Lab Anim Res.  2011 Mar;27(1):25-28.

Increased Nephrotoxicity after Combined Administration of Melamine and Cyanuric Acid in Rats

• Park D
• Kim TK
• Choi YJ
• Lee SH
• Bae DK
• Yang G
• Yang YH
• Joo SS
• Choi EK
• Ahn B
• Kim JC
• Kim KS
• Kim YB

Abstract

Renal toxicity by melamine in combination with cyanuric acid (1:1) was investigated. Male rats were orally administered melamine plus cyanuric acid (5, 50 or 400 mg/kg each) for 3 days. In contrast to a negligible effect by melamine alone (50 mg/kg, a no-observed-adverse-effect-level: NOAEL), co-administration with cyanuric acid markedly increased the concentrations of blood urea nitrogen and creatinine, as well as kidney weight. A high dose (400 mg/kg) of melamine plus cyanuric acid induced more severe kidney toxicity. The increased blood parameters for kidney toxicity and organ weight lasted longer than 4 days. Combined treatment with melamine and cyanuric acid (50-400 mg/kg each) resulted in many gold-brown crystals and toxic lesions in renal tubules, which were not observed in animals treated with melamine alone (50 mg/kg). These results indicate that only a 3-day exposure to melamine in combination with cyanuric acid causes severe renal damage, even at a NOAEL for melamine found in a 13-week toxicity study. Therefore, it is suggested that the tolerable daily intake or regulatory/management levels of melamine need to be re-considered for cases of co-exposure with cyanuric acid.

Keyword

Melamine; cyanuric acid; nephrotoxicity; renal crystal

MeSH Terms

Animals
Blood Urea Nitrogen
Creatinine
Humans
Kidney
Male
No-Observed-Adverse-Effect Level
Organ Size
Rats
Triazines
Creatinine
Triazines

Figure

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  Figure 1 Gross findings of the kidneys of rats given oral melamine (M) alone or in combination with cyanuric acid (C) for 3 days. Control, 1% carboxymethylcellulose (5 mL/kg); M5+C5, 5 mg/kg melamine+5 mg/kg cyanuric acid; M50, 50 mg/kg melamine; M50+C50, 50 mg/kg melamine+50 mg/kg cyanuric acid; M400+C400, 400 mg/kg melamine+400 mg/kg cyanuric acid.

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  Figure 2 Microscopic findings for the kidneys of rats given oral melamine plus cyanuric acid for 3 days. A, 50 mg/kg melamine alone, exhibiting normal features; B, 50 mg/kg melamine+50 mg/kg cyanuric acid, displaying many bluish brown crystals in distal tubules and collecting ducts with focal dilatation; C-F, 400 mg/kg melamine+400 mg/kg cyanuric acid, showing crystals in severely-dilated tubules filled with proteinaceous casts (C) and in an atrophic glomerulus (D), hyaline droplets in the epithelial cells of proximal tubules (E) and neutrophil infiltrations in tubular lumen and interstitium (F).

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