Melamine

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This article is about the chemical substance called melamine. The term
"melamine" may also be used to refer to the plastic melamine resin.
Not to be confused with the pigment melanin, the hormone melatonin, or the
melanotan peptides.
Melamine[1]

1,3,5-Triazine-2,4,6-
IUPAC name
triamine

2,4,6-Triamino-s-
triazine
Other names Cyanurotriamide
Cyanurotriamine
Cyanuramide

Identifiers

CAS number [108-78-1]

PubChem 7955

SMILES [show]

Properties

Molecular formula C3H6N6

 Molar mass 126.12 g/mol

Appearance White solid

Density 1574 kg/m3

Melting point
350 C, 623 K, 662 F

Boiling point
Sublimes
Solubility in water 3.1 g/l (20 C)
Except where noted otherwise, data are given for
materials in their standard state
(at 25 C, 100 kPa)
Infobox references

Melamine (pronounced /m l min/ melamine (helpinfo)) is an organic base and a trimer

of cyanamide, with a 1,3,5-triazine skeleton. Like cyanamide, it contains 66% nitrogen
by mass and, if mixed with resins, has fire retardant properties due to its release of
nitrogen gas when burned or charred, and has several other industrial uses. Melamine is
also a metabolite of cyromazine, a pesticide. It is formed in the body of mammals who
have ingested cyromazine.[2] It has been reported that cyromazine can also be converted
to melamine in plants.[3][4]

Melamine combines with cyanuric acid to form melamine cyanurate, which has been
implicated in the Chinese protein export contaminations.

Contents
[hide]
1 Etymology
2 Uses
3 Toxicity
o 3.1 Acute toxicity
o 3.2 Chronic toxicity
4 Regulation
5 Synthesis
o 5.1 Recent production of melamine in mainland China
6 Poisoning and kidney failure caused by melamine cyanurate
o 6.1 2007 Animal feed recalls
o 6.2 2008 Chinese scandal
 o 6.3 Testing for melamine and cyanuric acid in food
7 See also
8 References

9 External links

[edit] Etymology
The German word melamin was coined by combining the names of 2 other chemical
products: Melam (a distillation derivative of ammonium thiocyanate) and Amine. [5] [6]

[edit] Uses
Melamine is combined with formaldehyde to produce melamine resin, a very durable
thermosetting plastic, and melamine foam, a polymeric cleaning product. The end
products include countertops, dry erase boards, fabrics, glues, housewares and flame
retardants. Melamine is one of the major components in Pigment Yellow 150, a colorant
in inks and plastics.

Melamine also enters the fabrication of melamine poly-sulfonate used as superplasticizer

for making high-resistance concrete. Sulfonated melamine formaldehyde (SMF) is a
polymer used as cement admixture to reduce the water content in concrete while
increasing the fluidity and the workability of the mix during its 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 life-time.

The use of melamine as fertilizer for crops had been envisaged during the '50s and '60s
because of its high nitrogen content (2/3)[7]. However, the hydrolysis reactions of
melamine leading to the nitrogen mineralisation in soils are very slow, precluding a broad
use of melamine as fertilizing agent.

Melamine derivatives of arsenical drugs are potentially important in the treatment of

African trypanosomiasis[8]

Melamine use as non-protein nitrogen (NPN) for cattle was described in a 1958 patent.[9]
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.[10]

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 adding nitrogen-rich
compounds such as melamine. [11]

[edit] Toxicity
Melamine by itself is nontoxic in low doses, but when combined with cyanuric acid it can
cause fatal kidney stones due to the formation of an insoluble melamine cyanurate.[12]
Melamine is described as being "Harmful if swallowed, inhaled or absorbed through the
skin. Chronic exposure may cause cancer or reproductive damage. Eye, skin and
respiratory irritant. However, the toxic dose is on a par with common table salt with an
LD50 of more than 3 grams per kilogram of bodyweight.[13] FDA scientists explained that
when melamine and cyanuric acid are absorbed into the bloodstream, they concentrate
and interact in the urine-filled renal microtubules, 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.[14]

