Developmental Neurotoxicity (DNT) Studies for Chemical Safety Assessments: Basic Concepts, Experimental Strategies, and Future Directions.

Abstract

The 21st ESTP's (European Society of Toxicology Pathology) Annual Congress (2024) included a 3-hour scientific session on developmental neurotoxicity (DNT) as applied to chemical safety assessments. Key concepts of this session were to provide an introduction to public concerns around this endpoint, a status update on practical aspects of DNT studies, insights into the use of DNT studies within a regulatory context, as well as some pointers on how to evaluate specific parameters. Understanding the biological and technical variability in performing neuropathology examinations (such as morphometric evaluation) is critical during the course of DNT evaluation. Using thyroid hormone disruption as an example, challenges and pitfalls impacting data interpretation were discussed. Results from the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) Thyroid Task Force regarding thyroid hormone-related neurodevelopmental toxicity in humans and rodents were presented. Histopathological findings in the brain and potential changes in the cochlea of pups associated with thyroid hormone imbalance in dams during pregnancy were shown. A case presentation from an Extended One-Generation Reproductive Toxicity Study (EOGRTS) showing histopathological findings in the absence of changes with morphometric endpoints was included. In conclusion, all session participants underscored the need for integrated data evaluation for DNT risk assessment.