Absorption, distribution, metabolism and excretion (ADME) study with 2,2′,4,4′,5,6′-hexabromodiphenyl ether (BDE-154) in male Sprague–Dawley rats

Abstract

1. A metabolism study of orally administered 2,2′,4,4′,5,6′-hexabromodiphenyl ether (BDE-154; 11.3 μmoles kg⁻¹) was conducted in conventional and bile duct-cannulated male Sprague–Dawley rats.

2. In conventional rats, approximately 31% of the radiolabelled dose was retained at 72 h, and lipophilic tissues were the preferred sites for disposition.

3. Urinary excretion of BDE-154 was very low (1.0%), and parent compound was detected.

4. Cumulative biliary excretion was 1.3%, and glutathione conjugates were suggested.

5. Over 62% of the dose in conventional male rats was excreted in faeces, and was composed of parent compound (7.3%), free metabolites (13.1%), and covalently bound residues (41.4%). Faecal metabolites characterized by gas chromatography/mass spectrometry included multiple isomers of monohydroxylated hexa-/penta-/tetrabromodiphenyl ethers, and di-hydroxylated hexa/pentabromodiphenyl ethers.

6. The adipose tissue ¹⁴C was extractable BDE-154, but 40% of liver ¹⁴C was bound to macromolecules.

7. The study demonstrated the importance of performing individual polybrominated diphenyl ether (PBDE) metabolism studies to understand fully PBDE pharmacokinetics.

Keywords::

• brominated flame retardants (BFRs)
• brominated diphenyl ethers
• mammalian metabolism
• excretion
• 2,2′, 4, 4′, 5, 6′-hexabromodiphenyl ether (BDE-154)
• tissue disposition

Acknowledgements

The authors wish to thank Colleen Pfaff, who performed the animal studies and prepared the tissues samples; Barb Magelky, who performed the tissue combustion analyses; and Margaret Lorentzsen, who conducted the mass spectral analyses. The use of trade, firm, or corporation names in this paper is for the information and convenience of the reader only. Such use does not constitute an official endorsement or approval by the US Department of Agriculture (USDA) or the Agricultural Research Service of any product or service to the exclusion of others that may be suitable.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.