 | |||
| |||
 | |||
| Names | |||
|---|---|---|---|
| Preferred IUPAC name 1,3,5-Triazine-2,4,6-triamine | |||
| Other names 2,4,6-Triamino-s-triazine Cyanurotriamide Cyanurotriamine Cyanuramide | |||
| Identifiers | |||
| |||
3D model (JSmol) | |||
| ChEBI | |||
| ChemSpider |
| ||
| ECHA InfoCard | 100.003.288 | ||
| KEGG |
| ||
| UNII | |||
| |||
| |||
| Properties | |||
| C3H6N6 | |||
| Molar mass | 126.123 g·mol−1 | ||
| Appearance | White solid | ||
| Density | 1.573 g/cm3[1] | ||
| Melting point | 343 °C (649 °F; 616 K) (decomposition)[1] | ||
| Boiling point | Sublimes | ||
| 3240 mg/ L (20 °C)[2] | |||
| Solubility | very slightly soluble in hot alcohol[clarification needed],benzene,glycerol,pyridine insoluble inether,benzene,CCl4 | ||
| logP | −1.37 | ||
| Acidity (pKa) | 5.0 (conjugated acid)[3] | ||
| Basicity (pKb) | 9.0[3] | ||
| −61.8·10−6 cm3/mol | |||
Refractive index (nD) | 1.872[1] | ||
| Structure | |||
| Monoclinic | |||
| Thermochemistry | |||
Std enthalpy of combustion(ΔcH⦵298) | −1967 kJ/mol | ||
| Hazards | |||
| GHS labelling:[4] | |||
 | |||
| Warning | |||
| H351,H373 | |||
| P203,P260,P280,P318,P319,P405,P501 | |||
| 500 °C (932 °F; 773 K) | |||
| Lethal dose or concentration (LD, LC): | |||
LD50 (median dose) | 3850 mg/kg (rat, oral) | ||
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |||
Melamine/ˈmɛləmiːn/ ⓘ is anorganic compound with the formula C3H6N6. This white solid is atrimer ofcyanamide, with a1,3,5-triazine skeleton. Like cyanamide, it contains 66%nitrogen by mass, and its derivatives havefire-retardant properties due to its release of nitrogen gas when burned or charred. Melamine can be combined withformaldehyde and other agents to producemelamine resins. Such resins are characteristically durablethermosetting plastic used in high-pressuredecorative laminates such asFormica, melaminedinnerware including cooking utensils, plates, and plastic products,[5] laminate flooring, anddry erase boards.Melamine foam is used as insulation and soundproofing material, and inpolymeric cleaning products such asMagic Eraser.
Melamine gained infamy when Chinese food producersSanlu Group added it to baby formula in order to increase the apparent protein content, causing the2008 Chinese milk scandal.[6][7] Ingestion of melamine may lead toreproductive damage, orbladder orkidney stones, andbladder cancer. It is also an irritant when inhaled or in contact with the skin or eyes. The United Nations' food standards body, theCodex Alimentarius Commission, has set the maximum amount of melamine allowed in powderedinfant 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.
The German wordMelamin was coined by combining the wordsmelam (a derivative of ammonium thiocyanate) andamine.[8][9] Melamine is, therefore, unrelated etymologically to the rootmelas (μέλας, meaning 'black' in Greek), from which the wordsmelanin, a pigment, andmelatonin, a hormone, are formed.
In one large-scale application, melamine is combined withformaldehyde and other agents to producemelamine resins. Such resins are characteristically durablethermosetting plastic used in high-pressuredecorative laminates such asWilsonart, melamine dinnerware, laminate flooring, anddry erase boards.[10] Melamine cookware is notmicrowave-safe,[11] and can be identified from the fact it is "slightly heavier and noticeably thicker than its plastic counterparts."[12]
Melamine foam is used as insulation, soundproofing material and inpolymeric cleaning products, such asMagic Eraser.
Melamine is one of the major components inPigment Yellow 150, a colorant in inks and plastics.
Melamine also is used in the fabrication of melamine polysulfonate, used as asuperplasticizer for making high-resistanceconcrete. Sulfonatedmelamine formaldehyde (SMF) is a polymer used as acement 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.
