Key messages

• The project addresses critical gaps in developmental and reproductive toxicology (DART-ED) assessment by advancing mechanistic understanding and New Approach Methodologies (NAMs ↗) development across EATS (Estrogen, Androgen, Thyroid, Steroidogenesis) and non-EATS modalities.
• It supports regulatory needs by developing NAMs that integrate multiple endocrine pathways and life stage vulnerabilities, enabling more comprehensive and animal-free testing.
• The project has direct impact on REACH ↗, CLP, PPP, BP, and Cosmetics Regulation by providing scientifically grounded tools for ED identification and DART assessment.
• It will deliver human-relevant test methods, enhance predictive capacity of new and existing methods, and improve cross-species applicability.

Overview

Current gaps in endocrine disruptor (ED) identification, particularly related to developmental and reproductive toxicity (DART), will be addressed by generating new mechanistic knowledge, develop and refine test methods, and provide input to relevant Adverse Outcome Pathways (AOPs ↗). The work will support the development of novel New Approach Methodologies (NAMs), with a focus on both EATS (Estrogen, Androgen, Thyroid, Steroidogenesis) and non-EATS modalities, by also including pathways such as retinoic acid, glucocorticoid, aryl hydrocarbon receptor, and PPAR signalling.

Efforts will prioritise life stages with heightened vulnerability to endocrine disruption and develop NAMs capable of assessing multiple pathways simultaneously, incorporating signalling crosstalk between axes such as EAS active substances and T (thyroid signalling). These integrative approaches will strengthen mechanistic understanding and enhance the regulatory relevance of NAMs.

Project outcomes will contribute directly to EU regulatory processes and frameworks. These include supporting the Chemicals Strategy for Sustainability, improving ED identification under REACH and CLP ↗, enhancing animal-free testing strategies under the Plant Protection and Biocidal Products regulations ↗, and providing sensitive methods applicable to the Cosmetics Regulation ↗. The overall objective is to enable more robust, mechanistically informed, and harmonised approaches to ED assessment across chemical legislation.

Policy relevance

Project outcomes will provide new test methods and knowledge on their predictive capacity relative to adverse outcomes, hence be directly relevant for facilitating the EUs Roadmap to phasing out animal testing, but at the same time help ensure replacements are adequate in identifying substances of potential harm to humans. Project outcomes will also support the ‘one health’ strategy by integrating typical environmental-relevant methods for predicting human-relevant effect outcomes.