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ToxSci Advance Access published online on November 9, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfj038
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received September 1, 2005
Accepted November 5, 2005

Biotransformation and Toxicokinetics

Impact of Repeated Exposure on the Toxicokinetics of BDE 47 in Mice

D. F. Staskal 1*, J. J. Diliberto 2, and L. S. Birnbaum 2

1 UNC Curriculum in Toxicology, US EPA, MD B143-01, 109 TW Alexander Dr. Research Triangle Park, NC 27711
2 US EPA, ORD, NHEERL, ETD, US EPA, MD B143-01, 109 TW Alexander Dr. Research Triangle Park, NC 27711

* To whom correspondence should be addressed.
D. F. Staskal, E-mail: staskal.daniele{at}epa.gov


  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 five days following ten consecutive 1.0 mg/kg oral doses and compared with results from our previous study (Staskal et al. 2005). Results of the present study suggest greater retention of BDE 47 and non-linear 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.

Keywords: BDE 47; PBDE; toxicokinetics; brominated flame retardant.
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