory approval, and the amounts of how much of an active pharmaceutical ingredient is going to be used, therefore it has a reasonable level of predictability. The order of magnitudes by which those consumption rates vary is nine or ten orders of magnitude. In our risk assessment guidance for pharmaceuticals for this very reason, we have a predicted surface water concentration limit above which a full risk assessment is required, and below which there's only limited assessment of those compounds for that very reason. It's an incredibly difficult conversation to have for some reason. But if you think about that at the bottom end of this distribution range, and incidentally, the range of toxicology or toxicological potential of those compounds is just as wide, also varies by roughly nine to ten orders of magnitude. There are compounds that are incredibly toxicologically of low potency and use incredibly small amounts. So at the bottom end of that consumption range, I've asked ChatGPT to help me work this out, is the four hundredth of a typical weight of a grain of table salt in an Olympic-sized swimming pool. That's the lowest use of a pharmaceutical. Now, to expend testing capacity and you know energy and money to evaluate the hazard properties of such a compound, is that warranted? Is that going to bring us any further given the very low concentrations that substance will ever incur in the environment? My sense is we have really good tools in place to focus on the corners of the chemical space that are concerning, that are used in high rates or are very unpredictable. There are brand new chemistries, but many chemicals have near neighbors already in existence where we do have some understanding of their properties. We have ways of prioritizing where we should be focusing our attention. The blanket requirement for everything to have data to assess against these hazard criteria doesn't seem to be um yeah, we don't seem to be doing ourselves justice about what we already are capable of doing.

Chris 28:51

Yeah, it does sound like a very good counter-argument in my mind to taking that blanket approach because in the end, we have scarce resources, you know, in an economy or or or human attention. We have scarce resources, and we're going to need to make decisions about how we apply those resources. And ultimately, in this study that you've laid out, this is about putting resources in the right areas so that we can best use them and come to decisions more efficiently and quicker ultimately. I'm assuming that on the other side of this, there's the potential for certain medicines to no longer be available on the basis of these rules, which are bringing benefits to people.

Irene 29:37

Yes, now you're opening an entirely new wide field of consideration, right? Um, how do we balance uh potential environmental risk against the benefit to the patient? Yes, that's a conversation that is uh only beginning, right? So we're expecting an upgrade to the pharmaceutical legislation, which will for the first time include environmental risk into the risk-benefit analysis and weigh exactly this assessment, weigh those vectors against each other. It's a conversation that is long due, no doubt, but it's incredibly uh difficult to uh make uh those choices in a responsible way, right? Because it's not good enough to think about these things in isolation. And really, if we're opening uh our eyes to this and we think about how those you know, how a given medicine with an environmental uh risk profile as we understand it is used and to what purpose, you know, then we are entering the science of care pathway analysis where we are asking ourselves what is the not just the benefit to the patient, but also what happens if that patient isn't treated with this medicine. Um are they going to deteriorate? Are they going to need much more frequent or much more carbon-intensive, let's call it, medical intervention through the course of their life? The tools to calculate that, to understand these impacts over the lifetime of a medicine's use. You were scratching the surface on that.

Chris 31:19

Yes.

Irene 31:20

Always the spectre of making regrettable choices in that space.

Chris 31:26

Yes. And I think there's a seemingly unique situation happening now in the pharmaceutical sector and how this is all coming together. But I guess it's a broad principle, isn't it? That the same situation is being applied to plant protection products, biocides, and industrial chemicals, that these new rules that are being applied, these hazard-based rules, are really agnostic to how a chemical is used and in what and in what tonnage, and as a result, there's a detachment from potentially the actual real exposure and risk, but also a detachment from the benefits to society that those chemicals bring. And I think that you know we can go on to the reasons why we're not really seeing the end destination very clearly today. We're making a lot of decisions today, and we don't really know where it's going to lead us in the end. We have well-meaning effort catalyzed by environmental challenges and also the broader sustainability movement, which I think has triggered a lot of questions around some things which were our kind of precepts before about how we make and use chemicals. Yeah. There's a lot of important decisions being made today. It could be quite impactful. I was struck, I think there's some estimates in that paper about how many substances could be identified as especially PMT or vPvM in the pharmaceutical sectors. It was quite a high number. I dug out a reference by, I think the German Environment Agency did a study, and they were saying that it was more than 50% of the APIs, the active pharmaceutical ingredients that they looked at were showing to be persistent or very persistent. I'm guessing a lot of those are likely to be mobile as well.

