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출처: 약사의 미래를 준비하는 모임 원문보기 글쓴이: 새하얀
멜라민 => 멜라민 레진(플라스틱류), 식기류, 열안전성 플라스틱, 산업용 코팅 등에 쓰이는 공업용 원료.
그러나 분자구조에 질소를 함유하고 있기 때문에.. 식품검사에서 단백질이나 유제품 함유제품으로 속일 수 있어 불법적으로 사료나 식품첨가물로 사용함.
중국의 분유 파동이나 과자 파동이 대표적인 사례.
멜라민의 독성 작용 원리.
멜라민은 수용성 => 인체 흡수 후 혈액에 녹음 => 소변으로 배설(약 3시간 만에 배출 가능하다고 함)
그러나 멜라민이 과량으로 흡수되면 => 더 이상 녹기 힘들고 침전 현상이 일어남(특히 신장에 침전이 형성 되어 결석 발생)
더욱 심각한 문제는..
멜라민의 신체 대사물질인 cyanuric acid 이 멜라민과 결합하여 독성 작용이 증가됨.(침전도 잘 일어나고 독성도 심각해짐)
멜라민의 독성작용 결론
급성 => 멜라민 + cyanuric acid => 치명적인 신장결석 발생 => 사망
만성 => 신장결석, 요로결석, 방광결석, 신부전, 생식기 장해, 방광암, 피부자극 등..
Melamine[1] | |
---|---|
IUPAC name | 1,3,5-Triazine-2,4,6-triamine |
Other names | Cyanurotriamide Cyanurotriamine Cyanuramide |
Identifiers | |
CAS number | [108-78-1] |
PubChem | 7955 |
SMILES |
Nc1nc(N)nc(N)n1 |
Properties | |
Molecular formula | C3H6N6 |
Molar mass | 126.12 g/mol |
Appearance | White solid |
Density | 1574 kg/m3 |
Melting point |
350 °C, 623 K, 662 °F |
Boiling point |
Sublimes |
Solubility in water | 3.1 g/l (20 °C) |
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox references |
Melamine is an organic base with the chemical formula C3H6N6, with the IUPAC name 1,3,5-triazine-2,4,6-triamine. It is only slightly soluble in water.
Melamine is a 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.[2] It was also reported that cyromazine is converted to melamine in plants.[3][4]
Contents[hide] |
Melamine was first synthesized by 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
It can be understood as two steps. First, urea decomposes into cyanic acid in an endothermic reaction (NH2)2CO → HCNO + NH3. Then cyanic acid polymerizes to form melamine and carbon dioxide: 6 HCNO → C3H6N6 + 3 CO2. The second reaction is exothermic and the overall process is endothermic.
The above reaction can be carried out by either of two methods:catalyzed gas-phase production or high pressure liquid-phase production. In one method, molten urea is introduced onto a fluidized bed with catalyst for reaction. Hot ammonia gas is also present to fluidize the bed and inhibit deammonization. The effluent then is cooled. Ammonia and carbon dioxide in the off-gas are separated from the melamine-containing slurry. The slurry is further concentrated and crystallized to yield melamine.[5] Major manufacturers and licensors such as DSM, BASF and Eurotecnica have developed some proprietary methods.
The off-gas contains large amounts of ammonia. Therefore melamine production is often integrated into urea production which uses ammonia as feedstock.
Crystallization and washing of melamine generates a considerable amount of waste water, which is a pollutant if discharged directly into the environment. The waste water may be concentrated into a solid (1.5-5% of the weight) for easier disposal. The solid may contain approximately 70% melamine, 23% oxytriazines (ammeline, ammelide and cyanuric acid), 0.7% polycondensates (melem, melam and melon).[6]
Melamine is used combined with formaldehyde to produce melamine resin, a very durable thermosetting plastic, and melamine foam, a polymeric cleaning product. The end products include countertops, dry erase boards, fabrics, glues, housewares and flame retardants. Melamine is one of the major components in Pigment Yellow 150, a colorant in inks and plastics.
Melamine also enters the fabrication of melamine poly-sulfonate used as superplastizer for making high-resistance concrete. Sulfonated melamine formaldehyde (SMF) is a polymer used as cement admixture to reduce the water content in concrete while increasing the fluidity and the workability of the mix during its handling and pouring. It results in concrete with a lower porosity and a higher mechanical strength exhibiting an improved resistance to aggressive environments and a longer life-time.
