- Adverse effect
- biocidal products
- degree of separation
- ECETOC approach
- ecotoxicological assessment
- ecotoxicological perspectives
- ecotoxicological studies
- endocrine effects
- endocrine mode of action
- Guidance on Identifying Endocrine Disrupting Effects
- hazard based cut-off criterion
- Potency assessment
- Risk Assessment of Endocrine Disrupting Chemicals
- weight of evidence
- WHO/IPCS mode
WR 21 : Risk Assessment of Endocrine Disrupting Chemicals | November 2011
WR 21 Risk Assessment of Endocrine Disrupting Chemicals 9-10 May 2011, Florence
This report documents the outcome of a workshop organised by ECETOC to discuss the “RiskAssessment of Endocrine Disrupting Chemicals”. The workshop was 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, and 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 set 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 fourspecific 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 disrupting chemicals is required, which would be applicable under various regulatory regimes. There was general support for a requirement to demonstrate both an adverse effect in an intact organism (extendedto 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 disrupting chemicals. While it was seen as scientifically sound, most participants thought that the application of this criterion would depend on the degree of separation between a non-endocrine mediated lead effect and the endocrine-mediated effect, as well as the relative severity and seriousness of the lead versus ED-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 a 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 could be introduced as a surrogate for risk assessment following the legislative introduction of a hazard based cut-off criterion for endocrine disrupting chemicals. Equivalent categories already exist for repeated dose toxicity. The potency assessments (cut-off criterion) proposed by the German and British authorities (BfR and CRD respectively) and ECETOC would only apply to identify substances of high regulatory concern which would be refused marketing authorisation. All other (less potent) endocrine disrupting chemicals which are part of PPPs and biocides would still undergo standard risk assessment.