Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Melamine: Difference between pages

{{Short description|Fire-resistant chemical used in dinnerware, insulation, and cleaning products}}

{{Distinguish|Melanin|Melanine (disambiguation){{!}}Melanine|Melanie}}

{{About|the chemical compound|the chemically-related plastic|Melamine resin}}

{{Use mdy dates|date=April 2023}}

{{Chembox

| Verifiedimages = changed

| Watchedfields = changed

| verifiedrevid = 462248060

| Name = Melamine

| Reference =

| ImageFile_Ref = {{chemboximage|correct|??}}

| ImageFile = Structural formula of melamine.svg

| ImageSize = 180

| ImageAlt = Structural formula of melamine

| ImageFileL1 = Melamine-3D-balls-2.png

| ImageSizeL1 = 120

| ImageAltL1 = Ball-and-stick model of the melamine molecule

| ImageFileR1 = Melamine-3D-spacefill.png

| ImageFile2 = Melamine A.jpg

| ImageSizeR1 = 120

| ImageAltR1 = Space-filling model of the melamine molecule

| PIN = 1,3,5-Triazine-2,4,6-triamine

| SystematicName =

| OtherNames = 2,4,6-Triamino-''s''-triazine<br />Cyanurotriamide<br />Cyanurotriamine<br />Cyanuramide

| IUPACName =

| Section1 = {{Chembox Identifiers

| UNII_Ref = {{fdacite|correct|FDA}}

| SMILES = Nc1nc(N)nc(N)n1

| ChEBI_Ref = {{ebicite|correct|EBI}}

| KEGG = C08737

}}

| Section2 = {{Chembox Properties

| C=3|H=6|N=6

| Density = 1.573 g/cm³<ref name=crc>{{cite book | editor= Haynes, William M. | year = 2011 | title = CRC Handbook of Chemistry and Physics | edition = 92nd | publisher = [[CRC Press]] | isbn = 978-1439855119|page=3.516| title-link = CRC Handbook of Chemistry and Physics }}</ref>

| MeltingPtC = 343

| MeltingPt_notes = (decomposition)<ref name=crc/>

| BoilingPt_notes =

| Solubility = 3240 mg/ L (20 °C)<ref>{{PubChem|7955|Melamine}}</ref>

| SolubleOther = very slightly soluble in hot alcohol{{clarify|date=May 2020}}, [[benzene]], [[glycerol]], [[pyridine]] <br> insoluble in [[diethyl ether|ether]], [[benzene]], [[carbon tetrachloride|CCl₄]]

| LogP = −1.37

| pKa = 5.0 (conjugated acid)<ref name="Jang, Y.H. 2009">{{cite journal|author=Jang, Y.H., Hwang, S., Chang, S.B., Ku, J. and Chung, D.S.|title=Acid Dissociation Constants of Melamine Derivatives from Density Functional Theory Calculations|journal=The Journal of Physical Chemistry A|volume=113|issue=46|pages=13036–13040|doi=10.1021/jp9053583|pmid=19845385|year=2009|bibcode=2009JPCA..11313036J}}</ref>

| pKb = 9.0 <ref name="Jang, Y.H. 2009"/>

| RefractIndex = 1.872<ref name=crc/>

| MagSus = −61.8·10⁻⁶ cm³/mol

}}

| Section3 = {{Chembox Structure

| CrystalStruct = Monoclinic

}}

| Section4 = {{Chembox Thermochemistry

| DeltaHc = −1967 kJ/mol

}}

| Section5 =

| Section6 =

| Section7 = {{Chembox Hazards

| NFPA-S =

| AutoignitionPt = >

| AutoignitionPtC = 500

| PEL =

| LD50 = 3850 mg/kg (rat, oral)

}}

}}

[[File:Bernadotte & Bjørn Industridesign.jpg|thumb|Marking of product made of Melamine]]

'''Melamine''' {{IPAc-en|audio=En-melamine.oga|ˈ|m|ɛ|l|ə|m|iː|n}} is an [[organic compound]] with the formula C₃H₆N₆. This white solid is a [[trimer (chemistry)|trimer]] of [[cyanamide]], with a [[1,3,5-Triazine|1,3,5-triazine]] skeleton. Like cyanamide, it contains 66% [[nitrogen]] by mass, and its derivatives have [[fire retardant|fire-retardant]] properties due to its release of nitrogen gas when burned or charred. Melamine can be combined with [[formaldehyde]] and other agents to produce [[melamine resin]]s. Such resins are characteristically durable [[thermosetting plastic]] used in high pressure [[decorative laminate]]s such as [[Formica (plastic)|Formica]], melamine [[dinnerware]] including cooking utensils, plates, plastic products,<ref name=":0">{{Cite journal |last=Nutrition |first=Center for Food Safety and Applied |date=2022-12-19 |title=Melamine in Tableware Questions and Answers |url=https://www.fda.gov/food/economically-motivated-adulteration-food-fraud/melamine-tableware-questions-and-answers |journal=FDA |language=en}}</ref> laminate flooring, and [[dry erase boards]]. [[Melamine foam]] is used as insulation, soundproofing material and in [[polymeric]] cleaning products, such as [[Magic Eraser]].

Melamine-formaldehyde resin tableware was evaluated by the Taiwan Consumers' Foundation to have 20,000&nbsp;parts&nbsp;per&nbsp;billion of free melamine that could migrate out of the plastic into acidic foods if held at 160&nbsp;°F for two hours, such as if food was kept heated in contact with it in an oven.<ref name=":0" />

Melamine gained infamy because Chinese food producers added it to baby formula in order to increase the apparent protein content.<ref>{{cite journal |doi=10.1681/asn.2008101065 |title=Melamine Toxicity and the Kidney |date=2009 |last1=Hau |first1=Anthony Kai-Ching |last2=Kwan |first2=Tze Hoi |last3=Li |first3=Philip Kam-tao |journal=Journal of the American Society of Nephrology |volume=20 |issue=2 |pages=245–250 |pmid=19193777 }}</ref><ref>{{Cite journal |last1=Scholl |first1=Peter F. |last2=Bergana |first2=Marti Mamula |last3=Yakes |first3=Betsy Jean |last4=Xie |first4=Zhuohong |last5=Zbylut |first5=Steven |last6=Downey |first6=Gerard |last7=Mossoba |first7=Magdi |last8=Jablonski |first8=Joseph |last9=Magaletta |first9=Robert |last10=Holroyd |first10=Stephen E. |last11=Buehler |first11=Martin |date=July 19, 2017| title=Effects of the Adulteration Technique on the Near-Infrared Detection of Melamine in Milk Powder |journal=Journal of Agricultural and Food Chemistry |volume=65 |issue=28 |pages=5799–5809 |doi=10.1021/acs.jafc.7b02083 |pmid=28617599 |issn=0021-8561 }}</ref> Ingestion of melamine may lead to [[Reproduction|reproductive damage]], or [[Urinary bladder|bladder]] or [[kidney stone]]s, and [[bladder cancer]]. It is also an irritant when inhaled or in contact with the skin or eyes. The United Nations' food standards body, the [[Codex Alimentarius Commission|''Codex Alimentarius'' Commission]], has set the maximum amount of melamine allowed in powdered [[infant formula]] to 1&nbsp;mg/kg and the amount of the chemical allowed in other foods and animal feed to 2.5&nbsp;mg/kg. While not legally binding, the levels allow countries to ban importation of products with excessive levels of melamine.

