Schematic representation of the mechanisms of blueberry bud break after HC treatment. Red/green indicates metabolites whose relative content increases/decreases after HC treatment compared with CK.

Cyanamide notes (it was a polio vaccine that spurred these notes and by now polio has five mentions on the page and these are two of them)

August 12, 2023
by

I’m going to add some polio vaccine stuff at the top of these notes. Hilary Koprowski is the one mentioned on the Polio Hall of Fame page who was not included in the hideous monument, see What In God’s Name, even though he (and his work) have direct connection to those who are included. He did a chunk of his work at something called Lederle Laboratories, the pharmaceutical division of American Cyanamid. This is what Wikipedia has to say about him.

2007 Hilary Koprowski 

Hilary Koprowski (1916–2013) was a Polish virologist and immunologist active in the United States who demonstrated the world’s first effective live polio vaccine. He authored or co-authored over 875 scientific papers and co-edited several scientific journals. Koprowski received many academic honors and national decorations, including the Belgian Order of the Lion, the French Order of Merit and Legion of Honour, Finland’s Order of the Lion, and the Order of Merit of the Republic of Poland.

Koprowski was the target of accusations in the press related to the “oral polio vaccine AIDS hypothesis“, which posited that the AIDS pandemic originated from live polio vaccines such as Koprowski’s. This allegation has long been refuted by evidence showing that the human immunodeficiency virus was introduced to humans before his polio-vaccine trials were conducted in Africa. The case was settled out of court with a formal apology from Rolling Stone magazine.

In 1939, after Germany‘s invasion of Poland, Koprowski and his wife, likewise a physician, fled the country, using Koprowski family business connections in Manchester, England. Hilary went to Rome, where he spent a year studying piano at the Santa Cecilia Conservatory; while Irena went to France, where she gave birth to their first child, Claude Koprowski, and worked as an attending physician at a psychiatric hospital.

As the invasion of France loomed in 1940, Irena and the infant escaped from France via Spain and Portugal —where the Koprowski family reunited — to Brazil, where Koprowski worked in Rio de Janeiro for the Rockefeller Foundation. His field of research for several years was finding a live-virus vaccine against yellow fever. After World War II the Koprowskis settled in Pearl River, New York, where Hilary was hired as a researcher for Lederle Laboratories, the pharmaceutical division of American Cyanamid. Here he began his polio experiments, which ultimately led to the creation of the first oral polio vaccine. Koprowski served as director of the Wistar Institute, 1957–91, during which period Wistar achieved international recognition for its vaccine research and became a National Cancer Institute Cancer Center.[citation needed]

While at Lederle Laboratories, Koprowski created an early polio vaccine, based on an orally administered attenuated polio virus. In researching a potential polio vaccine, he had focused on live viruses that were attenuated (rendered non-virulent) rather than on killed viruses (the latter became the basis for the injected vaccine subsequently developed by Jonas Salk).

Koprowski viewed the live vaccine as more powerful, since it entered the intestinal tract directly and could provide lifelong immunity, whereas the Salk vaccine required booster shots. Also, administering a vaccine by mouth is easy, whereas an injection requires medical facilities and is more expensive.

Koprowski developed his polio vaccine by attenuating the virus in brain cells of a cotton rat, Sigmodon hispidus, a New World species that is susceptible to polio. He administered the vaccine to himself in January 1948 and, on 27 February 1950, to 20 children at Letchworth Village, a home for disabled persons in Rockland County, New York. Seventeen of the 20 children developed antibodies to polio virus — the other three apparently already had antibodies — and none of the children developed complications. Within 10 years, the vaccine was being used on four continents.

A few words about Letchworth Village, Irving Haberman, Robert F. Kennedy and Geraldo Rivera

Letchworth Village was a residential institution located in Rockland County, New York, in the hamlet of Thiells built for the physically and mentally disabled of all ages, from the newborn to the elderly. Opened in 1911, Letchworth Village at its peak consisted of over 130 buildings spread out over many acres of land. It was named for William Pryor Letchworth, who espoused reform in the treatment and care of the insane, epileptics, and poor children.

By the end of 1911, the first phase of construction had completed on the 2,362-acre “state institution for the segregation of the epileptic and feeble-minded.” With architecture modeled after Monticello, the picturesque community was lauded as a model institution for the treatment of the developmentally disabled, a humane alternative to high-rise asylums, having been founded on several guiding principles that were revolutionary at the time. Separate living and training facilities for children, able-bodied adults, and the infirm were not to exceed two stories or house over 70 inmates. Until the 1960s, the able-bodied labored on communal farms, raising enough food and livestock to feed the entire population.