Irene 33:10

Yes, exactly. And then how do you weigh that information up against everything else? And what at the moment isn't envisaged, to then, you know, ask that very question: what is the inherent toxicological potential of these compounds and what are the likely use rates? Is this something, you know, like a paracetamol that, you know, a very large proportion of humanity are going to consume? Or is this potentially directed at a rare disease? Ignoring that information which is available at the point of marketing approval and simply focusing on a hazard criterion seems to me to be not scientific. And it's actually not aligned either with the overall mission statement of ECHA, for instance, you know, which is which you know, which says that their purpose is to identify potentially harmful chemicals, provide scientific opinions on how to manage their risks first and foremost, and then potentially to restrict the use of those chemicals, right? So something that doesn't hang together.

Chris 34:14

Yes, yes, yeah. I guess they've got a tough job at ECHA, they're handed this regulation, they have to implement it, and they have constraints from a legal perspective, and they almost get the marching orders, you know, before, I mean they do provide technical input to emerging policy as well, but once the policies are there, they have to implement them. And that's the same thing with industrial chemicals, the new hazard criteria of persistent, mobile, toxic, and very persistent, very mobile, or PMT, vPvM for short, they're here now in terms of that they're implemented in the CLP regulation. So chemicals should be being evaluated and classified according to those new hazards. But the reality is that there simply isn't the data available to do those classifications, neither for mobility nor the persistence. And one of my concerns is that we made that decision to bring those hazard classes in with a very poor view of how many chemicals would actually fulfil the criteria in the end. I understand that at the moment, when the chemical strategy for sustainability was announced, it said quite clearly in there that these hazard classes ultimately would find themselves their way into REACH as classes of substance of very high concern (SVHC). And if you're a substance of very high concern, then you're on the track towards phase out in Europe and you go through the authorisation process. So that seemed a clear statement of ambition in 2020. What I'm struggling to see now is is that still the plan? Will PMT and vPvM become new hazard classes under Article 57 of REACH? Because if they do, then that is major consequences. And when I look back at the impact assessments, the estimates were that between 1 and 3% of registered chemicals would fulfil these criteria in the end. And I just can't, you know, I really struggle to see how that those estimates are credible, given that we have very little simulation test data available, we don't have effective computational tools to predict these endpoints. The guidance that we use to evaluate persistence continues to evolve and become more stringent, and then most importantly, there's this whole issue of the transformation products of chemicals. So when they are degrading in the environment, they're transformed into different things, and if one of those transformation products meets the persistence criteria, then everything kind of rolls back up to the parent compound. And again, we had seemingly very little sight of how big an issue transformation products would be for these new hazard classes, given that when something is degrading, it's generally becoming more polar, which means it's going to become more mobile. So the likelihood that you're going to have a transformation product that is vPvM, so it doesn't even have to be toxic, seems very high to me. So yeah, that's another thing that's kind of troubling me at the moment.

Irene 37:25

Yes, I agree with absolutely everything you said. My sense is also that it's going to lead to some form of environmental hazard classification for a much, much greater share of compounds than that couple of percent that was envisaged in the first place. I don't want to make guesses exactly how many that is going to be. But I am very confident that it's not going to be helpful that level of classification. That's not going to be helpful in identifying and prioritizing compounds that really deserve very stringent regulatory attention and focus to prevent future harm.

