1,3,5-triazine-2,4,6-triamine phosphate

Toxic effects on livestock and pets

Description of key information

Melamine was detected in feed of various animals: dogs, cats, pigs, fish, and shrimps. In reviews and case studies it is reported that melamine in the feed can cause renal toxic effects, crystals and/or stones in the urinary tract.

Additional information

Melamine was detected in feed of various animals: dogs, cats, pigs, fish, shrimps. In reviews and case studies it is reported that melamine in the feed can cause renal toxic effects, crystals and/or stones in the urinary tract. A recent review of the many reports is provided in WHO 2009, http://www.who.int/foodsafety/fs_management/Melamine_3.pdf.

A combination of 2 adulterants in pet foods, melamine and cyanuric acid, contributed to the deaths of hundreds of cats and dogs in 2007. The complex situation led to a massive recall of pet foods and caused a great deal of public concern. The AAVLD (American Veterinary Medical Association) survey found 347 cases that met diagnostic criteria for "pet food-induced nephrotoxicity" from April 5 -June 6 (2007). The cases involved 235 cats and 112 dogs, with 61% of the cats and 74% of the dogs having died. It was stated that the survey probably found only a percentage of the actual cases. More cats than dogs might have become ill because of cats' relatively small sizes. Even among dogs, small-to medium-sized dogs were affected the most. The problem with melamine and cyanuric acid (both were in the adulterated pet food) is that they can combine to form crystals in animal bodies. The crystals apparently can impair renal function. A pilot study found that neither melamine nor cyanuric acid alone had an observable effect on renal function, but the combination caused acute renal failure. In a similar study in pigs preliminary results suggested that the combination of melamine and cyanuric acid is a more potent nephrotoxin then either is individually (Burns 2007).

The massive recall of pet foods that began in March 2007 has been attributed to adulteration of wheat gluten with melamine, a nitrogen-rich (66.6%) compound associated with kidney failure. Based on studies in rats and mice and on one 1945 study in dogs, melamine and its by-products are thought to be only slightly toxic. Tissue samples from kidneys and urinary tracts of affected cats contained crystals of melamine and cyanuric acid. In the course of researching a book about pet food, Nestle et al. have come across studies suggesting that melamine adulteration has been a common practice and that melamine alone is toxic to sheep and cattle at doses similar to those that caused signs of renal disease in cats and dogs. The 1945 study investigated the legitimate use of melamine as a diuretic in dogs. At a dose of approximately 120 mg of melamine/kg of body weight, the dogs developed urinary crystals but no other adverse signs. In the 1960s, South African investigators thought melamine might be a good source of nonprotein nitrogen for ruminants. But at doses of approximately 250 mg/kg sheep refused food and lost weight, if fed low-quality hay, some died. Another investigator conducted a dose-response study. Doses of 25 to 100 g killed sheep, and necropsies revealed tubular damage and kidneys packed with melamine crystals. When given lower doses, sheep refused food, especially when water was restricted. Results of the studies suggested that melamine doses of approximately 250 mg/kg could kill some, but not all, sheep in a few weeks. In the 1970s, doses as low as 100 mg/kg induced four of six steers to refuse feed. The studies cited seem relevant to the recent recalls of melamine (Nestle 2007).

The major pet food recall associated with acute renal failure in dogs and cats focused initially on melamine as the suspect toxicant. In the course of the investigation, cyanuric acid was identified in addition to melamine in the offending food. The purpose of this study was to characterize the toxicity potential of melamine, cyanuric acid, and a combination of melamine and cyanuric acid in cats. In this pilot study, melamine was added to the diet of 2 cats at 0.5 % and 1 %, respectively. Cyanuric acid was added to the diet of 1 cat at increasing doses of 0.2%, 0.5%, and 1 % over the course of 10 days. Melamine and cyanuric acid were administered together at 0%, 0.2%, 0.5%, and 1 % to 1 cat per dose group. No effect on renal function was observed in cats fed with melamine or cyanuric acid alone. Cats dosed with a combination were euthanized at 48 hours after dosing because of acute renal failure. Urine and touch impressions of kidneys from all cats dosed with the combination revealed the presence of fan-shaped, birefringent crystals. Histopathologic findings were limited to the kidneys and included crystals primarily within tubules of the distal nephron, severe renal interstitial edema, and hemorrhage at the corticomedullary junction. The kidneys contained estimated melamine concentrations of 496 to 734 mg/kg wet weight and estimated cyanuric acid concentrations of 487 to 690 mg/kg wet weight. The results demonstrate that the combination of melamine and cyanuric acid is responsible for acute renal failure in cats (Puschner 2007).

Effects of dietary melamine on growth, excreta, plasma, and residue in the tissue of male and female broiler chickens was investigated in a 5-week feeding study. The safe levels of melamine in broiler diets were determined based on BW gain (BWG) and melamine residue in the breast meat.The toxic effects of dietary melamine concentrations are similar between male and female broiler chickens. The toxic level of melamine in broiler diets is 4292 mg/kg based on the BWG of broiler chickens, according to the authors, but more likely the NOAEL is 5000 mg/kg. Less than 814 mg/kg melamine in broiler diets should be maintained to satisfy human food safety regulations for melamine residue of 2.5 mg melamine / kg breast meat (Kim 2019).