June 7, 2017 by Becky Brown & Owen Green

A workshop hosted by DG Environment was held between the 30th May and the 1st June 2017 in Brussels to discuss priorities for further development and validation of test methods and testing approaches for evaluating endocrine disruptors. The workshop was attended by regulators, international experts and relevant stakeholders with the aim of identifying gaps in the available test methods for evaluating endocrine disrupters, considering ways to address these gaps and finally prioritising the development of new test guidelines. wca working with partners at Risk and Policy Analysis (RPA) were involved in organising and facilitating the workshop and also preparing relevant background documents.

The workshop covered both human health and the environment and included targeted presentations combined with breakout groups for expert discussion. Particularly, from a human health perspective prioritisation can be a challenge as it is difficult to rate one disease type as being more relevant than another. Therefore, there was considerable discussion on the best way to prioritise test methods which included the technical readiness of the proposed method, cost and animal use.

All groups highlighted in vitro assays which provide a mechanism of action beyond the traditional estrogen, androgen, thyroid and steroidogenesis pathways (EATS) as an area of interest (e.g. retinoid pathways). The logistical challenges regarding conducting and interpreting large scale studies with multiple endpoints for mammals, birds and fish were also discussed. Despite the difficulties there was a general agreement that additional mechanistic endpoints that could be measured as part of existing test methods would be an advantage.

From a human health perspective female reproductive health, metabolic disorders and neuro-development (thyroid system) were highlighted as priority areas across most breakout groups. Opinion was very much divided as to the preferred way forward to enhance the identification of potential endocrine disrupting substances in mammalian systems. Should new guideline studies be developed incorporating new test methods or should existing guidelines be enhanced with additional improved assays? To develop and validate new assays would not be advantageous to identifying endocrine disrupting potential if it cannot be linked to an adverse outcome associated with endocrine disruption. Whilst enhancing existing guideline studies with new and improved assays such as circulating hormone assays was generally accepted as the most useful way forward, there was a concern that this action would, from a regulatory viewpoint, invalidate previously conducted studies. Irrespective of this view, the general consensus was that, in the short term, more targeted in vitro mechanistic assays would certainly support any indications of endocrine disruption potential shown in the regulatory framework studies. In the long term, it was likely that a more specific testing strategy would need to be developed for identification of endocrine disrupting potential which, in turn, may result in the need for new test guidelines.

For the environment, it was considered that more experience with the new “gold standard” Medaka Extended One Generation Reproduction Test (MEOGRT) test for fish would be an advantage. For example, generating data for a wider range of positive control substances to aid interpretation of the study. The thyroid system was a data gap (particularly for fish) and several recommendations for new mechanistic endpoints discussed at a recent DG Environment and ANSES workshop on thyroid disruption were highlighted as being important. Areas for long term research priorities included a better understanding of invertebrate endocrine systems (particularly molluscs) and the behavioural and immune effects of endocrine disrupters on wildlife.

If you would like more information, please contact Becky Brown or Owen Green

Related information and topics:

Endocrine Disruption: What Does the Future Hold for Safety Assessment?

Adverse Outcome Pathways (AOPs) and Regulatory Acceptance

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