Identification and characterization of toxicity of contaminants in pet food leading to an outbreak of renal toxicity in cats and dogs
Identification and characterization of toxicity of contaminants in pet food leading to an outbreak of renal toxicity in cats and dogs
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DOI：
10.1093/toxsci/kfn160
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发表时间：
2008-11-01
影响因子：
3.8
通讯作者：
Daston, George P.
中科院分区：
文献类型：
--
作者：
Dobson, Roy L. M.;Motlagh, Safa;Daston, George P.
本文描述了与2007年春季北美发生的宠物食品大召回事件有关的研究。猫和狗急性肾功能衰竭的临床观察与食用由为大量公司生产的合同制造商生产的湿宠物食品有关。受影响的大量食品都是用中国原产的小麦面筋制成的。宠物食品和面筋的污染物分析使用了几种配置的高效液相色谱(HPLC)和质谱仪(MS)，发现了一些简单的三嗪化合物，主要是三聚氰胺和三聚氰酸，三聚氰胺、三聚氰胺、氨基甲酸胺和N-甲基三聚氰胺的浓度较低。三聚氰胺和三聚氰酸，已经过测试，不会产生急性肾脏毒性。一些三嗪类化合物的溶解性很差，三聚氰胺三聚氰酸酯化合物也是如此。对死于急性肾功能衰竭的猫和狗的病理评估表明，肾小管中存在结晶。我们假设这些晶体是由难溶的三嗪、三聚氰胺-三聚氰酸络合物或其组合组成的。SD大鼠给予三聚氰胺或三聚氰胺单独100 mg/kg，三聚氰胺和三聚氰酸的混合物(400/400 mg/kg/d)，或所有四种化合物的混合物(400 mg/kg/d三聚氰胺，40 mg/kg/d的其他化合物)。无论是三聚氰胺还是三聚氰胺单独都不会对肾脏产生任何影响，但这两种混合物都会对肾脏造成显著的损害，并导致肾单位的结晶。HPLC-MS/MS证实肾脏中存在三聚氰胺和三聚氰酸。对来自大鼠或猫(来自兽医诊所的捐赠材料)肾脏的单个晶体的红外显微光谱证实，它们是三聚氰胺-三聚氰酸共晶体。受污染面筋的晶体产生了类似的光谱。这些结果建立了受污染的面筋和不良反应之间的因果联系，并为两种表面上无害的化合物如何联合产生不良影响提供了机制解释，即通过在肾小管形成不溶于水的沉淀物，导致进行性肾小管阻塞和退化。
This paper describes research relating to the major recall of pet food that occurred in Spring 2007 in North America. Clinical observations of acute renal failure in cats and dogs were associated with consumption of wet pet food produced by a contract manufacturer producing for a large number of companies. The affected lots of food had been formulated with wheat gluten originating from China. Pet food and gluten were analyzed for contaminants using several configurations of high-performance liquid chromatography (HPLC) and mass spectrometry (MS), which revealed a number of simple triazine compounds, principally melamine and cyanuric acid, with lower concentrations of ammeline, ammelide, ureidomelamine, and N-methylmelamine. Melamine and cyanuric acid, have been tested and do not produce acute renal toxicity. Some of the triazines have poor solubility, as does the compound melamine cyanurate. Pathological evaluation of cats and dogs that had died from the acute renal failure indicated the presence of crystals in kidney tubules. We hypothesized that these crystals were composed of the poorly soluble triazines, a melamine-cyanuric acid complex, or a combination. Sprague dawley rats were given up to 100 mg/kg ammeline or ammelide alone, a mixture of melamine and cyanuric acid (400/400 mg/kg/day), or a mixture of all four compounds (400 mg/kg/day melamine, 40 mg/kg/day of the others). Neither ammeline nor ammelide alone produced any renal effects, but the mixtures produced significant renal damage and crystals in nephrons. HPLC-MS/MS confirmed the presence of melamine and cyanuric acid in the kidney. Infrared microspectroscopy on individual crystals from rat or cat (donated material from a veterinary clinic) kidneys confirmed that they were melamine-cyanuric acid cocrystals. Crystals from contaminated gluten produced comparable spectra. These results establish the causal link between the contaminated gluten and the adverse effects and provide a mechanistic explanation for how two apparently innocuous compounds could have adverse effects in combination, that is, by forming an insoluble precipitate in renal tubules leading to progressive tubular blockage and degeneration.