== Etymology ==

The German word ''[[:de:Melamin|Melamin]]'' was coined by combining the words [[Melam (chemistry)|melam]] (a derivative of ammonium thiocyanate) and [[amine]].<ref>{{cite web

|title=Melamine

|work=The American Heritage Dictionary of the English Language

|edition=Fourth

|year=2000

|access-date=September 28, 2008

|url=http://www.bartleby.com/61/24/M0202400.html

|archive-url=https://web.archive.org/web/20081201105219/http://www.bartleby.com/61/24/M0202400.html

|archive-date=December 1, 2008

}}</ref><ref>{{cite journal |last1=Bann |first1=Bernard |last2=Miller |first2=Samuel A. |date=1958 |title=Melamines and derivatives of melamine |journal=[[Chemical Reviews]] |volume=58 |pages=131–172 |doi=10.1021/cr50019a004}}</ref> Melamine is, therefore, unrelated etymologically to the root {{lang|grc-Latn|melas}} ({{lang|grc|μέλας}}, meaning 'black' in Greek), from which the words [[melanin]], a pigment, and [[melatonin]], a hormone, are formed.

== Uses ==

=== Plastics and building materials ===

In one large-scale application, melamine is combined with [[formaldehyde]] and other agents to produce [[melamine resin]]s. Such resins are characteristically durable [[thermosetting plastic]] used in high-pressure [[decorative laminate]]s such as [[Wilsonart (plastic)|Wilsonart]], melamine dinnerware, laminate flooring, and [[dry erase boards]].<ref>{{cite encyclopedia |author1=Deim, H. |author2=Matthias, G. |author3=Wagner, R. A. |chapter=Amino Resins |encyclopedia=Ullmann's Encyclopedia of Industrial Chemistry |year=2012 |publisher=Wiley-VCH |place=Weinheim |doi=10.1002/14356007.a02_115.pub2 |isbn=978-3527306732}}</ref> Melamine cookware is not [[microwave oven|microwave]]-safe.<ref>{{cite web |url=https://www.fda.gov/food/economically-motivated-adulteration-food-fraud/melamine-tableware-questions-and-answers |title=Melamine in Tableware Questions and Answers |date=December 19, 2022 |location=United States |publisher=[[Food and Drug Administration]] |quote=Foods and drinks should not be heated on melamine-based dinnerware in microwave ovens. |access-date=December 21, 2022}}</ref>

[[Melamine foam]] is used as insulation, soundproofing material and in [[polymeric]] cleaning products, such as [[Magic Eraser]].

Melamine is one of the major components in [[Pigment Yellow 150]], a colorant in inks and plastics.

Melamine also is used in the fabrication of melamine polysulfonate, used as a [[Plasticizer#Plasticizers for concrete production|superplasticizer]] for making high-resistance [[concrete]]. Sulfonated [[melamine formaldehyde]] (SMF) is a polymer used as a [[Water reducer|cement 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.

=== Fertilizers ===

Melamine was once envisioned as fertilizer for crops during the 1950s and 1960s because of its high nitrogen content (2/3).<ref>{{Cite journal

| last1 = Hauck | first1 = R. D.

|first2= H. F. |last2=Stephenson

| year = 1964

| title = Fertilizer Nitrogen Sources, Nitrification of Triazine Nitrogen

| journal = Journal of Agricultural and Food Chemistry

| volume = 12 |issue = 2

| pages = 147–151

| doi = 10.1021/jf60132a014

}}</ref> However, melamine is much more expensive to produce than other common nitrogen fertilizers, such as [[urea]]. The mineralization (degradation to ammonia) for melamine is slow, making this product both economically and scientifically impractical for use as a fertilizer.{{Citation needed|date=June 2023}}

[[Image:Melamine dinnerware.JPG|thumb|right|Melamine dinnerware]]

=== Fire-retardant additives ===

Melamine and its salts are used as [[fire-retardant]] additives in paints, plastics, and paper.<ref>Ashford, Robert D. (2011) ''Ashford's Dictionary of Industrial Chemicals'', 3rd ed. Wavelength. p. 5713. {{ISBN|9780952267430}}.</ref> 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.<ref>{{Cite web

|title=Melamine Fibres

|website=Polymer Properties Database

|url=http://polymerdatabase.com/Fibers/Melamine.html

}}</ref>

=== Food additive ===

Melamine is sometimes illegally added to food products in order to increase the apparent protein content. Standard tests, such as the [[Kjeldahl method|Kjeldahl]] and [[Dumas method|Dumas]] 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.<ref>{{cite journal |doi=10.1111/j.1541-4337.2010.00114.x|title=Total Protein Methods and Their Potential Utility to Reduce the Risk of Food Protein Adulteration |journal=Comprehensive Reviews in Food Science and Food Safety |volume=9 |issue=4 |pages=330–357 |year=2010 |last1=Moore |first1=Jeffrey C. |last2=Devries |first2=Jonathan W. |last3=Lipp |first3=Markus |last4=Griffiths |first4=James C. |last5=Abernethy |first5=Darrell R.|pmid=33467839 |doi-access= }}</ref>

=== Medicine ===

Melamine derivatives of [[arsenical]] drugs are potentially important in the treatment of [[African trypanosomiasis]].<ref>{{cite book |doi=10.1016/S0065-308X(06)63002-9 |chapter=Targeting of Toxic Compounds to the Trypanosome's Interior |title=Advances in Parasitology |volume=63 |pages=[https://archive.org/details/advancesparasito63bake/page/125 125–183] |year=2006 |last1=Barrett |first1=Michael P. |last2=Gilbert |first2=Ian H. |isbn=9780120317639 |pmid=17134653 |chapter-url=https://archive.org/details/advancesparasito63bake/page/125}}</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>Colby, Robert W. and Mesler, Robert J. Jr. (1958) "Ruminant feed compositions". {{US Patent|2819968}}.</ref> 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.<ref name="MelamineNPN1978">{{cite journal |doi=10.2527/jas1978.4761338x |title=Melamine as a Dietary Nitrogen Source for Ruminants |journal=Journal of Animal Science |volume=47 |issue=6 |pages=1338–1344 |year=1978 |last1=Newton |first1=G. L. |last2=Utley |first2=P. R. }}</ref>

