title: 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.
authors: Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Starkville, MS, USA. Electronic address: nvinas@igbb.msstate.edu.
authors: Natàlia
authors: N
authors: Garcia-Reyero
authors: Environmental Laboratory, US Army Engineer Research and Development Center, Vicksburg, MS, USA.
authors: B Lynn
authors: BL
authors: Escalon
authors: Centro de Investigación y Desarrollo, CID-CSIC, Barcelona, Catalonia, Spain.
authors: Eva
authors: E
authors: Prats
authors: Environmental Laboratory, US Army Engineer Research and Development Center, Vicksburg, MS, USA.
authors: Jacob K
authors: JK
authors: Stanley
authors: Department of Environmental Chemistry, IDAEA-CSIC, Barcelona, Catalonia, Spain.
authors: Benedicte
authors: B
authors: Thienpont
authors: Environmental Laboratory, US Army Engineer Research and Development Center, Vicksburg, MS, USA.
authors: Nicolas L
authors: NL
authors: Melby
authors: Department of Environmental Chemistry, IDAEA-CSIC, Barcelona, Catalonia, Spain.
authors: Enrique
authors: E
authors: Barón
authors: Department of Environmental Chemistry, IDAEA-CSIC, Barcelona, Catalonia, Spain.
authors: Ethel
authors: E
authors: Eljarrat
authors: Department of Environmental Chemistry, IDAEA-CSIC, Barcelona, Catalonia, Spain.
authors: Damià
authors: D
authors: Barceló
authors: Chemotargets, IMIM-Hospital del Mar, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain.
authors: Jordi
authors: J
authors: Mestres
authors: Maladies Rares: Génétique et Métabolism, Université Bordeaux, Talence, France.
authors: Patrick J
authors: PJ
authors: Babin
authors: Environmental Laboratory, US Army Engineer Research and Development Center, Vicksburg, MS, USA.
authors: Edward J
authors: EJ
authors: Perkins
authors: Department of Environmental Chemistry, IDAEA-CSIC, Barcelona, Catalonia, Spain.
authors: Demetrio
authors: D
authors: Raldúa
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000819:agonists; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D003198:Computer Simulation; D005260:Female; D005411:Flame Retardants / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D019015:Geologic Sediments; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006801:Humans; D009474:Neurons / Q000187:drug effects; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists; D011960:Receptors, Estrogen / Q000819:agonists; D018570:Risk Assessment; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014877:Water Pollution, Chemical; D015027:Zebrafish / Q000196:embryology*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D000110:Acetylcholinesterase; D051792:Basic Helix-Loop-Helix Proteins; D002800:Cholinesterase Inhibitors; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; D014874:Water Pollutants, Chemical; D000097983:ERRalpha Estrogen-Related Receptor; C111235:AHR protein, human; C010902:decabromobiphenyl ether
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