Comparative evaluation and QSAR modeling of developmental neurotoxicity of novel brominated flame retardants in zebrafish

The novel brominated flame retardants (NBFRs) have received wide concerns due to their ubiquitous occurrence in the environment and their potential risks to ecosystems and human health. However, the toxicity data of NBFRs are still lacking, especially their toxicity comparison data, and toxicity predictions for untested NBFRs are extremely limited. In this study, eight commonly used NBFRs and decabromodiphenyl ether (BDE209) were selected to compare their toxicity at concentrations between 0.03 and 3.69 μM, by exposing zebrafish embryos until 120 h post-fertilization (hpf) and evaluating 18 toxicity indicators including basic development indicators and a series of behavioral indicators. The toxicity potency of the tested compounds ranked by the total number of significantly affected endpoints were pentabromobenzene (PBB) ≈ 2,4,6-tribromophenol (TBP) > BDE209 ≈ bis(2-ethylhexyl) tetrabromophthalate (TBPH) > pentabromotoluene (PBT) ≈ 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EHTBB) > 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) > hexabromobenzene (HBB) > decabromodiphenyl ethane (DBDPE). Almost all the tested compounds affected the locomotor behavior of zebrafish larvae, suggesting that the refined behavioral indicators were sensitive endpoints. Furthermore, the quantitative structure-activity relationship (QSAR) model we developed suggested that molecular surface area (MSA) might be the critical factor for determining the developmental neurotoxicity of NBFRs to zebrafish larvae, except for congeners with larger molecules (e.g. DBDPE, BTBPE). These findings would contribute to elucidating the toxicity differences among various NBFRs and provide important references for their toxicity prediction.