== Toxicity ==

The short-term lethal dose of melamine is on a par with common table salt, with an [[Median lethal dose|LD₅₀]] of more than 3&nbsp;grams per kilogram of bodyweight.<ref>{{cite news |url=http://www.sciencebase.com/science-blog/melamine-in-milk.html |title=Melamine in milk by David Bradley |date=September 17, 2008 |publisher=Sciencebase |access-date=September 27, 2008}}</ref> [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) scientists explained that when melamine and [[cyanuric acid]] are absorbed into the bloodstream, they concentrate and interact in the urine-filled [[renal 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 the [[Acute kidney injury|kidneys to malfunction]]<ref>{{cite news |url=https://www.usatoday.com/tech/science/2007-05-07-poison-pet-food-science_N.htm |title=Poison pet food woes seem to hit cats harder |date=August 5, 2007 |publisher=USA Today |access-date=October 1, 2008 |first=Elizabeth |last=Weise}}</ref> and lead to kidney stones, kidney failure, and death.<ref>{{Cite journal |last=Nutrition |first=Center for Food Safety and Applied |date=2022-12-19 |title=Melamine in Tableware Questions and Answers |url=https://www.fda.gov/food/economically-motivated-adulteration-food-fraud/melamine-tableware-questions-and-answers |journal=FDA |language=en}}</ref> Signs of melamine toxicity can include irritability, blood in the urine, little to no urine, symptoms of kidney infection, or high blood pressure.<ref>{{Cite journal |last=Nutrition |first=Center for Food Safety and Applied |date=2022-12-19 |title=Melamine in Tableware Questions and Answers |url=https://www.fda.gov/food/economically-motivated-adulteration-food-fraud/melamine-tableware-questions-and-answers |journal=FDA |language=en}}</ref>

The [[European Union]] set a standard for acceptable human consumption ([[tolerable daily intake]] or TDI) of melamine at 0.2&nbsp;mg per kilogram of body mass<ref>{{cite news |url=http://www.foodqualitynews.com/Legislation/EFSA-cuts-melamine-TDI-by-60-per-cent |title= EFSA cuts melamine TDI by 60 per cent |author= Harrington, Rory |publisher= FoodQualityNews.com |date= April 15, 2010 |access-date=April 16, 2010 }}</ref> (previously 0.5&nbsp;mg/kg), Canada declared a limit of 0.35&nbsp;mg/kg, and the US FDA's limit was put at 0.063&nbsp;mg/kg (previously 0.63&nbsp;mg/kg). The [[World 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&nbsp;mg per kilogram of body mass.<ref>{{cite news |url=http://www.healthnews.com/alerts-outbreaks/safe-melamine-levels-named-world-health-organization-2252.html |title=Safe Melamine Levels Named by World Health Organization |last=Endreszl |first=Lara |publisher=Health News |date=December 10, 2008 |archive-url=https://web.archive.org/web/20090318122335/http://www.healthnews.com/alerts-outbreaks/safe-melamine-levels-named-world-health-organization-2252.html |archive-date=March 18, 2009 }}</ref>

Toxicity of melamine can be mediated by [[intestinal microbiota]]. In culture, ''[[Raoultella terrigena]]'', which rarely colonizes mammalian intestines,<ref>{{cite web |last=Neergaard |first=Lauran |title=Study Examines Why Most Survived China's Melamine Scare |url=http://www.foodmanufacturing.com/news/2013/02/study-examines-why-most-survived-china%E2%80%99s-melamine-scare?et_cid=3091981&et_rid=41378128&linkid=http%3a%2f%2fwww.foodmanufacturing.com%2fnews%2f2013%2f02%2fstudy-examines-why-most-survived-china%25E2%2580%2599s-melamine-scare |work=Food Manufacturing News |publisher=Food Manufacturing |access-date=February 22, 2013 |date=February 14, 2013}}</ref> 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.<ref name=Zheng>{{cite journal |last1=Zheng |first1=X. |last2=Zhao |first2=A. |last3=Xie |first3=G. |last4=Chi |first4=Y. |last5=Zhao |first5=L. |last6=Li |first6=H. |last7=Wang |first7=C. |last8=Bao |first8=Y. |last9=Jia |first9=W. |last10=Luther |first10=M. |last11=Su |first11=M. |last12=Nicholson |first12=J. K. |last13=Jia |first13=W. |display-authors=1 |title=Melamine-induced renal toxicity is mediated by the gut microbiota |journal=Science Translational Medicine |date=2013 |volume=5 |issue=172 |pmid=23408055 |pages=172ra22 |doi=10.1126/scitranslmed.3005114|s2cid=23408614 }}</ref>

=== Acute toxicity ===

Melamine is reported to have an oral [[median lethal dose]] (LD₅₀) of 3248&nbsp;[[milligram|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&nbsp;mg/kg for rabbits. A study by Soviet researchers in the 1980s suggested that [[melamine cyanurate]], commonly used as a fire retardant,<ref>{{cite web |url=http://www.specialchem4polymers.com/tc/Melamine-Flame-Retardants/index.aspx?id=4004 |title=Flame Retardants Center: Melamine Compounds |publisher=Specialchem4polymers.com |date=April 19, 2010 |access-date=June 20, 2012 |archive-url=https://web.archive.org/web/20080922071156/http://www.specialchem4polymers.com/tc/Melamine-Flame-Retardants/index.aspx?id=4004 |archive-date=September 22, 2008 }}</ref> could be more toxic than either melamine or cyanuric acid alone.<ref>{{cite journal |title=Токсичные характеристики цианурата меламина, меламина и циануровой кислоты |author=Babayan, A. A. and Aleksandryan, A. V. |trans-title=Toxicological characteristics of melamine cyanurate, melamine and cyanuric acid |journal=Zhurnal Eksperimental'noi I Klinicheskoi Meditsiny |volume=25 |pages= 345–249 |year=1985}}</ref> For rats and mice, the reported LD₅₀ for melamine cyanurate was 4.1&nbsp;g/kg (given inside the stomach) and 3.5&nbsp;g/kg (via inhalation), compared to 6.0 and 4.3&nbsp;g/kg for melamine and 7.7 and 3.4&nbsp;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 to [[acute kidney injury]] in cats.<ref name="UCDavis">{{cite journal |doi=10.1177/104063870701900602|pmid=17998549|title=Assessment of Melamine and Cyanuric Acid Toxicity in Cats|journal=Journal of Veterinary Diagnostic Investigation|volume=19|issue=6|pages=616–24|year=2007|last1=Puschner|first1=B.|last2=Poppenga|first2=R. H.|last3=Lowenstine|first3=L. J.|last4=Filigenzi|first4=M. S.|last5=Pesavento|first5=P. A.|doi-access=free}}</ref> A 2008 study produced similar experimental results in rats and characterized the melamine and cyanuric acid in contaminated pet food from the 2007 outbreak.<ref name="Dobson">{{cite journal |doi=10.1093/toxsci/kfn160 |pmid=18689873|title=Identification and Characterization of Toxicity of Contaminants in Pet Food Leading to an Outbreak of Renal Toxicity in Cats and Dogs |journal=Toxicological Sciences |volume=106 |issue=1 |pages=251–262 |year=2008 |last1=Dobson |first1=R. L. M. |last2=Motlagh |first2=S. |last3=Quijano |first3=M. |last4=Cambron |first4=R. T. |last5=Baker |first5=T. R. |last6=Pullen |first6=A. M. |last7=Regg |first7=B. T. |last8=Bigalow-Kern |first8=A. S. |last9=Vennard |first9=T. |last10=Fix |first10=A. |last11=Reimschuessel |first11=R. |last12=Overmann |first12=G. |last13=Shan |first13=Y. |last14=Daston |first14=G. P. |doi-access=free}}</ref> A 2010 study from [[Lanzhou 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.<ref name=Lanzhou_2010/> 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.<ref name="Zheng"/>

