ChemCon Conferences’ Post

Transcript

I will take you through some definitions, and I know that's not the most exciting topic to talk about, especially if you're just before your coffee break, but I need to do this, because it's very important that we interpret things in the right way and look at all the different facets, before we decide if something is an endocrine disruptor or not. And I am an expert, so I like details. So an endocrine disruptor according to the WHO, is an exogenous substance or mixture that alters the function of the endocrine system and consequently causes adverse health effects in an intact organism or its offspring. Well, these are the hazard categories included in CLP. And they specify which types of data we would need to assess to come to a conclusion on if a substance is an endocrine disruptor or not. That can be human data, animal data and non animal data. And you have to look at the following aspects. So the activity; is there an adverse effect, but also is there a biologically plausible link between the endocrine activity and the adverse effect. I'm really happy. Alternatives to animal testing were already mentioned. And I'm really happy that it's in here that we can also refer to non animal data. And I also hope it will stimulate the further development of animal testing alternatives. And looking at the biologically plausible link, I think that will be the biggest challenge. And another challenge, as far as data interpretation, is looking at the difference between indeed category 2 and category 1. Because, what does that actually mean, that a serious doubt is raised. That can be, I think, open also to interpretation. I will get a bit more technical now and go further into these different aspects. And one of the things that the chemical strategy for sustainability also listed, is to build upon hazard and risk assessment experience for endocrine disruptors already done for pesticides and biocides. So we as experts, are really happy to see that, because one substance one assessment, so certainly one substance one hazard assessment. Now I want to take you through and show you this example without going too much into detail what is happening here, but to focus on the green, the orange and the red. To show you what, if you look at industrial chemicals, what we basically have and what we do not have. And you see that the arrows go from the green to the red, but actually the data we have now is in the red category. And when I came from my studies, I was very disappointed, because we did a study and then an adverse effect came out and we were never looking at the mechanism or nothing we did in the lab. But right now we have all these studies, but we, for industrial chemicals, don't know the green, that is the activation part. And the orange part, is the biologically plausible link. So you have some activation, you have key events on cellular tissue level, organ level. And that may lead to an adverse effect. But up to now, for classification and labeling, many times the adverse effect on its own was what we were dealing with. So this is toxicological very interesting, but I think something for other end points that we do not do as industry by default. The guidance is under development. That doesn't mean that we are empty handed. So there's experience from the biocides, pesticides and also for how to generate data. The OECD has prepared a guidance document that has been around for a while, that takes you through five steps of generating and assessing data. I've highlighted level two and three, which are in vitro assays to provide mechanistic data, and in vivo assays to provide mechanistic data. Because, again, as toxicologist and working mostly for industry, we are used to looking at level one, looking what there is. And then we maybe do some in vitro testing. But for these types of effects, we are used to looking at the adverse effects coming out of in vivo studies, so level four and five. Level two, there are different studies recommended. But as you can see, they are only on certain modalities. So that's the EATS. And I'll just show you in a second, there's actually a lot more going on in your body than that. And for example for the thyroid, since 2017, in vitro methods are under development, but there are still no OECD accepted guidance documents by which to do these studies to screen if thyroid hormones are disrupted. So how to get the data? Level three is in vivo mechanistic data. There are two recommended OECD test guidelines by the OECD. And level four and level five, if you look at those OECD guidelines, it's the repeated dose and reprotox studies, extended one gen and two gen study. Which I hope ring a bell with most of you, because these are the standard studies we do for industrial chemicals. Now a summary on how to get the data. I think for me as a toxicologist it's activity, biological plausibility, adversity, those steps. And then the first two will be most interesting and complex in the coming time. There's focus only on four modalities at the moment. For pesticides and biocides there are data requirements now included in the regulations. If you look at industrial chemicals, it's not clear yet what exactly we need to test. But also not all tests that we can do are fully developed. There are no OECD guidelines. And the REACH revision has been postponed, so also clarity for industrial chemicals for the testing requirements will be postponed. And the current testing for REACH, show only the adversity, will not be sufficient to identify an endocrine disruptor, at least in the sense of how it's worded for CLP. Summary. The ED categories are included in CLP. SDS's and labels need revisions. Of course, also all your dossiers if you gather more data. The guidance by ECHA is under development from a data perspective, so tox perspective not completely lost. There's the OECD guideline on what to do and how to assess it. But the first step is to reassess existing data. And there are no standardized guidelines available for all data requirements. So take home message. Start reviewing existing information and identify gaps. Key data gap is information about activity and mechanism. There's clear technical guidance needed and there may, I hope not, but may be data requirement differences between regulations. And I really appreciated that you said that with the first dossier submissions, there would be the possibility to talk about what is submitted. What I would like even more, is to be able to discuss the testing plan that you make before you invest a lot of resources in maybe going with a testing strategy, that's in the end not accepted. So thank you for your time and attention.