title: Neurobehavioral effects of tetrabromobisphenol A, a brominated flame retardant, in mice.
abstract: Tetrabromobisphenol A (TBBPA) is widely used as a flame retardant and is suspected to be stable in the environment with possible widespread human exposures. In the present study, we investigated the behavioral effects of TBBPA and measured the levels of TBBPA in the brain after oral administration in mice. Acute treatment with TBBPA (5mg/kg body weight) 3h before the open-field test induced an increase in the horizontal movement activities. In contextual fear conditioning paradigm, mice treated with TBBPA (0.1mg/kg or 5mg/kg body weight) showed more freezing behavior than vehicle-treated mice. In addition, TBBPA (0.1mg/kg body weight) significantly increased the spontaneous alternation behavior in the Y-maze test. The levels of TBBPA in the brain following TBBPA treatment were determined by using LC/ESI-MS/MS system. In the brain regions examined, high amounts of TBBPA were detected in the striatum after treatment with 0.1mg/kg or 5mg/kg body weight TBBPA, whereas non-specific accumulation of TBBPA in the brain was found after treatment with 250 mg/kg body weight TBBPA. These results suggest that TBBPA accumulates in brain regions including the striatum and induces the behavioral alterations. Together, the possibility of widespread human exposure to TBBPA warrants further studies to characterize its neurotoxicity.
authors.affiliation: Laboratory of Pharmacotherapy, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakajima
authors.forename: Daisuke
authors.initials: D
authors.lastname: Saigusa
authors.forename: Naomi
authors.initials: N
authors.lastname: Tetsu
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamakuni
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Tomioka
authors.forename: Takanori
authors.initials: T
authors.lastname: Hishinuma
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002853:Chromatography, Liquid; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005411:Flame Retardants / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D011075:Polybrominated Biphenyls / Q000493:pharmacokinetics / Q000633:toxicity*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D005411:Flame Retardants; D011075:Polybrominated Biphenyls; C020806:tetrabromobisphenol A