[edit] Acute toxicity

Melamine is reported to have an oral LD50 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
>1000 mg/kg for rabbits.[15] In a 1945 study, large doses of melamine were given orally to
rats, rabbits and dogs with "no significant toxic effects" observed.[16]

A study by USSR researchers in the 1980s suggested that melamine cyanurate,

commonly used as a fire retardant[17], could be more toxic than either melamine or
cyanuric acid alone.[18] For rats and mice, the reported LD50 for melamine cyanurate was
4.1 g/kg (given inside the stomach) and 3.5 g/kg (via inhalation), 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 conducted after recalls of contaminated pet food concluded that the
combination of melamine and cyanuric acid in diet does lead to acute renal failure in cats.
[19]

[edit] Chronic toxicity

Ingestion of melamine may lead to reproductive damage, or bladder or kidney stones,

which can lead to bladder cancer.[15][20][21][22][23]

A study in 1953 reported that dogs fed 3% melamine for a year had the following changes
in their urine: (1) reduced specific gravity, (2) increased output, (3) melamine
crystalluria, and (4) protein and occult blood.[24]
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."[25][26][27]

[edit] Regulation
In Europe, food or animal feed products containing more than 2.5 mg / kg are to be
immediately destroyed.[28]

In the US, the Food Safety and Inspection Service (FSIS) of the United States
Department of Agriculture (USDA) provides a test method for analyzing cyromazine and
melamine in animal tissues in its Chemistry Laboratory Guidebook which "contains test
methods used by FSIS Laboratories to support the Agency's inspection program, ensuring
that meat, poultry, dairy and egg products are safe, wholesome and accurately labeled."[29]
[30]
In 1999, in a proposed rule published in the Federal Register regarding cyromazine
residue, the United States Environmental Protection Agency (EPA) proposed "removing
melamine, a metabolite of cyromazine from the tolerance expression since it is no longer
considered a residue of concern."[31] Melamine, classified a controlled substance in
China[32], has been illegally used in the high profile 2008 baby milk scandal case which
led to the death of at least 4 infants[32].

On October 3, 2008, the U.S. Food and Drug Administration said that up to 2.5 parts per
million of melamine was safe for adults, but declined to set a standard for children. The
FDA also implied it would not permit the sale of food deliberately adulterated (rather
than accidentally contaminated) with melamine.[33] Rep. Rosa L. DeLauro, Chairwoman
of the House subcommitee which oversees the Food and Drug Administration
subcommittee, said anything less than zero tolerance would not protect consumers.[34]
DeLauro criticised the FDA's "acceptable level for melamine in food" was an insult to
consumers, and would give the impression that the FDA was condoning intentional
contamination.[35]

[edit] Synthesis
Melamine was first synthesized by the German chemist Justus von Liebig in 1834. In
early production, first calcium cyanamide is converted into dicyandiamide, then heated
above its melting temperature to produce melamine. However, today most industrial
manufacturers use urea in the following reaction to produce melamine:

6 (NH2)2CO C3H6N6 + 6 NH3 + 3 CO2

It can be understood as two steps.

First, urea decomposes into cyanic acid and ammonia in an endothermic reaction:

6 (NH2)2CO 6 HCNO + 6 NH3

Then, cyanic acid polymerizes to form melamine and carbon dioxide:

6 HCNO C3H6N6 + 3 CO2

The second reaction is exothermic but the overall process is endothermic.

