Merging scientific Evidence with Regulatory practices and Leveraging identification Of endocrine disruptors using New approach methodologies

Project Information

MERLON

Grant agreement ID: 101137411

DOI

10.3030/101137411

EC signature date 11 December 2023

Start date 1 January 2024

End date 31 December 2028

Funded under

• Health

Total cost

€ 7 587 975,00

EU contribution

€ 7 587 974,00

Coordinated by

DANMARKS TEKNISKE UNIVERSITET
Denmark

Periodic Reporting for period 1 - MERLON (Merging scientific Evidence with Regulatory practices and Leveraging identification Of endocrine disruptors using New approach methodologies)

Reporting period: 2024-01-01 to 2025-06-30

Summary of the context and overall objectives of the project

The European Union recognizes Endocrine Disrupting Chemicals (EDCs) as substances of high concern, motivating efforts to minimize human and environmental exposure through enhanced regulation and policy. A prevailing challenge, however, is that significant gaps persist in our understanding of the effects of EDCs during critical life stages, knowledge gaps that must be filled if we are to develop robust tools for EDC identification and regulation.

The MERLON project aims to address several critical gaps in understanding the impact of EDCs on human health, particularly in relation to sexual development and reproductive disorders. By leveraging New Approach Methodologies (NAMs) and cutting-edge techniques such as transcriptomics and Adverse Outcome Pathways, MERLON seeks to identify biomarkers and elucidate the quantitative relationships between EDC exposure and adverse effects on sexual development. The project's outcomes will contribute to the development of a roadmap for EDC identification, fostering collaboration with EU risk assessment bodies, public health authorities, regulators, and the broader scientific community to inform evidence-based regulations and policies.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The project has made substantial progress. Data from mother–child cohorts are being collected to examine associations between fetal exposure and later reproductive outcomes. Human testis and ovary cultures have been exposed to multiple endocrine disruptors, with RNA-seq libraries generated and tissues preserved for histology. Rat toxicity studies with the model compound DEHP are complete, with tissues and measurements available for mechanistic analysis, quantitative AOP development, and PBTK modeling. Chemical and hormone data have been collected for toxicokinetic analyses, and omics libraries are stored. Genetic mouse models of sexual brain differentiation are being applied, with promising preliminary results on region- and stage-specific effects of ED exposure. These studies will provide key mechanistic insights, strengthening causal toxicity pathways, AOP networks, and predictive NAMs. Development of ED-relevant NAMs is ongoing, including testis- and ovary-specific in vitro assays, brain models, and whole-organism NAMs (zebrafish, C. elegans, quail embryos) to support human-relevant toxicity assessments under NGRA frameworks. Finally, EU regulatory mapping shows that while updated legislation allows for NAM use in ED identification, in vivo data remain dominant. Based on this, we have proposed short- and long-term recommendations to better integrate NAMs into future testing and assessment strategies.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

NA at this stage.