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March 30, 2007 Melamine Update.

Menu Foods VIN Community Update

Monitoring Renal Function Guidelines

Food Recall Survey

Aminopterin Update

Melamine and Cyanuric acid - the APPARENT crystals

April 30, 1PM EST.
This Community Update is preliminary and based on rapidly changing and developing information. This information is current as of April 30, 1PM EST.

What is Melamine?
Melamine is a cyclic amino compound which is part of the triazine family of chemicals. It is produced from urea and exists as a monomeric powder.

What is Cyanuric Acid?
Cyanuric acid, like melamine, is a triazine compound. It differs from melamine in the side-chains bound to the triazine ring and is also a white powder form.

What are melamine and cyanuric acid used for?
Melamine monomers can be polymerized into melamine resins and then crosslinked with formaldehyde to form thermosetting plastic laminates, the most common of which is Formica. It is used in plastic utensils. It is also used as a flame retardant and a non-protein nitrogen source (fertilizer), when combined with appropriate microorganisms that can metabolize the compound into urea or ammonia.

Cyanuric acid is used mainly as a pH stabilizer in swimming pools, where it prevents the degradation of hypochlorite.

Are melamine or cyanuric acid toxic?
As far as we can ascertain, melamine is minimally toxic. In acute toxicity trials in rats and mice, LD50 was >3g/kg. Intravenous injections (0.3mM/kg) and acute oral administration of melamine (125mg/kg) to cats failed to induce any toxicity (Lipschitz & Stokey, 1944, J Pharm & Exp Ther). In chronic dosing studies, rats developed cystic calculi (bladder stones) and consequent carcinomas of the bladder after 6 months of administration. There is virtually no mention of nephrotoxicity in the published literature. It is considered a mild ecological toxin, and generally safe in a work environment (inhalation and dermal or mucosal contact).

Suprisingly, melamine has a diuretic action.

This PDF file (large), describes IN DETAIL, most of the toxicological data for melamine.

If extrapolated from toxicity studies in rats (and assuming cats have the same acute toxicity doses as rats), cats would need to consume about 4kg of food per day to approach the rat LD50.

Little is known about cyanuric acid. It does not appear to be toxic as a sole compound, unless vaporized, when it can form toxic gas compounds.

Are melamine and cyanuric acid present in the affected foods?
Yes. Studies have confirmed that both melamine and cyanuric acid are present in the affected foods. It is not present in other foods tested. It is present in the wheat gluten, corn gluten, or rice protein concentrate used in the manufacture of the affected foods.

Are melamine and cyanuric acid present in crystals from affected cats and dogs?
Yes. Recent studies at University of Guelph have tentatively identified the composition of the crystals as a combination of melamine and cyanuric acid. Fourier-transformed Infra Red Spectrograms of in-vitro precipitated crystals matched spectra from crystals obtained from cat urine. This suggests that the crystals are composed of melamine and cyanuric acid.

Is melamine cyanurate crystalluria a plausible hypothesis?
Yes. While we did not originally know how melamine alone could cause crystalluria, there is evidence that melamine precipitates with cyanuric acid. This precipitation reaction is used in monitoring cyanuric acid concentration in pool water (the so-called CYA test), in which melamine monomer is added to a sample of pool water. If sufficient cyanuric acid is present, the sample become cloudy.

We now suspect that a similar reaction is occurring in affected patients. Thus, it now appears that while neither melamine nor cyanuric acid are toxic as sole chemicals, they combine to form crystals that have been the hallmark of this outbreak of pet-food-associated renal failure.

Is melamine present in high concentrations in the affected foods?
Melamine was present at about a 1-3% concentration in the gluten used in the manufacture of affected foods. Therefore it is present in a 0.01-0.2% (10mg - 200mg/100g food) concentration in affected foods.

Q: Why would melamine be a contaminant of gluten or other ingredients?
In reality, nobody knows. However, the most plausible hypothesis is outlined here:

Nitrogen content of a food provides an indirect measure of the protein content of the food. Melamine and cyanuric acid are similar compounds (triazines) that contain nitrogen a non-protein nitrogen source. There is suspicion that melamine was added to wheat gluten (and potentially other ingredients) to artificially increase the nitrogen content of the ingredients, which would be interpreted as an increased protein content of the wheat gluten. Increased protein content in wheat gluten may command a higher price on the market. Thus, the adulteration of wheat gluten and other protein ingredients (rice protein concentrate) may have had financial motives.

Recent investigations by the New York Times have found evidence of widespread adulteration of feedstuffs in China with melamine.

Can melamine act as a marker for affected individuals?
We believe so. Since it appears to be present only in the contaminated foods, and is relatively easily detected in urine and kidneys of affected animals, melamine may be a reasonable marker of exposure to affected diets. This may help rule out dietary causes of acute renal failure. However, more information is needed to determine the validity of this hypothesis.

How can melamine be detected?
UCDavis is offering specific testing for melamine in affected foods and now in urine. The melamine assay cost on pet food or urine is $200/sample ($100 for California residents). This is the normal diagnostic rate using LC/MS or GC/MS technology for a specific compound - test code 8175.


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