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: In 2007, pet food contaminated with melamine caused hundreds of dogs and cats to develop renal failure all over the world. In 2008, over 294,000 infants consumed infant formula and developed kidney stones in China. Further investigation revealed that fish feed also contained melamine; this raised concerns about melamine residues in edible fish tissues, which could have caused the urinary tract stone epidemic. In Korea, catfish fed with assorted feed that included cuttlefish organs that contained melamine developed whitening syndrome and fell dead in some populations in 2008. This event raised suspicions about the toxicity of melamine and all feeds containing melamine were immediately recalled. In this study, we investigated the rates of melamine accumulation and depletion in muscle and viscera of catfish to propose proper withdrawal periods. One group of catfish was fed a commercially available diet that contained 30, 100 and 300 mg melamine per kg diet for 14 days. To investigate residual melamine contents in muscle and viscera, other experimental groups were fed a melamine free diet after being fed melamine for 7 days. The residual amount of melamine was analyzed by LC-MS/MS. The melamine concentration in muscle was estimated to be 3.7 mg/kg after 6 days of feeding with a diet containing 300 mg melamine/kg. After 2 days of culture with a melamine free diet, the residual melamine was depleted and the concentration had decreased from 1.15 mg/kg to 0.19 mg/kg in the muscle of catfish fed a diet containing 300 mg melamine/kg for 7 days. The residual amount of melamine was reduced to 0.03 mg/kg in muscle after 7 days of culture with a melamine free diet and was undetectable after a prolonged culture period of 14 days. Catfish tend to excrete melamine rapidly after oral administration and changes in body color were not observed during the short dosing period.12/2011; 44(6). DOI:10.5657/KFAS.2011.0577
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ABSTRACT: To investigate the nephrotoxic potential of melamine (MEL) and cyanuric acid (CA) in male Sprague-Dawley rats, 7-d repeated-dose studies were performed. The experimental groups of MEL100 and CA100 were orally administered with MEL and CA at 100 mg/kg/d for 7 d, respectively. In groups dosed with MEL-CA mixtures, melamine and cyanuric acid (1:1) were simultaneously administered at 4, 20, or 100 mg/kg/d for 7 d (i.e., MEL-CA4, MEL-CA20, or MEL-CA100, respectively). Body weights were not markedly affected in MEL100, CA100, and MEL-CA4 groups, but significantly reduced in MEL-CA 20 and 100 rats. Most parameters determined in sera and tissues were not markedly altered in MEL100, CA100, and MEL-CA4-treated rodents. However, BUN, creatinine, total protein, and kidney weights were significantly increased in MEL-CA20- and MEL-CA100-treated animals. Renal histopathologic findings also revealed signs of toxicity, including tubular dilatation, crystal deposition, granulomatous tubulo-interstitial inflammation, and tubular necrosis with regeneration. Data suggested that the combination of MEL and CA might be responsible for observed nephrotoxicity that was not seen following individual exposure to either MEL or CA alone. Subsequently, the concentrations of MEL and CA were determined in serum, urine, and kidney tissues by using liquid chromatography-mass spectrometry. Toxicokinetic studies indicated that MEL or CA alone might be eliminated almost completely within 24 h after dosing showing no accumulation in kidney. However, the combined MEL-CA dose produced marked accumulation of chemicals in blood and kidneys. These results suggested that combined MEL and CA might produce renal toxicity due to significant chemical accumulation in kidney accompanied by low excretion.Journal of Toxicology and Environmental Health Part A 10/2014; 77(22-24):1346-58. DOI:10.1080/15287394.2014.951592 · 1.83 Impact Factor
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ABSTRACT: Effects of melamine (MEL) and its analogue, cyanuric acid (CYA) at various doses on Asian seabass (Lates calcarifer Bloch) are described. Diet 1 (a basal diet without MEL and CYA); diets 2–5 (with MEL and CYA at inclusion levels 2.5, 5, 7.5, 10 g/kg diet, each); diet 6 (with only MEL at 10 g/kg diet); and diet 7 (with CYA alone added at 10 g/kg diet) were examined. It is obvious that those fish that received combined MEL–CYA as follows had low growth and feed conversion ratio (FCR) (P < 0.05): 7.5:7.5, 10:10 or MEL alone diets. Abnormalities were observed in the liver and kidney of fish with combined MEL and CYA supplementation. The renal tubules of fish that were fed with diets 2–5 had golden-brown melamine–cyanurate crystals. Fish given only one type of supplementation did not have such crystals in the kidneys. The highest MEL residue in fillet was detected in the fish that ingested MEL alone (10 g/kg diet). Levels of heat shock protein (Hsp) 70 were elevated in the liver of fish that had ingested MEL/CYA, in combination or alone (diets 2–7) (P < 0.05). There were no significant differences between the treatments (P > 0.05) in the level of Hsp70 in the kidneys of the fish. High dosages of MEL–CYA induced the activities of catalase and glutathione peroxidase in liver and kidneys.Aquaculture 01/2015; 435:336–346. DOI:10.1016/j.aquaculture.2014.10.009 · 1.83 Impact Factor