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Melamine

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

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]

 

Contents

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)[5]. 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[6]

Melamine use as non-protein nitrogen (NPN) for cattle was described in a 1958 patent.[7] 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.[8]

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. [9]

 

Regulation

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."[10][11] 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."[12] Melamine, classified a controlled substance in China[13], has been illegally used in the high profile 2008 baby milk scandal case which led to the death of at least 4 infants[13].

 

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.[14] 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.[15] 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.[16]

 

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.[17] In a 1945 study, large doses of melamine were given orally to rats, rabbits and dogs with "no significant toxic effects" observed.[18]

A study by USSR researchers in the 1980s suggested that melamine cyanurate, commonly used as a fire retardant[19]), could be more toxic than either melamine or cyanuric acid alone.[20] 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.[21]

 

Chronic toxicity

Ingestion of melamine may lead to reproductive damage, or bladder or kidney stones, which can lead to bladder cancer.[17][22][23][24][25]

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.[26]

A survey commissioned by the American Association of Veterinary Laboratory Diagnosticians suggested that crystals formed in the kidneys melamine combined with cyanuric acid, "don't dissolve easily. They go away slowly, if at all, so there is the potential for chronic toxicity."[27][28][29]

 

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.[30][31][32] 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[33] as well as in crystalline form in the kidneys and in urine of affected animals.[34] 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.[35] 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."[36] 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.[37]

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.[38]

 

2008 Chinese milk 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. By 22 September, nearly 53,000 illnesses, over 12,800 hospitalisations, and four infant deaths had been reported, caused by kidney stones and other renal failure.[39][40]

Melamine may have been added to fool government quality tests after water was added to fraudulently increase the milk's volume, since melamine will cause a false increase in the measurement of protein by increasing the nitrogen levels in the milk.[41][42] Officials estimate that about 20 percent of the dairy companies tested in China sell products tainted with melamine.[43]

 

Testing methods for melamine and cyanuric acid

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, and egg products are safe, wholesome and accurately labeled."[10][11]

On 9 November 2007, FDA presented a method of HPLC Determination of Melamine, Ammeline, Ammelide, and Cyanuric Acid Contamination in Wheat Gluten and Rice Protein Concentrate.[44]

 

Detection of melamine 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.

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.[45] Small amounts of melamine have also been reported in foodstuff as a metabolite product of cyromazine, an insecticide used on animals and crops.[46]

 

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 and 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.[47] 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).[48]

 

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."[49]

By early 2006, melamine production in mainland China is reported to be in "serious surplus".[50] In April 2007, DSM's melamine industry update painted a grave global picture.[51] 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.

 

Etymology

The German word Melamin was coined by combining the names of two other chemical products: Melam (a distillation derivative of ammonium thiocyanate) and Amin. [52] [53]

 

See also

  • 1,3,5-Triazine
  • Triazines
  • Non-protein nitrogen (others)
  • Cyanamide (precursor of melamine)
  • Cyanuric acid (degradation product of melamine)
  • Melamine cyanurate
  • Melam
  • 2008 Chinese milk scandal
  • International Reaction to the 2008 Dairy Scandal

 

