Teratological and Behavioral Screening of the National Toxicology Program 91-Compound Library in Zebrafish (Danio rerio)

Katharina Dach, Bianca Yaghoobi, Martin R. Schmuck, Dennis R. Carty, Kelly M. Morales, Pamela J Lein

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 wild-type 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 5 concentrations of each chemical or an equal amount of vehicle (0.5% DMSO) in embryo medium from 6 h post-fertilization (hpf) to 5 days post-fertilization (dpf). Fish were examined daily for mortality and teratogenic effects and photomotor behavior was assessed at 4 and 5 dpf. Of the 5 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.

Original languageEnglish (US)
Pages (from-to)77-91
Number of pages15
JournalToxicological sciences : an official journal of the Society of Toxicology
Volume167
Issue number1
DOIs
StatePublished - Jan 1 2019

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Zebrafish
Toxicology
Libraries
Screening
Fish
Toxicity
Fertilization
Teratology
Fishes
Mortality
Flame Retardants
Industrial chemicals
Toxic Actions
Polycyclic Aromatic Hydrocarbons
Embryonic Structures
Dimethyl Sulfoxide
Pesticides
Teratogenesis
Functional groups
Rodentia

ASJC Scopus subject areas

  • Toxicology

Cite this

Teratological and Behavioral Screening of the National Toxicology Program 91-Compound Library in Zebrafish (Danio rerio). / Dach, Katharina; Yaghoobi, Bianca; Schmuck, Martin R.; Carty, Dennis R.; Morales, Kelly M.; Lein, Pamela J.

In: Toxicological sciences : an official journal of the Society of Toxicology, Vol. 167, No. 1, 01.01.2019, p. 77-91.

Research output: Contribution to journalArticle

Dach, Katharina ; Yaghoobi, Bianca ; Schmuck, Martin R. ; Carty, Dennis R. ; Morales, Kelly M. ; Lein, Pamela J. / Teratological and Behavioral Screening of the National Toxicology Program 91-Compound Library in Zebrafish (Danio rerio). In: Toxicological sciences : an official journal of the Society of Toxicology. 2019 ; Vol. 167, No. 1. pp. 77-91.
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