In October, Grace Panter and Becky Brown participated in a “Capacity building workshop to support environmental endocrine disrupter assessment under UK chemicals regulation” co-organised by the National Centre for Replacement, Refinement and Reduction of animals in Research (NC3Rs), the UK Health and Safety Executive (HSE) and Corteva Agriscience. Despite being UK focused this cross-sector workshop on ED assessment discussed a range of topics and identified ongoing challenges relevant to the broader regulatory, scientific, and industry communities. While progress is being made in several areas, challenges remain and several key areas requiring further work were identified, including:
- Improving data interpretation. For example, the fish vitellogenin (VTG) endpoint remains highly variable, but carries a lot of weight in the ED assessment and, as a result of on-going work, a Standard Project Submission Form (SPSF) will be submitted to OECD regarding a new guidance document for VTG assessment.
- Understanding the Mode of Action (MoA) of chemicals is essential for hazard assessment. However, confusion often arises between MoA and Adverse Outcome Pathways (AOPs). MoA focuses on the chemical properties and biological mechanisms, while AOPs are chemical agnostic and describe a sequence of biological events that may lead to adverse effects. Despite this distinction, regulators often require data linking a MoA to an AOP (even when this may not be necessary).
- New approach methodologies (NAMs) are being developed and although their current regulatory acceptance remains a challenge, it is hoped that they could shift testing approaches more towards in vitro studies and embryo-based studies for assessment of endocrine activity, and hopefully avoid/reduce the need for higher-tier in vivo
- In ecotoxicology, population-relevant apical endpoints potentially coupled with population modelling could be critical for assessing the population relevance of any endocrine mediated adverse effects. One key issue is how to handle effects observed at the individual level that may not necessarily translate into meaningful impacts on population dynamics. While apical endpoints, such as reproduction and survival, are crucial for understanding potential impacts, the challenge lies in determining whether individual-level effects have population relevance. It is hoped that population modelling may hold the potential to reduce animal testing in the long term by providing more accurate predictions based on fewer, more targeted studies.
- Revisiting/revision of existing test guidelines which are either out of date (i.e. based on experience for example where feeding regimes need amending) or where interpretation should reflect current science and practical experience.
- Harmonization of definitions across the test guidelines. One example was the definition of the maximum tolerated concentration setting in endocrine studies, which is inconsistent across the test guidelines and open to interpretation. More emphasis is required on justification of definitive concentration setting in final study reports.
- There may be an enormous regulatory demand created by the implementation of specific ED assessment requirements under EU Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) and Classification, Labelling and Packaging (CLP) regulations.
- Regulators face challenges in determining whether current studies are sufficient to draw conclusions regarding ED effects, which can lead to demands for additional testing. There was an emphasis on cross-sector collaboration and continued dialogue between Applicants and the Regulators to address these challenges and move toward more efficient and effective ED testing strategies.
The above is only a snapshot of some of the topics discussed in the workshop, and for more information on the meeting or on ED testing in general, please contact myself (grace.panter@wca-consulting.com) or Becky Brown (becky.brown@wca-consulting.com). A workshop summary will be made publicly available in the near future.
Further reading:
wca papers on endocrine disruption
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