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Cell-based approaches for screening and prioritization of chemicals that may cause developmental neurotoxicity
Citation:
SHAFER, TIM. Cell-based approaches for screening and prioritization of chemicals that may cause developmental neurotoxicity. Presented at Presentation at DuPont Haskell Research Laboratory, Delaware, DE, October 19, 2011.
Impact/Purpose:
The ultimate goal is to develop a suite of medium to high throughput assays that can screen and prioritize chemicals for their potential to cause developmental neurotoxicity
Description:
The National Academies report on Toxicity Testing in the 21st Century envisioned the use of in vitro toxicity tests using cells of human origin to predict the ability of chemicals to cause toxicity in vivo. Successful implementation of this strategy will ultimately result in faster and less expensive evaluation of many more chemicals than if current, animal based approaches are utilized. One particularly challenging area related to this vision is developmental neurotoxicity testing. These guideline protocols are time and resourse intensive and therefore not amenable to testing large numbers of chemicals:. To address this challenge, EPA researchers have adopted a cell-based approach to screen chemicals for their potential to cause developmental neurotoxicity. We are developing medium and high-throughput screens for critical processes in development including proliferation, differentiation, neurite outgrowth, and synaptogenesis. Several different cell models are being evaluated and or utilized, including neuroprogenitor cells from rodents and humans, primary cell cultures, and clonal cell lines. In addition, both morphological (e.g. neurite outgrowth) and functional (e.g. spontaneous firing rates on microelectrode arrays) endpoints are being evaluated. The ultimate goal is to develop a suite of medium to high throughput assays that can screen and prioritize chemicals for their potential to cause developmental neurotoxicity. This abstract does not reflect EPA policy.