Leveraging Embryonic Zebrafish To Prioritize ToxCast Testing

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.