Endocrine disruptor assessment

Many animals, typically fish, frogs and rats, are currently used in regulatory testing to determine whether manufactured chemicals cause endocrine disruption (ED) in humans and wildlife populations. Our work in this area aims to build the evidence base required to reduce the number of vertebrates used in in vivo studies  carried out to ensure the health of animals exposed to chemicals in the environment. We are leading a number of projects to ensure that the in vivo tests involved in ED assessment are as robust as possible, particularly focusing on aquatic species. This will reduce the need for tests to be repeated and the instances in which more complex and animal-intensive studies are triggered. 

Vitellogenin (VTG) in fish egg-yolk is commonly used to assess endocrine activity in ecotoxicological tests. VTG data can be highly variable, meaning that additional testing in fish may be required to address uncertainties in the VTG response. We are working to understand and address the causes of this variability, improve the robustness of VTG data and reduce unnecessary additional fish testing.

The European Union’s Registration, Evaluation, Authorisation and Restriction of Chemicals (EU REACH) Regulation is in place to ensure a high level of protection of human health and the environment from chemical substances that are manufactured, imported, placed on the market, or used within the EU. Two information requirement options specifically for the ED assessment of chemicals under EU REACH were proposed by the European Commission in 2021. Once implemented in the coming years, this will substantially increase demands for data from animal studies.

Supported by an expert working group across regulatory agencies, the agrochemical and industrial chemical industries and expert consultants, we have led an analysis of the potential animal use and financial resource associated with either of the new ED-specific information requirement options. The results of this analysis were presented in a report, which was shared with the Commission in June 2023.

The analysis showed that the number of new studies that may need to be conducted to meet the new information requirements could use tens of millions of animals, and the proposed approach would not be feasible in practice. Given the challenges with implementing either of the new requirements and the need to minimise the reliance on animal testing as much as possible, the working group also identified areas where further consideration and clarification is needed on several aspects prior to their implementation. These will be outlined in a publication that is currently in preparation.

We are currently leading several projects in collaboration with HESI and expert working groups to apply the 3Rs in aquatic ED tests:

• A review of the current status and opportunities for improving aquatic ED in vivo test guideline studies.
• Analysis of historical control data from amphibian metamorphosis assays and medaka extended one generation reproduction tests [1]. The outcome of these analyses will inform improvements in the design and performance of these tests and interpretation of the data.
• Optimising concentration setting for aquatic ED in vivo tests. This data-driven project will provide recommendations and guidance to increase confidence in test results and maximise the utility of information generated, to avoid unnecessary additional vertebrate testing and suffering of test animals.