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Predicting developmental neurotoxicity in rodents from larval zebrafish - - and vice versa
Citation:
Moser, V. C., R. Macphail, P. Phillips, M. Culbreth, Kathy Mcdaniel, K. Jarema, AND S. Padilla. Predicting developmental neurotoxicity in rodents from larval zebrafish - - and vice versa. Presented at Society of Toxicology meeting, March 10 - 14, 2013.
Impact/Purpose:
This abstract will be presented at the Society of Toxicology meeting March 10-14, 2013, San Antonio, TX
Description:
The complexity of standard mammalian developmental neurotoxicity tests limits evaluation of large numbers of chemicals. Less complex, more rapid assays using larval zebrafish are gaining popularity for evaluating the developmental neurotoxicity of chemicals; there remains, however, a pressing need to determine the utility of the model for predicting adverse neurobehavioral outcomes. We are undertaking studies to compare the developmental effects of chemicals in both larval zebrafish and rats. In addition, zebrafish studies show that transitions between light and dark periods can produce robust changes in activity that may be differentially altered by chemicals; an analogous behavior pattern is being studied in rats. Developmental heptachlor in rats increased motor activity in addition to altering righting reflex ontogeny, and impairing learning and memory in adult offspring. In zebrafish, developmental heptachlor produced marked increases in dark-induced activity and dysregulation of the light-dark patterning of activity. Preliminary studies with dimethyl phthalate (DMP) in zebrafish showed reduced habituation only during the dark period, perhaps reflecting changes in anxiety or cognitive behaviors. We evaluated developmental effects of DMP in rats using light-dark transition activity measures in addition to standard neurobehavioral toxicity tests including anxiety. Alterations were observed on several of these endpoints; however, the results were not always dose-related and were confounded by maternal toxicity at high doses. While these results suggest concordance between outcomes of two chemicals from different classes, considerably more comparisons with positive and negative controls are needed to understand the predictability of the larval zebrafish assay. Further exploration of analogous/homologous behavioral tests in both species may be beneficial in evaluating neurotoxic outcomes from developmental exposures, and in assessing the conformity of results. This is an abstract ofa proposed presentation and does not reflect US EPA policy.