Evaluation of Subchronic Toxicity of Pet Food Contaminated with Melamine and Cyanuric Acid in Rats

Abstract

Outbreaks of food-associated renal failure in pets occurred in Asia and the United States of America in 2004 and 2007. They were related to the combined intoxication of cyanuric acid and melamine. Our aims were to investigate cyanuric acid and melamine contamination of pet food and to examine subchronic toxicity in rats. Levels of 10%, 20%, 50%, and 50%-100% (w/w) of contaminated pet food were fed to rats for three months. Analytical results revealed that the tainted food contained significant levels of cyanuric acid and melamine in a ratio of 1:6.8. Rats fed the diet of 50%-100% for three months exhibited elevated serum blood urea nitrogen and creatinine, as well as dose-dependent melamine/cyanuric acid crystalinduced nephrotoxicity. The melamine/cyanuric acid crystals of various sizes were mixed with necrotic cell debris and inflammatory cells, accompanied by tubular dilation and interstitial fibrosis. The immunohistochemistry index of proliferative cellular nuclear antigen and osteopontin in the kidney of the 50%-100% group were elevated, indicating regeneration of renal cells and the formation of crystals. In conclusion, the combination ratio of cyanuric acid to melamine and the acidic urine content were two factors that, upon repeated exposure, determined the severity of the nephrotoxicity.

Screening of the toxic effects of a high melamine dose on the biochemical hematological and histopathological investigations in male rats

“…This result agrees with that of Chen et al (2009) who noticed that rats fed melamine-contaminated diets experienced only small changes in hematological parameters. The …”

“…The mean values of phosphorus ion in the melamine-supplemented group were significantly higher than that of the negative control. This result is consistent with that of Jeong et al (2006), Puschner et al (2007, and Chen et al (2009).…”

“…This result is in agreement with Chen et al (2009). On the other hand, the mean values of body weight decreased El Rabey et al 961 significantly (p < 0.01) after the fourth week, compared with the negative control.…”

“…This result is consistent with Gao et al (2012) who reported pathological changes in the heart, testes, spleen, and urinary bladder of rats as a result of the long-term melamine supplementation. On the other hand, Chen et al (2009) found that testes weight in male rats was increased as a result of melamine toxicity.…”

Melamine–cyanurate complexes and oxidative stress markers in trout kidney following melamine and cyanuric acid long-term co-exposure and withdrawal

“…These crystals formed micro-obstructions within the proximal and distal tubules of the nephrons and caused renal failure (Dobson et al 2008;Reimschuessel et al 2008;Chen et al 2009;Kim et al 2010). Extensive numbers of crystals in the renal tubules rise intrarenal pressure causing the collapse of the capillaries and inducing acute renal failure via crystal nephropathy (Conger et al 1976).…”