=== 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>{{cite web |url=https://www.cdc.gov/niosh/ipcsneng/neng1154.html |title=International Chemical Safety Card |publisher=Cdc.gov |access-date=June 20, 2012 |archive-url=https://web.archive.org/web/20120605150753/http://www.cdc.gov/niosh/ipcsneng/neng1154.html |archive-date=June 5, 2012 }}</ref><ref>[https://www.osha.gov/dts/chemicalsampling/data/CH_250440.html OSHA] – Chemical sampling information</ref><ref>[http://monographs.iarc.fr/ENG/Monographs/vol73/volume73.pdf WHO] – Some Chemicals that Cause Tumors of the Kidney or Urinary Bladder in Rodents and Some Other Substances{{page needed|date=February 2014}}</ref><ref>{{cite journal |doi=10.1016/0273-2300(85)90044-3|pmid=3903881|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=[[Regulatory Toxicology and Pharmacology]]|volume=5|issue=3|pages=294–313|year=1985|last1=Heck|first1=Henry d'A.|last2=Tyl|first2=Rochelle W.}}</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) [[Polyuria|increased output]], (3) melamine [[crystalluria]], and (4) [[Proteinuria|protein]] and [[Hematuria|occult blood]].<ref>Tusing, T.W. "Chronic Feeding – Dogs", cited by "Summary of toxicity data – trichloromelamine" by California Environmental Protection Agency, last revised on February 4, 2002, [http://www.cdpr.ca.gov/docs/toxsums/pdfs/1023.pdf URL] {{webarchive|url=https://web.archive.org/web/20070625030357/http://www.cdpr.ca.gov/docs/toxsums/pdfs/1023.pdf |date=June 25, 2007 }} Retrieved September 5, 2007</ref>

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."<ref name="MSUsurvey">{{cite web |url=http://news.msu.edu/story/957

| title = Culprit in pet food deaths may be combination of contaminants

| publisher = [[Michigan State University]]

| date = November 29, 2007

| access-date = December 7, 2007}}</ref><ref name="AAVLDproceedings">{{cite web

|url=https://aavld.memberclicks.net/assets/documents/2007%20AAVLD%20Procdngs%20book%20(2).pdf

| title = Proceedings of the American Association of Veterinarian Laboratory Diagnosticians 50th Annual Conference

|publisher = [[AAVLD]]

|date = October 2007 |archiveurl=https://web.archive.org/web/20180920092404/https://aavld.memberclicks.net/assets/documents/2007%20AAVLD%20Procdngs%20book%20(2).pdf |archivedate=September 20, 2018

|access-date=May 16, 2021

}}</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=[[American Veterinary Medical Association|AVMA]]

|date=November 2007

|access-date=November 30, 2007

|archive-url=https://web.archive.org/web/20071122165749/http://www.avma.org/onlnews/javma/dec07/071201c.asp

|archive-date=November 22, 2007

}}</ref>

===Metabolism===

Melamine is a [[metabolite]] of [[cyromazine]], a [[pesticide]].<ref>{{cite web|url=http://www.emea.europa.eu/pdfs/vet/mrls/077000en.pdf |title=Cyromazine |date=January 2001 |publisher=European Medicines Agency |access-date=June 20, 2012 |url-status=dead |archive-url=https://web.archive.org/web/20081010173725/http://www.emea.europa.eu/pdfs/vet/mrls/077000en.pdf |archive-date=October 10, 2008 }}</ref> It has been reported that cyromazine can also be converted to melamine in plants.<ref>{{cite journal |doi=10.1021/jf00093a057|title=Disposition of cyromazine in plants under environmental conditions|journal=Journal of Agricultural and Food Chemistry|volume=38|issue=3|pages=860–864|year=1990|last1=Lim|first1=Lori O.|last2=Scherer|first2=Susan J.|last3=Shuler|first3=Kenneth D.|last4=Toth|first4=John P.}}</ref><ref>{{cite book|title=Pesticide Residues in Food, 1992 Evaluations: Residues|chapter-url=http://www.fao.org/ag/AGP/AGPP/Pesticid/JMPR/Download/92/Cyromazi.PDF |chapter=Cyromazine|year=1993|publisher=Food & Agriculture Org.|isbn=978-92-5-103341-8|pages=265–|archive-url=https://web.archive.org/web/20121021011626/http://www.fao.org/ag/AGP/AGPP/Pesticid/JMPR/Download/92/Cyromazi.PDF |archive-date=October 21, 2012 }}</ref>

=== Treatment of urolithiasis ===

Fast diagnosis and treatment of acute obstructive [[urolithiasis]] may prevent the development of acute kidney failure. Urine alkalinization and stone liberalization have been reported to be the most effective treatments in humans.<ref name=Lanzhou_2010/>

== Regulation in food and feed ==

The United Nations' food standards body, [[Codex Alimentarius Commission]], has set the maximum amount of melamine allowed in powdered infant formula to 1&nbsp;mg/kg and the amount of the chemical allowed in other foods and animal feed to 2.5&nbsp;mg/kg. While not legally binding, the levels allow countries to ban importation of products with excessive levels of melamine.<ref>{{cite web |url=https://www.who.int/mediacentre/news/releases/2010/melamine_food_20100706/en/index.html |archive-url=https://web.archive.org/web/20100707181411/http://www.who.int/mediacentre/news/releases/2010/melamine_food_20100706/en/index.html |url-status=dead |archive-date=July 7, 2010 |title=International experts limit melamine levels in food |date=July 6, 2010 |access-date=July 7, 2010 |quote=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. |publisher=[[World Health Organization]] }}</ref>

== Synthesis and reactions==

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

{{block indent| 6 (NH₂)₂CO → C₃H₆N₆ + 6 NH₃ + 3 CO₂}}

In the first step, urea decomposes into [[cyanic acid]] and ammonia:

{{block indent| (NH₂)₂CO → HNCO + NH₃}}

Cyanic acid polymerizes to [[cyanuric acid]], which condenses with the liberated ammonia forming melamine. The released water reacts with cyanic acid, which helps to drive the reaction:

{{block indent| 6 HNCO + 3 NH₃ → C₃H₆N₆ + 3 CO₂ + 3NH₃}}

The above reaction can be carried out by either of two methods: [[catalysis|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.<ref>{{cite book|title=Kirk-Othmer encyclopedia of chemical technology|edition=3rd |volume=7|pages= 303–304|year= 1978|isbn= 9780471485162|author1=Kirk-Othmer }}</ref> Major manufacturers and licensors such as [[Orascom Construction Industries]], [[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 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>{{cite journal |doi=10.1021/ie00088a020|title=Recovery of solids from melamine waste effluents and their conversion to useful products|journal=Industrial & Engineering Chemistry Research|volume=28|issue=4|pages=500–504|year=1989|last1=Lahalih|first1=Shawqui M.|last2=Absi-Halabi|first2=M.}}</ref> In the Eurotecnica process, however, there is no solid waste and the contaminants are decomposed to [[ammonia]] and [[carbon dioxide]] and sent as off gas to the upstream [[urea]] plant; accordingly, the waste water can be recycled to the melamine plant itself or used as clean cooling water make-up.<ref>[https://www.bcinsight.com/sitemap_issue_articles.asp?issueID=219 "How a golden chemical became greeneer"], Nitrogen+Syngas, Issue 293, May–June 2008.</ref>

Melamine reacts with [[acid]] and related compounds to form [[melamine cyanurate]] and related crystal structures, which have been implicated as contaminants or biomarkers in [[Chinese protein adulteration]]s.