Melamine is also used to make fertilizers.
Melamine derivatives of arsenical drugs are potentially important in the treatment of African trypanosomiasis[7]
Melamine use as non-protein nitrogen (NPN) for cattle was described in a 1958 patent.[8] In 1978, however, a study concluded that melamine "may not be an acceptable non-protein N source for ruminants" because its hydrolysis in cattle is slower and less complete than other nitrogen sources such as cottonseed meal and urea.[9]
Melamine is sometimes unethically added to food products in order to increase the apparent protein content. Standard tests such as the Kjeldahl and Dumas tests estimate protein levels by measuring the nitrogen content, so they can be misled by adding nitrogen-rich compounds such as melamine. [10]
The Food Safety and Inspection Service (FSIS) of the United States Department of Agriculture (USDA) provides a test method for analyzing cyromazine and melamine in animal tissues in its Chemistry Laboratory Guidebook which "contains test methods used by FSIS Laboratories to support the Agency's inspection program, ensuring that meat, poultry, dairy and egg products are safe, wholesome and accurately labeled."[11][12] In 1999, in a proposed rule published in the Federal Register regarding cyromazine residue, the United States Environmental Protection Agency (EPA) proposed "removing melamine, a metabolite of cyromazine from the tolerance expression since it is no longer considered a residue of concern."[13] Melamine, classified a controlled substance in China[14], has been illegally used in the high profile 2008 baby milk scandal case which led to the death of at least 4 infants[14].
Melamine by itself is nontoxic in low doses, but when combined with cyanuric acid it can cause fatal kidney stones.[15]
Melamine is reported to have an oral LD50 of >3000 mg/kg based on rat data. It is also an irritant when inhaled or in contact with the skin or eyes. The reported dermal LD50 is >1000 mg/kg for rabbits.[16] In a 1945 study, large doses of melamine were given orally to rats, rabbits and dogs with "no significant toxic effects" observed.[17]
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[18]) could be more toxic than either melamine or cyanuric acid alone.[19] For rats and mice, the reported LD50 for melamine cyanurate was 4.1 g/kg (given inside the stomach) and 3.5 g/kg (via inhalation), compared to 6.0 and 4.3 g/kg for melamine and 7.7 and 3.4 g/kg for cyanuric acid, respectively.
A toxicology study conducted after recalls of contaminated pet food concluded that the combination of melamine and cyanuric acid in diet does lead to acute renal failure in cats.[20]
Ingestion of melamine may lead to reproductive damage, or bladder or kidney stones, which can lead to bladder cancer.[16][21][22][23][24]
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.[25]
Wilson Rumbeiha, an associate professor in Michigan State University’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.”[26][27][28]
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.[29][30][31] 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 imported from a single source in China, Xuzhou Anying Biologic Technology[32] as well as in crystalline form in the kidneys and in urine of affected animals.[33] 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 appearance of increased protein content in animal feed.[34]
Melamine has also been purposely added as a binder to fish and livestock feed manufactured in the United States and traced to suppliers in Ohio and Colorado.[35]
In September 2008 Sanlu recalled all powdered milk in the north-west China's Gansu province where melamine was reported to have been used in 22 brands of infant formula, making more than 53,000 infants ill and hospitalizing almost 12,900.[36] Melamine has also been found in products produced by Yili Industrial Group Co, and Mengniu Dairy Co.[37] As of 18 September 2008 there had been four confirmed infant deaths from the contamination of powdered milk with melamine with a number of survivors diagnosed with acute kidney failure.[38]
Melamine may have been added to fool government quality tests after water was added to fraudulently increase the milk's volume. The adulterant melamine was added to the milk to allow the company to dilute the milk with water and circumvent government regulations, since melamine will cause a false increase in the measurement of protein by increasing the nitrogen levels in the milk.[39][40]Officials estimate that about 20 percent of the dairy companies tested in China sell products tainted with melamine.[41]
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."[11][12]
On 24 April, 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."[citation needed]
On 7 May, 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."[42] 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.[43]
On 15 May, the process for testing meat from swine was validated by USDA's Food Safety and Inspection Service (FSIS).[44]
On 9 November 2007, FDA presented a method of HPLC Determination of Melamine, Ammeline, Ammelide, and Cyanuric Acid Contamination in Wheat Gluten and Rice Protein Concentrate.[45]
Between the late 1990s and early 2000s, both consumption and production of melamine grew considerably in mainland China. In the United States Geological Survey 2004 Minerals Survey Yearbook, in a report on worldwide nitrogen production, the author stated that "(mainland) China continued to plan and construct new ammonia and urea plants using coal gasification technology."[46]
By early 2006, melamine production in mainland China is reported to be in "serious surplus".[47] In April 2007, DSM's melamine industry update painted a grave global picture.[48] 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.