It was conceived by the progressives of the time as a major departure from the almshouses of the 19th century. The facility was thought to have had great potential and was a great improvement from past facilities. It was a farming village of nearly four square miles, In the words of the 1927 Rockland County Red Book, “subdivided as far as possible in order to avoid the tendency toward institutionalism.”

Letchworth was described as an ideal center for the mentally challenged and praised by the state at first. Yet rumors such as the mistreatment of patients and horrific experimenting continued to circulate long after its closing. Former worker Dr. Little presented in an annual report in 1921 that there were three categories of “feeble-mindedness”: the “moron” group, the “imbecile” group, and the “idiot” group. The last of these categories is the one that could not be trained, Dr. Little said, and so they should not be taken into Letchworth Village, because they were unable to “benefit the state” by doing the various jobs that were assigned to the male patients, included loading thousands of tons of coal into storage facilities, building roads, and farming acres of land.

Many of the patients were young children. In 1921, the 13th Annual Report lists the number of patients admitted that year. Out of 506 people, 317 were between the ages of 5 and 16, and 11 were under the age of 5 years. Visitors observed that the children were malnourished and looked sick. The Letchworth staff claimed in the report that there was a scarcity of food, water, and other necessary supplies, but that was not the case. Children were often the subjects of testing and some of the cruelest neglect. Many of the children were able to comprehend learning but were not given the chance because they were thought of as “different.” By the 1950s, the Village was overflowing with 4,000 inhabitants.

Buteux, Lindsay. “Letchworth: The Village of Secrets”. Student Outlook Press. Retrieved 4 December 2012.

In the 1940s, Irving Haberman did a set of photographs which revealed the true nature of what was going on. Until this point, the conditions of the facility weren’t apparent to the public. Haberman’s photos exposed the terrible conditions of the facilities as well as the dirty, unkempt patients. Naked residents huddled in sterile day rooms. The photos showed the patients to be highly neglected. These photos pushed the public to question the institution and demand answers. Haberman knew that these photos would bring attention to the Letchworth facility.

  • Trent, James W. (1994). Inventing the Feeble Mind: A History of Mental Retardation in the United States. University of California Press. p. 226.

Looks like they got the attention of a few people…In February 1950, while Letchworth still enjoyed a good reputation (what?) amongst health professionals (despite rumors of overcrowding and maltreatment), Letchworth’s Dr. George Jervis asked Dr. Hilary Koprowski to test his live-virus polio vaccine at Letchworth Village to compare it to the alternatives available then. Koprowski viewed these experiments as a positive first step toward a better polio vaccine…I’m not saying he is an off the boat nazi, even though he certainly looks like one, but they do have a history of doing just that kind of thing in just those kinds of places and in just that kind of ridiculous order. And who else would go spend a year playing piano in Rome while they are throwing a war? How were they escaping to nearly every place on earth (and right ahead of the nazis?) with all hell breaking loose? There is some bullshit afoot here for sure but I’m a little creeped out and it’s not really my focus. It sure does keep coming up, however.

In 1972, ABC News featured Letchworth Village in its piece “Willowbrook: The Last Great Disgrace”. The documentary, by ABC New York’s investigative reporter Geraldo Rivera, looked at how intellectually disabled people, particularly children, were being treated in the State of New York. United States Senator Robert F. Kennedy previously had toured the Willowbrook facility in 1965 and called it a “snake pit.” Kennedy was not allowed to take cameras into the buildings, however, so the average citizen had no idea how bad the conditions inside Willowbrook actually were. Kennedy’s speeches about the conditions there, although impassioned, attracted little attention and resulted in little or no improvement in conditions at the facility.

Rivera, on the other hand, arrived at Willowbrook with a full camera crew, and when the documentary was aired, there was widespread outrage at how the residents at Willowbrook, many of them children, were being mistreated. Although Rivera’s documentary focused on the Willowbrook State School on Staten Island, Rivera also visited Letchworth Village, as well as facilities in California. While he found that a great deal of progress had been made in the caring for, and training of, disabled people in California, he saw the situation in New York’s facilities as backward and cruel.