==Drug derivatives==

Melamine is part of the core structure for a number of drugs including [[almitrine]], [[altretamine]], [[cyromazine]], [[ethylhexyl triazone]], [[iscotrizinol]], [[meladrazine]], [[melarsomine]], [[melarsoprol]], [[tretamine]], [[trinitrotriazine]], and others.<ref name="MATSUI1972">{{cite journal|last1=Matsui |first1=Kohji|title=Syntheses and Reactions of s-Triazine Derivatives|journal=Journal of Synthetic Organic Chemistry, Japan |volume=30 |issue=1 |year=1972 |pages=19–35 |issn=0037-9980 |doi=10.5059/yukigoseikyokaishi.30.19 | language = ja|doi-access=free }}</ref>

== Production in mainland China ==

Between the late 1990s and early 2000s, both consumption and production of melamine grew considerably in [[mainland China]]. By early 2006, melamine production in mainland 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 |access-date=April 21, 2007}}</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.

Surplus melamine has been an [[adulterant]] for [[feedstock]] and [[milk]] 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 the [[Chinese 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.<ref name="Milk Trial">{{cite news |title=Tainted milk trial opens in China |url=http://news.bbc.co.uk/2/hi/asia-pacific/7799986.stm |work=BBC|date=December 26, 2008 |access-date=January 7, 2009}}</ref><ref name="Chinese Milk Scam Duo Face Death">{{cite news|title=Chinese Milk Scam Duo Face Death|url=http://news.bbc.co.uk/2/hi/asia-pacific/7843972.stm|work=BBC |date=January 22, 2009|access-date=January 22, 2009}}</ref>

== Melamine poisoning by tainted food ==

Melamine has been involved in several food recalls after the discovery of severe [[kidney]] damage to children and pets poisoned by melamine-adulterated food.

=== 2007 animal-feed recalls ===

{{Further|2007 pet food recalls|Chinese protein adulteration}}

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>[https://web.archive.org/web/20070412203503/http://www.cnn.com/2007/US/03/30/pet.food.recall.ap/index.html Dry food added to pet food recall list]. CNN. March 30, 2007</ref><ref>{{cite web|url=http://www.avma.org/aa/menufoodsrecall/products.asp |title=Pet food recall |publisher=AVMA |access-date=June 20, 2012 |url-status=dead |archive-url=https://web.archive.org/web/20070415115544/http://www.avma.org/aa/menufoodsrecall/products.asp|date=April 11, 2007 |archive-date=April 15, 2007 }}</ref><ref>[http://www.naturalbalanceinc.com/press_release.html Press release by Natural Balance Pet Foods] {{webarchive |url=https://web.archive.org/web/20120511090139/http://www.naturalbalanceinc.com/press_release.html |date=May 11, 2012 }}</ref> 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 (food)|wheat gluten]] imported from a single source in China, Xuzhou Anying Biologic Technology<ref>[https://www.fda.gov/AnimalVeterinary/SafetyHealth/RecallsWithdrawals/ucm129932.htm Melamine Pet Food Recall – Frequently Asked Questions]. FDA.gov (Updated October 7, 2009)</ref> as well as in crystalline form in the kidneys and in urine of affected animals.<ref>{{cite web|url=https://www.fda.gov/bbs/topics/NEWS/2007/NEW01599.html |title=FDA: Pet food recall |website=Fda.gov |access-date=June 20, 2012}}</ref> 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 [[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 mainland China, reporting that this melamine scrap was being produced by at least one plant processing coal into melamine.<ref name="NYTfiller">{{cite news |last1=Barboza |first1=David |last2=Barrionuevo |first2=Alexei |title=Filler in Animal Feed Is Open Secret in China |url=https://www.nytimes.com/2007/04/30/business/worldbusiness/30food.html?pagewanted=1&hp |newspaper=The New York Times |date=April 30, 2007 |access-date=April 30, 2007 }}</ref> 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."<ref name="NYTarrest">{{cite news |author1=Barboza, David |author2=Barrionuevo, Alexei |name-list-style=amp |title=China Makes Arrest in Pet Food Case |url=https://www.nytimes.com/2007/05/04/business/worldbusiness/04food.html?hp|work=The New York Times|date=May 3, 2007 |access-date=May 3, 2007}}</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|access-date=April 30, 2007 |archive-url = https://web.archive.org/web/20050726235336/http://www.sdmingquan.com/template/product_e.htm |archive-date = July 26, 2005}}</ref>

Another recall incident in 2007 involved melamine which had been purposely added as a [[binder (material)|binder]] to fish and livestock feed manufactured in the United States. This was traced to suppliers in Ohio and Colorado.<ref name="IHTusadult">{{cite news |author=Martin, Andrew |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| work=The New York Times|date=May 31, 2007 |access-date=June 1, 2007}}</ref>

=== 2008 Chinese outbreak ===

{{Further|2008 Chinese milk scandal}}

In September 2008, several companies, including [[Nestlé]], were implicated in a scandal involving milk and [[infant formula]] which had been [[Adulterant|adulterated]] with melamine, leading to kidney stones and other [[kidney 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.<ref name="sick">

