ECETOC workshop brings together experts to debate proposed guidance on interpreting endocrine disrupting effects

This 29-30 June in Barcelona, Spain, ECETOC convened a workshop to discuss “Guidance on Interpreting Endocrine Disrupting Effects'. Fifty-five invited experts (from academia, regulatory bodies and industry) debated an approach developed by a related ECETOC task force published earlier this year in the form of an ECETOC Technical Report no. 106. The proposed approach provides 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 and to open a forum for critical analysis. It also provided an opportunity to propose improvements to the scheme.

Format
The workshop consisted of a series of invited presentations: The first of which 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.

Feedback on the proposed guidance
Overall the ECETOC evaluation framework was considered scientifically sound and was viewed as a valuable contribution to the definition of specific scientific criteria that are required for the determination of endocrine disrupting properties. However, whilst it was acknowledged that the ECETOC framework was particularly suited for chemicals with comprehensive toxicology and ecotoxicology databases, it was lacking guidance for those chemicals with poor databases. In particular practical guidance is lacking with respect to what data needs to be generated for chemicals with partial or significant data gaps (in respect to the ECETOC scheme). To this end, it was recommended that additional case studies should be included in the ECETOC evaluation framework using both data poor and data rich chemicals.

To refine further the ECETOC evaluation framework, Workshop participants recommended to include the systematic and structured approach of the WHO/IPCS conceptual framework for evaluating the mode of action for cancer and non-cancer endpoints. This conceptual framework is part of a large project on the harmonisation of approaches for the assessment of risk from exposure to chemicals.

It was also agreed that approaches for determining endocrine disrupting properties should be consistent and harmonised for the three inter-related pieces of EU legislation that concern chemicals under REACH, biocides and plant protection products directives.

Break-out sessions
Several conclusions also arose from the break-out group sessions. These can be summarised as follows:

First, it was considered inappropriate to introduce a new class of chemical toxicity specifically for the endocrine disrupters given that the adverse effects resulting from endocrine disruption can be detected in apical studies (reproductive, development and chronic toxicity studies as well as the cancer bioassays) and they are, therefore covered by the existing EU or GHS classifications.

It was also recognised that there was no scientific reason to approach the toxicity resulting from an endocrine mode of action differently to other types of toxicity (e.g. neuro-, immuno-) resulting from non-endocrine modes of action.

Overall, there was a general consensus that European regulatory decisions to authorise or not authorise chemicals purely on the basis of hazard in the absence of proper risk assessment was not scientifically justified and contradicted approaches taken by other authorities outside Europe. However, it was recommended that appropriate risk assessment should be performed which takes into account a number of issues i.e. threshold of biological responses, potential “low dose' effects and mixtures of chemicals acting by similar modes of action