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Correction to This Article
In a graphic with a May 7 A-section article about the chemicals suspected of contaminating pet food, one part of the amino acid arginine? was mislabeled as N2H (two nitrogen atoms and one hydrogen atom). It should have been labeled NH (one nitrogen and one hydrogen). Also, the diagram of a molecule of cyanuric? acid omitted a line representing a chemical bond.
How Two Innocuous Compounds Combined to Kill Pets

By David Brown
Washington Post Staff Writer
Monday, May 7, 2007

What do a dead cat in Ontario and a motel swimming pool in Phoenix have in common?

In certain circumstances, they both contain melamine-cyanuric acid crystals.

Scientists seeking the chemical culprits in the widening pet food scare have come across some unusual chemistry that may help them understand how two largely nontoxic compounds ended up killing an unknown number of cats and dogs.

At the end of March, investigators detected a man-made compound called melamine in wheat gluten produced in China and sold to U.S. manufacturers as a pet food thickener. The contaminated samples contained various amounts -- from 0.2 percent to 8 percent -- of the chemical.

Melamine has been used for decades in manufacturing. In its chainlike "polymerized" form, it is used to make dishes, flame-retardant fibers and industrial coatings.

Also found in the gluten in smaller concentrations was cyanuric acid. The man-made chemical is used to stabilize chlorine in outdoor swimming pools, especially in regions such as the American Southwest where the sun's rays are quick to dissipate that disinfectant. Two other compounds, ammeline and ammelide, were present in even smaller amounts.

The four compounds have similar chemical structures. One can easily be made into another with the right chemical reaction. All contain relatively large amounts of the element nitrogen. Of the 15 atoms in a molecule of melamine, six are nitrogen. It also has three atoms of carbon and six of hydrogen. Ammeline has five nitrogen atoms, ammelide has four, and cyanuric acid has three.

All living things need nitrogen. The element is an essential ingredient of proteins, which make up most of the human body that isn't bone or water. It is an essential ingredient of DNA as well.

Organisms can survive for short periods on carbon, oxygen and hydrogen -- sugar. But if they want to grow or reproduce, they need nitrogen. Plants can get nitrogen out of the soil or the air, but animals have a harder time. They must take in protein already made by plants or other animals. That's what the female mosquito is seeking when she's out for blood -- a source of abundant nitrogen with which to make the protein and DNA in her eggs.

If you add melamine to almost anything, the amount of nitrogen in the final mixture will rise simply because, gram for gram, melamine contains so much of the element. Since the food industry generally measures total "nitrogen content" and equates it with "protein content," a few shovelfuls of melamine can appear to turn a low-protein meal into a high-protein one.

And what's wrong with that? Can't the body use the nitrogen in melamine?

Actually, it can't.

Melamine is an extremely small molecule, and most of it is absorbed through the intestinal tract before it is digested. It circulates in the bloodstream until it gets to the kidneys, where it slips easily into the fluid that eventually becomes urine. Melamine can also enter other organs. That is how it could have ended up in the tissue of farm animals that ate scraps of melamine-laced pet food -- as apparently was the case in 2.7 million chickens and 345 pigs slaughtered and consumed in recent months.

(Late last week, the federal government identified another 20 million chickens that had eaten tainted feed and took steps to keep them off the market.)

As a practical matter, though, only a small amount of melamine would ever end up in Buffalo wings or pulled pork. Melamine's chemical structure makes it water-soluble, and it doesn't accumulate in fat. After an oral dose of melamine, more than half is out of the bloodstream and into the urine in three hours.

The purpose of urine is to concentrate water-soluble waste products and to keep them dissolved. But water's dissolving power has its limits. Melamine and other chemicals can reach concentrations that exceed those limits. When the water can't hold any more, the chemical substance begins to form crystals.

Studies done decades ago found that rats fed melamine for two years developed stones in their urine, which led to bladder cancer in some. When rats were fed in one serving a large amount of melamine -- the equivalent of a 150-pound person eating a pound -- about half died.

At low doses, however, melamine is nontoxic. In fact, microcapsules and chains made of melamine have been used experimentally in animals as vehicles for delivering long-acting drugs.

Veterinarians investigating the mysterious pet deaths realized that most of the animals died of kidney failure and had kidney stones containing melamine. Although little is known about melamine toxicity in cats and dogs, it seems unlikely, based on the rat studies, that the pets could have consumed fatal amounts of the chemical.

Last month, however, toxicologists at the University of Guelph in Ontario detected another compound in the stones from cats suffering kidney failure -- cyanuric acid. Initially, the ratio was thought to be about two parts melamine to one part cyanuric acid. More recent and more precise measurements suggest an even split.

Ten days ago, Guelph scientists Brent Hoff and Grant Maxie combined melamine and cyanuric acid in a sample of cat urine. They produced crystals that, when examined for their chemical and physical properties, were virtually identical to the stones taken from the ill or dead cats.

The crystals are a lattice of six molecules -- three of melamine and three of cyanuric acid -- held together by weak links called hydrogen bonds.

When melamine is added to water that contains cyanuric acid, the reaction clouds the solution. It's that reaction -- and the degree of cloudiness -- that tells pool maintenance workers how much cyanuric acid is in the water, and whether more is needed. When the reaction occurs in a pet's kidneys, however, it can have altogether different and deadly effects.

So how might a plastic and a pool chemical (and their cousins, ammeline and ammelide) have gotten into pet food?

Nobody knows.

But one theory is that they were leftovers from a chemical company's production of something else. In an act of fraud that substituted cheap scrap for more expensive protein, someone put the compounds into the wheat gluten, thinking they would never be discovered and never cause a problem.

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