The EU ED debate (or debacle?)

By U. Memmert (Eurofins REG AG) & L. Abbott-Williams (Eurofins Agroscience Services Ltd)

You may well have seen the recent headlines ‘European Commission stalls again on EDC criteria vote.’ It appears that Europe cannot decide on a decisive course of action to address the issue of EDCs (Endocrine-Disrupting Chemicals).  Here, we look at some of the reasons why this subject is so controversial…

In response to growing global concerns about the impact that some chemicals may have on human health and the environment, the EC (European Commission) is working on a proposal for sciencebased criteria for the identification of chemicals as endocrine disruptors; a requirement of the PPPR (Plant Protection Products Regulation) and BPR (Biocidal Products Regulation).

In June 2016, the EC presented a draft proposal outlining criteria for identifying substances with endocrine-disrupting properties, currently applicable to plant protection products and biocidal products. This was met with widespread resistance and despite a revision of the draft proposal in November 2016, the EU Standing Committee on PAFF (Plants, Animals, Food and Feed) member states were still divided. In December 2016, a third revision was presented to PAFF members. In this version, the EC split the text of the PPPR proposal into two draft acts, one containing the criteria and another one containing the amendment to possible derogations. This gave the member states and later the European Parliament the option to express their opinions on each separately. However, after an intense discussion, an indicative vote suggested the qualified majority were not in favour of the revised proposals.

In late February 2017, during a follow-up meeting with experts and Member States, the EC discussed the latest version of its proposal for identifying EDCs but did not ask the PAFF standing committee to vote formally.  Why?  Was it due to concerns that the majority of member states were still opposed to the latest draft proposal? With only 11 member states rumoured to be in favour, the remaining 16 either abstained or were against the revised proposal. This meeting, with no conclusion, suggests that experts remain dubious of the proposal and perhaps the EC’s approach to the subject of EDCs.

Supporters of the draft proposal maintain that the issue lies in the wording, surmising that a few textual tweaks will solve the discrepancies, though several European consumer bodies, political figures and NGOs are quick to oppose that viewpoint. Key resistance arguments focus on the approach that the EC is taking regarding exemptions.

Currently, a plant protection product (PPP) with endocrine-disrupting properties can only be approved for marketing authorisation if there is negligible exposure to humans or non-target organisms under realistic conditions of use. A biocidal product with endocrine-disrupting properties can at present be approved if the risks are negligible or the substance is essential to prevent or control a serious danger to human health, animal health or the environment. Additionally, exemption can occur where not approving the substance would have a disproportionate negative impact on society when compared with the risk arising from the use of the substance.

The EC has retained its proposed change to the exemption from “negligible exposure” to “no adverse effects” in the actual draft regulations for PPPs and biocidal products. Also, non-approval of EDCs can be overruled where there is evidence demonstrating that the adverse effects identified are not relevant to humans or at the (sub) population level for non-target organisms.
Furthermore, hazard-based cut-off criteria will not be applied to growth regulators with an intended endocrine mode of action.

The issue lies in the interpretation of the EC’s proposal - it is widely believed by NGOs that the exemptions will allow the widespread use of endocrine-disrupting pesticides, and is not in line with what the law originally set out to achieve. Combine that with the requirement for a high burden of proof to identify EDCs and the fact that only PPPs and biocidal products have been taken into consideration, and it is easy to see why many member states will want amendments and clarification to the draft proposal.

In 2013, EFSA (European Food Safety Authority) published a scientific opinion on the hazard assessment of endocrine disrupters. In contrast to the hazard-based cut-off criteria of EDCs in the current PPPR and BPR, this document includes the opinion of the experts that “a risk assessment (taking into account hazard and exposure data/predictions) makes best use of available information. EDCs can therefore be treated like most other substances of concern for human health and the environment, i.e. be subject to risk assessment and not only to hazard assessment” (EFSA, 2013). In February 2016, the outcome of the EHRA Pellston workshop - organised by the Society of Environmental Toxicology and Chemistry (SETAC), with forty-eight international experts - was that an environmental risk assessment of EDCs is scientifically sound and reliable if data on environmental exposure and effects are robust (Leopold et al., 2017). This is in agreement with the present ED regulations in USA and Japan, highlighting the complexities facing both the EC and EU member states.

In April 2017, at a follow-up meeting with experts from Member States Competent Authorities, the proposal regarding growth-regulators in the biocide regulation was the sole subject discussed. This is an indication of how painstaking progress is; small steps are needed to transform the attempts of the EC on the legislation level regarding the EDC regulation.

