Melamine 553468 224096353 2008-07-07T08:13:00Z Downwards 671535 /* Chronic toxicity */ {{chembox new | Reference = <ref>''Merck Index'', 12th Edition, '''5853'''.</ref> | ImageFileL1 = Melamine.svg | ImageSizeL1 = 150px | ImageFileR1 = Melamine-3D-balls.png | ImageSizeR1 = 150px | IUPACName = 1,3,5-Triazine-2,4,6-triamine | OtherNames = Cyanurotriamide<br>Cyanurotriamine<br>Cyanuramide | Section1 = {{Chembox Identifiers | Abbreviations = | CASNo = 108-78-1 | EINECS = | PubChem = 7955 | SMILES = Nc1nc(N)nc(N)n1 | InChI = | RTECS = | MeSHName = | ChEBI = | KEGG = | ATCCode_prefix = | ATCCode_suffix = | ATC_Supplemental =}} | Section2 = {{Chembox Properties | Formula = C<sub>3</sub>H<sub>6</sub>N<sub>6</sub> | MolarMass = 126.12 g/mol | Appearance = White solid | Density = 1574 kg/m<sup>3</sup> | MeltingPtC = 350 | Melting_notes = | BoilingPt = Sublimes | Boiling_notes = | Solubility = 3.1g/l (20°C) | SolubleOther = | Solvent = | pKa = | pKb = }} | Section7 = {{Chembox Hazards | EUClass = | EUIndex = | MainHazards = | NFPA-H = | NFPA-F = | NFPA-R = | NFPA-O = | RPhrases = | SPhrases = | RSPhrases = | FlashPt = | Autoignition = | ExploLimits = | PEL = }} }} :''This article is about the chemical substance called melamine. The term "melamine" is also used to describe [[melamine resin]], a [[plastic]] material.'' {{distinguish2|[[melanin]], a pigment found in skin and hair}} '''Melamine''' is an organic base with the chemical formula [[carbon|C<sub>3</sub>]][[hydrogen|H<sub>6</sub>]][[nitrogen|N<sub>6</sub>]], with the [[IUPAC]] name '''1,3,5-triazine-2,4,6-triamine'''. It is only slightly soluble in water. Melamine is a [[trimer (chemistry)|trimer]] of [[cyanamide]]. Like cyanamide, it is 66% [[nitrogen]] (by mass) and provides [[fire retardant]] properties to resin formulas by releasing nitrogen when burned or charred. [[Dicyandiamide]] (or [[cyanoguanidine]]), the dimer of cyanamide, is also used as a fire retardant. Melamine is a [[metabolite]] of [[cyromazine]], a [[pesticide]]. It is formed in the body of mammals who have ingested cyromazine.<ref>[http://www.emea.europa.eu/pdfs/vet/mrls/077000en.pdf Report on cyromazine of the European Medicines Agency]</ref> It was also reported that cyromazine is converted to melamine in plants.<ref>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 [http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/1990/38/i03/f-pdf/f_jf00093a057.pdf?sessid=6006l3]</ref><ref>[http://www.fao.org/ag/AGP/AGPP/Pesticid/JMPR/Download/92/Cyromazi.PDF [[FAO]] report on cyromazine]</ref> ==Synthesis== Melamine was first synthesized by [[Justus von Liebig|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 (NH<sub>2</sub>)<sub>2</sub>CO → C<sub>3</sub>H<sub>6</sub>N<sub>6</sub> + 6 NH<sub>3</sub> + 3 CO<sub>2</sub> It can be understood as two steps. First, urea decomposes into [[cyanic acid]] in an [[endothermic reaction]] (NH<sub>2</sub>)<sub>2</sub>CO → HCNO + NH<sub>3</sub>. Then cyanic acid polymerizes to form melamine and carbon dioxide: 6 HCNO → C<sub>3</sub>H<sub>6</sub>N<sub>6</sub> + 3 CO<sub>2</sub>. The second reaction is [[exothermic]] and the overall process is endothermic. The above reaction can be carried out by either of two methods:[[catalysis|catalyzed]] [[gas|gas-phase]] production or [[high pressure]] [[liquid|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.<ref>Kirk-Othmer encyclopedia of chemical technology, 3rd edition, Vol.7, p303-304, 1978.</ref> Major manufacturers and licensors such as [[DSM Melamine(company)|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 (chemistry)|melam]] and [[Melon (chemistry)|melon]]).<ref>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).</ref> ==Uses== Melamine is used combined with [[formaldehyde]] to produce [[melamine resin]], a very durable [[thermosetting plastic]], and of [[melamine foam]], a [[polymer]]ic cleaning product. The end products include countertops, dry erase boards, fabrics, [[glue]]s, housewares and flame retardants. Melamine is one of the major components in Pigment Yellow 150, a colorant in inks and plastics. Melamine is also used to make fertilizers. Melamine derivatives of [[arsenical]] drugs are potentially important in the treatment of African [[trypanosomiasis]]<ref>Barrett MP, Gilbert IH. Targeting of toxic compounds to the trypanosome's interior.Adv Parasitol. 