Melamine was once envisioned as fertilizer for crops during the 1950s and 1960s because of its high (66% by mass) nitrogen content.[13] However, melamine is much more expensive to produce than other common nitrogen fertilizers, such asurea. The mineralization (degradation to ammonia) for melamine is slow, making this product both economically and scientifically impractical for use as a fertilizer.[citation needed]
Melamine and its salts are used asfire-retardant additives in paints, plastics, and paper.[14] 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.[15]
Melamine is sometimes illegally added to food products in order to increase the apparent protein content. Standard tests, such as theKjeldahl andDumas 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.[16]
Melamine derivatives ofarsenical drugs are potentially important in the treatment ofAfrican trypanosomiasis.[17]
Melamine use asnon-protein nitrogen (NPN) for cattle was described in a 1958 patent.[18] In 1978, however, a study concluded that melamine "may not be an acceptable non-protein N source for ruminants" because itshydrolysis in cattle is slower and less complete than other nitrogen sources such ascottonseed meal and urea.[19]
The short-term lethal dose of melamine is on a par with common table salt, with anLD50 of more than 3 grams per kilogram of bodyweight.[20]U.S. Food and Drug Administration (FDA) scientists explained that when melamine andcyanuric acid are absorbed into the bloodstream, they concentrate and interact in the urine-filledrenal 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 thekidneys to malfunction[21] and lead to kidney stones, kidney failure, and death.[5] Signs of melamine toxicity can include irritability, blood in the urine, little to no urine, symptoms of kidney infection, or high blood pressure.[5]
TheEuropean Union set a standard for acceptable human consumption (tolerable daily intake or TDI) of melamine at 0.2 mg per kilogram of body mass[22] (previously 0.5 mg/kg), Canada declared a limit of 0.35 mg/kg, and the US FDA's limit was put at 0.063 mg/kg (previously 0.63 mg/kg). TheWorld 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.[23]
Toxicity of melamine can be mediated byintestinal microbiota. In culture,Raoultella terrigena, which rarely colonizes mammalian intestines,[24] 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.[25]
Melamine is reported to have an oralmedian lethal dose (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 greater than 1000 mg/kg for rabbits. A study by Soviet researchers in the 1980s suggested thatmelamine cyanurate, commonly used as a fire retardant,[26] could be more toxic than either melamine or cyanuric acid alone.[27] 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 in animals conducted after recalls of contaminated pet food concluded that the combination of melamine and cyanuric acid in diet does lead toacute kidney injury in cats.[28] A 2008 study produced similar experimental results in rats and characterized the melamine and cyanuric acid in contaminated pet food from the 2007 outbreak.[29] A 2010 study fromLanzhou 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 (ammeline) and cyanuric acid.[30] 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.[25]
Ingestion of melamine may lead toreproductive damage, orbladder orkidney stones, which can lead tobladder cancer.[31][32][33][34]
A study in 1953 reported that dogs fed 3% melamine for a year had the following changes in their urine: (1) reducedspecific gravity, (2)increased output, (3) melaminecrystalluria, and (4)protein andoccult blood.[35]
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."[36][37][38]
Melamine is ametabolite ofcyromazine, apesticide.[39] It has been reported that cyromazine can also be converted to melamine in plants.[40][41]
Fast diagnosis and treatment of acute obstructiveurolithiasis may prevent the development of acute kidney failure. Urine alkalinization and stone liberalization have been reported to be the most effective treatments in humans.[30]
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 160 °F (71 °C) for two hours, such as if food were kept heated in contact with it in an oven.[5]
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.[42]
Melamine was first synthesized by the German chemistJustus von Liebig in 1834. In early production, firstcalcium cyanamide was converted intodicyandiamide, which was heated above its melting temperature to produce melamine. Today most industrial manufacturers useurea in the following reaction to produce melamine:
In the first step, urea decomposes intocyanic acid and ammonia:
Cyanic acid polymerizes tocyanuric 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 orhigh pressure liquid-phase production. In one method, molten urea is introduced onto afluidized bed with catalyst for reaction. Hotammonia gas is also present to fluidize the bed and inhibit deammonization. The effluent then is cooled. Ammonia andcarbon dioxide in the off-gas are separated from the melamine-containing slurry. The slurry is further concentrated and crystallized to yield melamine.[43] Major manufacturers and licensors such asOrascom Construction Industries,BASF, andEurotecnica 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 (1.5–5% of the weight) for easier disposal. The solid may contain approximately 70% melamine, 23% oxytriazines (ammeline,ammelide, andcyanuric acid), 0.7% polycondensates (melem,melam, andmelon).[44] In the Eurotecnica process, however, there is no solid waste and the contaminants are decomposed toammonia andcarbon dioxide and sent as off gas to the upstreamurea plant; accordingly, the waste water can be recycled to the melamine plant itself or used as clean cooling water make-up.[45]
Melamine reacts withacid and related compounds to formmelamine cyanurate and related crystal structures, which have been implicated as contaminants or biomarkers inChinese protein adulterations.
