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Food Chem Toxicol 2012 Dec;50(12):4389-97

Timing and route of exposure affects crystal formation in melamine and cyanuric exposed male and female rats: gavage vs. feeding.

Sprando RL, Reimschuessel R, Stine CB, Black T, Olejnik N, Scott M, Keltner Z, Bandele O, Ferguson M, Nemser SM, Tkachenko A, Evans E, Crosby T, Woodling K, Loukotkova L, da Costa GG


Effects of the dosing matrix and timing on the onset of renal crystal formation were evaluated in male and non-pregnant female rats (Fisher 344) exposed to both melamine (MEL) and cyanuric acid (CYA) for 28days. Rats were fed ground feed containing 60ppm MEL and 60ppm CYA, (5mg/kgbw/day equivalent), or exposed via oral gavage to carboxymethylcellulose containing 5mg/kgbw MEL followed by 5mg/kgbw CYA either consecutively (<1min apart) or delayed 45min after MEL. Staggered gavage exposure to MEL/CYA caused extensive renal crystal formation as compared to when the two compounds were administered consecutively or in feed. Treatment related effects included reduced weight gain, feed consumption, and testicular weight and increased kidney weight, water consumption and urine output. Animals from the staggered MEL/CYA gavage exposure group became ill and were removed after 9days of exposure. Approximately 1week after the initiation of exposure microscopic urinalysis revealed MEL/CYA crystals in both groups of gavaged animals but not in the MEL/CYA feed treatment groups. Urinary crystals were smaller (10mum) in animals consecutively gavaged. In contrast the urinary crystals were larger (20-40mum) and frequently clumped in the animals in the staggered gavage group.

Category: Journal Article
PubMed ID: #22963836 DOI: 10.1016/j.fct.2012.07.051
Includes FDA Authors from Scientific Area(s): Food Animal and Veterinary Toxicological Research
Entry Created: 2012-09-13 Entry Last Modified: 2013-01-10