What next? This is the big question. At this time, the EC has not scheduled a date for further discussion on the criteria for the PPPR. 

There is pressure to accept the derogation regarding the acceptance of growth regulators with intended endocrine mode of action since many of these substances typically have a low toxicity profile; they are regularly used for integrated pest management and some are approved for use in organic farming. Hence, a class of generally rather safe chemicals would be lost by default, without the possibility of derogation. 

The other critical point is the term “adverse effects” in the definition of ED properties. It is widely agreed that an EDC is defined by three criteria: i) the presence of an adverse effect in an intact (nontarget) organism or its progeny; ii) it has an endocrine mode of action; and iii) a plausible causal relationship between the endocrine activity and the adverse effect. This definition gives a lot of scope for an array of questions and discussions. What is an adverse effect, in detail? What is required to demonstrate endocrine activity and a plausible causal relationship between both?

Huge efforts have been made in recent years to develop scientifically-based decision criteria for the identification and regulation of EDCs by scientific experts and by national authorities. In December 2016, in order to aid progress in this complex area, an outline of a “Draft Guidance Document for the Implementation of the Hazard-based Criteria to Identify Endocrine Disrupters” was presented. This was prepared by the ECHA (European Chemicals Agency) and EFSA, in collaboration with the JRC (Joint Research Centre) at the request of the EC. The focus of the guidance document (GD) will be on the data and information needed to identify an endocrine mode of action and whether observed endocrine activity would result in adverse effects in intact organisms. The outline document, prepared by ECHA and EFSA’s scientific staff, describes a work plan for the drafting process including timelines, responsibilities, foreseen consultations with relevant parties, procedures for adoption of the final guidance document, and a draft table of contents of the ED guidance document. This gives a first impression of the prospective GD. The drafting process for the GD by the ECHA-EFSA-JRC team is scheduled to last until May 2017 followed by the public consultation of the draft GD which will start in June 2017. 

The next steps after public consultations until the launch of endorsement as regulatory guidance will take an additional seven months, so the final GD can be expected earliest 2018. Even if the proposals of the EC for the amended PPPR and BPR are accepted by the EU member states in the coming months, the intense discussion with stakeholders and the public will continue regarding the outline of the guidance document with the criteria to identify EDCs. There is no quick solution. It is worth noting that the ECHA-EFSA guidance document is very likely to be relevant for substances covered by the REACH regulation and the Cosmetic Product Regulation (CPR).

The methodology to identify potential EDCs was developed by JRC in the context of an impact assessment (JRC, 2016). In March 2017, the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) provided detailed guidance on how the ECHA-EFSA draft outline could be implemented (ECETOC, 2017). From this document and existing EFSA scientific opinion (EFSA, 2013) it is certain that expert judgement is required to assess on a case-by-case basis relevant data at the molecular to individual and/or population level to identify EDCs, starting from the evaluation of the data quality through to a weight-of-evidence assessment in order to conclude if the chemical can be defined as an EDC or not, or if more data are required. 

Despite the development of a detailed guidance document, such expert judgements and weight-ofevidence assessments will allow for discussions between stakeholders and competent authorities regarding the outcome in this very complex matter during the substance-specific regulation. 

Notably, specific laboratory tests are available only for the identification of EDCs with oestrogenic, androgenic, thyroid and steroidogenesis (EATS) mode of action. However, the endocrine system in vertebrates also consists of other important endocrine pathways, e.g., the hypothalamus-pituitaryadrenal (HPA) axis and several others. Study protocols for the testing of non-EATS modalities relevant to mammals, fish and other vertebrates are not available yet. Also, official test protocols for measurement of endocrine activity in the majority of invertebrates are still quite rare, and a range of major groups such as reptiles have not yet been considered.
 
The development and validation of official OECD or US-EPA test guidelines for the testing of EATS modalities in fish has taken about 20 years, and this task is still not completely finished today. And let’s not forget that several further guidance documents will be required for the evaluation of adverse effects caused by the other endocrine modalities. 

Based on this, how much time will be required for the development of all the missing test guidelines for other modes of action and for invertebrates? 

In response, there appears to be no end in sight regarding the discussions about EDCs in the future.

For more information, please contact Ulrich Memmert Regulatory Affairs Manager, Eurofins regulatory AG