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ICCVAM Biennial Report 2018-2019

Biennial Progress Report 2018-2019 Interagency Coordinating Committee on the Validation of Alternative Methods
https://ntp.niehs.nih.gov/go/892666

Incorporating Genetic Susceptibility into Developmental Neurotoxicity Screening via Population Diversity

The potential for neurotoxicity in children following exposure to environmental chemicals remains a high public priority due to concerns about recent increases in the prevalence of neurological disorders such as attention deficit hyperactivity disorder and autism. Neurotoxicity risk for an individual depends on a number of factors, including interactions between an individual’s variation in genetic makeup and exposures to neurotoxic chemicals in the environment. To investigate the role of genetic diversity in susceptibility to neurotoxicity, scientists at NIEHS, EPA, and FDA are using a genetically diverse set of cells to evaluate a curated set of chemicals with neurotoxic potential. Neural progenitor cells were derived from a set of mice bred to maximize genetic diversity, yielding 200 male and female genetically different cell lines. The panel of cell lines will be exposed to varying concentrations of the chemical test set and assessed using a high-content imaging assay called cell painting. The compiled dataset will be used to identify chemicals with a range of developmental neurotoxicity potencies. These data will inform data-driven uncertainty factors that account for interindividual variability, allowing for adequate protection of genetically sensitive subpopulations.

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