Abstract
Biological methylation and hydride formation of metals and metalloids are ubiquitous environmental processes that can lead to the formation of chemical species with significantly increased mobility and toxicity. Whereas much is known about the interaction of metal(loid)s with microorganisms in environmental settings, little information has been gathered on respective processes inside the human body as yet. Here, we studied the biotransformation and excretion of bismuth after ingestion of colloidal bismuth subcitrate (215 mg of bismuth) to 20 male human volunteers. Bismuth absorption in the stomach and upper intestine was very low, as evidenced by the small quantity of bismuth eliminated via the renal route. Total bismuth concentrations in blood increased rapidly in the first hour after ingestion. Most of the ingested bismuth was excreted via feces during the study period. Trace levels of the metabolite trimethylbismuth [(CH3)3Bi] were detected via low temperaturegas chromatography/inductively coupled plasma-mass spectrometry in blood samples and in exhaled air samples. Concentrations were in the range of up to 2.50 pg/ml (blood) and 0.8 to 458 ng/m3 (exhaled air), with high interindividual variation being observed. Elimination routes of bismuth were exhaled air (up to 0.03‰), urine (0.03–1.2%), and feces. The site of (CH3)3Bi production could not be identified in the present study, but the intestinal microflora seems to be involved in this biotransformation if accompanying ex vivo studies are taken into consideration.
Footnotes
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This work was supported by the German Research Foundation, Deutsche Forschungsgemeinschaft, Forschergruppe 415 [Grant DFG RE 581/3-3].
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.107.020313.
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ABBREVIATIONS: (CH3)3Bi, trimethylbismuth; ICP-MS, inductively coupled plasma mass spectrometry; GC/EI-MS/ICP-MS, parallel electron impact mass spectrometry and inductively coupled plasma mass spectrometry detection after gas chromatography separation; GC, gas chromatography; EI-MS, electron impact mass spectrometry; LT-GC/ICP-MS, low temperature-gas chromatography coupled with inductively coupled plasma-mass spectrometry; IAC, interaggregate calibration; AUC, area under the curve; (CH3)2BiH, dimethylbismuth hydride; CH3BiH2, methylbismuth dihydride; BiH3, bismuth trihydride.
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The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.
- Received June 11, 2008.
- Accepted October 29, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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