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Research ArticleArticle

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

Simone I. Hoehle, Gabriel A. Knudsen, J. Michael Sanders and I. Glenn Sipes
Drug Metabolism and Disposition February 2009, 37 (2) 408-416; DOI: https://doi.org/10.1124/dmd.108.023937
Simone I. Hoehle
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Gabriel A. Knudsen
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J. Michael Sanders
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I. Glenn Sipes
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Abstract

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.

Footnotes

  • This work was supported by the National Toxicology Program/National Institute of Environmental Health Science (NIEHS) (Contract N01-ES-45529) and in part by the Intramural Research Program of the National Institutes of Health and NIEHS. We also acknowledge support provided by the Analytical Core of the NIEHS-funded Southwest Environmental Health Science Center [Grant P30-ES 06694].

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.108.023937.

  • ABBREVIATIONS: BMP, 2,2-bis(bromomethyl)-1,3-propanediol; BFR, brominated flame retardant; F-344, Fischer 344; HPLC, high-performance liquid chromatography; JVC, jugular vein cannula; BDC, bile duct cannula; LSC, liquid scintillation counting; LC, liquid chromatography; MS/MS, tandem mass spectrometry; LOQ, limit of quantification; MS, mass spectrometry; GI, gastrointestinal; ADME, absorption, distribution, metabolism, and excretion; UGT, UDP glucuronosyltransferase; TBBPA, tetrabromobisphenol A.

    • Received August 14, 2008.
    • Accepted November 20, 2008.
  • U.S. Government work not protected by U.S. copyright.
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Drug Metabolism and Disposition: 37 (2)
Drug Metabolism and Disposition
Vol. 37, Issue 2
1 Feb 2009
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Research ArticleArticle

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

Simone I. Hoehle, Gabriel A. Knudsen, J. Michael Sanders and I. Glenn Sipes
Drug Metabolism and Disposition February 1, 2009, 37 (2) 408-416; DOI: https://doi.org/10.1124/dmd.108.023937

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Research ArticleArticle

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

Simone I. Hoehle, Gabriel A. Knudsen, J. Michael Sanders and I. Glenn Sipes
Drug Metabolism and Disposition February 1, 2009, 37 (2) 408-416; DOI: https://doi.org/10.1124/dmd.108.023937
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