{{cite news |author= Scott McDonald |title=Nearly 53,000 Chinese children sick from milk |url=https://www.pantagraph.com/business/nearly-53-000-chinese-children-sick-from-milk/article_f488da13-1892-5e0d-af24-6abbe90846f2.html |archiveurl=https://web.archive.org/web/20210516031620/https://www.pantagraph.com/business/nearly-53-000-chinese-children-sick-from-milk/article_f488da13-1892-5e0d-af24-6abbe90846f2.html |archivedate=May 16, 2021 |journal=[[The Pantagraph]] |location= |publisher= |date=September 21, 2008 |volume= |issue= |page= |issn=2641-7634 |accessdate=May 16, 2021 }}</ref><ref name="sick2">Jane Macartney, [http://www.timesonline.co.uk/tol/news/world/asia/article4800458.ece China baby milk scandal spreads as sick toll rises to 13,000], ''[[The Times]]'' (September 22, 2008)</ref><ref>{{cite web|url=http://whqlibdoc.who.int/publications/2009/9789241597951_eng.pdf|title=Toxicological and Health Aspects of Melamine and Cyanuric Acid|date=2009|publisher=[[WHO]]|access-date=August 13, 2009}}</ref> In a study published in the ''[[New England Journal of Medicine]]'', it was reported that melamine exposure increased the incidence of urinary tract stones by seven times in children.<ref>{{cite journal |doi=10.1056/NEJMoa0809550 |pmid=19196669 |title=Melamine-Contaminated Powdered Formula and Urolithiasis in Young Children |journal=New England Journal of Medicine |volume=360 |issue=11 |pages=1067–74 |date=2009 |last1=Guan |first1=Na |last2=Fan |first2=Qingfeng |last3=Ding |first3=Jie |last4=Zhao |first4=Yiming |last5=Lu |first5=Jingqiao |last6=Ai |first6=Yi |last7=Xu |first7=Guobin |last8=Zhu |first8=Sainan |last9=Yao |first9=Chen |last10=Jiang |first10=Lina |last11=Miao |first11=Jing |last12=Zhang |first12=Han |last13=Zhao |first13=Dan |last14=Liu |first14=Xiaoyu |last15=Yao |first15=Yong|doi-access=free }}</ref> 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.<ref>{{cite news |url=http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10532214 |title=Fonterra says somebody sabotaged milk |date=September 15, 2008 |newspaper=NZ Herald |access-date=September 22, 2008}}</ref><ref>{{cite news |url=http://news.bbc.co.uk/2/hi/asia-pacific/7616346.stm |title=Toxic milk toll rockets in China |date=September 15, 2008 |publisher=BBC News |access-date=September 22, 2008}}</ref> Officials estimate that about 20% of the dairy companies tested in China sell products tainted with melamine.<ref>{{cite web |url=https://news.yahoo.com/s/ap/20080917/ap_on_re_as/as_china_baby_formula_recall;_ylt=Ah6kOst99plhMAY4QLFtXkes0NUE%20%20Yahoo!%20-%20China%20reports%203rd%20death%20in%20tainted%20milk%20scandal |title=6,200 Chinese babies ill, 3 die from tainted milk |last=Tran |first=Tini |date=September 17, 2008 |publisher=Yahoo! News |access-date=September 22, 2008 |url-status=dead |archive-url=https://web.archive.org/web/20080921003955/http://news.yahoo.com/s/ap/20080917/ap_on_re_as/as_china_baby_formula_recall |archive-date=September 21, 2008}}</ref> On January 22, 2009, three of those involved in the scandal (including one conditional sentence) were sentenced to death in a Chinese court.{{cn|date=June 2024}}

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 the [[Centre for Food Safety|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.<ref>{{cite news|url=http://news.bbc.co.uk/2/hi/asia-pacific/7692400.stm |title= Hong Kong widens China food tests |date=October 27, 2008 | access-date=October 27, 2008 | publisher=BBC News }}</ref>

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.<ref>{{cite news |title=Melamine tainted milk re-emerges in northwest China plant |url=http://news.xinhuanet.com/english2010/china/2010-07/09/c_13392414.htm|work=[[Xinhua]] |date=July 9, 2010 |access-date=July 9, 2010 |archive-url=https://web.archive.org/web/20100711055941/http://news.xinhuanet.com/english2010/china/2010-07/09/c_13392414.htm|archive-date=July 11, 2010}}</ref><ref>{{cite news |author=Wines, Michael |title=Tainted Dairy Products Seized in Western China |url=https://www.nytimes.com/2010/07/10/world/asia/10china.html |work=[[New York Times]] |date=July 9, 2010 |access-date=July 9, 2010 }}</ref>

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.<ref>{{cite journal |doi=10.1056/NEJMe0900361|pmid=19196666|title=Melamine, Powdered Milk, and Nephrolithiasis in Chinese Infants|journal=[[The New England Journal of Medicine]] |volume=360|issue=11|pages=1139–41|date=2009|last=Langman|first=Craig B. }}</ref>

Urinary [[Calculus (medicine)|calculi]] specimens were collected from 15 cases treated in Beijing and were analyzed as unknown objects for their components at Beijing Institute of Microchemistry using [[infrared spectroscopy]], [[nuclear magnetic resonance]], and [[high performance liquid chromatography]]. The result of the analysis showed that the calculus was composed of melamine and [[uric acid]], and the molecular ratio of uric acid to melamine was around 2:1.<ref name="SUN_2009">{{cite journal|pmid=19236798 |title=Diagnosis and treatment of melamine-associated urinary calculus complicated with acute renal failure in infants and young children |journal=Chinese Medical Journal |date=2009 |volume=122 |issue=3 |pages=245–51 |last1=Sun |first1=N. |last2=Shen |first2=Y. |last3=Sun |first3=Q. |last4=Li |first4=X. R. |last5=Jia |first5=L. Q. |last6=Zhang |first6=G. J. |last7=Zhang |first7=W. P. |last8=Chen |first8=Z. |last9=Fan |first9=J. F. |last10=Jiang |first10=Y. P. |last11=Feng |first11=D. C. |last12=Zhang |first12=R. F. |last13=Zhu |first13=X. Y. |last14=Xiao |first14=H. Z. }}</ref>

In a 2009 study of 683 children diagnosed in Beijing in 2008 with [[nephrolithiasis]] and 6,498 children without nephrolithiasis aged < 3 years, investigators found that in children exposed to melamine levels < 0.2&nbsp;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 the [[World Health Organization]].<ref name="Gang_2009">{{cite journal |doi=10.1007/s00467-009-1298-3 |pmid=19727838 |title=The risk of melamine-induced nephrolithiasis in young children starts at a lower intake level than recommended by the WHO |journal=Pediatric Nephrology |volume=25 |issue=1 |pages=135–41 |date=2009 |last1=Li |first1=Gang |last2=Jiao |first2=Shufang |last3=Yin |first3=Xiangjun |last4=Deng |first4=Ying |last5=Pang |first5=Xinghuo |last6=Wang |first6=Yan|s2cid=360958 }}</ref>

In a study published in 2010, researchers from [[Beijing 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."<ref name="LIU_2010">{{cite journal |doi=10.1503/cmaj.091063 |pmid=20176755 |title=Urinary tract abnormalities in Chinese rural children who consumed melamine-contaminated dairy products: A population-based screening and follow-up study |journal=Canadian Medical Association Journal |volume=182 |issue=5 |pages=439–43 |date=2010 |last1=Liu |first1=J.-m. |last2=Ren |first2=A. |last3=Yang |first3=L. |last4=Gao |first4=J. |last5=Pei |first5=L. |last6=Ye |first6=R. |last7=Qu |first7=Q. |last8=Zheng |first8=X. |pmc=2842835}}</ref> Another 2010 follow-up study from [[Lanzhou University]] attributed the [[uric acid]] stone accumulation after ingestion of melamine to a rapid aggradation of metabolites such as [[cyanuric acid]] diamide ([[ammeline]]) and cyanuric acid and reported that urine alkalinization and stone liberalization were the most effective treatments.<ref name=Lanzhou_2010>{{cite journal |doi=10.1007/s00240-010-0279-0 |pmid=20517603 |title=Melamine-induced infant urinary calculi: A report on 24 cases and a 1-year follow-up |journal=Urological Research |volume=38 |issue=5 |pages=391–5 |date=2010 |last1=Zhang |first1=Xiangbo |last2=Bai |first2=Jinliang |last3=Ma |first3=Pengcheng |last4=Ma |first4=Jianhua |last5=Wan |first5=Jianghou |last6=Jiang |first6=Bin|s2cid=23832448 }}</ref>