Rivera accompanied Bronx congressman Mario Biaggi to Letchworth Village, arriving two hours early because Rivera correctly suspected that the staff would be ordered to clean and dress the children before the camera crew arrived. Biaggi described the children there as being subjected to “[t}he worst possible conditions I’ve ever seen in my life”.

The documentary showed the residents of Willowbrook and Letchworth Village, many of them children, living in awful, dirty and overcrowded conditions, with a lack of clothing, bathing, and attention to their most basic needs. The facilities were incredibly understaffed, and there was little or no actual schooling, training, or even simple activities to keep residents occupied.

Rivera saw the overcrowding and neglect as a direct result of inadequate funding and the ignorant attitudes in wider society. The potential of individual patients was far from being realized. This confronting report helped lead to far-reaching reform of disability services throughout the United States.

Letchworth was closed in 1996, leaving the buildings to decay. Many who worked at the Village refuse to speak of their experiences. Old methods of segregating patients and the disabled were changed to including them in society and bringing a normalization to them. Patients were moved to more up-to-date facilities in the county.

Numbered grave markers of people who died while patients at Letchworth Village in Thiells, New York from 1914 through 1967. There also is a large memorial stone at the entrance of the cemetery, erected in 2007, with a plaque bearing the names of those buried there.[Applebome, Peter (13 December 2007). “Giving Names to Souls Forgotten No Longer”. The New York Times.] The names are not keyed to the numbered graves. They also built a new cemetery nearby but did not move the bodies. Interesting. Maybe there are no bodies. Given their record of bodysnatching, and covering up misdeeds, spanning all of recorded history, I find it odd. Or, if there are bodies, maybe they are afraid to dig them up?

Albert Sabin‘s early work with attenuated-live-virus polio vaccine was developed from attenuated polio virus that Sabin had received from Koprowski.

In addition to his work on the polio vaccine, Koprowski (along with Stanley Plotkin and Tadeusz Wiktor) did significant work on an improved vaccine against rabies. The group developed the HDCV rabies vaccine in the 1960s at the Wistar Institute. It was licensed for use in the United States in 1980.

Koprowski was president of Biotechnology Foundation Laboratories, Inc, and head of the Center for Neurovirology at Thomas Jefferson University. In 2006 he was awarded a record 50th grant from the National Institutes of Health. He served as a consultant to the World Health Organization and the Pan American Health Organization.

British journalist Edward Hooper publicized a hypothesis that Koprowski’s research into a polio vaccine in the Belgian Congo in the late 1950s might have caused AIDS. The OPV AIDS hypothesis has, however, been rejected within much of the medical community and is contradicted by at least one article in the journal Nature, which claims the HIV-1 group M virus originated in Africa 30 years before the OPV trials were conducted. The journal Science refuted Hooper’s claims, writing: “[I]t can be stated with almost complete certainty that the large polio vaccine trial… was not the origin of AIDS.” Is it me or is this the worst debunking ever? Most of the medical community will do whatever their masters tell them to do so that is absolutely meaningless. So they are left with one article explaining why this scientific wonder was stomping around the Congo but definitely not bringing back plague and pestilence nobody ever heard of before but which was definitely documented in that area decades earlier? Documented by whom? And how exactly did they do that? Weren’t they still figuring out where hemorrhoids came from back then? What in hell is going on here? Fortunately, I don’t have time to dive into that pile of crazy right now but I will guess the biggest problem with those particular conspiracy theories is that they aren’t nearly big enough.

Koprowski rejected the claim, based on his own analysis. In a separate court case, he won a regretful clarification, and a symbolic award of $1 in damages, in a defamation suit against Rolling Stone, which had published an article repeating similar false allegations. A concurrent defamation lawsuit that Koprowski brought against the Associated Press was settled several years later; the settlement’s terms were not publicly disclosed.

Koprowski’s original reports from 1960 to 1961 detailing part of his vaccination campaign in the Belgian Congo are available online from the World Health Organization.