2006;63:125-83. </ref> Melamine use as [[Chinese protein export scandal#Non-protein nitrogen as legitimate and illegitimate feed additive|non-protein nitrogen]] (NPN) for cattle was described in a 1958 patent.<ref>"Ruminant feed compositions, Robert W. Colby and Robert J. Mesler Jr., U.S. Patent No. 2819968, 1958</ref> In 1978, however, a study concluded that melamine "may not be an acceptable nonprotein N source for ruminants" because its [[hydrolysis]] in cattle is slower and less complete than other nitrogen sources such as [[cottonseed meal]] and urea.<ref name="MelamineNPN1978">“Melamine as a dietary nitrogen source for ruminants", G.L.Newton and P.R.Utley, Journal of Animal Science, vol.47, p1338-44, 1978, [http://olericulture.org/000/298/000298197.html Abstract]</ref> ==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, and egg products are safe, wholesome and accurately labeled."<ref name=FSIScyro>{{cite web |title=CYROMAZINE AND MELAMINE |url=http://www.fsis.usda.gov/ophs/clg/Cyromazine.pdf |publisher=[[USDA]] [[FSIS]] |date=July 1991 |accessdate=2007-04-27}}</ref><ref name=FSISCLG>{{cite web |title=Chemistry Laboratory Guidebook |url=http://www.fsis.usda.gov/science/Chemistry_Lab_Guidebook/index.asp |publisher=[[USDA]] [[FSIS]] |accessdate=2007-04-27}}</ref> In 1999, in a proposed rule published in the [[Federal Register]] regarding cyromazine residue, the [[United States Environmental Protection Agency]] (EPA) proposed "remov[ing] melamine, a metabolite of cyromazine from the tolerance expression since it is no longer considered a residue of concern."<ref name=EPACyr> [http://www.epa.gov/fedrgstr/EPA-PEST/1999/September/Day-15/p24047.htm Environmental Protection Agency. Cyromazine; Pesticide Tolerance]</ref> ==Toxicity==<!-- This section is linked from [[Timeline of the 2007 pet food recalls]] --> Little is known with respect to melamine toxicity in human subjects. Animal studies have shown that melamine is not metabolized in rats, and is excreted unchanged.<ref>{{cite journal | author = RW Mast ''et al'' | title =Metabolism, disposition and excretion of [14C]melamine in male Fischer 344 rats | journal =Food and Chemical Toxicology | volume = 21 | issue = 6 | pages = 807–810 | date= December 1983 | pmid = 6686586 | doi =10.1016/0278-6915(83)90216-8 }} </ref> ===Acute toxicity=== Melamine is reported to have an oral [[median lethal dose|LD<sub>50</sub>]] of >3000 [[milligram|mg]]/kg based on rat data, which makes it only minimally toxic ([[Sodium chloride|table salt]] has a similar LD<sub>50</sub> value). It is also an irritant when inhaled or in contact with the skin or eyes. The reported dermal LD<sub>50</sub> is >1000 mg/kg for rabbits.<ref name="melaminemsds"/> In a 1945 study, large doses of melamine were given orally to rats, rabbits and dogs with "no significant toxic effects" observed.<ref>{{cite |author=W.L. Lipschitz, E. Stokey |title= The mode of action of three new diuretics:melamine, adenine and formoguanamine |publisher=Journal of Pharmacology And Experimental Therapeutics, Vol. 83, Issue 4, 235-249 |date=1945}}</ref> There does not seem to be any reported human case of acute intoxication directly caused by melamine. A study by [[USSR]] researchers in the 1980s suggested [[melamine cyanurate]] (a salt formed between melamine and [[cyanuric acid]], commonly used as a fire retardant<ref>[http://www.specialchem4polymers.com/tc/Melamine-Flame-Retardants/index.aspx?id=4004 Flame Retardants Center: Melamine Compounds]</ref>) could be more toxic than either melamine or cyanuric acid alone.<ref>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]]<!--was 05-07-2007-->.</ref> For rats and mice, the reported LD<sub>50</sub> 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.