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Use of HCI to screen for developmental neurotoxicity
Citation:
Mundy, W. Use of HCI to screen for developmental neurotoxicity. Presented at Society of Toxicology, Phoenix, AZ, March 23 - 27, 2014.
Impact/Purpose:
Abstract will be presented at Society of Toxicology Meeting, March 23-27, 2014, Phoenix, AZ
Description:
The development of the nervous system is a prolonged process. It starts with the generation of neuroepithelial cells during embryogenesis and is not complete until the final stages of synaptic remodeling in the young adult. The outcome is a functionally connected neural network that characterizes the mature brain. Chemical- induced changes in neurodevelopment have traditionally been studied after dosing pregnant animals and evaluating effects on brain chemistry, morphology, and behavior in the offspring. This testing strategy focuses on assessing the apical effects of chemicals after developmental exposure and is time consuming, costly and uses large numbers of animals. Thus, few of the thousands of chemicals in commerce with potential human exposure have been tested for developmental neurotoxicity (US EPA, 1998; Judson et al., 2009). In addition, apical tests of developmental neurotoxicity provide little data on mode or mechanism of action, which hinders the ability to extrapolatethe results of animal studies to humans. In order to move away from in vivo tests towards a faster and less expensive assessment of the developmental neurotoxicity potential of chemicals, a new testing paradigm is needed. In 2007 a report entitled “Toxicity Testing in the 2l’ Century: A Vision and a Strategy” was released by the US National Research Council (NRC, 2007). The report recommended the development of in cHico and in vitro model, based on human biology, to accelerate the acquisition of data on chemical toxicity. This approach is based on the identification of cellular toxicity pathways that underlie adverse outcomes observed in the whole organism. Knowledge of the molecular targets that, when perturbed by chemicals, activate these toxicity pathways would allow for the development and use of in vitro high throughput assays that are capable of screening large numbers of chemicals. See attached abstract for complete abstract