Document Detail

Pharmacokinetics of melamine and cyanuric acid and their combinations in F344 rats.
MedLine Citation:
PMID:  22228804     Owner:  NLM     Status:  MEDLINE    
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 United States. Although individually these compounds present low toxicity in a range of experimental animals, coexposure 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 preformed melamine cyanurate complex. Although the oral coadministration of 1 mg/kg body weight 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 preformed 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.
Cristina C Jacob; Linda S Von Tungeln; Michelle Vanlandingham; Frederick A Beland; Gonçalo Gamboa da Costa
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-01-06
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  126     ISSN:  1096-0929     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-20     Completed Date:  2012-07-16     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  317-24     Citation Subset:  IM    
Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079, USA.
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MeSH Terms
Area Under Curve
Chromatography, Liquid
Rats, Inbred F344
Tandem Mass Spectrometry
Triazines / administration & dosage,  pharmacokinetics*
Grant Support
Reg. No./Substance:
0/Triazines; H497R4QKTZ/cyanuric acid; N3GP2YSD88/melamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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