<ref name=UCDavis>{{cite web |title=Assessment of melamine and cyanuric acid toxicity in cats |last=Puschner et al. |url=http://jvdi.org/cgi/content/abstract/19/6/616 |publisher=Journal of Veterinary Diagnostic Investigation |date=November 2007 |accessdate=2007-11-16}}</ref> ===Chronic toxicity=== Ingestion of melamine may lead to [[reproduction|reproductive damage]], or [[urinary bladder|bladder]] or [[kidney stone]]s, which can lead to bladder [[cancer]].<ref name="melaminemsds">[http://ptcl.chem.ox.ac.uk/MSDS/ME/melamine.html MSDS] </ref><ref>[http://www.cdc.gov/niosh/ipcsneng/neng1154.html International Chemical Safety Card] </ref><ref>[http://www.osha.gov/dts/chemicalsampling/data/CH_250440.html OSHA] &ndash; Chemical sampling information</ref><ref>[http://monographs.iarc.fr/ENG/Monographs/vol73/volume73.pdf WHO] &ndash; Some Chemicals that Cause Tumors of the Kidney or Urinary Bladder in Rodents and Some Other Substances</ref><ref>{{cite journal | author = HD Heck and RW Tyl | title =The induction of bladder stones by terephthalic acid, dimethyl terephthalate, and melamine (2,4,6-triamino-s-triazine) and its relevance to risk assessment | journal = Regul Toxicol Pharmacol. | volume =5 | issue =3 | pages =294–313 | date= September 1985 | pmid = 3903881 | doi =10.1016/0273-2300(85)90044-3}} </ref> 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.<ref>T.W. Tusing, "Chronic Feeding - Dogs", cited by "Summary of toxicity data - trichloromelamine" by California Environmental Protection Agency, last revised on 04-02-2002, [http://www.cdpr.ca.gov/docs/toxsums/pdfs/1023.pdf URL] accessed on 05-09-2007</ref> Wilson Rumbeiha, an associate professor in MSU’s Diagnostic Center for Population and Animal Health, commenting on results from a survey commissioned by the American Association of Veterinary Laboratory Diagnosticians and designed and implemented by MSU toxicologists presented at the AAVLD's October 2007 meeting, said: "Unfortunately, these [melamine cyanurate] crystals don’t dissolve easily. They go away slowly, if at all, so there is the potential for chronic toxicity.”<ref name=MSUsurvey>{{cite web |url=http://msutoday.msu.edu/research/index.php3?article=07Dec2007-5 |title=Culprit in pet food deaths may be combination of contaminants |publisher=[[Michigan State University]] |date=[[December 7]] [[2007]] |accessdate=2007-12-07}}</ref><ref name=AAVLDproceedings>{{cite web |url=http://data.memberclicks.com/site/aavld/2007%20AAVLD%20Procdngs%20book%20(2).pdf |title=Proceedings of the American Association of Veterinarian Laboratory Diagnosticians 50th Annual Conference |publisher=[[AAVLD]] |date=October2007 |accessdate=2007-11-30}}</ref><ref name=AVMAsurvey>{{cite web |url=http://www.avma.org/onlnews/javma/dec07/071201c.asp |title=Researchers examine contaminants in food, deaths of pets |publisher=[[AVMA]] |date=November 2007 |accessdate=2007-11-30}}</ref> ===2007 pet food recalls=== {{See|2007 pet food recalls}} 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.<ref>[http://www.cnn.com/2007/US/03/30/pet.food.recall.ap/index.html CNN: Dry food added to pet food recall list]</ref><ref>[http://www.avma.org/aa/menufoodsrecall/products.asp AVMA: Pet food recall]</ref><ref>[http://www.naturalbalanceinc.com/press_release.html Press release by Natural Balance Pet Foods]</ref> On 30 March 2007, the US [[Food and Drug Administration]] reported finding white granular melamine in the pet food, in samples of white granular [[wheat gluten (food)|wheat gluten]] imported from a single source in China, Xuzhou Anying Biologic Technology<ref>[http://www.fda.gov/cvm/MenuFoodRecallFAQ.htm FDA FAQ: Where did the contaminated wheat gluten come from?]</ref> as well as in crystalline form in the kidneys and in urine of affected animals.