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. After a single oral administration of [(14)C]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.
Hoehle
Simone I
SI
Department of Pharmacology, College of Medicine, The University of Arizona, P.O. Box 245050, Tucson, AZ 85724-5050, USA.
Knudsen
Gabriel A
GA
Sanders
J Michael
JM
Sipes
I Glenn
IG
D000042:Absorption / Q000187:drug effects / Q000502:physiology; D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism; D001769:Blood; D002273:Carcinogens / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D004603:Elements, Radioactive; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D011409:Propylene Glycols / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D002273:Carcinogens; D004603:Elements, Radioactive; D011409:Propylene Glycols; C060080:2,2-bis(bromomethyl)-1,3-propanediol