Evaluation of the renal effects of experimental feeding of melamine and cyanuric acid to fish and pigs

被引:143
作者
Reimschuessel, Renate [1 ]
Gieseker, Charles M. [1 ]
Miller, Ron A.
Ward, Jeffrey [1 ]
Boehmer, Jamie [1 ]
Rummel, Nathan [1 ]
Heller, David N. [1 ]
Nochetto, Cristina [1 ]
de Alwis, G. K. Hemakanthi [1 ]
Bataller, Neal
Andersen, Wendy C. [2 ]
Turnipseed, Sherri B. [2 ]
Karbiwnyk, Christine M. [2 ]
Satzger, Duane [3 ]
Crowe, John B. [3 ]
Wilber, Nancy R. [4 ]
Reinhard, Mary K. [5 ]
Roberts, John F. [5 ]
Witkowski, Mark R. [3 ]
机构
[1] US FDA, Ctr Vet Med, Laurel, MD 20708 USA
[2] US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA
[3] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA
[4] Acad Anim Hosp, Ft Lauderdale, FL 33308 USA
[5] Univ Florida, Coll Vet Med, Dept Infect Dis & Pathol, Gainesville, FL 32611 USA
关键词
D O I
10.2460/ajvr.69.9.1217
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
Objective-To determine whether renal crystals can be experimentally induced in animals fed melamine or the related triazine compound cyanuric acid, separately or in combination, and to compare experimentally induced crystals with those from a cat with triazine-related renal failure. Animals-75 fish (21 tilapia, 24 rainbow trout, 15 channel catfish, and 15 Atlantic salmon), 4 pigs, and 1 cat that was euthanatized because of renal failure. Procedures-Fish and pigs were fed a target dosage of melamine (400 mg/kg), cyanuric acid (400 mg/kg), or melamine and cyanuric acid (400 mg of each compound/kg) daily for 3 days and were euthanatized 1, 3, 6, 10, or 14 days after administration ceased. Fresh, frozen, and formalin-fixed kidneys were examined for crystals. Edible tissues were collected for residue analysis. Crystals were examined for composition via Raman spectroscopy and hydrophilic-interaction liquid chromatography-tandem mass spectrometry. Results-All animals fed the combination of melamine and cyanuric acid developed gold-brown renal crystals arranged in radial spheres (spherulites), similar to those detected in the cat. Spectral analyses of crystals from the cat, pigs, and fish were consistent with melamine-cyanurate complex crystals. Melamine and cyanuric acid residues were identified in edible tissues of fish. Conclusions and Clinical Relevance-Although melamine and cyanuric acid appeared to have low toxicity when administered separately, they induced extensive renal crystal formation when administered together. The subsequent renal failure may be similar to acute uric acid nephropathy in humans, in which crystal spherulites obstruct renal tubules.
引用
收藏
页码:1217 / 1228
页数:12
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