Until the [[2007 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.<ref>{{cite web|url=http://irmm.jrc.ec.europa.eu/melamine |title=About melamine |publisher=Irmm.jrc.ec.europa.eu |date=February 2, 2012 |access-date=June 20, 2012 |url-status=dead |archive-url=https://web.archive.org/web/20120212141029/http://irmm.jrc.ec.europa.eu/melamine |archive-date=February 12, 2012 }}</ref> 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.<ref>Breidbach, A., Bouten, K., Kroger, K., Ulberth, F. [http://irmm.jrc.ec.europa.eu/html/activities/melamine/EUR23809EN_melamine.pdf "Melamine Proficiency Test 2009"]. ec.europa.eu {{webarchive|url=https://web.archive.org/web/20091015233952/https://irmm.jrc.ec.europa.eu/html/activities/melamine/EUR23809EN_melamine.pdf |date=October 15, 2009 }}</ref>

In October 2008, the [[U.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.<ref>U.S. FDA Laboratory Information Bulletin No 4421 – {{cite web |url=http://www.cfsan.fda.gov/~frf/lib4421.html |title=US FDA/CFSAN - Determination of Melamine and Cyanuric Acid Residues in Infant Formula using LC-MS/MS - Lib. 4421 |access-date=October 16, 2008 |url-status=dead |archive-url=https://web.archive.org/web/20081010110710/http://www.cfsan.fda.gov/~frf/lib4421.html |archive-date=October 10, 2008 }}</ref> Similar recommendations have been issued by other authorities, like the Japanese Ministry of Health, Labor and Welfare,<ref>[https://web.archive.org/web/20081031022345/http://www.forth.go.jp/keneki/kanku/syokuhin/tsuuchi/2008/10/3_1.pdf Japanese Ministry of Health, Labor and Welfare]. forth.go.jp</ref> both based on liquid chromatography – mass spectrometry ([[LC/MS]]) detection after hydrophilic interaction liquid chromatography ([[HILIC]]) separation.<ref>Zwitterionic HILIC separation of melamine and cyanuric acid – {{cite web |url=http://www.sequant.com/melamine |title=Strategies for Determination of Melamine by HILIC|date=October 3, 2008 |access-date=October 16, 2008 |url-status=dead |archive-url=https://web.archive.org/web/20081006060206/http://www.sequant.com/melamine |archive-date=October 6, 2008 }}</ref>

The existing methods for melamine determination using a triple [[quadrupole]] liquid chromatography – mass spectrometry (LC/MS) after [[solid phase extraction]] ([[Solid 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.<ref>

{{Cite news

| last = Hodge

| first = James

| date = December 12, 2008

| title = Dairy detection: monitoring melamine in milk

| work = Chemical Science

| publisher = Royal Chemical Society, RCS Publishing

| issue = 2

| url = http://www.rsc.org/Publishing/ChemScience/Volume/2009/02/Dairy_Detection.asp

| access-date = January 4, 2009

}}

</ref>

Ultrasound-assisted extractive electrospray ionization mass spectrometry (EESI-[[Mass spectrometry|MS]]) has been developed at ETH Zurich (Switzerland) by Zhu, [[Konstantin Chingin|Chingin]] et al., (2008)<ref>{{cite journal |doi=10.1039/b818541g |title=Rapid detection of melamine in untreated milk and wheat gluten by ultrasound-assisted extractive electrospray ionization mass spectrometry (EESI-MS) |journal=Chemical Communications |issue=5 |pages=559–61 |date=2009 |last1=Zhu |first1=Liang |last2=Gamez |first2=Gerardo |last3=Chen |first3=Huanwen |last4=Chingin |first4=Konstantin |last5=Zenobi |first5=Renato |pmid=19283290}}</ref> for a rapid detection of melamine in untreated [[food sampling|food samples]]. [[Ultrasound]]s are used to [[nebulize]] the melamine-containing liquids into a fine spray. The spray is then ionised by [[extractive electrospray ionisation]] (EESI) and analysed using [[tandem 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.<ref>{{Cite journal |date=Jun 2021 |title=Determination of melamine contamination in chocolates containing powdered milk by high-performance liquid chromatography (HPLC) |pmc=8172743 |last1=Abedini |first1=R. |last2=Jahed Khaniki |first2=G. |last3=Molaee Aghaee |first3=E. |last4=Sadighara |first4=P. |last5=Nazmara |first5=S. |last6=Akbari-Adergani |first6=B. |last7=Naderi |first7=M. |journal=Journal of Environmental Health Science & Engineering |volume=19 |issue=1 |pages=165–171 |doi=10.1007/s40201-020-00590-w |pmid=34150227 }}</ref>

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, the [[ESI-MS]] technique allows now high-throughput analysis of melamine traces in complex mixtures.<ref>{{cite journal |doi=10.1039/b818059h|title=High-throughput trace melamine analysis in complex mixtures|journal=Chemical Communications|issue=5|pages=556–8|date=2009|last1=Huang|first1=Guangming|last2=Ouyang|first2=Zheng|last3=Cooks|first3=R. Graham|pmid=19283289}}</ref>

The Melaminometer<ref>[http://openwetware.org/wiki/User:Jonathan_Cline/Notebook/Melaminometer Melaminometer]</ref><ref>

{{cite web

| last = McKenna

| first = Phil

| date = January 7, 2009

| title = Rise of the garage genome hackers

| work = New Scientist

| url = https://www.newscientist.com/article/mg20126881.400-rise-of-the-garage-genome-hackers.html?full=true

| access-date = February 17, 2009

}}

</ref><ref>

{{cite news

| last = Marcus

| first = Wohlsen

| date = December 26, 2008

| title = Amateurs are trying genetic engineering at home

| work = Copyright 2008 The Associated Press

| url = https://www.usatoday.com/tech/science/genetics/2008-12-26-diy-dna_N.htm

| access-date = February 17, 2009

</ref>

was a hypothetical design for a [[synthetic biology]] circuit, to be used for detecting melamine and related chemical analogues such as [[cyanuric acid]]. The conceptual project is hosted at [[OpenWetWare]] as open source biology in collaboration with [[DIYbio]] and has been discussed in various newspapers in the context of homebrew biotechnology. As of October 2009, the design has not been verified.

