Melamine

Melamine is an organic compound with the formula C₃H₆N₆. This white solid is a trimer of cyanamide, with a 1,3,5-triazine skeleton. Like cyanamide, it contains 66% nitrogen by mass, and its derivatives have fire-retardant properties due to its release of nitrogen gas when burned or charred. Melamine can be combined with formaldehyde and other agents to produce melamine resins. Such resins are characteristically durable thermosetting plastic used in high-pressure decorative laminates such as Formica, melamine dinnerware including cooking utensils, plates, and plastic products, laminate flooring, and dry erase boards. Melamine foam is used as insulation and soundproofing material, and in polymeric cleaning products such as Magic Eraser.
Melamine gained infamy when Chinese food producers Sanlu Group added it to baby formula in order to increase the apparent protein content, causing the 2008 Chinese milk scandal. Ingestion of melamine may lead to reproductive damage, or bladder or kidney stones, and bladder cancer. It is also an irritant when inhaled or in contact with the skin or eyes. The United Nations' food standards body, the Codex Alimentarius Commission, has set the maximum amount of melamine allowed in powdered infant formula to 1 mg/kg and the amount of the chemical allowed in other foods and animal feed to 2.5 mg/kg. While not legally binding, the levels allow countries to ban importation of products with excessive levels of melamine.

Etymology

The German word Melamin was coined by combining the words melam and amine. Melamine is, therefore, unrelated etymologically to the root melas, from which the words melanin, a pigment, and melatonin, a hormone, are formed.

Uses

Plastics and building materials

In one large-scale application, melamine is combined with formaldehyde and other agents to produce melamine resins. Such resins are characteristically durable thermosetting plastic used in high-pressure decorative laminates such as Wilsonart, melamine dinnerware, laminate flooring, and dry erase boards. Melamine cookware is not microwave-safe, and can be identified from the fact it is "slightly heavier and noticeably thicker than its plastic counterparts."
Melamine foam is used as insulation, soundproofing material and in polymeric cleaning products, such as Magic Eraser.
Melamine is one of the major components in Pigment Yellow 150, a colorant in inks and plastics.
Melamine also is used in the fabrication of melamine polysulfonate, used as a superplasticizer for making high-resistance concrete. Sulfonated melamine formaldehyde is a polymer used as a cement admixture to reduce the water content in concrete while increasing the fluidity and the workability of the mix during handling and pouring. It results in concrete with a lower porosity and a higher mechanical strength, exhibiting an improved resistance to aggressive environments and a longer lifetime.

Fertilizers

Melamine was once envisioned as fertilizer for crops during the 1950s and 1960s because of its high nitrogen content. However, melamine is much more expensive to produce than other common nitrogen fertilizers, such as urea. The mineralization for melamine is slow, making this product both economically and scientifically impractical for use as a fertilizer.
Image:Melamine dinnerware.JPG|thumb|right|Melamine dinnerware

Fire-retardant additives

Melamine and its salts are used as fire-retardant additives in paints, plastics, and paper. A melamine fiber, Basofil, has low thermal conductivity, excellent flame resistance and is self-extinguishing; this makes it useful for flame-resistant protective clothing, either alone or as a blend with other fibres.

Food adulterant

Melamine is sometimes illegally added to food products in order to increase the apparent protein content. Standard tests, such as the Kjeldahl and Dumas tests, estimate protein levels by measuring the nitrogen content, so they can be misled by the addition of nitrogen-rich, but non-proteinaceous compounds such as melamine. There are instruments available today that can differentiate melamine nitrogen from protein nitrogen.

Medicine

Melamine derivatives of arsenical drugs are potentially important in the treatment of African trypanosomiasis.
Melamine use as non-protein nitrogen for cattle was described in a 1958 patent. In 1978, however, a study concluded that melamine "may not be an acceptable non-protein N source for ruminants" because its hydrolysis in cattle is slower and less complete than other nitrogen sources such as cottonseed meal and urea.

Toxicity

The short-term lethal dose of melamine is on a par with common table salt, with an LD₅₀ of more than 3 grams per kilogram of bodyweight. U.S. Food and Drug Administration scientists explained that when melamine and cyanuric acid are absorbed into the bloodstream, they concentrate and interact in the urine-filled renal tubules, then crystallize and form large numbers of round, yellow crystals, which in turn block and damage the renal cells that line the tubes, causing the kidneys to malfunction and lead to kidney stones, kidney failure, and death. Signs of melamine toxicity can include irritability, blood in the urine, little to no urine, symptoms of kidney infection, or high blood pressure.
The European Union set a standard for acceptable human consumption of melamine at 0.2 mg per kilogram of body mass, Canada declared a limit of 0.35 mg/kg, and the US FDA's limit was put at 0.063 mg/kg. The World Health Organization's food safety director estimated that the amount of melamine a person could stand per day without incurring a bigger health risk, the TDI, was 0.2 mg per kilogram of body mass.
Toxicity of melamine can be mediated by intestinal microbiota. In culture, Raoultella terrigena, which rarely colonizes mammalian intestines, was shown to convert melamine to cyanuric acid directly. Rats colonized by R. terrigena showed greater melamine-induced kidney damage compared to those not colonized.

