Our Research

Our approach was to develop a testing battery of in vivo, in vitro and in silico models with human relevance for testing and screening chemicals for endocrine disrupting properties impacting on neurodevelopment. The project concept was based on two pilars.

• Module 1: Test method development. Establishment of correlative and causal links between the modulation of endocrine pathways and DNT endpoints. 
• Module 2: Human & regulatory relevance of the developed test methods. Establishment of human relevance by linking experimental and epidemiological evidence and regulatory impact by continuous interaction with stakeholders.

Key accomplishments of ENDpoiNTs:

1. Improved Testing Methodologies

• Identified hormonal pathways crucial for neurodevelopment.
• Developed high-throughput assays (New Approach Methodologies - NAMs) targeting these pathways.
• 3 NAMs are in the validation phase and will be submitted to the OECD test guideline program.
• 21 predictive models (QSARs) are available as first tier screening for endocrine-induced neurodevelopmental effects.
• ENDpoiNTs database including statistical analyses tools is available as invaluable tool to make all produced data FAIR.
• New testing and screening methods to identify endocrine disrupting chemicals (EDCs) that induce human developmental  neurotoxicity (DNT)
• Generate new scientific knowledge on the link between endocrine disruption and DNT at the molecular, cellular, tissue, organism and behavioural level.
• Provide strategies to integrate these methods into European and international chemical regulatory frameworks.

2.  Integration of OMICs Data

• Combined data from in vitro, in vivo, and epidemiological studies.
• Identified biomarkers that link endocrine disruption to adverse neurodevelopmental outcomes.

3. Advancement in Adverse Outcome Pathways (AOPs)

• Extending established AOPs by integrating causal links between ED and DNT, and developed novel AOP networks.
• These elements enhance the understanding of how endocrine disruption leads to developmental neurotoxicity.

Test compounds

For the ENDpoiNTs project, a set of test compounds were selected that are  relevant for endocrine-induced developmental neurotoxicity (DNT) and are also relevant to human health. ENDpoiNTs studied a sets of test compounds that were tailored for specific research questions. The chosen in vitro and in vivo assays and endpoints were tested for their responsiveness to the identified relevant endocrine pathways. One of the main aims of ENDpoiNTs was to causally link disruption of endocrine pathways to developmental neurotoxicity endpoints on different levels (molecular, cellular, organismal) that are relevant for human health. The following test compounds were selected which are known or suspected endocrine disruptors associated with impaired human neurodevelopment: