NIH Reporter #5R44ES036902-03

Development of a Comprehensive Hen's Egg Model for Genotoxicity Testing

This award funds the development and validation of a non-animal hen's egg model for genotoxicity testing to assess DNA damage potential of chemicals, meeting upcoming regulatory guidelines.

Description

Evaluating pharmaceuticals and various industrial chemicals for their capacity to cause DNA damage is a crucial step in protecting human health due to their potential to cause cancer and contribute to other diseases. As regulatory agencies shift away from the use of animals in risk assessment, toxicological risk assessment is in need of a reliable non-animal model to evaluate chemicals for DNA damaging potential. We will develop, optimize, and validate a comprehensive hen’s egg model for assessing chemicals for DNA damage potential, while fulfilling upcoming regulatory guidelines. The hen’s egg is a unique system in that it is not considered an animal model due to deficiencies in brain activity and pain perception early in development. Yet, similar to in vivo models, the hen’s egg has endogenous metabolic activity and functioning hepatic and hemopoietic organ systems. We will leverage these features to develop an assay that evaluates genotoxicity in the blood and liver, automating micronuclei quantification in erythrocytes and hepatocytes using flow cytometry and high content imaging. The assay will also assess genotoxic and cytotoxic biomarkers, providing insights into organ-specific toxicity and genotoxic modes of action. The development, optimization, and validation of this hen’s egg genotoxicity assay will meet the critical need for an accurate, metabolically-active in vitro genotoxicity assay, fulfilling upcoming regulatory requirements.

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