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>{{cite journal |vauthors=Ishiwata H, Inoue T, Yamazaki T, Yoshihira K |title=Liquid chromatographic determination of melamine in beverages |journal=Journal of the Association of Official Analytical Chemists |date=1987 |volume=70 |issue=3 |pages=457–460 |doi=10.1093/jaoac/70.3.457 |pmid=3610957|doi-access=free }}</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>{{cite journal |id={{INIST |16514561}} |doi=10.1016/j.aca.2004.09.038 |title=Residue determination of cyromazine and its metabolite melamine in chard samples by ion-pair liquid chromatography coupled to electrospray tandem mass spectrometry |journal=Analytica Chimica Acta |volume=530 |issue=2 |pages=237–243 |date=2005 |last1=Sancho |first1=J.V. |last2=Ibáñez |first2=M. |last3=Grimalt |first3=S. |last4=Pozo |first4=Ó.J. |last5=Hernández |first5=F.}}</ref>

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.<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

|access-date=April 27, 2007

|url-status=dead

|archive-url=https://web.archive.org/web/20070616050029/http://www.fsis.usda.gov/ophs/clg/Cyromazine.pdf

|archive-date=June 16, 2007

}}</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]]

| access-date = April 27, 2007}}</ref> In 2007, the FDA began using a [[high performance liquid chromatography]] test to determine the melamine, [[ammeline]], [[ammelide]], and [[cyanuric acid]] contamination in food.<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 = [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]]

| date = April 25, 2007

| access-date = May 9, 2007

| archive-date = December 20, 2008

| archive-url = https://web.archive.org/web/20081220121758/http://acs.confex.com/acs/mwrm07/techprogram/P51682.HTM

| url-status = dead

}}</ref> Another procedure is based on surface-enhanced [[Raman spectroscopy]] ([[Surface Enhanced Raman Spectroscopy|SERS]]).<ref name="He">{{cite journal |doi=10.1007/s11694-008-9038-0|title=A new approach to measure melamine, cyanuric acid, and melamine cyanurate using surface enhanced Raman spectroscopy coupled with gold nanosubstrates|journal=Sensing and Instrumentation for Food Quality and Safety| volume=2| pages=66–71|date=2008| last1=He| first1=Lili| last2=Liu| first2=Yang| last3=Lin| first3=Mengshi|last4=Awika|first4=Joseph|last5=Ledoux|first5=David R.| last6=Li| first6=Hao| last7=Mustapha| first7=Azlin|s2cid=93425738}}</ref><ref name="Lin">{{cite journal |doi=10.1111/j.1750-3841.2008.00901.x| pmid=19019134| title=Detection of Melamine in Gluten, Chicken Feed, and Processed Foods Using Surface Enhanced Raman Spectroscopy and HPLC|journal=Journal of Food Science| volume=73| issue=8| pages=T129-34|date=2008| last1=Lin|first1=M.|last2=He|first2=L.|last3=Awika|first3=J.|last4=Yang|first4=L.|last5=Ledoux|first5=D.R.|last6=Li|first6=H.|last7=Mustapha|first7=A.}}</ref>

Member states of the European Union are required under Commission Decision 2008/757/EC<ref>[http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:273:0018:0020:EN:PDF European Commission decision (2008/798/EC) imposing special conditions governing the import of products containing milk or milk products originating from China]</ref> 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&nbsp;mg/kg are immediately destroyed.

==Detection in biological specimens==

The presence of melamine in urine specimens from children who consumed adulterated milk products has been determined by liquid chromatography-mass spectrometry.<ref>{{cite book| author = Baselt RC| title = Disposition of toxic drugs and chemicals in man | year = 2014 | publisher = Biomedical Publications | location = Seal Beach, Ca. | isbn = 978-0-9626523-9-4 | pages = 1213–1214 }}</ref>

== Melamine on metal surfaces ==

It is reported that melamine molecules adsorbed on gold<ref name="a1">{{ cite journal| title = Melamine Structures on the Au(111) Surface| journal = J. Phys. Chem. C | year = 2008 | volume = 112| issue = 30 | pages = 11476–11480 | doi = 10.1021/jp8033769 | last1 = Silly | first1 = Fabien | last2 = Shaw | first2 = Adam Q. | last3 = Castell | first3 = Martin R. | last4 = Briggs | first4 = G. A. D. | last5 = Mura | first5 = Manuela | last6 = Martsinovich | first6 = Natalia | last7 = Kantorovich | first7 = Lev }}</ref> or silver<ref name="a3">{{ cite journal | title = Two commensurate hydrogen-bonded monolayer structures of melamine on Ag(111) | journal = Surface Science | year = 2011 | volume = 605| issue = 1–2 | pages = 1–6 | doi = 10.1016/j.susc.2010.09.006 | last1 = Schmitz | first1 = Christoph H. | last2 = Ikonomov | first2 = Julian | last3 = Sokolowski | first3 = Moritz | bibcode = 2011SurSc.605....1S }}</ref> 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 classical [[Monte Carlo method|Monte Carlo]]<ref name="a2">{{ cite journal |author1=Šimėnas, M. |author2=Tornau, E. E. | title = A model of melamine molecules ordering on metal surfaces| journal = J. Chem. Phys. | year = 2014 | volume = 141|issue=5 | pages = 054701 | doi = 10.1063/1.4891245 |pmid=25106594 |bibcode=2014JChPh.141e4701A }}</ref> and [[Density functional theory|DFT]]<ref name="a4">{{ cite journal |author1=Mura, M. |author2=Martsinovich, N. |author3=Kantorovich, L. | title = Theoretical study of melamine superstructures and their interaction with the Au(111) surface| journal = Nanotechnology | year = 2008 | volume = 19|issue=46 | pages = 465704 | doi = 10.1088/0957-4484/19/46/465704 |pmid=21836259 |bibcode=2008Nanot..19T5704M |s2cid=25890258 }}</ref> methods.

== See also ==

* [[Zhao Lianhai]]

== References ==

{{Reflist|30em}}

== External links ==

{{Wiktionary|melamine}}

* [https://fscimage.fishersci.com/msds/96668.htm Melamine Materials Safety Data Sheet (MSDS)]

* [https://web.archive.org/web/20081001230407/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).

* [https://www.fda.gov/oc/opacom/hottopics/petfood.html FDA Web Page with Information on Pet Food Recall (due to Melamine contamination)]

* [http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:273:0018:0020:EN:PDF European Commission decision (2008/798/EC) imposing special conditions governing the import of products containing milk or milk products originating from China]

* [https://web.archive.org/web/20090616191404/http://www.fertilizer.org/ifa/Home-Page/SUSTAINABILITY/Melamine Statement on melamine from the International Fertilizer Industry Association]

* [http://whqlibdoc.who.int/publications/2009/9789241597951_eng.pdf Toxicological and Health Aspects of Melamine and Cyanuric Acid: Report of a WHO Expert Meeting In collaboration with FAO]

* [http://www.MelmacCentral.com Melmac Central's History on Melamine ].

{{Consumer Food Safety}}

[[Category:Aromatic bases]]

[[Category:Commodity chemicals]]

[[Category:Polyamines]]

[[Category:Triazines]]

[[Category:Woodworking materials]]