Effects of BDE-209 contaminated sediments on zebrafish development and potential implications to human health

Abstract

Polybrominated diphenyl ethers are compounds widely used as flame-retardants, which are of increasing environmental concern due to their persistence, and potential adverse effects. This study had two objectives. First, we assessed if BDE-209 in sediment was bioavailable and bioaccumulated into zebrafish embryos. Secondly, we assessed the potential impact on human and environmental health of bioavailable BDE-209 using human in vitro cell assays and zebrafish embryos. Zebrafish were exposed from 4h to 8days post-fertilization to sediments spiked with 12.5mg/kg of BDE-209. Zebrafish larvae accumulated ten fold more BDE-209 than controls in unspiked sediment after 8days. BDE-209 impacted expression of neurological pathways and altered behavior of larvae, although BDE-209 had no visible affect on thyroid function or motoneuron and neuromast development. Zebrafish data and in silico predictions suggested that BDE-209 would also interact with key human transcription factors and receptors. We therefore tested these predictions using mammalian in vitro assays. BDE-209 activated human aryl hydrocarbon receptor, peroxisome proliferator activating receptors, CF/b-cat, activator protein 1, Oct-MLP, and the estrogen receptor-related alpha (ERRα) receptor in cell-based assays. BDE-209 also inhibited human acetylcholinesterase activity. The observation that BDE-209 can be bioaccumulated from contaminated sediment highlights the need to consider this as a potential environmental exposure route. Once accumulated, our data also show that BDE-209 has the potential to cause impacts on both human and environmental health.

Keywords: AChE; AOP; Acetylcholinesterase; AhR; BDE-209; Behavior; CPF; DEGs; Dpf; GC-NICI–MS; HTS; Hpf; MIE; Microarrays; Neurotoxicity; PBDE; SPLE; T4; ZF; Zebrafish; acetylcholinesterase; adverse outcome pathway; aryl hydrocarbon receptor; chlorpyrifos; days post-fertilization; decabromodiphenyl ether; differentially expressed genes; gas chromatography coupled to mass spectrometry working with negative ion chemical ionization; high-throughput screening; hours post-fertilization; molecular initiating event; polybrominated diphenyl ether; qPCR; real-time quantitative polymerase chain reaction; selective pressurized liquid extraction; thyroxine; zebrafish.