Melamine is a common stable chemical used to produce a variety of materials, including resins, laminates, glues, adhesives, coatings, and flame retardants (WHO 2008). It is a residual byproduct of metabolism of the pesticide cyromazine in plant and animal tissues (Lim et al. 1990; FAO/WHO 2010). Cyromazine is not approved for use in the United States but has approval in other countries that might export plant or animal products. Melamine contains relatively high nitrogen content (66% by mass), and this property has been exploited by some to raise nitrogen concentrations in products tested with conventional nitrogen-detection methods. Specifically, standardized protein-test methods rely on nitrogen concentration as a proxy for protein content, so the high nitrogen content of melamine can be used to increase the tested protein content of a food artificially.
Melamine and its analogues have been found to have low oral toxicity in laboratory animals. Short-term exposures to melamine require high doses (LD50, about 3 g/kg in rats) to cause acute toxic effects (WHO 2009). The toxic effects appear to be restricted primarily to the kidney and bladder. Despite its low toxicity in laboratory animals, melamine has been associated with several outbreaks of toxicity in humans and companion animals. In animals, the consumption of feed that contains melamine and cyanuric acid has been shown to cause nephrolithiasis (kidney stones) and renal failure at much lower doses than would occur with either chemical alone (Puschner et al. 2007).
China is recognized as the leading manufacturer of industrial melamine in the world and uses it in a wide array of products. One of the byproducts of industrial melamine production is a less concentrated version known as melamine scrap. Melamine scrap is reported to contain impurities, including cyanuric acid, which may increase its potential toxicity in humans and animals (Bradley 2008a,b). Recently, it has been reported that melamine scrap has been used in abundant quantities for years as a “protein powder” to boost the nitrogen values of livestock feedstuffs produced in China (Reuters 2008). Furthermore, similar protein powder concoctions have allegedly been added directly to liquid milk to ensure that the milk passes protein-quality standards (Ma 2008).
Melamine made headlines in the United States in 2007 when numerous pets presented with illnesses related to renal malfunction or failure and sudden death. Initially, the widespread occurrences were sufficiently disparate in location, food sources, and presentation as not to manifest a singular clinical picture of food toxicity. However, as the number of affected dogs and cats rose above an estimated 1,000, veterinary diagnostic laboratories and FDA became involved in investigating the root cause of the clinical presentations. As the search for causation narrowed, melamine and cyanuric acid were identified in pet-food