Leveraging Embryonic Zebrafish to Prioritize ToxCast Testing

Abstract

On the basis of two pilot high-content screens of ToxCast Phase I chemicals, we previously demonstrated that exposure of zebrafish embryos to abamectin and butafenacil abolished spontaneous activity and induced severe anemia, respectively. Therefore, the objective of this study was (1) to determine whether high-throughput in vitro screening data from the ToxCast program would have prioritized abamectin and butafenacil for further testing and (2) to determine whether a single three-day zebrafish embryo assay is a strong predictor of Toxicological Priority Index (ToxPi) scores derived from ToxCast data. Using publically available ToxCast assay end point data and target information, we calculated assay hit rates, developed hazard classifications, and relied on the ToxPi Graphical User Interface to generate ToxPi charts and scores within a biological process-driven configuration. Overall, our findings suggest that embryonic zebrafish may be valuable for prioritizing ToxCast testing as well as addressing toxicity pathways that may not be represented by the ToxCast assay battery.