Chris 38:08

Yes. And I think that the for the people that want to see more action on chemicals, I can understand their frustration because I think the progress has been slow, particularly on the REACH side, and there's also been this issue of data gaps and this seeming impasse because in 2020 there were fewer than 500 simulation tests available for REACH registered chemicals, and there's been a few new ones requested since. If you wanted to run this process through to its end, then there would be a lot more of these tests generated, but they're very expensive, technically challenging to run and to interpret as well. And that's another area that is related to persistence, where I think people are starting to question now as persistence becomes a more and more important property for the management of chemicals, both from a scientific interest and a policy perspective. I think it's shining a light on the issues of data gaps and also the robustness of the tools themselves. And you spoke there of the issues with soil studies and the environmental realism of some of those tests. And I've seen the same challenges identified also for the aquatic compartments, so the water sediment test and recently the OECD 309 test has been discussed quite a bit as well.

Irene 39:24

Yes. Oh dear. The OECD 309 test, right? It doesn't make any sense to me how one can hope to understand degradation in surface waters by just harvesting that surface water and putting it into a laboratory study. Surface waters are replenished in terms of their microbial degradation potential from the underlying sediment phase. You know, that is undeniably the case. So I really struggle with the scientific value of an OECD 309 study. An OECD 308 study, it's a water sediment study with the limitations of it being conducted at ambient temperature and under the exclusion of light. I think there's quite a bit of information that you can gain from a study like that. But as you already said, it's technically very challenging to do studies like that well. It requires radio labelled test items, particularly if you really need to also understand the breakdown products that are forming under those conditions. Um and it is at the end of the day, Chris, it is only part of the story, right? So in my role at AstraZeneca, I'm looking after the eco-pharmacovigilance program that we have. Jason Snape, who was on your podcast a few episodes back, was in charge when we initiated that program here at the company. I'm looking after that program now. And part of what we do conducting eco-pharmacovigilance for our substances is to gather data reported in the public published peer-reviewed scientific literature on environmental detects of our APIs. And so I have a very good view at on what levels active pharmaceutical ingredients that in my role I have responsibility for are being found in the environment. And you know, that tells me that it isn't simply determined by the persistence of a molecule, it is determined by many factors, and one of the key drivers in that are the use rates. It can surprise nobody that over-the-counter medicines that people are using are also found at higher concentrations in the environment. So you know, there isn't enough attention being paid, in my view, to uh the uh all the factors that determine environmental risk, and that environmental occurrence is determined by persistence and by use, and environmental risk then also needs to factor in the ecotoxicological potency of those compounds.

Chris 42:03

And it's even things like the receiving water and the dilution, right, that plays a huge role. The rate at which water is transported in a river can have a very big effect on removing the chemical from the immediate environment and out in the ocean. I suppose it all depends on the geography as well, right? And within Europe we have some very, very big rivers, but you know, the UK is to some degree a different story.

Irene 42:28

Well, and also not to forget the wastewater treatment infrastructure that is or isn't in place, right? So it took people by surprise that in environments that were considered reasonably pristine, you know, there were readily detectable levels of active pharmaceutical ingredients in those waters, but that's to do with lack of connectivity to wastewater treatment in certain rural and remote areas. So the other thing that's important to me, Chris, is when it comes to monitoring data, you know, we are still learning about how to do that well. A few years back in 2021, it was spearheaded by Graham Merrington from WCA, a SETAC workshop was instigated to come up with an assessment system for the quality and reliability, relevance and reliability of monitoring data. What came out of this was the CREED system, which we then went into great detail in a workshop in Copenhagen in 2022, you know, when we had all come just out of lockdown and were pleased to be with fellow scientists again. And this system was then published in 2024. And it what it is, is a tool to not only look at existing monitoring data and ask yourself can I use this for the purpose that I want to use it for? Is it relevant to what I'm trying to do and is it reliable? But it also allows you to record that decision in a transparent way so that others can then see how you've come to that conclusion. Then turning it on its head, it actually is a really good guide for someone. Who's been blessed with funding to conduct some environmental monitoring to make sure that they're designing their monitoring study in a way that that data really then has optimal usability at the end of the day, and also go to their funding body and say, yes, to do it well costs this much, these are the things that I need to do, otherwise, we're really wasting money generating information that's no use to anyone.