  • LeBrun A, Cerf J, Gelfand HM, Courtois G, Plotkin SA, Koprowski H (1960) “Vaccination with the CHAT strain of type 1 attenuated poliomyelities virus in Leopoldville, Belgian Congo 1. Description of the city, its history of poliomyelitis, and the plan of the vaccination campaign”, Bull World Health Organ. 22:203-13 online Archived 2008-10-31 at the Wayback Machine
  • Plotkin SA, LeBrun A, Koprowski H (1960) “Vaccination with the CHAT strain of type 1 attenuated poliomyelitis virus in Leopoldville. Belgian Congo 2. Studies of the safety and efficacy of vaccination”, Bull World Health Organ 22:215-34 online Archived 2012-02-06 at the Wayback Machine
  • Plotkin SA, LeBrun A, Courtois G, Koprowski H (1961) “Vaccination with the CHAT strain of type 1 attenuated poliomyelitis virus in Leopoldville, Congo 3. Safety and efficacy during the first 21 months of study” Bull World Health Organ 24:785-92 online Archived 2012-02-06 at the Wayback Machine

Main article: Oral polio vaccine AIDS hypothesis

Koprowski received many honorary degrees, academic honors, and national decorations, including the Order of the Lion from the King of Belgium, the French Order of Merit for Research and Invention, a Fulbright Scholarship, and appointment as Alexander von Humboldt Professor at the Max Planck Institute for Biochemistry in Munich. In 1989 he received the San Marino Award for Medicine and the Nicolaus Copernicus Medal of the Polish Academy of Sciences in Warsaw.

Koprowski received numerous honors in Philadelphia, including the Philadelphia Cancer Research Award, the John Scott Award and, in May 1990, the most prestigious honor of his home city, the Philadelphia Award. He was a Fellow of the College of Physicians of Philadelphia, which in 1959 presented him with its Alvarenga Prize.

Koprowski was a member of the National Academy of Sciences, the American Academy of Arts and Sciences, the New York Academy of Sciences, and the Polish Institute of Arts and Sciences of America. He held foreign membership in the Yugoslav Academy of Sciences and Arts, the Polish Academy of Sciences, the Russian Academy of Medical Sciences, and the Finnish Society of Sciences and Letters.

  • Directory [of] PIASA Members, p. 25.

On June 3, 1983, Koprowski received an honorary doctorate from the Faculty of Medicine at Uppsala University, Sweden.

On 22 March 1995, Koprowski was made a Commander of Finland‘s Order of the Lion by Finland’s president. On 13 March 1997 he received the Legion d’Honneur from the French government. On 29 September 1998 he was presented by Poland’s president with the Grand Cross of Poland’s Order of Merit.

On 25 February 2000 Koprowski was honored with a reception at Philadelphia‘s Thomas Jefferson University celebrating the 50th anniversary of the first administration of his oral polio vaccine. At the reception, he received commendations from the United States Senate, the Pennsylvania Senate, and Pennsylvania Governor Tom Ridge.

On 13 September 2004, Koprowski was presented with the Pioneer in NeuroVirology Award by the International Society for NeuroVirology at the 6th International Symposium on NeuroVirology held in Sardinia. On 1 May 2007, Koprowski was awarded the Albert Sabin Gold Medal by the Sabin Vaccine Institute in Baltimore, Maryland.

In 2014 Drexel University established the Hilary Koprowski Prize in Neurovirology in honor of Dr. Koprowski’s contributions to the field of neurovirology. The prize is awarded annually in conjunction with the International Symposium on Molecular Medicine and Infectious Disease, which is sponsored by the Institute for Molecular Medicine and Infectious Disease (IMMID) within the Drexel University College of Medicine. During the Symposium, the prize recipient is asked to deliver an honorary lecture.

They sure do give a lot of awards and honors while everybody is sick and dying mostly on other side of the doors to their dementofests. Something is not at all right with all that. It probably goes without saying but I remain all but convinced there is not a thing these assholes are up to, then or now, worth a single life or even a hair on the head of the people.

See also

So that brings us to Cyanamide and a few other things.

Cyanamide is an organic compound with the formula CN2H2. This white solid is widely used in agriculture and the production of pharmaceuticals and other organic compounds. It is also used as an alcohol-deterrent drug. The molecule features a nitrile group attached to an amino group. Derivatives of this compound are also referred to as cyanamides, the most common being calcium cyanamide (CaCN2) which is also included in these notes.

Not to be confused with Cyanimide or Cyanogen

Cyanamide – Tautomers and self-condensations

Containing both a nucleophilic and electrophilic site within the same molecule, cyanamide undergoes various reactions with itself. Cyanamide exists as two tautomers, one with the connectivity N≡C–NH2 and the other with the formula HN=C=NH (“carbodiimide” tautomer). The N≡C–NH2 form dominates, but in a few reactions (e.g. silylation) the diimide form appears to be important.