<ref>[http://www.fda.gov/bbs/topics/NEWS/2007/NEW01599.html FDA:Pet food recall]</ref> Further vegetable protein imported from China was later implicated. See [[Chinese protein export contamination]]. The practice of adding "melamine scrap" to animal feed is reported to be widespread in China in order to give the [[Chinese protein export scandal#Protein testing in the food industry|appearance of increased protein content]] in animal feed.<ref name=NYTfiller/> Melamine has also been purposely added as a [[binder (material)|binder]] to fish and livestock feed manufactured in the United States and traced to suppliers in Ohio and Colorado.<ref name=IHTusadult/> The presence of melamine has not been conclusively linked to the deaths of animals, as this chemical was previously thought to be non-toxic at low doses. ====Official US statements==== On [[April 27]] US [[FDA]] subjected all vegetable proteins imported from China, intended for human or animal consumption, to detention without physical examination, including: Wheat Gluten, Rice Gluten, Rice Protein, Rice Protein Concentrate, Corn Gluten, Corn Gluten Meal, Corn By-Products, Soy Protein, Soy Gluten, Proteins (includes amino acids and protein hydrosylates), and Mung Bean Protein.<ref name=FDAimp>{{cite web |title=IMPORT ALERT #99-29, "DETENTION WITHOUT PHYSICAL EXAMINATION OF ALL VEGETABLE PROTEIN PRODUCTS FROM CHINA FOR ANIMAL OR HUMAN FOOD USE DUE TO THE PRESENCE OF MELAMINE AND/OR MELAMINE ANALOGS" |url=http://www.fda.gov/ora/fiars/ora_import_ia9929.html |publisher=[[FDA]] |date=[[April 27]] [[2007]] |accessdate=2007-05-01}}</ref> On [[April 28]], the [[U.S. Department of Agriculture]] (USDA) and the FDA, in a joint press release acknowledged that pork from hogs fed melamine-contaminated feed had entered the human food supply, stating: "Based on information currently available, FDA and USDA believe the likelihood of illness after eating pork from swine fed the contaminated product would be very low."<ref name=USDAFDA>{{cite web |title=Joint Update: FDA/USDA Update on Tainted Animal Feed |url=http://www.fda.gov/bbs/topics/NEWS/2007/NEW01620.html |publisher=[[USDA]] and [[FDA]] |date=[[April 28]] [[2007]] |accessdate=2007-04-30}}</ref> On [[April 30]], the USDA and the FDA updated their [[April 28]] food safety position to include poultry, reflecting contaminated feed being fed to chickens in Indiana.<ref name=USDAFDA2>{{cite web |title=Joint Update: FDA/USDA Trace Adulterated Animal Feed to Poultry |url=http://www.fda.gov/bbs/topics/NEWS/2007/NEW01621.html |publisher=[[USDA]] and [[FDA]] |date=[[April 30]] [[2007]] |accessdate=2007-05-01}}</ref> On [[May 7]], the USDA and the FDA issued a joint press release reflecting the combined judgment of five federal agencies with regard to the risk to humans in consuming meat from animals fed feed contaminated with tainted pet food scraps, concluding: "There is very low risk to human health" in such cases involving pork and poultry. The risk assessment was conducted by scientists from FDA, the Food Safety and Inspection Service (FSIS) of [[USDA]], [[Centers for Disease Control and Prevention|CDC]], the [[United States Environmental Protection Agency]] (EPA), and [[U.S. Customs and Border Protection]]: "In the most extreme risk assessment scenario, when scientists assumed that all the solid food a person consumes in an entire day was contaminated with melamine at the levels observed in animals fed contaminated feed, the potential exposure was about 2,500 times lower than the dose considered safe"<ref name=USDAFDA3>{{cite web |title=FDA/USDA Joint News Release: Scientists Conclude Very Low Risk to Humans from Food Containing Melamine |url=http://www.fda.gov/bbs/topics/NEWS/2007/NEW01629.html |publisher=[[USDA]] and [[FDA]] |date=[[May 7]] [[2007]] |accessdate=2007-05-07}}</ref> using criteria established prior to current research focusing on the apparent increased toxicity related to the interaction of melamine and cyanuric acid ''[[in vivo]]'',<ref name=NYTcyantox>{{cite news |first=David |last=Barboza |title=Another Chemical Emerges in Pet Food Case |url=http://www.nytimes.com/2007/05/09/business/worldbusiness/09food.html?