On 30 April 2007, The New York Times reported that the addition of "melamine scrap" into fish and livestock feed to give the false appearance of a higher level of protein was an "open secret" in many parts of mainland China, reporting that this melamine scrap was being produced by at least one plant processing coal into melamine.[34] 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.”[49] 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.[50]
As per 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, melan and melon).[51]
On 3 May 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 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."[52]
On 12 September 2008, Xinhua News Agency widely reported adulteration of baby food formula with melamine. The substance caused kidney stones as large as 1 cm in diameter in many babies. The adulterated baby formula was manufactured by Sanlu Group, a leading Chinese dairy producer owned by Arla Foods. Sanlu ordered a recall of more than 10,000 tonnes of the potentially contaminated formula produced before 6 August 2008.
The Chinese Ministry of Health confirmed two infant deaths in the northwestern Gansu Province. In that same province, 59 babies have been hospitalized. Similar numbers have been reported all across mainland China, in Shaanxi Province and Ningxia Hui Autonomous Region in the northwest, Shandong, Jiangsu and Anhui provinces in the east and in the central provinces of Hubei and Hunan. In fact, an official report of China showed a number of Chinese milk vendors adulterate melamine to improve the nitrogen content.
The United States Food and Drug Administration has issued a warning regarding the sale of Chinese-made baby formula, which is illegal in the United States. The Chinese Ministry of Health is conducting an investigation.
On 15 September 2008, China’s Ministry of Health announced that 1,253 babies in China became sick after drinking melamine-contaminated baby formula, with 340 hospitalized and 53 in a serious condition. A 5-month-old boy and 8-month-old girl from Gansu Province died on 1 May and 22 July respectively.[53] By September 23rd, the estimated number of affected children had risen to 53,000.[54]
Until the 2007 pet food recalls, melamine had not routinely been monitored in food, except in the context of plastic safety or insecticide residue. This could be due to the previously assumed low toxicity of melamine, and the relatively expensive methods of detection.
Because melamine resin is often used in food packaging and tableware, melamine at ppm level (1 part per million) in food and beverage has been reported due to migration from melamine-containing resins.[55] Small amounts of melamine have also been reported in foodstuff as a metabolite product of cyromazine, an insecticide used on animals and crops.[56] Romer Labs now offers a rapid Melamine test kit (AgraQuant Melamine ELISA test kit).
How Two Innocuous Compounds Combined to Kill Pets
By David Brown
Washington Post Staff Writer
Monday, May 7, 2007; A08
What do a dead cat in Ontario and a motel swimming pool in Phoenix have in common?
In certain circumstances, they both contain melamine-cyanuric acid crystals.
Scientists seeking the chemical culprits in the widening pet food scare have come across some unusual chemistry that may help them understand how two largely nontoxic compounds ended up killing an unknown number of cats and dogs.
At the end of March, investigators detected a man-made compound called melamine in wheat gluten produced in China and sold to U.S. manufacturers as a pet food thickener. The contaminated samples contained various amounts -- from 0.2 percent to 8 percent -- of the chemical.
Melamine has been used for decades in manufacturing. In its chainlike "polymerized" form, it is used to make dishes, flame-retardant fibers and industrial coatings.
Also found in the gluten in smaller concentrations was cyanuric acid. The man-made chemical is used to stabilize chlorine in outdoor swimming pools, especially in regions such as the American Southwest where the sun's rays are quick to dissipate that disinfectant. Two other compounds, ammeline and ammelide, were present in even smaller amounts.
