Overview

Every day, chemicals are released into the environment leading to human exposure (e.g. through the food we eat, the air we breathe, and the products we use) and exposure of natural animal and plant populations. Many of these substances can interfere with hormone systems, potentially affecting our health and the environment. Identifying these endocrine disrupting substances, which can mimic, block, or interfere with hormones, is therefore crucial to ensure their regulation and guarantee public and environmental safety.

The objective of this project is to provide a framework for the creation of Integrated Approaches to Testing and Assessment (IATAs ↗), which combine multiple sources of information to conclude on the toxicity of chemicals. Specifically, this project aims to develop IATAs for evaluating endocrine disruption, a priority health effect outlined in the European Chemicals Strategy for Sustainability ↗ priority areas: disruption of the thyroid hormone system, and anti-androgenic action. Disruption of either of these mechanisms can lead to important defects during embryonic development, which may persist later in life (e.g. leading to impaired cognitive function, or affected male reproductive health).

This project brings together researchers, regulators, and industry experts to refine the IATA frameworks.

By creating flexible, science-driven tools that are capable of adapting to different regulatory needs, this work will not only fill critical knowledge gaps but also ensure that decision-makers have the best possible tools to protect human health and ecosystems.

For this, a modular approach is envisioned to allow IATA adjustments to specific regulatory needs. This effort will not only structure and pinpoint key gaps but also facilitate the direct regulatory application of project outcomes.

Achievements & Results

Mechanistic IATA models identifying key mechanisms and effects involved in both thyroid and anti-androgenic endocrine activity and disruption, applicable for both human health and environmental protection and describing the links between them, were developed. The work utilised previously published OECD IATA approaches (OECD IATA guidance ↗; Jacobs et al. 2020 ↗; Louekari and Jacobs, 2024 ↗). Adverse Outcome Pathways (AOPs) available in the AOP wiki and a review of relevant literature were taken together and underpinned by expert knowledge. The OECD Conceptual framework (CF) for the identification of endocrine disruptors (OECD Guidance Document 150 ↗), which is also the basis of the EFSA ↗-ECHA ↗ guidance on the assessment of endocrine disruptors, was applied and updated as appropriate. Method inventories for thyroid hormone system disruption and anti-androgenic activity were created, organised according to the differen OECD CF levels, annotated as a function of their readiness level, and aligned with the mechanistic models. Case studies were then developed describing how the IATA models may be implemented in selected, specific regulatory decision-making scenarios.

Policy relevance

Criteria for the identification of endocrine disruptors have been stipulated for the Biocidal or Plant Protection Products Regulations, and a guidance document, i.e. “Guidance for the identification of EDs in the context of Regulations (EU) No 825/2012 and (EC) No 1107/2009) ↗”, was written by ECHA and EFSA to guide identification of EDs to comply with these obligations. Endocrine disruptors for human and environmental health have recently been added as new hazard classes to the CLP (classification, labelling and packaging) regulation, and a Guidance on the Application of the CLP Criteria has been published by ECHA (ECHA, 2024 ↗). In that context there was a need to create an overview of available methods for the evaluation of endocrine disruptors for both human and environmental health, both validated methods and methods that are close to or under validation, and to structure the methods according to IATA development principles. A modular approach is envisioned to allow for tailoring an IATA to specific regulatory needs. An endocrine disruptor IATA framework could benefit all EU agencies and European regulators dealing with endocrine disruptor assessment (e.g. ECHA and EFSA, national regulatory authorities), as well as the different regulations addressing this hazard class thus contributing to the harmonization of data requirements among EU and member state agencies. This project will support better regulatory decision making and improve the hazard identification of endocrine disrupting chemicals with the long-term aim to limit exposure and improve human as well as environmental health. The use of predictive methods and NAMs ↗ will be explored, with the potential to significantly reduce the need for long-term, low-throughput and costly toxicity tests requiring large numbers of animals, thus contributing to the replacement of animal tests.