Data from: Teratological and behavioral screening of the National Toxicology Program 91-compound library in zebrafish (Danio rerio)

Dach, Katharina, University of California, Davis

Yaghoobi, Bianca, University of California, Davis

Schmuck, Martin R., University of California, Davis

Carty, Dennis R., University of California, Davis

Morales, Kelly M., University of California, Davis

Lein, Pamela J., University of California, Davis

Published Oct 23, 2018 on Dryad. https://doi.org/10.5061/dryad.r841282

Cite this dataset

Dach, Katharina et al. (2018). Data from: Teratological and behavioral screening of the National Toxicology Program 91-compound library in zebrafish (Danio rerio) [Dataset]. Dryad. https://doi.org/10.5061/dryad.r841282

Abstract

To screen the tens of thousands of chemicals for which no toxicity data currently exists, it is necessary to move from in vivo rodent models to alternative models, such as zebrafish. Here, we used dechorionated Tropical 5D wildtype zebrafish embryos to screen a 91-compound library provided by the National Toxicology Program (NTP) for developmental toxicity. This library contained 86 unique chemicals that included negative controls, flame retardants, polycyclic aromatic hydrocarbons (PAHs), drugs, industrial chemicals and pesticides. Fish were exposed to five concentrations of each chemical or an equal amount of vehicle (0.5% DMSO) in embryo medium from 6 h post-fertilization (hpf) to 5 d post-fertilization (dpf). Fish were examined daily for mortality and teratogenic effects and photomotor behavior was assessed at 4 and 5 dpf. Of the five negative control compounds in the library, none caused mortality/teratogenesis, but two altered behavior. Chemicals provided in duplicate produced similar outcomes. Overall, 13 compounds caused mortality/teratology but not behavioral abnormalities, 24 only affected behavior, and 18 altered both endpoints, with behavior affected at concentrations that did not cause mortality/teratology (55/86 hits). Of the compounds that affected behavior, 52% caused behavioral abnormalities at either 4 or 5 dpf. Compounds within the same functional group caused different behavioral abnormalities, while similar behavioral patterns were caused by compounds from different groups. Our data suggest that behavior is a sensitive endpoint for developmental toxicity screening that integrates multiple modes of toxic action and is influenced by the age of the larval fish at the time of testing.

Usage notes

Behavior Screen

Zip file containing Excel files of photomotor behavior data assessed at 4 and 5 days post-fertilization for each individual chemical. The sheets titled “4 dpf” and “5 dpf” show the total distance moved in mm per 1 min bins and per light cycle for individual larvae. Sheets “4 dpf Behavior,” “4 dpf AUC,” “5 dpf Behavior” and “5 dpf AUC” are graphical depictions of this data. Sheet “Sheet1” is the statistical summary of the analysis and sheets “Sheet2” through “Sheet 13” are the cycle-specific results of Equation 1 (see section titled "Behavior screen" in paper).

Behavior.zip

Mortality/teratology screen

At 1, 2, 3, 4, and 5 dpf, embryos were examined for mortality and developmental malformations. Traditional endpoints of zebrafish teratology were scored, including arrested development, yolk sac edema, pericardial edema, red heart, deformities of the body axis, notochord aberrations, and malformations of craniofacial structures or the caudal fin (Fig. 2). Morphological assessments were quantified using a binary scale of either normal or abnormal morphology. For each exposure and each endpoint in the screen, the number of fish that were dead or exhibited a teratogenic effect was divided by the total number of fish within each group (n = 32 per exposure). If the incidence of mortality or of any individual teratogenic endpoint within any exposure group was more than 30% greater than that observed for the DMSO controls within the same spawn, it was considered a hit.

Morphology_Dryad.xlsx