_r=1&oref=slogin |publisher=[[New York Times]] |date=[[May 9]] [[2007]] |accessdate=2007-05-09}}</ref> for which there is no established safe dosage. FDA and USDA are in the process of identifying a group of experts to convene a scientific advisory board that would be charged with reviewing the risk assessment and contributing to future scientific analysis related to the risk of melamine and its compounds to humans and animals.<ref name=USDAFDA3/> Risks to human health from this mode of entering the human food supply have been said to be low according to a number of FDA, CDC and university toxicologists, though it was acknowledged that how melamine had harmed cats and dogs remains something of a mystery.<ref name=NYTtox>{{cite news |first=Donald |last=McNeil |title=Pet Food Chemical Unlikely to Pose Threat to Humans, Experts Say, as U.S. Continues Inquiry |url=http://www.nytimes.com/2007/05/02/washington/02food.html?_r=1&oref=slogin |publisher=[[New York Times]] |date=[[May 2]] [[2007]] |accessdate=2007-05-06}}</ref> On [[May 10]], on further inquiry into the risk to animal and human health of ingesting melamine and cyanuric acid in combination, Dr. David Acheson, Assistant Commissioner for Food Protection with the FDA said: "I'm not aware of any published studies on that. I have seen some preliminary data that would indicate that they are [[additive]]. When you put the two together, they are additive rather than [[synergistic]].... The risk assessors also estimated that even if synergism were to occur, it would be unlikely to result in more than a tenfold increase in overall toxicity, and that still gives you a very large margin of safety." No data supporting additivity was produced at this time. No basis for estimating a tenfold increase in risk in the case of synergism was offered.<ref name=USDAFDAmay10>{{cite web |title=TRANSCRIPT OF FDA-USDA UPDATE ON ADULTERATED ANIMAL FEED |url=http://www.usda.gov/wps/portal/!ut/p/_s.7_0_A/7_0_1OB?contentidonly=true&contentid=2007/05/0138.xml |publisher=[[USDA]] and [[FDA]] |date=[[May 10]] [[2007]] |accessdate=2007-05-11}}</ref> On [[May 15]] USDA announced that pigs that ate melamine-tainted food has been cleared for human consumption. About 56,000 pigs have been affected in several states. However, no tests have been carried out on the effects of cyanuric acid in pork as well as possible affects of interaction with melamine in the body. While the statement also said that there is no evidence of [[bioaccumulation]] of melamine alone, no mention was made whether bioaccumulation might be affected by the interaction of melamine and cyanuric acid ''in vivo''.<ref name=USDAmay15/> On [[May 25]], in a US FDA/CSFAN Interim Melamine and Analogues Safety/Risk Assessment, FDA stated: "While it is entirely possible that the analogues are more or less potent than the parent compound, melamine, we have no information that assesses the relative potency of the three analogues as compared to melamine; therefore, for the purpose of this interim assessment, we have made an assumption of equal potency. It has been hypothesized that melamine may interact synergistically with its three analogues, but no studies have been conducted that specifically test this hypothesis. Very preliminary work suggests that if it does occur, the formation of lattice crystals, particularly between melamine and cyanuric acid, takes place at very high dose levels and is a threshold and concentration dependent phenomenon that would not be relevant to low levels of exposure. Although still under investigation, it now appears that the combination of melamine and cyanuric acid has been linked to the acute renal failure in cats and dogs that have eaten the suspect pet foods...."<ref name=FDAinterim>{{cite web |title=Interim Melamine and Analogues Safety/Risk Assessment |url=http://www.cfsan.fda.gov/~dms/melamra.html |publisher=[[FDA]] |date=[[May 25]] [[2007]] |accessdate=2007-05-30}}</ref> On [[May 30]] the FDA issued a press release stating that two US-based animal feed manufacturers had been adulterating livestock feed and fish/shrimp feed with melamine.