Renal crystal formation after combined or sequential oral administration of melamine and cyanuric acid

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, 0.1–20mg/kg body weight (bw) of each compound, either once or repeatedly for 4, 14 or 28days (d). In catfish, the No Observable Adverse Effects Levels (NOAELs) for crystal formation for single, 4d or 14d dosing were 10, 2.5 and 0.5mg/kgbw, respectively. In trout, the respective NOAELs were 2.5, 2.5 and 0.5mg/kgbw. No renal crystals formed in catfish fed 0.1mg/kgbw of each compound for 28d. Sequential administration of 20mg/kgbw of MEL followed by 20mg/kgbw of CYA or vise-versa, with waiting periods of 1, 3, 7, 14 or 21d 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.