Cyanamide dimerizes to give 2-cyanoguanidine (dicyandiamide). This dimerization is hindered or reversed by acids and is inhibited by low temperatures. The cyclic trimer is called melamine.

Melamine

Like cyanamide, it contains 67% nitrogen by mass, and its derivatives have 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 resins. Such resins are characteristically durable thermosetting plastic used in high pressure decorative laminates such as Formica, melamine dinnerware including cooking utensils, plates, plastic products, 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 parts per billion of free melamine that could migrate out of the plastic into acidic foods if held at 160 °F for two hours, such as if food was kept heated in contact with it in an oven.

Melamine was once illegally added to baby formula in China, in order to increase the apparent protein content. Ingestion of melamine may lead to reproductive damage, or bladder or kidney stones, 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, has set the maximum amount of melamine allowed in powdered infant formula to 1 mg/kg and the amount of the chemical allowed in other foods and animal feed to 2.5 mg/kg. While not legally binding, the levels allow countries to ban importation of products with excessive levels of melamine.

  • Scholl, Peter F.; Bergana, Marti Mamula; Yakes, Betsy Jean; Xie, Zhuohong; Zbylut, Steven; Downey, Gerard; Mossoba, Magdi; Jablonski, Joseph; Magaletta, Robert; Holroyd, Stephen E.; Buehler, Martin (July 19, 2017). “Effects of the Adulteration Technique on the Near-Infrared Detection of Melamine in Milk Powder”. Journal of Agricultural and Food Chemistry. 65 (28): 5799–5809. doi:10.1021/acs.jafc.7b02083. ISSN 0021-8561. PMID 28617599.

Etymology

The German word Melamin was coined by combining the words melam (a derivative of ammonium thiocyanate) and amine. Melamine is, therefore, unrelated etymologically to the root melas (μέλας, meaning ‘black’ in Greek), from which the words melanin, a pigment, and melatonin, a hormone, are formed.

  • “Melamine”. The American Heritage Dictionary of the English Language (Fourth ed.). 2000. Archived from the original on December 1, 2008. Retrieved September 28, 2008.
  • Bann, Bernard; Miller, Samuel A. (1958). “Melamines and derivatives of melamine”. Chemical Reviews. 58: 131–172. doi:10.1021/cr50019a004.

Uses

Plastics and building materials

Melamine dinnerware

In one large-scale application, melamine is combined with formaldehyde and other agents to produce melamine resins. Such resins are characteristically durable thermosetting plastic used in high-pressure decorative laminates such as Formica, melamine dinnerware, laminate flooring, and dry erase boards. Melamine cookware is not microwave-safe.

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 superplasticizer for making high-resistance concrete. Sulfonated melamine formaldehyde (SMF) is a polymer used as a 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). 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]

  • Hauck, R. D.; Stephenson, H. F. (1964). “Fertilizer Nitrogen Sources, Nitrification of Triazine Nitrogen”. Journal of Agricultural and Food Chemistry. 12 (2): 147–151. doi:10.1021/jf60132a014.

Fire-retardant additives

Melamine and its salts are used as fire-retardant additives in paints, plastics, and paper. A melamine fibre, 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.

Food additive

Melamine is sometimes illegally added to food products in order to increase the apparent protein content. Standard tests, such as the Kjeldahl and Dumas tests, estimate protein levels by measuring the nitrogen content, so they can be misled by the addition of nitrogen-rich compounds such as melamine. There are instruments available today which can differentiate melamine nitrogen from protein nitrogen.

Medicine

Melamine derivatives of arsenical drugs are potentially important in the treatment of African trypanosomiasis.

Non-protein nitrogen

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

  • Colby, Robert W. and Mesler, Robert J. Jr. (1958) “Ruminant feed compositions”. U.S. Patent 2,819,968.
  • Newton, G. L.; Utley, P. R. (1978). “Melamine as a Dietary Nitrogen Source for Ruminants”. Journal of Animal Science. 47 (6): 1338–1344. doi:10.2527/jas1978.4761338x.

Non-protein nitrogen (or NPN) is a term used in animal nutrition to refer collectively to components such as urea, biuret, and ammonia, which are not proteins but can be converted into proteins by microbes in the ruminant stomach. Due to their lower cost compared to plant and animal proteins, their inclusion in a diet can result in economic gain, but at too high levels cause a depression in growth and possible ammonia toxicity, as microbes convert NPN to ammonia first before using that to make protein.

