Absorption, distribution, metabolism, and excretion of 2,2-bis(bromomethyl)-1,3-propanediol in male fischer-344 rats.
نویسندگان
چکیده
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.
منابع مشابه
DMD #32110 1 In vitro glucuronidation of 2,2-bis(bromomethyl)-1,3-propanediol by microsomes and hepatocytes from rats and humans
متن کامل
In vitro glucuronidation of 2,2-bis(bromomethyl)-1,3-propanediol by microsomes and hepatocytes from rats and humans.
2,2-Bis(bromomethyl)-1,3-propanediol (BMP) is a brominated flame retardant used in unsaturated polyester resins. In a 2-year bioassay BMP was shown to be a multisite carcinogen in rats and mice. Because glucuronidation is the key metabolic transformation of BMP by rats, in this study the in vitro hepatic glucuronidation of BMP was compared across several species. In addition, the glucuronidatio...
متن کاملOn the Structure of Some Pentaerythritol-Related Molecular Crystals with Pseudotetrahedral Molecular Structure. Ordered Structure of 2,2-Bis(bromomethyl)-l,3-propanediol and Orientationally Disordered Structure of 2-Chloromethy 1-2-methyl-1,3-dichloropropane; C1 NQR*
für Naturforschung in cooperation with the Max Planck Society for the Advancement of Science under a Creative Commons Attribution 4.0 International License. Dieses Werk wurde im Jahr 2013 vom Verlag Zeitschrift für Naturforschung in Zusammenarbeit mit der Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. digitalisiert und unter folgender Lizenz veröffentlicht: Creative Commons Namen...
متن کاملسنتز و مشخصه یابی پلی(2،2- بیس(آزیدو‌متیل)-3،1-پروپیلن‌آدیپات) به عنوان بایندر پرانرژی
polyester polyol can be used in high energy propellant as a binder.In this research, polyazido polyester was synthesized from direct polycondensation reaction between adipic acid and 2,2-bis(bromomethyl)-1,3-propanediol. Then, azidation of poly bromoester afford polyazidoester as an energetic polyester. polyazidoester have identified and characterized by FTIR,HNMR,GPC,DSC and elemental analysis...
متن کاملA mechanistic approach to understanding species differences in felbamate bioactivation: relevance to drug-induced idiosyncratic reactions.
In an attempt to understand the species-selective toxicity of felbamate (2-phenyl-1,3-propanediol dicarbamate, FBM), which is thought to result from bioactivation to 2-phenylpropenal, FBM metabolism was evaluated in rats and humans. The formation of 2-phenylpropenal was monitored by the amount of its mercapturates excreted in urine. The data show a relative 5-fold increase in mercapturate excre...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Drug metabolism and disposition: the biological fate of chemicals
دوره 37 2 شماره
صفحات -
تاریخ انتشار 2009