title: Bioaccumulation and behavioral effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in perinatally exposed mice.
abstract: Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants that have become pervasive environmental contaminants and may contribute to adverse health outcomes. We evaluated in mice the developmental neurotoxicity of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), one of the most abundant PBDE congeners detected in animal and human tissues. Female C57BL/6J mice were exposed to daily doses of 0, 0.03, 0.1 or 1mg/kg beginning 4 weeks prior to conception, continuing through gestation and lactation, and ending at weaning on postnatal day (PND) 21. Levels of BDE-47 in blood, brain, liver and adipose tissues of dams were markedly increased after 4 weeks of exposure, around the time of mating, and continued to increase through the time of parturition. Blood levels of BDE-47 in the dosed dams were within the range reported in humans. BDE-47 tissue levels in the dams decreased between parturition and weaning, possibly reflecting mobilization during lactation. Brain BDE-47 levels in the offspring at PND 1 approached those of the dams at parturition. Perinatal exposure to BDE-47 resulted in significant dose dependent growth retardation, slower motor performance in several behavioral tests, and mice exposed to 1mg/kg/day BDE-47 showed altered performance in the Morris water maze. There were no differences between groups in the numbers of pyramidal neurons in hippocampus CA1. These results document accumulation of BDE-47 in several organ systems following exposure to low-levels of BDE-47, and provide evidence that such exposure is associated with early behavioral deficits in exposed neonates.
authors.affiliation: Center for Children's Environmental Health, University of California-Davis, One Shields Avenue, Davis, CA 95616, United States.
authors.forename: Tram Anh
authors.initials: TA
authors.lastname: Ta
authors.forename: Claire M
authors.initials: CM
authors.lastname: Koenig
authors.forename: Mari S
authors.initials: MS
authors.lastname: Golub
authors.forename: Isaac N
authors.initials: IN
authors.lastname: Pessah
authors.forename: Lihong
authors.initials: L
authors.lastname: Qi
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Aronov
authors.forename: Robert F
authors.initials: RF
authors.lastname: Berman
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005865:Gestational Age; D055768:Halogenated Diphenyl Ethers; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D011075:Polybrominated Biphenyls / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000523:psychology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D014886:Weaning
chemical_list: D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D011075:Polybrominated Biphenyls; C511295:2,2',4,4'-tetrabromodiphenyl ether