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. [36] Major
manufacturers and licensors such as DSM, 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 is a pollutant if discharged directly into the environment. The waste water may be
concentrated into a solid (1.5-5% of the weight) for easier disposal. The solid may
contain approximately 70% melamine, 23% oxytriazines (ammeline, ammelide and
cyanuric acid), 0.7% polycondensates (melem, melam and melon).[37]

[edit] Recent production of melamine in mainland China

Between the late 1990s and early 2000s, both consumption and production of melamine
grew considerably in mainland China. In the United States Geological Survey 2004
Minerals Survey Yearbook, in a report on worldwide nitrogen production, the author
stated that "(mainland) China continued to plan and construct new ammonia and urea
plants using coal gasification technology."[38]

By early 2006, melamine production in mainland China is reported to be in "serious

surplus".[39] In April 2007, DSM's melamine industry update painted a grave global
picture.[40] Between 2002 and 2007, while the global melamine price remained stable, a
steep increase in the price of urea (feedstock for melamine) has reduced the profitability
of melamine manufacturing. Currently, China is the world's largest exporter of melamine,
while its domestic consumption still grows by 10% per year. However, reduced profit has
already caused other joint melamine ventures to be postponed there.
Surplus melamine has been a popular adulterant for feedstock and baby formula in
mainland China for several years now, because it can make diluted or poor quality
material appear to be higher in protein content by elevating the total nitrogen content
detected by some simple protein tests.

[edit] Poisoning and kidney failure caused by melamine

cyanurate
[edit] 2007 Animal feed recalls

Further information: 2007 pet food recalls and Chinese protein export
contamination

In 2007 a pet food recall was initiated by Menu Foods and other pet food manufacturers
who had found their products had been contaminated and caused serious illnesses or
deaths in some of the animals that had eaten them.[41][42][43] In March 2007, the US Food
and Drug Administration reported finding white granular melamine in the pet food, in
samples of white granular wheat gluten imported from a single source in China, Xuzhou
Anying Biologic Technology[44] as well as in crystalline form in the kidneys and in urine
of affected animals.[45] Further vegetable protein imported from China was later
implicated.

In April 2007, The New York Times reported that the addition of "melamine scrap" into
fish and livestock feed to give the false appearance of a higher level of protein was an
"open secret" in many parts of mainland China, reporting that this melamine scrap was
being produced by at least one plant processing coal into melamine.[46] Four days later,
the New York Times reported that, despite the widely reported ban on melamine use in
vegetable proteins in mainland China, at least some chemical manufacturers continued to
report selling it for use in animal feed and in products for human consumption. Li
Xiuping, a manager at Henan Xinxiang Huaxing Chemical in Henan Province, stated,
"Our chemical products are mostly used for additives, not for animal feed. Melamine is
mainly used in the chemical industry, but it can also be used in making cakes."[47]
Shandong Mingshui Great Chemical Group, the company reported by the New York
Times as producing melamine from coal, produces and sells both urea and melamine but
does not list melamine resin as a product.[48]

Another recall incident in 2007 involved melamine which had been purposely added as a
binder to fish and livestock feed manufactured in the United States. This was traced to
suppliers in Ohio and Colorado.[49]

[edit] 2008 Chinese scandal

 Further information: 2008 Chinese milk scandal

In September 2008, several companies were implicated in a scandal involving milk and
infant formula which had been adulterated with melamine, leading to kidney stones and
other renal failure, especially among young children. By 22 September, nearly 53,000
people had become ill, with more than 12,800 hospitalizations and four infant deaths.[50]
[51]

Melamine may have been added to fool government protein content tests after water was
added to fraudulently dilute the milk. Because of melamine's high nitrogen content (66%
by mass versus approx. 10-12% for typical protein), it can cause the protein content of
food to appear higher than the true value.[52][53] Officials estimate that about 20 percent of
the dairy companies tested in China sell products tainted with melamine.[54]

In October 2008, "Select Fresh Brown Eggs" imported to Hong Kong from the Hanwei
Group in Dalian in northeastern China, were found to be contaminated with nearly twice
the legal limit of melamine. York Chow, the health secretary of Hong Kong, said he
thought animal feeds might be the source of the contamination and announced that the
Hong Kong Centre for Food Safety would henceforward be testing all mainland Chinese
pork, farmed fish, animal feed, chicken meat, eggs, and offal products for melamine. [55]

[edit] Testing for melamine and cyanuric acid in food

Until the 2007 pet food recalls, melamine had not routinely been monitored in food,
except in the context of plastic safety or insecticide residue. This could be due to the
previously assumed low toxicity of melamine, and the relatively expensive methods of
detection.

