Animal-Free Assays for endocrine disruption – from science to Regulatory Acceptance

The AFARA project studies the process of acceptance and implementation of animal-free models in the human risk assessment of Endocrine Disrupting Chemicals (EDCs). EDCs are increasingly linked to a wide range of human diseases acting via the endocrine system and include substances like Bisphenol A, phthalates, PFAS and parabens. Safequarding public health from the potentially harmful effects of exposure to EDCs requires robust and human-relevant testing strategies. The AFARA project started in February 2023 and will run for 5 years.

Risk assessment is necessary to protect us against the possible health effects of exposure to EDCs. To date, risk assessment of EDCs incorporates laboratory animal testing but this is increasingly being criticized. From a societal point of view on animal welfare, there is growing pressure to move away from the use of animal studies in testing of chemicals and products. From a scientific point of view, the translation of results from animals to people introduces another (unnecessary) layer of complexity in its interpretation and several human-relevant processes cannot be tested in animals. Therefore, the current reality of risk assessment of EDCs does not match with the societal and scientific urgency to use animal-free and human-relevant testing strategies. Animal-free testing methods are key for better diagnosis of important EDC associated diseases and dysfunctions. These testing strategies will help to generate data on endocrine activity and development of endocrine related human diseases while minimising the reliance on existing animal models, thereby promoting a more relevant and ethical approach to risk assessment.

Project goals

AFARA aims to facilitate the pathways for regulatory acceptance of existing models for endocrine disruption (ED) that are both human-relevant and animal-free. The project will identify the challenges and opportunities within the existing European legal and regulatory frameworks for the use of animal-free models for EDC identification. In addition, AFARA will evaluate ways to accelerate development and implementation of animal-free models for identification of thyroid disrupting chemicals (TDCs) and metabolism disrupting chemicals (MDCs). Through productive interactions with a wide range of consortium partners, cooperation partners and stakeholders, drivers and barriers for regulatory acceptance of animal-free testing strategies for the risk assessment for TDCs will be evaluated. The TDC case will therefore be implemented as a learning case, whilst the lessons learned will be implemented in the MDC case. The results from the AFARA project will ensure that model developers and other stakeholders in the ED field have increased ability to apply the pathways to regulatory acceptance of animal-free methods for EDC identification.

Consortium

AFARA combines academic expertise across the natural sciences (toxicologists), social sciences (science, technology and innovation studies) and humanities (ethics and law) with key public sector expertise on EDC regulation. It works together with industry, NGOs, regulatory authorities and model developers to achieve better protection of citizens from EDC-related harm and reduce the use of animal testing. RIVM colleagues involved include Ellen Hessel, Anne Kienhuis, Wieneke Bil, Bas Bokkers and Esther de Jong. The coordination team of AFARA consists of the Project Coordinator (PC), the Vice-Coordinator for Science (VC-Science), Vice-Coordinator for Impact (VC-Impact) and the Project Manager (PM). The PC, VC-Impact and PM are all from Utrecht University and the VC-Science is from RIVM. RIVM is WP lead of WP2 and Utrecht University is WP lead of WP1, 3 and 4. RIVM is involved in all WPs.

Role of RIVM

RIVM will contribute based on its expertise in model development and and risk assessment. In the AFARA project, we will employ testing strategies for EDCs that are human relevant and fully rely on animal-free models, thereby gaining and sharing experience on the use of animal-free testing strategies in safety and risk assessment with active involvement of our consortium partners and stakeholders in the field.

Funding

The AFARA project is part of the research programme Safety assessment via animal-free models which is financed by the Dutch Research Council (NWO) under project number NWA.1395.20.008.