WR 21 Risk Assessment of Endocrine Disrupting Chemicals 9-10 May 2011, Florence
Recent European legislation has created a hazard based cut-off criterion that only supports the marketing and use of chemicals on the basis that they do not induce endocrine disruption in humans and/or wildlife species. In June 2009, ECETOC held a workshop to discuss the task force report “Guidance on Identifying Endocrine Disrupting Effects (TR106)”. This provided a stimulating discussion on the scientific basis for identifying endocrine disrupting chemicals. A considerable amount of work has also been done by individual member states who have produced refined approaches that have significantly developed the thinking in this area. This workshop was therefore organised by ECETOC to debate, combine and consolidate these rapidly evolving approaches.
Held in Florence on the 9th and 10th of May 2011, thirty-eight invited experts (from academia, regulatory bodies and industry) discussed approaches for the risk assessment of endocrine disrupting chemicals. The aims of the workshop were to evaluate emerging guidance produced by regulatory authorities, academic and industry scientists, identify areas of concordance and difference, consolidate the common scientific themes, provide a platform for constructive debate on areas of difference, and invite a wider critique of the proposed approaches.
The workshop consisted of a series of invited presentations. The first set of presentations dealt with human safety, whilst the second covered environmental safety. National initiatives and developments to define and test criteria for the identification of endocrine disrupting chemicals were presented. This was followed by presentations from the ECETOC Task Force on the ECETOC approach, which included refinements and further development of their original proposal “Guidance on Identifying Endocrine Disrupting Effects (TR106)” (ECETOC, 2009a).
The presentations were followed by four syndicate discussion sessions, which addressed four specific themes. Each theme was considered from both toxicological and ecotoxicological perspectives.
Theme I was concerned with the use of weight of evidence (WoE) for decision making. The participants concluded that a consistent approach for the WoE of endocrine disrupters is required, which would be applicable under various regulatory regimes. There was general support for requirement to demonstrate both an adverse effect in an intact organism (extended to population level impacts for the ecotoxicological assessment) and a plausible endocrine mode-of-action. For human health assessment there was general support for using the WHO/IPCS mode-of-action framework (WHO/IPCS, 2007). For ecotoxicological assessment it was acknowledged that no direct equivalent to this WHO/IPCS framework exists, but several specific WoE frameworks for the evaluation of endocrine disrupting effects have been published. These should be evaluated and combined for the requirements under current legislation.
Theme II covered discussions on the human and population relevance of endocrine related endpoints. It was noted that there were some rodent cases for which non-relevance to humans has been demonstrated, but that the number of such cases is low. The default position is to assume human relevance.
Specific guidance was considered necessary to aid in the identification of endpoints in ecotoxicological studies that are of population relevance. Some endpoints are clearly directly population related, whereas others are more diagnostic in nature, and in order to infer their population relevance, they need to be used as part of a cluster of endpoints.
Theme III dealt with the evaluation of lead toxic effects and the specificity of endocrine effects when identifying endocrine disrupters. While it was seen as scientifically sound, most participants thought that the application of this criterion would depend on the degree of separation between the (other) lead effect and the endocrine-mediated effect. The acceptable degree of separation should be assessed on a case by case basis, and for EDs of very high concern a factor of 10 was suggested as a conservative starting point. This could be a useful approach for the REACH legislation, which requires that individual exposure scenarios need to be addressed to guarantee safety for different uses of the same chemical. For ecotoxicological assessments the participants felt that further work was required before an absolute value for the degree of separation could be recommended.
Theme IV was concerned with using potency to differentiate between endocrine disrupting chemicals. It was highlighted that the concept of potency assessment was introduced as a surrogate for risk assessment following the legislative introduction of a hazard based cut-off criterion for endocrine disrupters. Equivalent categories already exist for repeated dose toxicity. The potency assessments proposed by the German and British authorities (BfR and CRD respectively) and ECETOC only apply to deciding whether substances of high regulatory concern are caught by the cut-off criterion and are therefore refused marketing authorisation. All other (less potent) endocrine disrupters would still undergo standard risk assessment.