Workshop Report 16 – Guidance on Interpreting Endocrine Disrupting Effects + Addendum

WR 16 and Addendum : Guidance on Interpreting Endocrine Disrupting Effects and Addendum | October 2009

Please note that this version of the report includes the addendum that was previously published separately; it can be found just before the table of contents.

This report documents the outcome of a workshop organised by ECETOC to discuss ?Guidance on Interpreting Endocrine Disrupting Effects?.  The workshop was held in Barcelona on the 29th and 30th of June 2009.  Fifty-five invited experts (from academia, regulatory bodies and industry) discussed an approach developed by an ECETOC Task Force and distributed to participants in the form of a Task Force report (ECETOC, 2009).  This report outlined an approach developed by the Task Force providing guidance in the form of flowcharts that could be used as a decision tree for the identification of endocrine disrupting effects in human health (toxicology) and environmental assessments (ecotoxicology).  The aim of the workshop was to assess the suitability of such an approach.  It was also intended as an open forum for critical analysis and an opportunity to propose improvements to the scheme.

The workshop consisted of a series of invited presentations.  The first outlined the regulatory background to the issue.  The second reported on German national initiatives to develop toxicology criteria for endocrine disrupters.  This was followed by presentations from the ECETOC Task Force introducing the ECETOC approach, including detailed explanations (with case studies) for its application in the toxicology and ecotoxicology fields.

The presentations were followed by four syndicate discussion sessions, each addressing specific issues:

The first breakout group directly evaluated the suitability of the ECETOC approach (see Section 4.1).  This group endorsed the ECETOC approach as a means of identifying endocrine disrupting effects in a structured manner.  However, it was acknowledged the approach was best suited for data rich substances (such as plant protection products) and further guidance may be required for substances where less data are available.  Considerations of mode of action coverage, identifying what constitutes an adverse effect (particularly in ecotoxicity assessments), weight of evidence approaches and the interplay between toxicology and ecotoxicology studies were also discussed.

The second breakout group discussed the appropriateness of risk assessment for endocrine disrupting substances (see Section 4.2).  There was a strong consensus that it is scientifically inappropriate to base decisions on hazard alone.  A thorough risk assessment of all the factors, which may be involved in evaluating the potential risk of using a substance with endocrine disrupting properties, is required.  However, uncertainties in estimating exposures in target animals at various stages of maturation was discussed, although, the group acknowledged that it was better to assess such issues rather than to reject a substance based on hazard potential alone.

The third breakout group discussed whether there was a basis to treat endocrine disruption differently to any other mode of action (see Section 4.3).  There was a consensus that there was no basis to treat endocrine disruption differently.  However, the discussions highlighted several points when additional attention was required specifically in relation to low dose effects, timing of exposure and cumulative exposure.

The fourth breakout group discussed the way forward in developing science-based legislation (see Section 4.4).  The group agreed that the framework for evaluating endocrine disrupters should be adapted as a function of the legislation.  In the short term, for implementing the revision to the plant protection products directive 91/414 (EC, 2006a), it is important to use risk principles and to develop guidance documents built upon integrating hazard evaluation with exposure assessment.  The ECETOC guidance provided a structured, science-based process for assessments.  It would be useful if REACH (EC, 2006b), the plant protection products and biocides directives used the same evaluation principles and approaches for determining endocrine disruption.  The ECETOC guidance was a very useful starting point for such a consistent approach.  However, consideration should be given to further work to improve the ECETOC approach.  This may be achieved by more case studies of applications of the ECTOC framework and to have additional venues for more in depth discussions.

In conclusion, there was participant endorsement of the ECETOC approach as a science-based evaluative framework.  However, areas for further development and improvement were raised.  In particular, it was suggested that the systematic and structured approach of the WHO/IPCS conceptual framework for evaluating the mode of action for cancer and non-cancer endpoints be included.  In general the participants supported the view that toxicity resulting from endocrine disruption should be subject to risk assessment as is the case for other forms of toxicity.  The ECETOC guidance scheme is an appropriate approach.  Greater consideration of data poor substances is needed.  The ECETOC Task Force is grateful for the expert input and intends to use the thinking and suggestions proposed at the workshop to refine the guidance.