TitleThe multi-dimensional embryonic zebrafish platform predicts flame retardant bioactivity.
Publication TypeJournal Article
Year of Publication2020
AuthorsTruong, L, Marvel, S, Reif, DM, Thomas, DG, Pande, P, Dasgupta, S, Simonich, MT, Waters, KM, Tanguay, RL
JournalReprod Toxicol
Date Published2020 09

Flame retardant chemicals (FRCs) commonly added to many consumer products present a human exposure burden associated with adverse health effects. Under pressure from consumers, FRC manufacturers have adopted some purportedly safer replacements for first-generation brominated diphenyl ethers (BDEs). In contrast, second and third-generation organophosphates and other alternative chemistries have limited bioactivity data available to estimate their hazard potential. In order to evaluate the toxicity of existing and potential replacement FRCs, we need efficient screening methods. We built a 61-FRC library in which we systemically assessed developmental toxicity and potential neurotoxicity effects in the embryonic zebrafish model. Data were compared to publicly available data generated in a battery of cell-based in vitro assays from ToxCast, Tox21, and other alternative models. Of the 61 FRCs, 19 of 45 that were tested in the ToxCast assays were bioactive in our zebrafish model. The zebrafish assays detected bioactivity for 10 of the 12 previously classified developmental neurotoxic FRCs. Developmental zebrafish were sufficiently sensitive at detecting FRC structure-bioactivity impacts that we were able to build a classification model using 13 physicochemical properties and 3 embryonic zebrafish assays that achieved a balanced accuracy of 91.7%. This work illustrates the power of a multi-dimensional in vivo platform to expand our ability to predict the hazard potential of new compounds based on structural relatedness, ultimately leading to reliable toxicity predictions based on chemical structure.

Alternate JournalReprod Toxicol
PubMed ID32827657
PubMed Central IDPMC7892636
Grant ListP30 ES000210 / ES / NIEHS NIH HHS / United States
P30 ES030287 / ES / NIEHS NIH HHS / United States
P42 ES016465 / ES / NIEHS NIH HHS / United States
R56 ES030007 / ES / NIEHS NIH HHS / United States