Background Paper on Toxicology of Melamine and Its Analogues* Prepared for the WHO Expert Meeting on Toxicological and Health Aspects of Melamine and Cyanuric Acid In collaboration with FAO
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چکیده
* The opinions and information in this paper are those of the authors and do not represent the views and/or policies of the United States Food and Drug Administration. 1.1 Absorption, distribution, metabolism and excretion of melamine (MEL) 1.1.1 Rats MEL is rapidly absorbed and attains maximal plasma concentrations in 60 min following administration of a single oral dose to male Fischer 344 rats. It appears to distribute to the body water, as concentrations in blood, plasma and liver are similar. The plasma half-life is approximately 2.7 h (Mast et al., 1983). Radiolabelled MEL measurements support the conclusion that urinary elimination is virtually the only route of excretion (93% ± 4% of dose). Excretion of MEL by respiration and faeces were each less than 1% of the administered dose. The urinary half-life is 3 h, and urinary clearance 2.5 mg/min (Mast et al., 1983). MEL is eliminated essentially unchanged by the kidney. The percentage of urinary 14 C present as MEL was the same as the radiochemical purity of the dosed material. Almost all (97–100%) 14 C in the liver, blood and plasma was present as MEL. The authors concluded that the male Fischer 344 rat does not metabolize MEL, because all radioactivity in plasma and urine was in the same form as that administered in the dosing solution (Worzalla et al., 1974; Mast et al., 1983). 1.1.2 Pigs MEL administered intravenously to five weanling pigs at a dose of 6.13 mg/kg body weight (bw) had a half-life of 4.04 ± 0.37 h, clearance of 0.11 ± 0.01 l/h per kilogram and volume of distribution of 0.61 ± 0.04 l/kg (Baynes et al., 2008). To establish an appropriate withdrawal interval, a physiologically based pharmacokinetic model for MEL was developed for rats and extrapolated to pigs. The rat model underpredicted plasma concentrations, but better predicted tissue residues. Correlation values for plasma, kidney and liver were 0.59, 0.76 and 0.73, respectively. The pig model underpredicted early plasma time points but had greater accuracy at later time points, which is relevant to withdrawal times (Buur, Baynes & Riviere, 2008). Limited information is available for other species. MEL has been detected in urine of dogs (Lipschitz & Stokey, 1945) and in urine of cats sickened during the pet food episode of 2007 (Brown et al., 2007). In a case report, MEL has been found to be excreted in the milk of cows exposed to …
منابع مشابه
Background Paper on the Chemistry of Melamine Alone and in Combination with Related Compounds* Prepared for the WHO Expert Meeting on Toxicological and Health Aspects of Melamine and Cyanuric Acid In collaboration with FAO
* The views presented in this article do not necessarily reflect those of the United States Food and Drug Administration. 1 This chemistry background paper briefly summarizes key information on melamine related to past contamination incidents, uses, chemical structures and physicochemical properties (including the related triazines: cyanuric acid, ammeline and ammelide), manufacturing processes...
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