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TITLE:  Renal crystal formation after combined or sequential oral administration of melamine and cyanuric acid
 
AUTHORS:  Reimschuessel R;Evans ER;Stine CB;Hasbrouck N;Mayer TD;Nochetto C;Gieseker CM;
 
YEAR:  2010
 
MONTH:  Oct
 
TYPE:  JOUR
 
REFMAN INDEX:  595
 
JOURNAL FULL:  Food and Chemical Toxicology
 
VOLUME:  48
 
ISSUE:  10
 
START PAGE:  2898
 
END PAGE:  2906
 
KEYWORDS:  adverse effects;Body Weight;CATFISH;Crystal;Cyanuric acid;Disease;FATTY-ACIDS;FISH;INDUCED STONES;Infant;Kidney;Mammals;Melamine;MODEL;NEPHROPATHY;No observable adverse effect level;RAINBOW-TROUT;SINGLE;toxicity;Trout;URINARY-BLADDER;WEIGHT;ZEBRAFISH;
 
ABSTRACT:  We evaluated renal melamine-cyanurate crystal spherulite formation after single and repeated ingestion of both melamine (MEL) and cyanuric acid (CYA) in catfish and trout. MEL and CYA were co-administered orally over a range of doses, 0.1-20 mg/kg body weight (bw) of each compound, either once or repeatedly for 4, 14 or 28 days (d). In catfish, the No Observable Adverse Effects Levels (NOAELs) for crystal formation for single, 4 d or 14 d dosing were 10, 2.5 and 0.5 mg/kg bw, respectively. In trout, the respective NOAELs were 2.5, 2.5 and 0.5 mg/kg bw. No renal crystals formed in catfish fed 0.1 mg/kg bw of each compound for 28 d. Sequential administration of 20 mg/kg bw of MEL followed by 20 mg/kg bw of CYA or vise-versa, with waiting periods of 1, 3, 7, 14 or 21 d between compound dosing also induced renal crystal formation in fish. These studies show that both catfish and trout are sensitive, non-mammalian models, for renal crystal formation following MEL and CYA ingestion. Since fish generally excrete chemicals more slowly than mammals, they may provide a 'worst case scenario' model for higher risk populations, such as infants or persons with compromised renal function. Published by Elsevier Ltd
 
AFFILIATIONS:  US FDA, Ctr Vet Med, Laurel, MD 20708 USA
 
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