Melamine is part of the core structure for a number of drugs includingalmitrine,altretamine,cyromazine,ethylhexyl triazone,iscotrizinol,meladrazine,melarsomine,melarsoprol,tretamine,trinitrotriazine, and others.[46]
Between the late 1990s and early 2000s, both consumption and production of melamine grew considerably inmainland China. By early 2006, melamine production in mainland China is reported to be in "serious surplus".[47]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 anadulterant forfeedstock andmilk 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. Actions taken in 2008 by the Government of China have reduced the practice of adulteration, with the goal of eliminating it. As a result of theChinese milk scandal, court trials began in December 2008 for six people involved in adding melamine in food products, ending in January 2009 with two of the convicts being sentenced to death and executed.[48][49]
Melamine has been involved in several food recalls after the discovery of severekidney damage to children and pets poisoned by melamine-adulterated food.
In 2007, a pet food recall was initiated byMenu 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.[50][51][52] In March 2007, the USFood and Drug Administration reported finding white granular melamine in the pet food, in samples of white granularwheat gluten imported from a single source in China, Xuzhou Anying Biologic Technology[53] as well as in crystalline form in the kidneys and in urine of affected animals.[54] 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 thefalse 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.[55] 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 inHenan 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."[56] Shandong Mingshui Great Chemical Group, the company reported by the New York Times as producing melamine fromcoal, produces and sells both urea and melamine but does not listmelamine resin as a product.[57]
Another recall incident in 2007 involved melamine which had been purposely added as abinder to fish and livestock feed manufactured in the United States. This was traced to suppliers in Ohio and Colorado.[58]
In September 2008, several companies, includingNestlé, were implicated in a scandal involving milk andinfant formula which had beenadulterated with melamine, leading to kidney stones and otherkidney failure, especially among young children. By December 2008, nearly 300,000 people had become ill, with more than 50,000 infant hospitalizations and six infant deaths.[59][60][61] In a study published in theNew England Journal of Medicine, it was reported that melamine exposure increased the incidence of urinary tract stones by seven times in children.[62] 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 approximately 10–12% for typical protein), it can cause the protein content of food to appear higher than the true value.[63][64] Officials estimate that about 20% of the dairy companies tested in China sell products tainted with melamine.[65] On January 22, 2009, three of those involved in the scandal (including one conditional sentence) were sentenced to death in a Chinese court.[66]
In October 2008, "Select Fresh Brown Eggs" exported 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 theHong 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.[67]
As of July 2010, Chinese authorities were still reporting some seizures of melamine-contaminated dairy product in some provinces, though it was unclear whether these new contaminations constituted wholly new adulterations or were the result of illegal reuse of material from the 2008 adulterations.[68][69]
On characterization and treatment of urinary stones in affected infants,The New England Journal of Medicine printed an editorial in March 2009, along with reports on cases from Beijing, Hong Kong and Taipei.[70]
Urinarycalculi specimens were collected from 15 cases treated in Beijing and were analyzed as unknown objects for their components at Beijing Institute of Microchemistry usinginfrared spectroscopy,nuclear magnetic resonance, andhigh performance liquid chromatography. The result of the analysis showed that the calculus was composed of melamine anduric acid, and the molecular ratio of uric acid to melamine was around 2:1.[71]
In a 2009 study of 683 children diagnosed in Beijing in 2008 withnephrolithiasis and 6,498 children without nephrolithiasis aged < 3 years, investigators found that in children exposed to melamine levels < 0.2 mg/kg per day, the risk for nephrolithiasis was 1.7 times higher than in those without melamine exposure, suggesting that the risk of melamine-induced nephrolithiasis in young children starts at a lower intake level than the levels recommended by theWorld Health Organization.[72]
In a study published in 2010, researchers fromBeijing University studying ultrasound images of infants who fell ill in the 2008 contamination found that while most children in a rural Chinese area recovered, 12 per cent still showed kidney abnormalities six months later. "The potential for long-term complications after exposure to melamine remains a serious concern," the report said. "Our results suggest a need for further follow-up of affected children to evaluate the possible long-term impact on health, including renal function."[73] Another 2010 follow-up study fromLanzhou University attributed theuric acid stone accumulation after ingestion of melamine to a rapid aggradation of metabolites such ascyanuric acid diamide (ammeline) and cyanuric acid and reported that urine alkalinization and stone liberalization were the most effective treatments.[30]
Until the2007 pet food recalls, melamine had not routinely been monitored in food, except in the context of plastic safety or insecticide residue.
