PT  - JOURNAL ARTICLE
AU  - Simone I. Hoehle
AU  - Gabriel A. Knudsen
AU  - J. Michael Sanders
AU  - I. Glenn Sipes
TI  - Absorption, Distribution, Metabolism, and Excretion of 2,2-Bis(bromomethyl)-1,3-propanediol in Male Fischer-344 Rats
AID  - 10.1124/dmd.108.023937
DP  - 2009 Feb 01
TA  - Drug Metabolism and Disposition
PG  - 408--416
VI  - 37
IP  - 2
4099  - http://dmd.aspetjournals.org/content/37/2/408.short
4100  - http://dmd.aspetjournals.org/content/37/2/408.full
SO  - Drug Metab Dispos2009 Feb 01; 37
AB  - 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 (<15%). The total amount of radioactivity remaining in tissues at 72 h after a single oral administration of BMP (100 mg/kg) was less than 1% of the dose, and repeated daily dosing did not lead to retention in tissues. After intravenous administration, the radiolabel found in blood decreased rapidly. Excretion profiles were similar to those after oral administration. Parent BMP and BMP glucuronide were present in blood plasma after oral or intravenous dosing. After an intravenous dose of BMP (15 mg/kg) the hepatic BMP glucuronide was primarily exported into the bile (>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. U.S. Government work not protected by U.S. copyright.