<ref name=FDAMay30>{{cite web |title="Tembec and Uniscope Voluntary Recall Feed Ingredients, FDA Asks Feed Manufacturers to Avoid Ingredients Containing Melamine" |url=http://www.fda.gov/bbs/topics/NEWS/2007/NEW01643.html |publisher=[[FDA]] |date=[[May 30]] [[2007]] |accessdate=2007-05-30}}</ref><ref name=IHTusadult>{{cite news |author=Andrew Martin |title=Poison used in China is found in U.S.-made animal feed |url=http://www.iht.com/articles/2007/05/31/business/food.1-65273.php |publisher=The New York Times|date=[[May 31]] [[2007]] |accessdate=2007-06-01}}</ref> In addition to now testing a wide variety of imported food products and ingredients for melamine contamination, FDA has also "asked the Centers for Disease Control and Prevention (CDC) to use its surveillance network to monitor for signs of human illness, such as increased [[renal failure]], that could indicate contamination of the human food supply."<ref name=FDArenal>{{cite web |title=Testimony By Stephen F. Sundlof, D.V.M., Ph.D., Director, FDA Center for Veterinary Medicine, Department of Health and Human Services before The Senate Agriculture, Rural Development, and Related Agencies Appropriations Subcommittee |url=http://www.fda.gov/ola/2007/petfood041207.html |publisher=[[FDA]] |date=[[April 12]] [[2007]] |accessdate=2007-05-03}}</ref> ====Official EC statements==== On [[June 7]] (updated [[July 4]]), the [[European Food Safety Authority]] (EFSA), in EFSA's Provisional Statement on a Request from the European Commission Related to Melamine and Structurally Related Compounds such as Cyanuric acid in Protein-rich Ingredients Used for Food and Feed, concluded: "EFSA provisionally recommends to apply a TDI of 0.5 mg/kg b.w. for the total of melamine and its analogues .... A source of uncertainty is the combined toxicity of melamine and cyanuric acid and their possible synergistic effects in relation to the recently observed toxicity linked to the acute renal failure and death of pet animals (cats and dogs) in the U.S. This mechanism is currently under investigation."<ref name=EFSAprovisional>{{cite web |title=EFSA's Provisional Statement on a Request from the European Commission Related to Melamine and Structurally Related Compounds such as Cyanuric acid in Protein-rich Ingredients Used for Food and Feed |url=http://www.efsa.europa.eu/EFSA/Statement/efsa_statement_melamine_en_rev1.pdf |publisher=[[EFSA]] |date=[[July 4]] [[2007]] |accessdate=2007-11-21}}</ref> On [[June 21]] The Health & Consumer Protection Directorate-General of the [[European Commission]] (EC) in reporting the Summary Minutes of the Meeting of the Standing Committee on the Food Chain and Animal Health (June 7 & 8) directed that "in case food producing animals have been fed with feed contaminated with melamine and related compounds, there is for the purpose of protecting human health, taking into account the conclusions of the EFSA statement, no need to take restrictive measures as regards the animals which have been fed with contaminated feed and as regards food of animal origin originating from animals fed with contaminated feed."<ref name=ECfax>{{cite web |title=Summary Minutes of the Meeting of the Standing Committee on the Food Chain and Animal Health |url=http://ec.europa.eu/food/committees/regulatory/scfcah/animalnutrition/summary07062007_en.pdf |date=[[June 21]], [[2007]] |accessdate=2007-11-25 }}</ref> == 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."<ref name=FSIScyro>{{cite web |title=CYROMAZINE AND MELAMINE |url=http://www.fsis.usda.gov/ophs/clg/Cyromazine.pdf |publisher=[[USDA]] [[FSIS]] |date=July 1991 |accessdate=2007-04-27}}</ref><ref name=FSISCLG>{{cite web |title=Chemistry Laboratory Guidebook |url=http://www.fsis.usda.gov/science/Chemistry_Lab_Guidebook/index.asp |publisher=[[USDA]] [[FSIS]] |accessdate=2007-04-27}}</ref> On [[April 24]], Stephen Sundlof, director of the FDA's Center for Veterinary Medicine, told reporters: "We have found cyanuric acid. It is somewhat related to melamine. Another compound that is very high in nitrogen and we are testing for that compound as well."