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Xenobiotica
the fate of foreign compounds in biological systems
Volume 47, 2017 - Issue 3
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Animal Pharmacokinetics and Metabolism

Disposition of the emerging brominated flame retardant, bis(2-ethylhexyl) tetrabromophthalate, in female Sprague Dawley rats: effects of dose, route and repeated administration

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Pages 245-254 | Received 11 Mar 2016, Accepted 01 Apr 2016, Published online: 21 Apr 2016
 

Abstract

1. Bis(2-ethylhexyl)-tetrabromophthalate (BEH-TEBP; CAS No. 26040-51-7; PubChem CID: 117291; MW 706.15 g/mol, elsewhere: TeBrDEPH, TBPH, or BEHTBP) is used as an additive brominated flame retardant in consumer products.

2. Female Sprague Dawley rats eliminated 92–98% of [14C]-BEH-TEBP unchanged in feces after oral administration (0.1 or 10 μmol/kg). A minor amount of each dose (0.8–1%) was found in urine after 72 h. Disposition of orally administered BEH-TEBP in male B6C3F1/Tac mice was similar to female rats.

3. Bioaccumulation of [14C]-radioactivity was observed in liver and adrenals following 10 daily oral administrations (0.1 μmol/kg/day). These tissues contained 5- and 10-fold higher concentrations of [14C]-radioactivity, respectively, versus a single dose.

4. IV-administered [14C]-BEH-TEBP (0.1 μmol/kg) was slowly eliminated in feces, with >15% retained in tissues after 72 h. Bile and fecal extracts from these rats contained the metabolite mono-ethylhexyl tetrabromophthalate (TBMEHP).

5. BEH-TEBP was poorly absorbed, minimally metabolized and eliminated mostly by the fecal route after oral administration. Repeated exposure to BEH-TEBP led to accumulation in some tissues. The toxicological significance of this effect remains to be determined. This work was supported by the Intramural Research Program of the National Cancer Institute at the National Institutes of Health (Project ZIA BC 011476).

Acknowledgements

The authors would like to thank Ms. Sherry Coulter, Ms. Samantha Hall, Mr. Ethan Hull, Ms. Katelyn McIntosh and Mr. Abdella Sadik for technical assistance.

Declaration of interest

This work was supported by the Intramural Research Program of the National Cancer Institute at the National Institutes of Health (Project ZIA BC 011476).

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