Following the 2008 health scare in China over powdered milk, the Joint Research Centre
of the European Commission set-up a website about methods to detect melamine
(http://irmm.jrc.ec.europa.eu/melamine[3]).

In October 2008, the U.S. FDA issued new methods for the analysis of melamine and
cyanuric acid in infant formulations in the Laboratory Information Bulletin No 4421 [56].
Similar recommendations have been issued by other authorities, like the Japanese
Ministry of Health, Labor and Welfare [57], both based on LC MS/MS detection after
HILIC separation [58]

Because melamine resin is often used in food packaging and tableware, melamine at ppm
level (1 part per million) in food and beverage has been reported due to migration from
melamine-containing resins.[59] Small amounts of melamine have also been reported in
foodstuff as a metabolite product of cyromazine, an insecticide used on animals and
crops.[60]
The Food Safety and Inspection Service (FSIS) of the United States Department of
Agriculture (USDA) provides a test method for analyzing cyromazine and melamine in
animal tissues. [29][30] In 2007, the FDA began using a high performance liquid
chromatography test to determine the melamine, ammeline, ammelide, and cyanuric acid
contamination in food.[61] Another procedure is based on surface-enhanced Raman
spectroscopy (SERS). [62][63]

printable version

Questions and Answers on melamine

What is melamine?

Melamine is an organic base chemical most commonly found in the form of white crystals
rich in nitrogen

What is melamine generally used for?

Melamine is widely used in plastics, adhesives, countertops, dishware, whiteboards.

Why was melamine added into milk and powdered infant formula

In China, where adulteration has occurred, water has been added to raw milk to increase its
volume. As a result of this dilution the milk has a lower protein concentration. Companies
using the milk for further production (e.g. of powdered infant formula) normally check the
protein level through a test measuring nitrogen content. The addition of melamine increases
the nitrogen content of the milk and therefore its apparent protein content.

Addition of melamine into food is not approved by the FAO/WHO Codex Alimentarius
(food standard commission), or by any national authorities.

Has melamine been found in other food products?

In 2007, melamine was found in wheat gluten and rice protein concentrate exported from
China and used in the manufacture of pet food in the United States. This caused the death
of a large number of dogs and cats due to kidney failure.

In the present event, melamine contamination has been found in a number of different
brands of powdered infant formula, in one brand of a frozen yogurt dessert and in one
brand of canned coffee drink. All these products were most probably manufactured using
ingredients made from melamine-contaminated milk.

What are the health effects of melamine consumptions in humans?

While there are no direct human studies on the effect of melamine data from animal studies
can be used to predict adverse health effects. Melamine alone causes bladder stones in
animal tests. When combined with cyanuric acid, which may also be present in melamine
powder, melamine can form crystals that can give rise to kidney stones.

These small crystals can also block the small tubes in the kidney potentially stopping the
production of urine, causing kidney failure and, in some cases, death. Melamine has also
been shown to have carcinogenic effects in animals in certain circumstances, but there is
insufficient evidence to make a judgment on carcinogenic risk in humans.

What are the symptoms and signs of melamine poisoning?

Irritability, blood in urine, little or no urine, signs of kidney infection, high blood pressure

What is the treatment for kidney stones and kidney failure?

Patients may receive various types of treatment, depending on the severity of the kidney
effects. Treatment may include infusion of fluids and urine alkalinisation, correction of
electrolyte and acid-base disturbance, haemodialysis or peritoneal dialysis, or surgical
removal of kidney stones.

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