NTP scopes the future of developmental neurotoxicity screening
Scientists in the National Toxicology Program (NTP) published a proof-of-concept study that characterized a set of in vitro and alternative animal assays for their ability to measure how chemicals affected a variety of neurodevelopmental processes. The paper, which leads off a special issue on developmental neurotoxicity (DNT) in the journal Toxicological Sciences, describes the approach to creating the chemical library that was provided to project collaborators; development of a data analysis strategy; the structure of the web application that provides access to results; and key issues and knowledge gaps to address so that the approach can be used in regulatory decision-making.
NTP needs new approaches to assess DNT for classes of chemicals, such as flame retardants, polycyclic aromatic compounds, and perfluorinated compounds, including mixtures. Project collaborators used the chemical library in cell-based assays that targeted specific neurodevelopmental processes and in the alternative animal models of zebrafish and planaria. NTP scientists structured the resulting data to make it directly comparable across studies, then designed a method to identify DNT active chemicals and their potencies, to aid in prioritizing compounds for further testing. Finally, they developed an interactive web application to allow data exploration and visualization, called Developmental NeuroToxicity Data Integration and Visualization Enabling Resource (DNT-DIVER).
Nine companion papers highlight details of the data analysis pipeline, findings from the zebrafish and planaria studies, how chemicals that showed DNT activity could be compared across models, and insight on using the approach in regulatory decision-making. (KL)
Citation: Behl M, Ryan K, Hsieh JH, Parham F, Shapiro AJ, Collins BJ, Sipes NS, Birnbaum LS, Bucher JR, Foster PMD, Walker NJ. Paules RS, Tice RR. 2018. Screening for developmental neurotoxicity at the National Toxicology Program: the future is here. Toxicol Sci; doi:10.1093/toxsci/kfy278 [Online 28 November 2018].