Acute toxicity

Melamine is reported to have an oral median lethal dose of 3248 mg/kg based on rat data. It is also an irritant when inhaled or in contact with the skin or eyes. The reported dermal LD₅₀ is greater than 1000 mg/kg for rabbits. A study by Soviet researchers in the 1980s suggested that melamine cyanurate, commonly used as a fire retardant, could be more toxic than either melamine or cyanuric acid alone. For rats and mice, the reported LD₅₀ for melamine cyanurate was 4.1 g/kg and 3.5 g/kg, compared to 6.0 and 4.3 g/kg for melamine and 7.7 and 3.4 g/kg for cyanuric acid respectively.
A toxicology study in animals conducted after recalls of contaminated pet food concluded that the combination of melamine and cyanuric acid in diet does lead to acute kidney injury in cats. A 2008 study produced similar experimental results in rats and characterized the melamine and cyanuric acid in contaminated pet food from the 2007 outbreak. A 2010 study from Lanzhou University attributed kidney failure in humans to uric acid stone accumulation after ingestion of melamine resulting in a rapid aggregation of metabolites such as cyanuric acid diamide and cyanuric acid. A 2013 study demonstrated that melamine can be metabolized to cyanuric acid by gut bacteria. In particular, Klebsiella terrigena was determined to be a factor in melamine toxicity. In culture, K. terrigena was shown to convert melamine to cyanuric acid directly. Cyanuric acid was detected in the kidneys of rats administered melamine alone, and the concentration after Klebsiella colonization was increased.

Chronic toxicity

Ingestion of melamine may lead to reproductive damage, or bladder or kidney stones, which can lead to bladder cancer.
A study in 1953 reported that dogs fed 3% melamine for a year had the following changes in their urine: reduced specific gravity, increased output, melamine crystalluria, and protein and occult blood.
A survey commissioned by the American Association of Veterinary Laboratory Diagnosticians suggested that crystals formed in the kidneys when melamine combined with cyanuric acid, "don't dissolve easily. They go away slowly, if at all, so there is the potential for chronic toxicity."

Metabolism

Melamine is a metabolite of cyromazine, a pesticide. It has been reported that cyromazine can also be converted to melamine in plants.

Treatment of urolithiasis

Fast diagnosis and treatment of acute obstructive urolithiasis may prevent the development of acute kidney failure. Urine alkalinization and stone liberalization have been reported to be the most effective treatments in humans.

Contamination

Melamine-formaldehyde resin tableware was evaluated by the Taiwan Consumers' Foundation to have 20 parts per million of free melamine that could migrate out of the plastic into acidic foods if held at for two hours, such as if food were kept heated in contact with it in an oven.

Regulation in food and feed

The United Nations' food standards body, Codex Alimentarius Commission, has set the maximum amount of melamine allowed in powdered infant formula to 1 mg/kg and the amount of the chemical allowed in other foods and animal feed to 2.5 mg/kg. While not legally binding, the levels allow countries to ban importation of products with excessive levels of melamine.

Synthesis and reactions

Melamine was first synthesized by the German chemist Justus von Liebig in 1834. In early production, first calcium cyanamide was converted into dicyandiamide, which was heated above its melting temperature to produce melamine. Today most industrial manufacturers use urea in the following reaction to produce melamine:
In the first step, urea decomposes into cyanic acid and ammonia:
Cyanic acid polymerizes to cyanuric acid, which condenses with the liberated ammonia forming melamine. The released water reacts with cyanic acid, which helps to drive the reaction:
The above reaction can be carried out by either of two methods: catalyzed gas-phase production or high pressure liquid-phase production. In one method, molten urea is introduced onto a fluidized bed with catalyst for reaction. Hot ammonia gas is also present to fluidize the bed and inhibit deammonization. The effluent then is cooled. Ammonia and carbon dioxide in the off-gas are separated from the melamine-containing slurry. The slurry is further concentrated and crystallized to yield melamine. Major manufacturers and licensors such as Orascom Construction Industries, BASF, and Eurotecnica have developed some proprietary methods.
The off-gas contains large amounts of ammonia. Therefore, melamine production is often integrated into urea production, which uses ammonia as feedstock.
Crystallization and washing of melamine generates a considerable amount of waste water, which may be concentrated into a solid for easier disposal. The solid may contain approximately 70% melamine, 23% oxytriazines, 0.7% polycondensates. In the Eurotecnica process, however, there is no solid waste and the contaminants are decomposed to ammonia and carbon dioxide and sent as off gas to the upstream urea plant; accordingly, the waste water can be recycled to the melamine plant itself or used as clean cooling water make-up.
Melamine reacts with acid and related compounds to form melamine cyanurate and related crystal structures, which have been implicated as contaminants or biomarkers in Chinese protein adulterations.