Chris 44:24

Yeah, I know, because there's tons and tons of monitoring data starting to be generated now, and that's giving us a lot of new insights about chemicals and the environment, and we need to try and make sense of all that. But like you say, the quality of that information is really, really important, and sounds like CREED did uh made really good steps to focus on that aspect and help to move the whole enterprise forward.

Irene 44:50

So, you know, I'm having lots of conversations about these topics with people in the field and outside of the field, and what strikes me is that often there's a perception that the problem comes from elsewhere. Right? It's always easy to speculate what regulators aren't doing, or what academic scientists are looking at or choosing to look at, or what industry may or may not be doing. But I think we would all be better off as individual scientists to remember what is it that I actually know and understand well, and am I scrutinizing my own level of understanding or am I taking someone else's word for it? You know, have I extrapolated beyond my area of expertise? Should I go and learn some more about this? And and if my curiosity pinches me, should I then maybe take the time to follow down that route and really learn some more? Or you know, what valuable conversation can I have with someone in another stakeholder group working on a similar problem to get their point of view? Because I don't see how else we can really tackle these complex problems in a way that takes us forward.

Chris 46:06

Yeah, I I think when you describe the evidence that there are other things that are as or more important to ultimately the concentrations of these chemicals that are being found in the environment and thus the exposures and the likely risks of those compounds. That surely should give people pause to become so fixated on one specific property at the expense of other things. I mean, it's it's fine, I think, to increase the effort to try to understand environmental persistence because I think it's been a property that has been overlooked for a long time. Um, but are we at risk of actually having a regrettable outcome, as you say, an unintended consequence of the way that policy is evolving, especially within Europe?

Irene 46:57

Yes. I I very much share that concern when I do get gloomy about the state of the world. I always try and dial it back to what is within my you know zone of influence and what is it that I can learn more about and communicate better about to do my little bit to contribute to this conversation.

Chris 47:20

Yes, I mean, well, you certainly do like to have a conversation with people when we're at these events, which I think that is part of the grassroots activity, that the bottom-up activity that is so important, but perhaps also gets neglected, is talking to people and having those opportunities to meet face to face and to have discussions and perhaps challenge each other's ideas. Do you see that enough people are having those kinds of discussions in those different fora to try to hash this out? I get the sense that five years ago, during perhaps the height of COVID and also the height of the chemical strategy and the the so-called green wave in Europe, that the whole kind of concept of risk assessment took a beating, and people have almost given up on defending it as a means of managing the use of chemicals. And something that occurred to me was that our society has evolved over the last decades through the technological progress that's brought us all these different chemicals that we use in daily life and all these different benefits that they bring, and underpinning that has been this risk assessment paradigm that has been used. But more and more now we move towards this sort of hazard-driven approach, and and that's that's you know, ultimately that's that's likely to lead us to you know having access to fewer chemicals in the end, and and you know, do people fully understand that? I wonder whether a lot of the underpinning assumptions of the development that we've had, you know, they're not self-evident and that they need to be reiterated or you know, people need to be brought up to speed. And one example is that I don't think it's a very well-known fact that we use and emit these chemicals to the environment and that people will get exposed to chemicals in their daily lives, you know, within the public's awareness, let's say. And that I think is another source of some of the alarm and potentially less than great policies emerging off the back of that.

Irene 49:16

Yes, and and one of the things that I'm observing, so there are definitely still pockets of um opportunity to have tripartite conversations, right? So SETAC conferences are where you and I have spent time talking to each other, are one of those places that still make room for those conversations. But also, for instance, the PREMIER project that you know AstraZeneca co-leads together with Radboud University and that includes academic partners and EFPIA companies and in the same conversation, which are about exactly this need to prioritize the focus for pharmaceutical ingredients that in terms of their level of concern in the environment, right? So those pockets that allow dialogue still exist, right? And it is about trust and respect that enables those conversations, right? I trust you, whichever uh part of the stakeholder landscape you're coming from, that you you come with good intentions, and we've had an opportunity to build this trust, and we've had the opportunity to learn about each other's experience and knowledge that builds respect, right? And only on that basis can those difficult conversations be had. I am very much concerned that we lose opportunities more and more, but we have to stay optimistic that we can continue to grow and evolve.

