Guidance for the identification of endocrine disruptors in the context of EU Pesticide and Biocide regulations
July 31st, 2018
Guidance, drafted by ECHA and EFSA, on identification of endocrine disruptors (EDs) in the context of EU pesticide and Biocide Regulations was published on 7th June. According to the guidance, a substance is considered as having endocrine disrupting properties if it meets all of the following criteria:
- it shows an adverse effect in an intact organism or its progeny, or non-target organisms, which is a change in the morphology, physiology, growth, development, reproduction or life span of an organism, system or (sub)population that results in an impairment of functional capacity, an impairment of the capacity to compensate for additional stress or an increase in susceptibility to other influences;
- it has an endocrine mode of action (MOA), i.e. it alters the function(s) of the endocrine system;
- the adverse effect is a consequence of the endocrine mode of action.
Therefore, there should be a biologically plausible link (relevant to humans or non-target organisms at a population level) between the endocrine activity and the adverse effect.
The guidance stipulates that a conclusion on whether the ED criteria are met should always be drawn with respect to humans and non-target organisms. However, there may be data available on non-target organisms relevant for the assessment of the ED properties in humans, and because of the high level of conservation of the endocrine system across taxonomic groups these data might also be relevant to other vertebrates.
Where the evidence available indicates that the criteria are not met for mammals, the assessment for non-target organisms should proceed by considering fish and amphibians, because these are the taxa where standardised test methods and knowledge on how to interpret the results are available. Information on other taxa (e.g. birds and reptiles) should be considered if available.
There may be cases in which due to the knowledge on the physico-chemical and (eco)toxicological properties of the substance, an ED assessment does not appear scientifically necessary or testing for this purpose not technically possible. In such cases the guidance states that consideration should be given to whether possible adaptations to the data requirements would apply to the ED assessment in its entirety or only with respect to humans or non-target organisms.
The guidance refers to the Guidance Document on Standardized Test Methods for the Evaluation of Chemicals for Endocrine Disruption, No. 150 (OECD GD 150), which provides guidance on how to interpret the outcome of individual tests and how to build a weight of evidence for assessment of ED potential. In the current guidance, the parameters from the OECD GD 150 are grouped as either in vitro mechanistic, in vivo mechanistic, estrogen, androgen, thyroid, steroidogenic (EATS)-mediated or sensitive to, but not diagnostic of, EATS. The ‘EATS-mediated’ parameters listed in the OECD GD 150 drive the assessment strategy because, by providing evidence for both endocrine activity and the resulting potentially adverse effects, they are considered indicative of an endocrine MoA.
The guidance goes on to describe the assessment strategy, which is based on the three conditions stipulated in the ED criteria (adversity, endocrine activity, and a biologically plausible link between the two) and on the grouping of the parameters as described above. The assessment is described in several steps as follows:
- The first step of the assessment strategy requires gathering of all available relevant information.
- Then in step two the information is assembled into lines of evidence, integrating information for both adversity and endocrine activity.
- Step three involves an initial analysis of the evidence, which includes a decision tree with different possible scenarios. The scenarios are driven by the availability of ‘EATS-mediated’ parameters and/or evidence of endocrine activity and provide indication whether the available evidence allows to conclude that a substance does not meet the ED criteria, or that additional information is needed, or that a MoA analysis is required to conclude on the ED properties.
- Step four aims to establish if there is a biologically plausible link between observed adverse effects and endocrine activity. Depending on the available evidence the information that may need to be generated and included in the dossier to further investigate the adversity or the endocrine activity is identified. In the final step a conclusion on whether the ED criteria are met with respect to humans and non-target organisms is drawn and transparently documented, including the remaining uncertainties. Different situations are outlined, depending on the outcome of the MoA analysis.
PFA is maintaining a watching brief on how the guidance develops and especially with respect to how criteria may be adopted for REACH.