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Aminopterin? Melamine? Cyromazine? The pet food situation grows murkier

See all the posts related to the pet food recall.

The pet food story continues to develop. Though some authorities are still reporting that the rat poison aminopterin is the main culprit as the contamination that has killed over a dozen animals (and possible hundreds more), recent analysis has muddied the waters, naming the compound melanime:

A massive North American pet-food recall widened yesterday as a U.S. company withdrew a brand of dry cat food for fear it contains melamine, the contaminant that forced Mississauga-based Menu Foods to pull products from shelves across the continent.

Hills Pet Nutrition recalled its Prescription Diet m/d Feline Dry food after melamine, a chemical used as a fertilizer in Asia and to make plastic kitchenware, was identified as the likely culprit in the Menu Foods recall - one of the largest of its kind in North America.

"Hills is taking this precautionary action because during a two-month period in early 2007, wheat gluten for this product was provided by a company that also supplied wheat gluten to Menu Foods," the company said in a statement on its website.

But here's the interesting thing. As a fertilizer, the compound ought not to be a concern. A fertilizer breaks down and supplies the crops with the raw components (nitrogen, phosphorous, etc) that is needed to grow, components that might not be present in sufficient concentration the heavily farmed soil. Though ideally the fertilizer is completely broken down and absorbed before the plant is served as food, being a fertilizer, in trace amounts, you wouldn't expect it to be so dangerous, if at all.

In any case, fertilizer is applied while the crop is being grown. It is exposed to sunlight and washed by rain and by artificial irrigation. It is mixed and crushed during harvesting. Just how much could remain in heavily processed final product?

And at the end of the day, fertilizer is meant to be in the food chain. Obviously not in its raw form, but the idea that some fertilizer traces could be responsible seems like a stretch.

So I checked into melamine, also known as cyanuramide, and guess what? It's not a fertilizer. Melamine is a pesticide in the triazine class:

Typically herbicides or microbiocides containing a triazine ring. Frequently found in groundwater, along with their transformation products.

Triazine compounds are used to target parasitic protozoa:

Polyamine biosynthesis and function has been shown to be a good drug target in some parasitic protozoa and it is proposed that the pathway might also represent a target in the malaria parasite Plasmodium falciparum. A series of 1,3,5-triazine-substituted polyamine analogues were tested for activity against Plasmodium falciparum in vitro. The series showed activity against the parasites and were generally more active against the chloroquine-resistant line K1 than the chloroquine-susceptible line NF54. Simple unbranched analogues had better activity than analogues carrying branched or cyclic central chains. Addition of multiple triazine units in general led to increased activity of the compounds.

Unlike aminopterin, the toxicity of melamine is very low:

The toxicity to mammals is also low. Studies ranging from skin irritation to carcinogenicity are available. Melamine is not genotoxic but it causes carcinomas of the urinary bladder at high doses in male rats only. Formation of bladder stones occurred and these calculi are necessary for the induction of tumours. Carcinomas are induced by continuous irritation of the bladder epithelium by the calculi, so that melamine acts only indirectly as a non-genotoxic carcinogen. A threshold concept can be used. Melamine is not irritating to skin and eye, not sensitising and not teratogenic.

As an eat-a-nibble-and-drop-dead poison, melamine doesn't seem to make the grade. It doesn't even come close.

So what's going on here? Maybe it's not melamine, but something that is somehow related to melamine. Melamine is a relatively benign substance as these things go. But melamine is a metabolite of cyromazine, meaning that detecting melamine might be an indicator that cyromazine was present and eaten.

As it happens, that is exactly how the melamine was detected -- not in the food, but in the animal urine:

[Stephen Sundlof, director of the FDA’s Center for Veterinary Medicine,] also indicated that the presence of melamine in the urine of cats that died from kidney failure was revealed through testing. He stressed that melamine was not determined to be the source of illness or deaths in the affected animals.

So it was metabolized melamine. And we know melamine is a metabolite of cyromazine. So what is cyromazine?

It is a insecticide used to control larva infestations:

Cyromazine is the active ingredient in the formulation, Larvadex 2SL, the formulation currently being requested for registration in California. The only proposed use for Larvadex 2SL is as a fly larvacide for direct application on chicken manure. Larvadex 2SL and other cyromazine formulations are registered for use in other states through the United States Environmental Protection Agency (U.S. EPA). Trigard 75W is a wettable powder formulation that is used on celery and lettuce. Larvadex Premix formulations consist of coarsely ground cyromazine that is mixed with chicken feed and used as a "passthroughtt pesticide to inhibit the development of fly larvae in chicken manure.

Looking into Trigard 75W, we learn it is a insecticide and a miticide, and that is a registered for unrestricted use.

Am I finally on to something?

Unfortunately, I don't think so. Cyromazine is virtually nontoxic to mammals:

Cyromazine is practically nontoxic (acutely) to mammals and birds. Exposure estimates for these organisms are <0.05 ppm. Acute toxicity for birds is 1785 ppm maximum. Safety factor is 105-106 for birds. Acute toxicity for mammals is 1000 ppm maximum. Safety factor is again 105 - 106.

The bottom line to all this is that it is hard to see how melamine is responsible for what we've been seeing. It isn't that toxic, and even the parent compound, cyromazine, is virtually non-toxic to mammals.

I suspect we'll be seeing some more back-and-forth between testing labs. But if pet owners think the culprit has finally been nailed down, I have a feeling that they are going to be disappointed. Menu Foods is trying to sell this development as the final chapter in the story. Of course they are. I'm not ready to believe that, though.

Here is a corporate missive about the pet food recall pushing the melamine theory very aggressively.

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