NPN can also be used to artificially raise crude protein values, which are measured based on nitrogen content, as protein is about 16% nitrogen and the only major component of most food which contains nitrogen is protein. The source of NPN is typically a chemical feed additive, or sometimes chicken waste and cattle manure.

Nonruminants such as cats, dogs and pigs (and humans) cannot utilize NPN. NPN are given to ruminants in the form of pelleted urea, ammonium phosphate and/or biuret. Sometimes slightly polymerized special urea-formaldehyde resin or a mixture of urea and formaldehyde (both are also known as formaldehyde-treated urea) is used in place of urea, because the former provides a better control on the nitrogen release. This practice is carried out in China and other countries, such as Finland, India and France.

  • “Nonprotein Nitrogen Poisoning, Merck Veterinary Manual, 9th ed”. Merck Co. Retrieved 27 April 2007.
  • “Untreated and formaldehyde-treated urea as nitrogen sources for young growing bulls”, J. Setala, L. Syrjala-Qvist, P. Aspila, Journal of the Scientific Agricultural Society of Finland vol.54, p53-62, 1982
  • “Evaluation of slow release urea formaldehyde complexes (SRUFC’S) as partial substitutes of protein in crossbred calves”, V.K. Sharma, B.N. Gupta, Asian Journal of Dairy Research vol.4, p119-25, 1985
  • “Influence of Niacin Supplementation on In Vivo Digestibility and Ruminal Digestion in Dairy Cows” M. Doreau and J. F. Ottou, Journal of Dairy Science, vol.79 (12) 1996

Cyanuric acid has also been used as NPN. For example, Archer Daniels Midland manufactures an NPN supplement for cattle, which contains biuret, triuret, cyanuric acid and urea. FDA permits a certain amount of cyanuric acid to be present in some additives used in animal feed and also drinking water.

See also

Toxicity

The short-term lethal dose of melamine is on a par with common table salt, with an LD50 of more than 3 grams per kilogram of bodyweight. 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 kidneys to malfunction and lead to kidney stones, kidney failure, and death. Signs of melamine toxicity can include irritability, blood in the urine, little to no urine, symptoms of kidney infection, or high blood pressure.

The European Union set a standard for acceptable human consumption (tolerable daily intake or TDI) of melamine at 0.2 mg per kilogram of body mass (previously 0.5 mg/kg), Canada declared a limit of 0.35 mg/kg, and the US FDA’s limit was put at 0.063 mg/kg (previously 0.63 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 mg per kilogram of body mass.

Toxicity of melamine can be mediated by intestinal microbiota. In culture, Klebsiella terrigena, which rarely colonizes mammalian intestines, was shown to convert melamine to cyanuric acid directly. Rats colonized by K. terrigena showed greater melamine-induced kidney damage compared to those not colonized.

Acute toxicity

Melamine is reported to have an oral median lethal dose (LD50) of 3248 mg/kg based on rat data. It is also an irritant when inhaled or in contact with the skin or eyes. The reported dermal LD50 is >1000 mg/kg for rabbits. A study by Soviet researchers in the 1980s suggested that melamine cyanurate, commonly used as a fire retardant, could be more toxic than either melamine or cyanuric acid alone. 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.

  • “Flame Retardants Center: Melamine Compounds”. Specialchem4polymers.com. April 19, 2010. Archived from the original on September 22, 2008. Retrieved June 20, 2012.
  • Babayan, A. A. and Aleksandryan, A. V. (1985). “Токсичные характеристики цианурата меламина, меламина и циануровой кислоты” [Toxicological characteristics of melamine cyanurate, melamine and cyanuric acid]. Zhurnal Eksperimental’noi I Klinicheskoi Meditsiny. 25: 345–249.

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. A 2008 study produced similar experimental results in rats and characterized the melamine and cyanuric acid in contaminated pet food from the 2007 outbreak. 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.[29] 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.

Chronic toxicity

Ingestion of melamine may lead to reproductive damage, or bladder or kidney stones, which can lead to bladder cancer.

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.

  • Tusing, T.W. “Chronic Feeding – Dogs”, cited by “Summary of toxicity data – trichloromelamine” by California Environmental Protection Agency, last revised on February 4, 2002, URL Archived June 25, 2007, at the Wayback Machine Retrieved September 5, 2007

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.”

