Clinicopathologic, histologic, and toxicologic findings in 70 cats inadvertently exposed to pet food contaminated with melamine and cyanuric acid
ABSTRACT To document clinicopathologic, histologic, and toxicologic findings in cats inadvertently exposed to pet food contaminated with melamine and cyanuric acid.
70 cats from a single cattery inadvertently fed contaminated food that was the subject of a March 2007 recall.
Clinical signs, clinicopathologic and histopathologic findings, and results of toxicologic analyses were recorded.
Clinical signs were identified in 43 cats and included inappetence, vomiting, polyuria, polydipsia, and lethargy. Azotemia was documented in 38 of the 68 cats for which serum biochemical analyses were performed 7 to 11 days after consumption of the contaminated food. One cat died, and 13 were euthanized. Histologic examination of kidney specimens from 13 cats revealed intratubular crystalluria, tubular necrosis with regeneration, and subcapsular perivascular inflammation characterized by perivascular fibroplasia or fibrosis and inflammation with intravascular fibrin thrombi. Toxicologic analyses revealed melamine and cyanuric acid in samples of cat food, vomitus, urine, and kidneys.
In cats unintentionally fed pet food contaminated with melamine and cyanuric acid, the most consistent clinical and pathologic abnormalities were associated with the urinary tract, specifically tubular necrosis and crystalluria.
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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, 0.1-20mg/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, 4d or 14 d dosing were 10, 2.5 and 0.5mg/kg bw, respectively. In trout, the respective NOAELs were 2.5, 2.5 and 0.5mg/kg bw. No renal crystals formed in catfish fed 0.1mg/kg bw of each compound for 28 d. Sequential administration of 20mg/kg bw of MEL followed by 20mg/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.Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 10/2010; 48(10):2898-906. DOI:10.1016/j.fct.2010.07.024
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ABSTRACT: As an industrially synthesized chemical, melamine has been applied in a wide range of areas. However, many questions on the adverse effect and toxicity of melamine have been emerged, recently. In this investigation, the cytotoxicity of melamine on PC12 cells was evaluated. Furthermore, the effect of melamine on the transient outward potassium current (I(A)) and the delayed rectifier potassium current (I(K)) in hippocampal CA1 pyramidal neurons of rat was studied using whole-cell patch-clamp technique. The results showed that melamine-induced cell death in a concentration and time-dependent manner, and produced a concentration-dependent inhibition in amplitudes of I(A) and I(K) at any concentrations (5x10(-4), 5x10(-5), and 5x10(-6)g/ml). Moreover, at higher concentration (5x10(-4)g/ml), melamine had observable effects of the steady-state inactivation of I(A), that is melamine shifted inactivation curve of I(A) towards hyperpolarization. The spontaneous firing frequency was increased as well. These results suggest that the regulation of I(A) and I(K) induced by melamine would make neurons display aberrant firing properties and abnormal neuronal discharge, which could be a possible underlying mechanism for the melamine-induced neurotoxicity.Toxicology in Vitro 11/2009; 24(2):397-403. DOI:10.1016/j.tiv.2009.10.019
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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 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.Toxicologic Pathology 10/2009; 37(7):959-68. DOI:10.1177/0192623309347910