Dose level selection for developmental and reproductive toxicology (DART) studies: Insights from the EUROTOX 2024...

In 2022, the European Chemicals Agency (ECHA) issued updated advice on high-dose selection for developmental and reproductive toxicity (DART) studies, aiming to ensure reproductive hazards are identified without causing excessive toxicity or severe suffering in test animals. However, the advice faced much criticism from the scientific community with concerns around animal welfare and use of unnecessarily high doses. To better understand the background to the advice and explore the implications of this guidance, a satellite workshop was held at EUROTOX 2024 in Copenhagen, in collaboration with ECHA, that brought together over 120 global stakeholders from industry, regulatory bodies, academia, and contract research organisations. Discussions focused on the interpretation and application of the advice across OECD test guidelines (TGs 414, 421/422, and 443), highlighting areas of uncertainty, such as dose spacing, sex-specific sensitivity, and balancing fertility versus developmental endpoints. Interactive sessions revealed differing interpretations and underscored the need for clearer guidance. The workshop fostered mutual understanding and identified opportunities to refine the advice to better align scientific, regulatory, and animal welfare objectives. This report summarises key discussions and outlines the need for continued collaboration to support harmonised, scientifically justified dose selection practices that support both human health protection and 3Rs principles.