{{Fact|date=June 2008}} On [[May 7]], the FDA sent a letter to food manufacturers, to remind them "of their legal responsibility to ensure that all ingredients used in their products are safe for human consumption."<ref name=FDAlegal>{{cite web |title=Letter to Food Manufacturers Regarding Legal Responsibilities for the Safety of Food Ingredients |url=http://www.cfsan.fda.gov/~dms/protltr.html |publisher=[[FDA]] |date=[[May 7]] [[2007]] |accessdate=2007-05-09}}</ref> The FDA has made available to food manufacturers a procedure providing a general guide for the sample preparation and analysis of wheat gluten and pet food matrices for melamine using gas chromatography/mass spectrometry, the same methodology used by the [[FERN]] laboratories.<ref name=FDAgcms>{{cite web |title=GC-MS Screen for the Presence of Melamine and Cyanuric Acid |url=http://www.fda.gov/cvm/MelaminePresence.htm |publisher=[[FDA]] |date=[[April 25]] [[2007]] |accessdate=2007-05-09}}</ref> On [[May 15]], the process for testing meat from swine was validated by USDA's Food Safety and Inspection Service (FSIS).<ref name=USDAmay15>{{cite web |title=News Release |url=http://www.usda.gov/wps/portal/!ut/p/_s.7_0_A/7_0_1OB?contentidonly=true&contentid=2007/05/0144.xml |publisher=[[USDA]] |date=[[May 15]] [[2007]] |accessdate=2007-05-15}}</ref> On [[November 9]] [[2007]], FDA presented a method of HPLC Determination of Melamine, Ammeline, Ammelide, and Cyanuric Acid Contamination in Wheat Gluten and Rice Protein Concentrate.<ref name=FDAhplc>{{cite web |title=HPLC Determination of Melamine, Ammeline, Ammelide, and Cyanuric Acid Contamination in Wheat Gluten and Rice Protein Concentrate |url=http://acs.confex.com/acs/mwrm07/techprogram/P51682.HTM |publisher=[[FDA]] |date=[[April 25]] [[2007]] |accessdate=2007-05-09}}</ref> ==Reported widespread use in Chinese feed and food== {{Merge|2007 pet food recalls|date=December 2007}} ===Recent production of melamine in China=== Between the late 1990s and early 2000s, both consumption and production of melamine grew considerably in China. In the [[United States Geological Survey]] 2004 Minerals Survey Yearbook, in a report on worldwide nitrogen production, the author stated that "China continued to plan and construct new ammonia and urea plants using [[coal gasification]] technology."<ref name=USGSweb>{{cite web |first=Deborah |last=Kramer |title=Nitrogen|url=http://minerals.usgs.gov/minerals/pubs/commodity/nitrogen/nitromyb04.pdf|publisher=[[United States Geological Survey]]|date=2005|accessdate=2007-04-30}}</ref> By early 2006, melamine production in China is reported to be in "serious surplus".<ref name=ChinaChemR>{{cite news |first=Wang |last=Ruilin |title=Melamine capacity is serious surplus |url=http://goliath.ecnext.com/coms2/gi_0199-5152838/Melamine-capacity-is-serious-surplus.html#abstract |publisher=China Chemical Reporter|date=[[January 6]] [[2006]] |accessdate=2007-04-21}}</ref> In April 2007, DSM's melamine industry update painted a grave global picture.<ref>[http://www.dsm.com/en_US/downloads/dmm/Industry_update_6_April_2007.pdf Melamine industry update], by Royal DSM N.V., accessed on 2007-05-04</ref> 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. ===Media reports of melamine adulteration in China=== {{main|Chinese protein export contamination}} On [[April 30]], [[2007]], The [[New York Times]] reported that the addition of "melamine scrap" into fish and livestock feed to give the [[Chinese protein export scandal#Protein testing in the food industry|false appearance of a higher level of protein]] was an "open secret" in many parts of China, reporting that this melamine scrap was being produced at at least one plant processing coal into melamine.