Evaluation of subchronic toxicity of pet food contaminated with melamine and cyanuric acid in rats.
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 crystal-induced 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.
Chen
Kun-Chao
KC
Graduate Institute of Veterinary Pathobiology, National Chung-Hsing University, Taichung, Taiwan, ROC.
Liao
Chen-Wei
CW
Cheng
Fen-Pang
FP
Chou
Chi-Chung
CC
Chang
Shih-Chien
SC
Wu
Jhaol-Huei
JH
Zen
Jyh-Myng
JM
Chen
Yng-Tay
YT
Liao
Jiunn-Wang
JW
D000821:Animal Feed / Q000032:analysis*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005506:Food Contamination; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009183:Mycotoxins / Q000032:analysis / Q000633:toxicity; D053495:Osteopontin / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000139:chemically induced / Q000473:pathology / Q000662:veterinary; D018675:Toxicity Tests; D014227:Triazines / Q000032:analysis / Q000633:toxicity*
D009183:Mycotoxins; D018809:Proliferating Cell Nuclear Antigen; D014227:Triazines; D053495:Osteopontin; C004632:cyanuric acid; C011907:melamine