Summary of the SETAC Pellston Workshop® on Endocrine-Active Substances
Mike Roberts and Annegaaike Leopold, workshop co-chairs (on behalf of the Steering Committee)
The SETAC Pellston Workshop “Environmental Hazard and Risk Assessment Approaches for Endocrine-Active Substances” (EHRA) was held from 31 January–5 February at the Hilton Pensacola Beach in Florida, USA. Forty-eight experts participated1 in this Pellston-style workshop, bringing together scientists from around the globe and representing a wide spectrum of scientific opinions. The charge of the workshop delegates was to consider several chemical case studies and thrash out the underlying issues that have been fuelling serious scientific controversy.
You can read the full summary report here.
The workshop was successful at reaching consensus and will thereby contribute to the global process of managing these substances. The overall conclusion of this workshop was that if environmental exposure, effects on relevant taxa and life stages, and delayed effects and dose or concentration relationships are adequately characterized, then conducting environmental risk assessment of endocrine-disrupting substances (EDSs) is scientifically sound. In addition, the workshop recommended an approach for the evaluation of indicative (endocrine-specific and non-endocrine–specific) and apical endpoints to investigate whether or not observed effects for a given substance result from an endocrine mode of action.
The primary aim of the workshop was to provide objective advice to enable regulators and policy makers from industry or government to make considered, informed decisions on whether to select a hazard- or a risk-based approach for a given EDS under review. The workshop also aimed at highlighting remaining areas of scientific uncertainty and developing recommendations for research to resolve these issues.
The need for this Pellston workshop arose from recent developments of regulatory approaches to evaluate EDSs under several jurisdictions. These approaches have diverged, partly because until now there has been little consensus concerning some key scientific questions. In this spirited debate, some scientists believe that EDSs can be evaluated via standard risk assessment approaches. Others do not believe this is sufficiently precautionary. Some reasons why regulation by hazard has been championed include:
- The existence of non-monotonic dose or concentration responses
- The possible absence of thresholds of effect
- The claimed insensitivity of current toxicological and ecotoxicological tests to detect certain modes of action
- Short-term exposures to EDSs possibly leading to long-term consequences not addressed during testing
- Hazard assessment being less complex than risk assessment.
It has been suggested that these factors imply an inability to predict no-effect-doses or concentrations, and hence that EDSs should be regulated solely on the basis of hazard.
A unique effort has gone into collecting data for the case studies on each of six endocrine-active substances, representative of a range of endocrine modes of action and considered to be data-rich in relevant information at all levels of biological organization. The substances selected were ethinylestradiol, perchlorate, propiconazole, trenbolone (TRB), tributyltin (TBT) and vinclozolin. A review and synthesis was performed of the available data from a sub-selection of on average 200 papers, including data reported in scientific journals, and information openly published in regulatory review documents and summaries. Subsequently, data were assessed for relevance, reliability and scientific quality, and weighted accordingly. Where possible, the ToxRTool, a simple Excel-based system derived from the widely used Klimisch method, was employed. Given the lack of assessment tools, histopathology endpoints were assessed for reliability in a parallel exercise by a histopathology expert, and the results of this exercise were incorporated into the case study evaluations. The data were then organized in a framework to facilitate a weight-of-evidence evaluation for the substance and its endocrine activity. Following the hazard characterization, exposure estimates were incorporated in order to assess whether hazard- or risk–based decisions were justifiable.
The results of the case studies provided many examples of cross-cutting issues, common to several substances, that may impact decision-making. These cross-cutting issues were used to design the proposed strategy for deciding on whether a sound risk assessment of a particular EDS can be undertaken. Hence, the case studies were not comprehensive safety evaluations but provided the foundations for clarifying the key issues and procedures required to meet the workshop’s aims.
The outputs of the workshop will be a series of papers to be published in 2016. The first of these papers is an overall synthesis document, “Recommended approaches to the scientific evaluation of environmental hazards and risks of endocrine-active substances,” which provides guidance for scientists in regulatory authorities and industry on the likely problems to be faced in environmental hazard and risk assessment. The key contribution of this first paper is that it provides a strategy for deciding on whether a sound risk assessment of a particular EDS can be undertaken.
Four additional papers address cross-cutting issues identified in the case studies and are titled:
- Challenges in assigning endocrine-specific modes of action: Recommendations for researchers and regulators
- Uncertainties in biological responses that influence hazard and risk approaches to the regulation of endocrine-active substances
- Current limitations and recommendations to improve testing for the environmental assessment of endocrine-active substances
- Population-level adverse effects of endocrine-active substances
In addition to the papers referred to above, which are included in the publication plan of the EHRA Pellston workshop, a number of papers will be prepared separately. One of these papers will deal with the reliability assessment of data from histopathology endpoints. Two further publications will be prepared by the tributyltin and trenbolone groups, who will develop a review based on the data analysis performed for their case studies.
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