Project Overview - This project aims to identify novel endpoints sensitive to endocrine disruption (ED) in the adult nervous system and to develop assays by focusing on mechanisms of ED in relation to neurocognitive conditions.
Objectives
- Mechanistic Understanding of ED: Investigate the disruption of retinoid signaling pathways and their interactions with other nuclear receptors (CAR, PXR, PPARs, LXR, THR) and estrogen receptors (ERα, ERβ) in vertebrate models (adult human- and rat-derived neuronal/glial cell).
- Comparative Analysis Across Species: In collaboration with other partners assess heterodimeric signaling cascades (e.g., RXR-TR) in vertebrates and compare with invertebrates to identify commonalities in endocrine signaling and neurotoxic effects.
- Development of Adverse Outcome Pathways (AOPs): The experimental approach and the identification of the most relevant endpoints will be supported by the development of cross-species retinoid system-relevant AOPs which will integrate the data obtained in the project in an iterative process to define their taxonomic applicability.
- Advancing Regulatory Approaches: Incorporate non-EATS modalities into Integrated Approaches to Testing and Assessment (IATAs) and regulatory case studies, ensuring a broader perspective on endocrine disruption.
By addressing critical knowledge gaps in ED assessment, this project will contribute to a more comprehensive understanding of how endocrine disruptors affect the adult nervous system, ultimately informing improved regulatory and environmental protection strategies.
- Host Institution: Università degli Studi di Milano, Italy
- Lead Supervisor: Barbara Viviani, Laboratory of Toxicology and Risk Assessment, Neurotoxicity Unit
- Subject area: Neurotoxicology, New Approach Methodologies, Adverse Outcome Patways