title: Impact of repeated exposure on the toxicokinetics of BDE 47 in mice.
abstract: 2,2',4,4'-Tetrabromodiphenyl ether (BDE 47) is the major polybrominated diphenyl ether (PBDE) found in environmental samples and human tissue despite its small contribution to global production and usage. Currently, three toxicokinetic studies are available investigating single-dose exposures; this is the first study to investigate toxicokinetic parameters following repeated exposure to BDE 47. The disposition and excretion of BDE 47 was monitored in adult female C57BL/6 mice for 5 days following ten consecutive 1.0-mg/kg oral doses and compared with results from our previous study. Results of the present study suggest greater retention of BDE 47 and nonlinear disposition patterns following repeated exposure to this dose in mice. No target tissues of sequestration or potential toxicity were determined; however, some tissues, such as the liver, demonstrated patterns of interest following repeated exposure that were not previously observed in acute toxicokinetic studies. Repeated exposure to BDE 47 results in higher concentrations remaining in adipose tissue, which demonstrates its potential for bioaccumulation. The data also suggest that excretion of BDE 47 may be decreased following repeated exposure. These results, in combination with evidence of its persistence and toxicity, underlie the need to further understand BDE 47 toxicokinetics across species at steady-state conditions.
authors.affiliation: UNC Curriculum in Toxicology, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. dstaskal@chemrisk.com
authors.forename: D F
authors.initials: DF
authors.lastname: Staskal
authors.forename: J J
authors.initials: JJ
authors.lastname: Diliberto
authors.forename: L S
authors.initials: LS
authors.lastname: Birnbaum
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis; D004790:Enzyme Induction; D005243:Feces / Q000737:chemistry; D005260:Female; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008658:Inactivation, Metabolic; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010647:Phenyl Ethers / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011075:Polybrominated Biphenyls; D014018:Tissue Distribution
chemical_list: D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; C511295:2,2',4,4'-tetrabromodiphenyl ether; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1