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TISSUE DISTRIBUTION AND ELIMINATION OF BDE 47 IN MICE FOLLOWING A SINGLE ORAL DOSE
Citation:
Staskal, D., J J. Diliberto, M J. DeVito, AND L S. Birnbaum. TISSUE DISTRIBUTION AND ELIMINATION OF BDE 47 IN MICE FOLLOWING A SINGLE ORAL DOSE. Presented at Dioxin 2004, Berlin, Germany, Sept. 3-11, 2004.
Description:
2,2',4,4'-Tetrabromodiphenyl ether (BDE 47) is a polybrominated diphenyl ether (PBDE) congener which is part of a class of brominated flame retardants (BFRs) commonly used in a variety of highly flammable consumer goods. Concern for the effects of PBDEs has increased significantly in recent years as their presence has been detected in environmental samples and in human tissues at steadily increasing concentrations1. Despite its small contribution to the PBDE global production and usage, BDE 47 is the major congener found in environmental samples and human tissue. Limited toxicology studies suggest that BDE 47 is a developmental neurotoxicant and an endocrine disruptor1; however, several data gaps exist and must be investigated in order to evaluate the human health risk of BDE 47.
One of the major gaps in PBDE knowledge is a lack of basic toxicokinetic data. Orn and Wehler3 have previously reported limited toxicokinetic properties of BDE 47 in male C57 mice following a single oral dose (30 umol/kg). Our laboratory has also recently reported the effects of dose and route of exposure on the toxicokinetics of BDE 47 in mice2. This congener is well absorbed, not readily metabolized, and distributes as expected based on its lipophilic nature; adipose, liver, and skin were major tissues of disposition following an acute exposure. BDE 47 is readily excreted in the urine and feces: the dose being eliminated in the urine is excreted as parent compound, although this process appears to be saturable2.
This study investigated basic toxicokinetic properties of BDE 47 in female C57BL/6J mice. Here we report the effect of time on the absorption, distribution, and excretion following a single, oral dose of 14C-labeled BDE 47. Animals were administered 1.0mg/kg BDE 47, a dose chosen based on previous studies2. Distribution and elimination were monitored at several time points ranging from 1 hour to 21 days following exposure. Data from these basic toxicokinetic studies will be applied to studies investigating the toxicokinetics of BDE 47 in a developmental model as well as in the development of a physiologically-based pharmacokinetic (PBPK) model.