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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 and the hormones melatonin and melanotan.

Template:Chembox new Melamine 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.[1] It has been reported that cyromazine can also be converted to melamine in plants.[2][3]

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

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. [4] [5]

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)[6]. 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[7]

Melamine use as non-protein nitrogen (NPN) for cattle was described in a 1958 patent.[8] 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.[9]

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. [10]

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.[11] 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.[12] 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.[13]

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.[14] In a 1945 study, large doses of melamine were given orally to rats, rabbits and dogs with "no significant toxic effects" observed.[15]

A study by USSR researchers in the 1980s suggested that melamine cyanurate, commonly used as a fire retardant[16], could be more toxic than either melamine or cyanuric acid alone.[17] 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.[18]

Chronic toxicity

Ingestion of melamine may lead to reproductive damage, or bladder or kidney stones, which can lead to bladder cancer.[14][19][20][21][22]

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.[23]

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."[24][25][26]

Regulation

In Europe, food or animal feed products containing more than 2.5 mg / kg are to be immediately destroyed.[27]

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."[28][29] 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."[30] Melamine, classified a controlled substance in China[31], has been illegally used in the high profile 2008 baby milk scandal case which led to the death of at least 4 infants[31].

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.[32] 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.[33] 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.[34]

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.[35] 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).[36]

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."[37]

By early 2006, melamine production in mainland China is reported to be in "serious surplus".[38] In April 2007, DSM's melamine industry update painted a grave global picture.[39] 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.

Poisoning and kidney failure caused by melamine cyanurate

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.[40][41][42] 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[43] as well as in crystalline form in the kidneys and in urine of affected animals.[44] 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.[45] 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."[46] 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.[47]

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.[48]

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.[49][50]

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.[51][52] Officials estimate that about 20 percent of the dairy companies tested in China sell products tainted with melamine.[53]

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. [54]

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 [55]. Similar recommendations have been issued by other authorities, like the Japanese Ministry of Health, Labor and Welfare [56], both based on LC MS/MS detection after HILIC separation [57]

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.[58] Small amounts of melamine have also been reported in foodstuff as a metabolite product of cyromazine, an insecticide used on animals and crops.[59]

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. [28][29] In 2007, the FDA began using a high performance liquid chromatography test to determine the melamine, ammeline, ammelide, and cyanuric acid contamination in food.[60] Another procedure is based on surface-enhanced Raman spectroscopy (SERS). [61][62]

