Absorption, Distribution, Metabolism, and Excretion of 2,2-Bis(bromomethyl)-1,3-propanediol in Male Fischer-344 Rats

2,2-Bis(bromomethyl)-1,3-propanediol (BMP) is a brominated flame retardant, previously shown to be a multisite carcinogen in experimental animals. Studies were performed to characterize the dispositional and metabolic fate of BMP after oral or intravenous administration to male Fischer-344 rats. Aft...

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Veröffentlicht in:Drug metabolism and disposition 2009-02, Vol.37 (2), p.408-416
Hauptverfasser: Hoehle, Simone I., Knudsen, Gabriel A., Sanders, J. Michael, Sipes, I. Glenn
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Sprache:eng
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Zusammenfassung:2,2-Bis(bromomethyl)-1,3-propanediol (BMP) is a brominated flame retardant, previously shown to be a multisite carcinogen in experimental animals. Studies were performed to characterize the dispositional and metabolic fate of BMP after oral or intravenous administration to male Fischer-344 rats. After a single oral administration of [14C]BMP (10 or 100 mg/kg) >80% of the low dose and 48% of the high dose were excreted by 12 h in the urine predominantly as a glucuronide metabolite. After repeated daily oral doses for 5 or 10 days, route and rate of elimination were similar to those obtained after single administrations of BMP. In all studies, the radioactivity recovered in feces was low (50% within 6 h), but it underwent enterohepatic recycling with subsequent elimination in the urine. These data indicate that the extensive extraction and rapid glucuronidation by the liver limits exposure of internal tissues to BMP by greatly reducing its systemic bioavailability after oral exposure.
ISSN:0090-9556
1521-009X
DOI:10.1124/dmd.108.023937