You are here:
EVALUATING THE ABILITY OF IN VITRO ASSAYS BASED ON KEY EVENTS IN NEURODEVELOPMENT TO PREDICT DEVELOPMENTAL NEUROTOXICITY (DNT)
Citation:
Mundy, W. EVALUATING THE ABILITY OF IN VITRO ASSAYS BASED ON KEY EVENTS IN NEURODEVELOPMENT TO PREDICT DEVELOPMENTAL NEUROTOXICITY (DNT). Annual meeting of the SOT, New Orleans, LA, March 13 - 17, 2016.
Impact/Purpose:
Data analysis methods will help to determine predictive validity of a battery of assays for developmental neurotoxicity.
Description:
USABecause of the multitude of potential molecular targets for chemical disruption in the developing nervous system, our laboratory has developed in vitro assays that measure chemical disruption of key neurodevelopmental processes. These include proliferation, differentiation, apoptosis, axonal and dendritic development, synaptogenesis and network formation. The performance of each assay was validated using “training set chemicals” known to alter the individual neurodevelopmental process. To evaluate the ability of these assays, individually and collectively, to predict DNT, we have tested a set of over 50 chemical “DNT reference chemicals” and negative controls. For each assay, concentration-response relationships are established for both the neurodevelopmental endpoint of interest (e.g. proliferation) as well as cell health. This allows for the determination of the selectivity of each chemical on neurodevelopmental processes. Chemical effects were diverse in that some hit only a single endpoint, while others altered multiple endpoints. No single assay was predictive of DNT, but based on a selectivity score the battery of assays was able to discriminate between negative controls and DNT reference compounds.