| Pharmacokinetics of melamine and cyanuric acid, and their combinations in F344 rats. | |
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MedLine Citation:
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PMID: 22228804 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The intentional adulteration of pet food with melamine and cyanuric acid has been implicated in the kidney failure and death of a large number of cats and dogs in the USA. While individually these compounds present low toxicity in a range of experimental animals, co-exposure can lead to the formation of melamine cyanurate crystals in the nephrons, and eventual kidney failure. Given this mode of action, a good understanding of the pharmacokinetic profiles of melamine and cyanuric acid, and their combinations is essential to define properly the risk associated with different exposure scenarios. Previous studies have investigated the individual pharmacokinetic profiles of melamine and cyanuric acid. In this work, we report a comparison between the pharmacokinetic profiles of melamine and cyanuric acid administered individually, administered simultaneously as the individual compounds, and administered as a pre-formed melamine cyanurate complex. While the oral co-administration of 1 mg/kg bw of melamine and cyanuric acid did not alter significantly the pharmacokinetic profiles in relation to those determined upon individual oral administration of each compound, the administration of equal amounts of each triazine as the pre-formed melamine cyanurate complex significantly altered the pharmacokinetics, with reduced bioavailability of both compounds, lower observed maximum serum concentrations, delayed peak concentrations, and prolonged elimination half lives. These results indicate that in order to estimate properly the combined nephrotoxic potential of melamine and cyanuric acid, the experimental design of toxicological experiments and the evaluation of animal or human exposure scenarios should consider the detailed mode of exposure, with particular emphasis on any possible ex vivo formation of melamine cyanurate. |
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Authors:
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Cristina C Jacob; Linda S Von Tungeln; Michelle Vanlandingham; Frederick A Beland; Gonçalo Gamboa da Costa |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-6 |
Journal Detail:
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Title: Toxicological sciences : an official journal of the Society of Toxicology Volume: - ISSN: 1096-0929 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9805461 Medline TA: Toxicol Sci Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Biochemical Toxicology, US FDA National Center for Toxicological Research, Jefferson, AR 72079. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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