Chris 50:43

Yeah, no, I hope so. And I hope we can end this podcast on a positive note as well, because it's not all doom and gloom. But then that, you know, there are also some things that that are quite concerning. And I think the thing for me is that the end destination is so unclear and potentially severe in terms of the decisions that we make today with our rational thinking when we're coming up with a decision about how to deal with one particular situation, then that forms a precedent that then gets applied to lots of other things. I wondered if we could swerve away from this topic momentarily to how can we get better at assessing persistence? And I think you'd mentioned to me previously that part of this is about improving our means to predict persistence, and we can use that in different contexts from designing new chemicals through to regulation, but there's certainly an opportunity there to improve our methods both experimentally and computationally to try to better forecast persistence.

Irene 51:58

So I've I've traveled with this question for quite a while, right? So when when I joined Syngenta, this was the beginning of the realization in that industry that ultra-persistent substances were not going to developed at that time, were probably not going to deliver a return on investment. So from a business point of view, there was rising clarity that that was not a wise choice for R&D to develop compounds like this. And as a consequence of this recognition, there was a willingness to invest in a screening tool to direct the R&D effort into areas of a chemistry that were less at risk of being ultra persistent in the environment. Right. So it was what was called RASP Rapid Assessment of Soil Persistence tool, a two-week turnaround and five grams of soil to compare compounds in terms of their persistence, right? With a full understanding as to the limitations of that. So this was about generating rank orders of candidate compounds under considerations in the R&D project and feeding that information, you know, this direction, not so great, persistence is a bit high. How about we look over here? So this isn't about telling R&D projects you can't make that, you can't have that. That's a red flag. That's not what it is all about. It is about changing the direction of the super tanker that is an industrial R&D process into a direction with greater chances of success. Okay. So in the pesticide space, there's actually data available to these companies because they've been doing this for years now on their chemistries to have built predictive models on the basis of that data that allows them to do that very reasonably successfully in silico now. So in the pesticide space, that information exists and it underpins predictive tools and is used to direct R&D. In the pharmaceutical industry, we're not in that position. The testing for persistence is still almost exclusively done in support of marketing authorization applications. So when we need to construct an environmental risk assessment, when we go to the regulatory authorities and apply for approval for a substance. This richness of data and the applicability domain of the predictive tools that were developed for pesticides, it doesn't quite fit the chemical space for pharmaceuticals. There are some subtle differences between those two groups of compounds. So as a result, the pharmaceutical industry can't actually do that make that effort at the moment to inform their R&D projects about the potential environmental degradability of the substances that they are pursuing, because we don't have the predictive tools and we don't have a wealth of data that we're already sitting on. Predictive tools are uh developing and the science in that space is moving on as well. So at the moment, I'm looking after a young PhD student currently in her first year, Roisin Murphy. She's looked after by Helen Sneddon, professor of sustainable chemistry in York. And she's going to sort of uh for the course of her PhD use machine learning skills to try and make progress with this. So again, this isn't done in isolation. You know, there's obviously a lot of academic collaboration in that space. But my concern remains that without having a much more significant set of degradation data, and in the case of our industry, it isn't soil, it is really wastewater treatment sludge, that it sort of is the compartment of interest, without a much more robust and broad data set reaching across the chemical space of pharmaceutical ingredients, you know, we will always be hampered in that space. But like I said, I'm trying to do my little bit in that direction and looking forward to what the future brings in that space.