The four compounds have similar chemical structures. One can easily be made into another with the right chemical reaction. All contain relatively large amounts of the element nitrogen. Of the 15 atoms in a molecule of melamine, six are nitrogen. It also has three atoms of carbon and six of hydrogen. Ammeline has five nitrogen atoms, ammelide has four, and cyanuric acid has three.
All living things need nitrogen. The element is an essential ingredient of proteins, which make up most of the human body that isn't bone or water. It is an essential ingredient of DNA as well.
Organisms can survive for short periods on carbon, oxygen and hydrogen -- sugar. But if they want to grow or reproduce, they need nitrogen. Plants can get nitrogen out of the soil or the air, but animals have a harder time. They must take in protein already made by plants or other animals. That's what the female mosquito is seeking when she's out for blood -- a source of abundant nitrogen with which to make the protein and DNA in her eggs.
If you add melamine to almost anything, the amount of nitrogen in the final mixture will rise simply because, gram for gram, melamine contains so much of the element. Since the food industry generally measures total "nitrogen content" and equates it with "protein content," a few shovelfuls of melamine can appear to turn a low-protein meal into a high-protein one.
And what's wrong with that? Can't the body use the nitrogen in melamine?
Actually, it can't.
Melamine is an extremely small molecule, and most of it is absorbed through the intestinal tract before it is digested. It circulates in the bloodstream until it gets to the kidneys, where it slips easily into the fluid that eventually becomes urine. Melamine can also enter other organs. That is how it could have ended up in the tissue of farm animals that ate scraps of melamine-laced pet food -- as apparently was the case in 2.7 million chickens and 345 pigs slaughtered and consumed in recent months.
(Late last week, the federal government identified another 20 million chickens that had eaten tainted feed and took steps to keep them off the market.)
As a practical matter, though, only a small amount of melamine would ever end up in Buffalo wings or pulled pork. Melamine's chemical structure makes it water-soluble, and it doesn't accumulate in fat. After an oral dose of melamine, more than half is out of the bloodstream and into the urine in three hours.
The purpose of urine is to concentrate water-soluble waste products and to keep them dissolved. But water's dissolving power has its limits. Melamine and other chemicals can reach concentrations that exceed those limits. When the water can't hold any more, the chemical substance begins to form crystals.
Studies done decades ago found that rats fed melamine for two years developed stones in their urine, which led to bladder cancer in some. When rats were fed in one serving a large amount of melamine -- the equivalent of a 150-pound person eating a pound -- about half died.
At low doses, however, melamine is nontoxic. In fact, microcapsules and chains made of melamine have been used experimentally in animals as vehicles for delivering long-acting drugs.
Veterinarians investigating the mysterious pet deaths realized that most of the animals died of kidney failure and had kidney stones containing melamine. Although little is known about melamine toxicity in cats and dogs, it seems unlikely, based on the rat studies, that the pets could have consumed fatal amounts of the chemical.
Last month, however, toxicologists at the University of Guelph in Ontario detected another compound in the stones from cats suffering kidney failure -- cyanuric acid. Initially, the ratio was thought to be about two parts melamine to one part cyanuric acid. More recent and more precise measurements suggest an even split.
Ten days ago, Guelph scientists Brent Hoff and Grant Maxie combined melamine and cyanuric acid in a sample of cat urine. They produced crystals that, when examined for their chemical and physical properties, were virtually identical to the stones taken from the ill or dead cats.
The crystals are a lattice of six molecules -- three of melamine and three of cyanuric acid -- held together by weak links called hydrogen bonds.
When melamine is added to water that contains cyanuric acid, the reaction clouds the solution. It's that reaction -- and the degree of cloudiness -- that tells pool maintenance workers how much cyanuric acid is in the water, and whether more is needed. When the reaction occurs in a pet's kidneys, however, it can have altogether different and deadly effects.
So how might a plastic and a pool chemical (and their cousins, ammeline and ammelide) have gotten into pet food?
Nobody knows.
But one theory is that they were leftovers from a chemical company's production of something else. In an act of fraud that substituted cheap scrap for more expensive protein, someone put the compounds into the wheat gluten, thinking they would never be discovered and never cause a problem.
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