Technical report 130

SUMMARY

In December 2016, the European Chemicals Agency (ECHA) and the European Food Safety Authority (EFSA) published an Outline of draft Guidance Document for the implementation of the hazard-based criteria to identify endocrine disruptors (ECHA and EFSA, 2016) that was compiled with support from the Joint Research Centre (JRC). The Guidance Document that is outlined in ECHA and EFSA (2016) shall be applicable in the context of Regulation (EC) No 1107/2009 on the placing of plant protection products on the market (EP and Council of the EU, 2009) and Regulation (EU) No 528/2012 concerning the making available on the market and use of biocidal products (EP and Council of the EU, 2012). Section V of ECHA and EFSA (2016) presents seven steps of a Hazard identification strategy for endocrine disrupting properties that follow a weight-of-evidence (WoE) approach. As highlighted in ECHA and EFSA (2016), the identification of endocrine disruptors will be based exclusively on the evaluation of the relevant hazardous properties of a substance, and the Guidance is intended [to] be suitable for both applicants and regulatory authorities.

Against this background, the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) convened an Endocrine Disruptors Task Force (ED TF) to provide guidance on how the ECHA and EFSA (2016) draft outline can be put into practice. The ECETOC ED TF has focused its expertise on providing input for consideration under the seven steps of the hazard identification strategy presented in Section V of ECHA and EFSA (2016). This has resulted in the development of the ECETOC Seven Steps for the Identification of Endocrine Disrupting properties (ECETOC 7SI-ED). The ECETOC 7SI-ED, that covers both human and environmental health, aligns with the steps presented in ECHA and EFSA (2016).

In this ECETOC Report, the ECETOC 7SI-ED is presented as text and as a flow-chart with detailed explanatory notes on how to address each of the seven steps:

  • Step I: Gathering of relevant data with regard to adverse effects and endocrine modes-of-action (MoA);
  • Step II: Evaluation of quality, reliability, reproducibility and consistency of the data;
  • Step III: Evaluation and summary of the evidence for an adverse effect;
  • Step IV: Evaluation and summary of evidence for endocrine activity;
  • Step V: Integration of the evidence and evaluation of biological plausibility that adverse effect and endocrine activity are linked by specific endocrine MoA;
  • Step VI: Identification of uncertainties;
  • Step VII: Conclusions on endocrine disrupting properties.

While the ECETOC ED TF believes that a more comprehensive approach to the determination of endocrine disruptors, considering aspects beyond hazard data only, would best inform the process of assessment of endocrine disruptors, the ECETOC 7SI-ED has remained focused on the hazard aspects only as specific in the ECHA and EFSA (2016) outline. The ECETOC 7SI-ED builds on the World Health Organisation / International Programme on Chemical Safety (WHO/IPCS, 2002) definition for an endocrine disruptor and its three components. It offers guidance on how to evaluate and integrate information on each of the three components of the definition, i.e. how to consider (1) available apical studies to identify adverse effects that may be indicative of endocrine MoA; (2) in vitro and in vivo data on endocrine (or non-endocrine) activity; and (3) the biological plausibility that the adverse effect and endocrine activity are linked by a specific endocrine MoA. The ECETOC 7SI-ED describes how data and information that may be indicative of endocrine disrupting properties can be collected and evaluated, but it does not prescribe any specific testing.

The ECETOC 7SI-ED applies existing relevant scientific concepts and established best practice frameworks and methodologies e.g. the Joint Research Centre Toxicological data Reliability Assessment Tool (ToxR Tool); the OECD Conceptual Framework for Testing and Assessment of Endocrine Disrupters (OECD, 2012a); the OECD Guidance Document No. 150 (OECD, 2012b); and the most recent version of the WHO/IPCS MoA/species concordance framework (Meek et al., 2014a, b). By following the ECETOC 7SI-ED, the data for any regulated substance can be transparently organised and evaluated to reveal the WoE available, its strengths and uncertainties, to compare with the WHO/IPCS (2002) 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 whether, or not, a substance meets this regulatory definition.

While the ECETOC 7SI-ED is conceived as providing general guidance to fulfil the EU legislative remits on plant protection products and biocidal products (Commission, 2016), it does not constitute a hazard assessment strategy. Consistent with the seven steps outlined in Section V of ECHA and EFSA (2016) and the EU plant protection products and biocidal products legislation, the guidance proposed in the ECETOC 7SI-ED is restricted to the identification of endocrine disrupting properties. Notwithstanding, it is the opinion of the ECETOC ED TF 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 the determination whether acceptable risk can be demonstrated. Such an approach has already been implemented internationally, e.g., in the USA and Japan. The hazard characterisation and risk assessment of substances that are identified as possessing endocrine disrupting properties should also establish the human health or environmental population-specific relevance of observed effects. ECETOC Reports are available that provide guidance on how to conduct the hazard and risk assessment of endocrine disrupting substances and on how to establish the human health or environmental population-specific relevance of observed effects.

In conclusion, the ECETOC 7SI-ED is recommended as a tool to assess whether or not a substance possesses endocrine disrupting properties. It is based on robust scientific principles and has been designed to be practical and transparent in its utility with the framework being presented as a series of discrete logical steps, each of which is supported by a clear set of questions and considerations to guide decision-making.

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