<ref name=NYTfiller>{{cite news |author=David Barboza and Alexei Barrionuevo|title=Filler in Animal Feed Is Open Secret in China |url=http://www.nytimes.com/2007/04/30/business/worldbusiness/30food.html?pagewanted=1&hp |publisher=The New York Times|date=[[April 30]] [[2007]] |accessdate=2007-04-30}}</ref> This production has been described as also producing "melamine scrap" which is not "pure melamine but impure melamine scrap that is sold more cheaply as the waste product after melamine is produced by chemical and fertilizer factories here.”<ref name="xuzhounonfood">{{cite news |first=David |last=Barboza |title=China Food Mislabeled, U.S. Says |url=http://www.nytimes.com/2007/05/03/business/worldbusiness/03food.html?_r=1&ref=business&oref=slogin |publisher=New York Times |date=[[May 3]] [[2007]] |accessdate=2007-05-03}}</ref> 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.<ref name=SMGCGweb>{{cite web |title=Products|url=http://www.sdmingquan.com/template/product_e.htm |publisher=Shandong Mingshui Great Chemical Group|accessdate=2007-04-30}}</ref> As per [[melamine#synthesis|melamine synthesis]], the off-gas in production 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 (chemistry)|melon]]).<ref>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).</ref> On [[May 3]] the New York Times reported that, despite the widely reported ban on melamine use in vegetable proteins in China, at least some chemical manufacturers continue to report selling it for use in animal feed and in products for human consumption. Said Li Xiuping, a manager at Henan Xinxiang Huaxing Chemical in Henan Province: "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."<ref name=NYTarrest>{{cite news |author=David Barboza and Alexei Barrionuevo|title=China Makes Arrest in Pet Food Case |url=http://www.nytimes.com/2007/05/04/business/worldbusiness/04food.html?hp |publisher=The New York Times|date=[[May 3]] [[2007]] |accessdate=2007-05-03}}</ref> ==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 [[Parts per million|ppm]] level (1 part per million) in food and beverage has been reported due to migration from melamine-containing resins.<ref>H. Ishiwata, T. Inoue, T. Yamazaki, K. Yoshihira, K. "Liquid chromatographic determination of melamine in beverages", J. Assoc. Off. Anal. Chem. Vol.70, 457-60 (1987) [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3610957&dopt=Citation PUBMED], accessed 05-06-2007.</ref> Small amounts of melamine have also been reported in foodstuff as a metabolite product of cyromazine, an insecticide used on animals and crops.<ref>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) [http://cat.inist.fr/?aModele=afficheN&cpsidt=16514561 Abstract] accessed 05-06-2007.</ref> Romer Labs now offers a rapid Melamine test kit (AgraQuant Melamine ELISA test kit). ==See also== * [[1,3,5-Triazine]] * [[Triazine]]s ==References== {{Reflist}} ==External links== * [http://www.romerlabs.com Rapid Melamine ELISA Test Kit] * [http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@na+Melamine NLM Hazardous Substances Databank &ndash; Melamine] * [http://www.sciencelab.com/xMSDS-Melamine-9924600 Melamine Materials Safety Data Sheet (MSDS)] * [http://www.inchem.org/documents/sids/sids/108781.pdf OECD Screening Information Data Set (SIDS): Melamine] (High Production Volume Chemicals Screening Information,PDF, 89 pages). * [http://dailynews.att.net/cgi-bin/news?e=pri&dt=070406&cat=news&st=newsd8ob43780&src=ap AP Story April 6, 2007] * [http://www.freep.com/apps/pbcs.dll/article?AID=/20070323/NEWS05/703230404/1008&&&imw=Y List of Recalls] * [http://www.news24.com/News24/South_Africa/News/0,,2-7-1442_2101493,00.html The findings in South Africa] * [http://www.fda.gov/oc/opacom/hottopics/petfood.html FDA Web Page with Information on Pet Food Recall (due to Melamine contanimination )] * [http://www.oregonvma.org/news/recallnews.asp Oregon Veterinary Medical Association (OVMA) Pet Food Contamination Page] - News & developments updated regularly [[Category:Amines]] [[Category:Woodworking]] [[Category:Triazines]] [[de:Melamin]] [[el:Μελαμίνη]] [[es:Melamina]] [[fr:Mélamine]] [[it:Melammina]] [[nl:Melamine]] [[ja:メラミン]] [[pl:Melamina]] [[ru:Меламин]] [[fi:Melamiini]] [[sv:Melamin]] [[zh:三聚氰胺]]