Chris 56:08

Yeah, that sounds really interesting. And this kind of conceptual challenge of first of all obtaining data that we can use, but then finding out what how we can make sense of that data and use it to predict the properties of chemicals. Whilst very advanced in some areas, it seems like we've got some work to do in the persistence space and that should keep us busy for some time. I think part of the challenge as well with industrial chemicals is that we've been heavily dependent on these screening tests, so ready biodegradability tests, which I guess not so much in plant protection products and in pharmaceuticals, but certainly they've been the bread and butter for industrial chemicals. But what we're finding now is that you're fine to use a ready biodegradability test to show that a chemical is not persistent. You know, if it passes that test, then it's considered not persistent. But what do you do with all the chemicals that don't pass that test? And we kind of have this big question mark over all those chemicals now. And I think it goes back as well to some of the challenges with the simulation tests, the paucity of data, and also the cost to generate the data using some high-throughput or miniaturized designs seem to be where people are looking now. And there's this workshop coming up in Leipzig related to this as well on modernising assessment of persistence. So I think that should be an interesting event as well. Seems to have come out of nowhere, I have to say. This suddenly, you know, we've had 15 years worth of reducing and a reductionist approach with our persistence framework saying, no, you can't do that, and let's refine the guidance here and let's make this part more conservative. And then all of a sudden, there's this real uh seemingly a realization, you know, also amongst the regulators, and this seemingly renewed openness to look at different ways to address this property.

Irene 57:59

Yes, it's super exciting, right? I saw that too. I have great hopes that that is a light at the end of an ever-narrowing tunnel that we've seen seem to have looked down over the past years, that maybe there is an opportunity to re-engage and think more scientifically about this.

Chris 58:16

Yes. Well fingers crossed, and yeah, really look forward to seeing the work of Roisin, your PhD student, in the years ahead. I think that's a really important piece of the overall puzzle. Irene, we've really kind of been around the houses in our discussion here, but it's been really, really nice, and it's great to speak with a fellow biodegradation and persistence sort of enthusiast because there aren't so many of us, but seemingly, as we've said, this this property is becoming more and more impactful, and it has infinite challenges and questions and complexity sort of underpinning it. So thank you very much. I normally have two questions at the end of the podcast. So if there's time, I'll ask you first of all, what's a big goal that you're working towards in the months ahead?

Irene 59:07

So I've already mentioned the PREMIER Project, which is you know funded by the Innovative Health Initiative, which has been very active and very successful over the past years. It's coming to a conclusion next year. So we're going to have the final General Assembly meeting next summer. So it's all hands-on deck. And as always, in big projects, this is where all the strands come together. And yeah, so I'm very much looking forward to seeing those final deliverables on that project coming out.

Chris 59:35

Can I ask quick, is there a specific part that you've worked on?

Irene 59:39

Yeah, so in one of the work packages, we were looking at sustainable by design approaches specifically for active pharmaceutical ingredients and have developed some very detailed concepts on how one might go about persuading a pharmaceutical company to consider environmental properties for active pharmaceutical ingredients in development right from the get-go of the research effort. And that was really, really good fun. I was able to apply certain things that I'd learned in the pesticide world, uh, but rethink about them for the context of a pharmaceutical active ingredient.

Chris 1:00:15

Oh, very nice. Now I look forward to seeing all that work as it comes together. If you had to give yourself or somebody else starting out in their career today one piece of advice, what would it be?

Irene 1:00:27

Oh, sector hop is my advice. If you are a young scientist in your first degree or in your PhD and you're wondering what to do with all this learning that you're absorbing while studying, um, I would encourage you to sector hop. People who have worked at a regulatory authority and have then gone back into academia or have come out of academia and gone into a regulatory authority just to see those different angles. If we have young scientists who do this, go on this journey of experience and grow up understanding what it means to be in those respective stakeholder groups. I think that would be amazing in terms of breaking down some of those siloed approaches to thinking or barriers to conversation and joint progress.

Chris 1:01:17

Oh, thank you, Irene. That's a great one. Okay, well, thank you very much. And thank you to everyone who's been listening. Your time's really precious, and so I'm really grateful that you've spent it with us. If you've enjoyed this, please like, comment, subscribe, and spread the word about the Chemical Journeys podcast. Irene, thank you.

Irene 1:01:36

Thank you, Chris. It's for such a joy being here. Thank you.