See also

References

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  2. ^ Lori 0. Lim, Susan J. Scherer, Kenneth D. Shuler, and John P. Toth. Disposition of Cyromazine in Plants under Environmental Conditions J. Agric. Food Chem. 1990, 38, 860-864 [1]
  3. ^ FAO report on cyromazine
  4. ^ "Melamine. The American Heritage Dictionary of the English Language: Fourth Edition. 2000". Retrieved 2008-09-28.
  5. ^ Bann B. and Miller S.A. (1958) "Melamines and derivatives of melamine". Chemical Reviews, vol.58, 131-172.
  6. ^ Hauck, R.D. (1964). "Nitrification of triazine nitrogen". Fertilizer Nitrogen Sources. 12 (2): 147. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  7. ^ Barrett MP, Gilbert IH (2006). "Targeting of toxic compounds to the trypanosome's interior". Adv. Parasitol. 63: 125–83. doi:10.1016/S0065-308X(06)63002-9. PMID 17134653.
  8. ^ "Ruminant feed compositions, Robert W. Colby and Robert J. Mesler Jr., U.S. Patent No. 2819968, 1958
  9. ^ “Melamine as a dietary nitrogen source for ruminants", G.L.Newton and P.R.Utley, Journal of Animal Science, vol.47, p1338-44, 1978, Abstract |accessdate=2008-09-17
  10. ^ "Protein Pretense", Alison Snyder, Scientific American Magazine, August 2008 [2] |accessdate=2008-09-19
  11. ^ How Two Innocuous Compounds Combined to Kill Pets, Washington Post, May 7, 2007.
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  13. ^ "Poison pet food woes seem to hit cats harder". USA Today. 5 August 2007. Retrieved 2008-10-01.
  14. ^ a b MSDS
  15. ^ W.L. Lipschitz, E. Stokey (1945). "The mode of action of three new diuretics：melamine, adenine and formoguanamine". Vol. 83, Issue 4, 235–249. Journal of Pharmacology And Experimental Therapeutics. {{cite journal}}: |volume= has extra text (help); Cite journal requires |journal= (help)
  16. ^ Flame Retardants Center: Melamine Compounds
  17. ^ A.A. Babayan, A.V.Aleksandryan, "Toxicological characteristics of melamine cyanurate, melamine and cyanuric acid", Zhurnal Eksperimental'noi i Klinicheskoi Meditsiny, Vol.25, 345-9 (1985). Original article in Russian, English abstract retrieved from SciFinder on either 2007-07-05 or 2007-05-07.
  18. ^ Puschner; et al. (2007). "Assessment of melamine and cyanuric acid toxicity in cats". Journal of Veterinary Diagnostic Investigation. Retrieved 2007-11-16. {{cite web}}: Explicit use of et al. in: |last= (help); Unknown parameter |month= ignored (help)
  19. ^ International Chemical Safety Card
  20. ^ OSHA – Chemical sampling information
  21. ^ WHO – Some Chemicals that Cause Tumors of the Kidney or Urinary Bladder in Rodents and Some Other Substances
  22. ^ HD Heck and RW Tyl (1985). "The induction of bladder stones by terephthalic acid, dimethyl terephthalate, and melamine (2,4,6-triamino-s-triazine) and its relevance to risk assessment". Regul Toxicol Pharmacol. 5 (3): 294–313. doi:10.1016/0273-2300(85)90044-3. PMID 3903881. {{cite journal}}: Unknown parameter |month= ignored (help)
  23. ^ T.W. Tusing, "Chronic Feeding - Dogs", cited by "Summary of toxicity data - trichloromelamine" by California Environmental Protection Agency, last revised on 04-02-2002, URL accessed on 05-09-2007
  24. ^ "Culprit in pet food deaths may be combination of contaminants". Michigan State University. November 29, 2007. Retrieved 2007-12-07.
  25. ^ "Proceedings of the American Association of Veterinarian Laboratory Diagnosticians 50th Annual Conference" (PDF). AAVLD. 2007. Retrieved 2007-11-30. {{cite web}}: Unknown parameter |month= ignored (help)
  26. ^ "Researchers examine contaminants in food, deaths of pets". AVMA. 2007. Retrieved 2007-11-30. {{cite web}}: Unknown parameter |month= ignored (help)
  27. ^ Commission Decision 2008/798/EC
  28. ^ a b "CYROMAZINE AND MELAMINE" (PDF). USDA FSIS. 1991. Retrieved 2007-04-27. {{cite web}}: Unknown parameter |month= ignored (help)
  29. ^ a b "Chemistry Laboratory Guidebook". USDA FSIS. Retrieved 2007-04-27.
  30. ^ Environmental Protection Agency. Cyromazine; Pesticide Tolerance
  31. ^ a b "china bans melamine" (HTML). CBS. 2008. Retrieved 2008-09-19. {{cite web}}: Unknown parameter |month= ignored (help) Cite error: The named reference "bbc" was defined multiple times with different content (see the help page).
  32. ^ Associated Press, FDA: Tiny amount of melamine not harmful to adults
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  35. ^ Kirk-Othmer encyclopedia of chemical technology, 3rd edition, Vol.7, p303-304, 1978.
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  38. ^ Ruilin, Wang (6 January 2006). "Melamine capacity is serious surplus". China Chemical Reporter. Retrieved 2007-04-21.
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  40. ^ CNN: Dry food added to pet food recall list
  41. ^ AVMA: Pet food recall
  42. ^ Press release by Natural Balance Pet Foods
  43. ^ FDA FAQ: Where did the contaminated wheat gluten come from?
  44. ^ FDA:Pet food recall
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  55. ^ U.S. FDA Laboratory Information Bulletin No 4421 - http://www.cfsan.fda.gov/~frf/lib4421.html
  56. ^ Japanese Ministry of Health, Labor and Welfare - http://www.forth.go.jp/keneki/kanku/syokuhin/tsuuchi/2008/10/3_1.pdf
  57. ^ Zwitterionic HILIC separation of melamine and cyanuric acid - http://www.sequant.com/melamine
  58. ^ Ishiwata H, Inoue T, Yamazaki T, Yoshihira K (1987). "Liquid chromatographic determination of melamine in beverages". J Assoc Off Anal Chem. 70 (3): 457–60. PMID 3610957.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  59. ^ J.V. Sancho, M. Ibanez, S. Grimalt, O.J. Pozo, F. Hernandez, "Residue determination of cyromazine and its metabolite melamine in chard samples by ion-pair liquid chromatography coupled to electrospray tandem mass spectrometry", Analytica Chimica Acta Vol.530, p237-243 (2005) Abstract accessed 05-06-2007.
  60. ^ "HPLC Determination of Melamine, Ammeline, Ammelide, and Cyanuric Acid Contamination in Wheat Gluten and Rice Protein Concentrate". FDA. 25 April 2007. Retrieved 2007-05-09.
  61. ^ Lili He, Yang Liu, Mengshi Lin, Joseph Awika, David R. Ledoux, Hao Li, Azlin Mustapha, (2008). "A new approach to measure melamine, cyanuric acid, and melamine cyanurate using surface enhanced Raman spectroscopy coupled with gold nanosubstrates". Sens. & Instrumen. Food Qual. 2: 66–71. doi:10.1007/s11694-008-9038-0.{{cite journal}}: CS1 maint: extra punctuation (link) CS1 maint: multiple names: authors list (link)
  62. ^ Mengshi Lin, Lili He, Joseph Awika, Liyi Yang, David R. Ledoux, Hao Li, Azlin Mustapha, (2008). "Detection of melamine in gluten, chicken feed and processed foods using surface enhanced Raman spectroscopy and HPLC". Journal of Food Science. 73 (8): T129–T134.{{cite journal}}: CS1 maint: extra punctuation (link) CS1 maint: multiple names: authors list (link)
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