Screening for Developmental Neurotoxicity at the National Toxicology Program: The Future Is Here

Area of Science:

• Toxicology
• Neuroscience
• Environmental Health

Background:

• The National Toxicology Program (NTP) faces challenges in testing numerous chemicals for developmental neurotoxicity (DNT) due to resource and time constraints of traditional animal studies.
• Evaluating complex chemical classes like flame retardants and perfluoroalkyl substances requires efficient screening methods.
• Existing methods are insufficient for the scale of chemical evaluation needed, necessitating novel approaches.

Purpose of the Study:

• To develop and characterize a battery of in vitro and alternative animal assays for assessing DNT.
• To establish a rapid, biologically relevant screening approach for prioritizing chemicals for further investigation.
• To create a collaborative framework for evaluating chemical impacts on neurodevelopmental processes.

Main Methods:

• A collaborative project involving ~40 participants from academia, industry, and government was initiated.
• Data from cell-based assays and alternative animal models were generated using NTP-provided compounds.
• Benchmark concentration (BMC) modeling was employed to analyze and compare results across diverse assays.

Main Results:

• Assay results were analyzed using benchmark concentration (BMC) modeling for cross-assay comparison.
• A web application was developed to share results with collaborators and is now publicly accessible.
• The project successfully characterized a battery of assays for DNT screening.

Conclusions:

• The developed screening approach offers a viable strategy for prioritizing chemicals for DNT assessment.
• This method addresses limitations of traditional animal testing, enabling more efficient evaluation of chemical classes.
• Further research is needed to integrate this approach into regulatory decision-making processes.