In a previous blog, I discussed the European Commission’s (EC) proposal for criteria to identify endocrine disrupting chemicals (EDCs), highlighting its strengths and shortcomings. Subsequently, the EC asked the European Chemicals Agency (ECHA) and the European Food Safety Authority (EFSA) to jointly develop guidance for actual implementation of the proposed criteria. They published an outline for their proposed guidance last December.
In a recent development, the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) has added flesh to the bones of the ECHA/EFSA outline by publishing its proposal for a seven-step process for the identification of EDCs. (You can read ECETOC’s announcement here.)
As I will discuss below, the ECETOC proposal should be received favorably as it represents a sensible and pragmatic approach to what otherwise could be an overly complicated process.
The seven-step process
The way in which ECETOC defines an EDC establishes a crucial starting point for its seven-step process for identifying EDCs. As did the EC in its proposed criteria, ECETOC relies on the widely accepted World Health Organization’s International Programme on Chemical Safety definition of an EDC, which stipulates that a chemical 1) act through an endocrine mode of action to 2) cause an adverse effect.
Mirroring the joint ECHA/EFSA proposed outline, the ECETOC proposal includes a seven-step process:
I. gathering relevant data relating to adverse effects and endocrine modes of action;
II. evaluating data quality;
III. evaluating evidence for adverse effects;
IV. evaluating evidence for endocrine activity;
V. integrating the evidence and evaluating biological plausibility that adverse effect and endocrine activity are linked by specific endocrine mode of action;
VI. identifying uncertainties; and
VII. concluding on endocrine disrupting properties
According to ECETOC, the seven steps need not be followed in consecutive order; rather, the most appropriate sequence of steps should be determined on a case-by-case basis, requiring “expert judgment”.
The ECETOC guidance covers both human and environmental health. It also demonstrates how to integrate data from a variety of sources employing a Weight-of- Evidence (WoE) approach using best practices.
Positive Attributes of the ECETOC Guidance
The ECETOC guidance proposes applying existing, relevant scientific concepts and established best-practice frameworks and methodologies, e.g. the Joint Research Centre Toxicological data Reliability Assessment Tool (ToxR Tool) for assessing data reliability; the OECD Conceptual Framework for Testing and Assessment of Endocrine Disrupters; the OECD Guidance Document No.150; and the most recent version of the WHO/IPCS MoA/species concordance framework.
By following the ECETOC guidance, those charged with applying the EC criteria can transparently organize and evaluate the data for any regulated substance to reveal the WoE available, including its strengths and uncertainties, to compare with the WHO/IPCS definition for an endocrine disruptor and the scientific criteria set out in the context of the EU plant protection products and biocidal products legislation. This enables a conclusion to be drawn on whethera substance does or does not meet this regulatory definition.
Opportunities for Improvement
There is one constraint of using the ECETOC guidance. Similar to the EC criteria and the ECHA/EFSA outline, the guidance is restricted to only the hazard evaluation step, although its authors rightfully note that substances that are identified as possessing endocrine disrupting properties should undergo a comprehensive hazard and risk assessment. This entails the determination of safety thresholds, exposure assessment, potency assessment, and a determination of whether acceptable risk can be demonstrated. Such approaches have already been implemented internationally, e.g., in the USA, Canada, and Japan.
Although the joint ECHA/EFSA outline specifically references use of data derived from epidemiology and/or field studies for the purposes of identifying adverse effects (Step III), the ECETOC guidance is conspicuously silent on these data sources. The reasons for this omission are unknown, but may relate to the difficulties that regulatory agencies have historically faced in integrating evidence obtained from observational studies with evidence derived from experimental ones. The omission may not constitute a major problem, however, since the existing relevant tools that ECETOC relies upon can be adapted for use with observational studies. Still, one can’t help but think that ECETOC missed an opportunity to highlight the limitations and special challenges posed by observational studies. In 2013, EFSA provided some of its early thinking on uses of epidemiology and field studies that may signal how it and ECHA will tackle this issue in their forthcoming guidance. The US EPA has recently published a framework for how it intends to incorporate epidemiology and incident data into its risk assessments on pesticides; however, its experience to date with doing so suggests there are opportunities for improvement.
A public consultation on the ECHA/EFSA draft guidance is scheduled for the summer. In the meantime, ECETOC plans a series of case studies to test its own proposed guidance document into actual practice. Stay tuned for further developments.