User:Jonathan Cline/Notebook/Melaminometer/Toxicology Details

Toxicity Studies

• Killer pet food ingredients identified. The New Scientist Volume 196, Issue 2631, 24 November 2007, Page 4
• [Full Text] Identification and characterization of toxicity of contaminants in pet food leading to an outbreak of renal toxicity in cats and dogs. Toxicol Sci. 2008 Nov;106(1):251-62. Epub 2008 Aug 9.

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.

Several triazines, but predominantly melamine and cyanuric acid, were identified as the contaminants in a batch of wheat gluten that had been used as an ingredient in a number of brands of wet pet food. The total fraction of triazines in the contaminated gluten was on the order of 10¿13%. Assuming that wet cat foods contained up to 10% gluten and feeding according to manufacturer's guidance, this would have resulted in dosages of melamine and cyanuric acid in the 360¿430 mg/kg/day range, comparable to the 400 mg/kg/day used in the rodent experiments.

The nature of the toxicity may pose a challenge for traditional risk assessment methods, which are based on assessment of the toxicity of individual compounds. In this case, the toxicity of the melamine cyanurate complex is qualitatively different from that of melamine or cyanuric acid administered alone. The dose-response curve and no-observed adverse effect level for the mixture is almost certainly different from that of either compound alone. Recent press reports indicate that the use of melamine may be more widespread than thought in the animal feed industry. Given that ammeline, ammelide, and cyanuric acid are bacterial breakdown products of melamine, and could also be formed during melamine synthesis, it is plausible that exposures to mixtures of melamine and related compounds could happen again. Therefore, improving the risk assessment for melamine mixtures is a significant need.

• Ultrasonic extraction and determination of cyanuric acid in pet food. doi:10.1016/j.foodcont.2008.04.004