Following the deaths of children in China from powdered milk in 2008, the Joint Research Centre (JRC) of the European Commission in Belgium set up a website about methods to detect melamine.[74] In May 2009, the JRC published the results of a study that benchmarked the ability of labs around the world to accurately measure melamine in food. The study concluded that the majority of labs can effectively detect melamine in food.[75]
In October 2008, theU.S. Food and Drug Administration (FDA) issued new methods for the analysis of melamine and cyanuric acid in infant formulations in the Laboratory Information Bulletin No 4421.[76] Similar recommendations have been issued by other authorities, like the Japanese Ministry of Health, Labor and Welfare,[77] both based on liquid chromatography – mass spectrometry (LC/MS) detection after hydrophilic interaction liquid chromatography (HILIC) separation.[78]
The existing methods for melamine determination using a triplequadrupole liquid chromatography – mass spectrometry (LC/MS) aftersolid phase extraction (SPE) are often complex and time-consuming. However,electrospray ionization methods coupled with mass spectrometry allow a rapid and direct analysis of samples with complex matrices: the native liquid samples are directly ionized under ambient conditions in their original solution. In December 2008, two new fast and inexpensive methods for detecting melamine in liquids have been published.[79]
Ultrasound-assisted extractive electrospray ionization mass spectrometry (EESI-MS) has been developed at ETH Zurich (Switzerland) by Zhu,Chingin et al., (2008)[80] for a rapid detection of melamine in untreatedfood samples.Ultrasounds are used tonebulize the melamine-containing liquids into a fine spray. The spray is then ionised byextractive electrospray ionisation (EESI) and analysed usingtandem mass spectrometry (MS/MS). An analysis requires 30 seconds per sample. The limit of detection of melamine is a few nanograms of melamine per gram of milk.[81]
Huang et al. (2008) have also developed at Purdue University (US) a simpler instrumentation and a faster method by using a low-temperature plasma probe to ionize the samples. The major obstacles being solved, theESI-MS technique allows now high-throughput analysis of melamine traces in complex mixtures.[82]
The Melaminometer[83][84][85]was a hypothetical design for asynthetic biology circuit, to be used for detecting melamine and related chemical analogues such ascyanuric acid. The conceptual project is hosted atOpenWetWare as open source biology in collaboration withDIYbio and has been discussed in various newspapers in the context of homebrew biotechnology. As of October 2009, the design has not been verified.
Becausemelamine resin is often used in food packaging and tableware, melamine atppm level (1 part per million) in food and beverage has been reported due to migration from melamine-containing resins.[86] Small amounts of melamine have also been reported in foodstuff as a metabolite product ofcyromazine, an insecticide used on animals and crops.[87]
TheFood Safety and Inspection Service (FSIS) of theUnited States Department of Agriculture (USDA) provides a test method for analyzing cyromazine and melamine in animal tissues.[88][89] In 2007, the FDA began using ahigh performance liquid chromatography test to determine the melamine,ammeline,ammelide, andcyanuric acid contamination in food.[90] Another procedure is based on surface-enhancedRaman spectroscopy (SERS).[91][92]
Member states of the European Union are required under Commission Decision 2008/757/EC[93] to ensure that all composite products containing at least 15% of milk product, originating from China, are systematically tested before import into the Community and that all such products which are shown to contain melamine in excess of 2.5 mg/kg are immediately destroyed.
Following the 2008 melamine milk scandal, China restructured its food safety system by implementing the Food Safety Law, introducing stricter dairy industry regulations, and establishing independent third-party inspections to strengthen oversight and restore public trust.[94] The 2009 Food Safety Law also reorganized government oversight by placing food safety regulation under a uniform national framework that employs risk-based standards and adheres to international Codex Alimentarius Commission guidelines.[95]
The presence of melamine in urine specimens from children who consumed adulterated milk products has been determined by liquid chromatography-mass spectrometry.[96]
It is reported that melamine molecules adsorbed on gold[97] or silver[98] surface tend to arrange into honeycomb or closed-packed structures. Such a self-assembly occurs due to the inter-molecular hydrogen bond interaction. This ordering was further investigated using classicalMonte Carlo[99] andDFT[100] methods.
{{cite journal}}: CS1 maint: multiple names: authors list (link)Foods and drinks should not be heated on melamine-based dinnerware in microwave ovens.
{{cite journal}}: CS1 maint: multiple names: authors list (link)Establishment of maximum levels will help governments differentiate between low levels of unavoidable melamine occurrence that do not cause health problems, and deliberate adulteration – thereby protecting public health without unnecessary impediments to international trade.