References

  1. ^ Merck Index, 12th Edition, 5853.
  2. ^ Report on cyromazine of the European Medicines Agency
  3. ^ 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]
  4. ^ FAO report on cyromazine
  5. ^ Hauck, R.D.; H.F. Stephenson (1964). "Nitrification of triazine nitrogen". Fertilizer Nitrogen Sources 12 (2): 147. 
  6. ^ 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. 
  7. ^ "Ruminant feed compositions, Robert W. Colby and Robert J. Mesler Jr., U.S. Patent No. 2819968, 1958
  8. ^ “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
  9. ^ "Protein Pretense", Alison Snyder, Scientific American Magazine, August 2008 [2] |accessdate=2008-09-19
  10. ^ a b "CYROMAZINE AND MELAMINE" (PDF). USDA FSIS (July 1991). Retrieved on 2007-04-27.
  11. ^ a b "Chemistry Laboratory Guidebook". USDA FSIS. Retrieved on 2007-04-27.
  12. ^ Environmental Protection Agency. Cyromazine; Pesticide Tolerance
  13. ^ a b "china bans melamine" (HTML). CBS (September 2008). Retrieved on 2008-09-19.
  14. ^ How Two Innocuous Compounds Combined to Kill Pets, Washington Post, May 7, 2007.
  15. ^ "Melamine in milk by David Bradley", Sciencebase (17 Sep 2008). Retrieved on 2008-09-27. 
  16. ^ "Poison pet food woes seem to hit cats harder", USA Today (5 August 2007). Retrieved on 2008-10-01. 
  17. ^ a b MSDS
  18. ^ W.L. Lipschitz, E. Stokey, The mode of action of three new diuretics：melamine, adenine and formoguanamine, Journal of Pharmacology And Experimental Therapeutics, Vol. 83, Issue 4, 235-249, [[{{{date}}}]].
  19. ^ Flame Retardants Center: Melamine Compounds
  20. ^ 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.
  21. ^ Puschner et al. (November 2007). "Assessment of melamine and cyanuric acid toxicity in cats". Journal of Veterinary Diagnostic Investigation. Retrieved on 2007-11-16.
  22. ^ International Chemical Safety Card
  23. ^ OSHA – Chemical sampling information
  24. ^ WHO – Some Chemicals that Cause Tumors of the Kidney or Urinary Bladder in Rodents and Some Other Substances
  25. ^ HD Heck and RW Tyl (September 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. 
  26. ^ 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
  27. ^ "Culprit in pet food deaths may be combination of contaminants". Michigan State University (November 29, 2007). Retrieved on 2007-12-07.
  28. ^ "Proceedings of the American Association of Veterinarian Laboratory Diagnosticians 50th Annual Conference" (PDF). AAVLD (October 2007). Retrieved on 2007-11-30.
  29. ^ "Researchers examine contaminants in food, deaths of pets". AVMA (November 2007). Retrieved on 2007-11-30.
  30. ^ CNN: Dry food added to pet food recall list
  31. ^ AVMA: Pet food recall
  32. ^ Press release by Natural Balance Pet Foods
  33. ^ FDA FAQ: Where did the contaminated wheat gluten come from?
  34. ^ FDA:Pet food recall
  35. ^ David Barboza and Alexei Barrionuevo (30 April 2007). "Filler in Animal Feed Is Open Secret in China", The New York Times. Retrieved on 2007-04-30. 
  36. ^ David Barboza and Alexei Barrionuevo (3 May 2007). "China Makes Arrest in Pet Food Case", The New York Times. Retrieved on 2007-05-03. 
  37. ^ "Products". Shandong Mingshui Great Chemical Group. Retrieved on 2007-04-30.
  38. ^ Andrew Martin (31 May 2007). "Poison used in China is found in U.S.-made animal feed", The New York Times. Retrieved on 2007-06-01. 
  39. ^ Scott McDonald, "Nearly 53,000 Chinese children sick from milk", Associated Press (22 September 2008)
  40. ^ Jane Macartney, China baby milk scandal spreads as sick toll rises to 13,000, The Times (September 22, 2008)
  41. ^ "Fonterra says somebody sabotaged milk" (in English). NZ Herald (September 15, 2008). Retrieved on 2008-09-22.
  42. ^ "Toxic milk toll rockets in China" (in English). BBC NEWS (September 15, 2008). Retrieved on 2008-09-22.
  43. ^ Tran, Tini (September 17, 2008). "6,200 Chinese babies ill, 3 die from tainted milk" (in English). Yahoo! News. Retrieved on 2008-09-22.
  44. ^ "HPLC Determination of Melamine, Ammeline, Ammelide, and Cyanuric Acid Contamination in Wheat Gluten and Rice Protein Concentrate". FDA (25 April 2007). Retrieved on 2007-05-09.
  45. ^ 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. 
  46. ^ 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.
  47. ^ Kirk-Othmer encyclopedia of chemical technology, 3rd edition, Vol.7, p303-304, 1978.
  48. ^ SM Lahalih, M Absi-Halabi, "Recovery of solids from melamine waste effluents and their conversion to useful products", Industrial & Engineering Chemistry Research, vol.28, 500-504 (1989).
  49. ^ Kramer, Deborah (2005). "Nitrogen" (PDF). United States Geological Survey. Retrieved on 2007-04-30.
  50. ^ Ruilin, Wang (6 January 2006). "Melamine capacity is serious surplus", China Chemical Reporter. Retrieved on 2007-04-21. 
  51. ^ Melamine industry update, by Royal DSM N.V., accessed on 2007-05-04
  52. ^ "Melamine. The American Heritage Dictionary of the English Language: Fourth Edition. 2000.". Retrieved on 2008-09-28.
  53. ^ Bann B. and Miller S.A. (1958) "Melamines and derivatives of melamine". Chemical Reviews, vol.58, 131-172.

 

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