Metabolism

Melamine is a metabolite of cyromazine, a pesticide. It has been reported that cyromazine can also be converted to melamine in plants.

  • “Cyromazine” (PDF). European Medicines Agency. January 2001. Archived from the original (PDF) on October 10, 2008. Retrieved June 20, 2012.
  • Lim, Lori O.; Scherer, Susan J.; Shuler, Kenneth D.; Toth, John P. (1990). “Disposition of cyromazine in plants under environmental conditions”. Journal of Agricultural and Food Chemistry. 38 (3): 860–864. doi:10.1021/jf00093a057.
  • “Cyromazine” (PDF). Pesticide Residues in Food, 1992 Evaluations: Residues. Food & Agriculture Org. 1993. pp. 265–. ISBN 978-92-5-103341-8. Archived from the original (PDF) on October 21, 2012.

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.

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 mg/kg and the amount of the chemical allowed in other foods and animal feed to 2.5 mg/kg. While not legally binding, the levels allow countries to ban importation of products with excessive levels of melamine.

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:

6 (NH2)2CO → C3H6N6 + 6 NH3 + 3 CO2

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

(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:

6 HNCO + 3 NH3 → C3H6N6 + 3 CO2 + 3NH3

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. Major manufacturers and licensors such as Orascom Construction Industries, BASF, and Eurotecnica have developed some proprietary methods.

  • Kirk-Othmer (1978). Kirk-Othmer encyclopedia of chemical technology. Vol. 7 (3rd ed.). pp. 303–304. ISBN 9780471485162.

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, and melon). 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.

  • Lahalih, Shawqui M.; Absi-Halabi, M. (1989). “Recovery of solids from melamine waste effluents and their conversion to useful products”. Industrial & Engineering Chemistry Research. 28 (4): 500–504. doi:10.1021/ie00088a020.
  • “How a golden chemical became greeneer”, Nitrogen+Syngas, Issue 293, May–June 2008.

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 adulterations.

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.

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”. 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.

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 information: 2007 pet food recalls and 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. In March 2007, the US Food and Drug Administration reported finding white granular melamine in the pet food, in samples of white granular wheat gluten imported from a single source in China, Xuzhou Anying Biologic Technology as well as in crystalline form in the kidneys and in urine of affected animals. Further vegetable protein imported from China was later implicated.

In April 2007, The New York Times reported that the addition of “melamine scrap” into fish and livestock feed to give the false appearance of a higher level of protein was an “open secret” in many parts of mainland China, reporting that this melamine scrap was being produced by at least one plant processing coal into melamine. 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.” 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.

Another recall incident in 2007 involved melamine which had been purposely added as a binder to fish and livestock feed manufactured in the United States. This was traced to suppliers in Ohio and Colorado.

2008 Chinese outbreak

Further information: 2008 Chinese milk scandal

In September 2008, several companies, including Nestlé, were implicated in a scandal involving milk and infant formula which had been 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. 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. 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. Officials estimate that about 20% of the dairy companies tested in China sell products tainted with melamine. On January 22, 2009, three of those involved in the scandal (including one conditional sentence) were sentenced to death in a Chinese court.

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 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.

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.

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.

Urinary 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.

  • Sun, N.; Shen, Y.; Sun, Q.; Li, X. R.; Jia, L. Q.; Zhang, G. J.; Zhang, W. P.; Chen, Z.; Fan, J. F.; Jiang, Y. P.; Feng, D. C.; Zhang, R. F.; Zhu, X. Y.; Xiao, H. Z. (2009). “Diagnosis and treatment of melamine-associated urinary calculus complicated with acute renal failure in infants and young children”. Chinese Medical Journal. 122 (3): 245–51. PMID 19236798.

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 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.

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.” 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.

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. 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.

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. Similar recommendations have been issued by other authorities, like the Japanese Ministry of Health, Labor and Welfare, both based on liquid chromatography – mass spectrometry (LC/MS) detection after hydrophilic interaction liquid chromatography (HILIC) separation.

The existing methods for melamine determination using a triple quadrupole liquid chromatography – mass spectrometry (LC/MS) after 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.

Ultrasound-assisted extractive electrospray ionization mass spectrometry (EESI-MS) has been developed at ETH Zurich (Switzerland) by Zhu, Chingin et al., (2008) for a rapid detection of melamine in untreated food samples. Ultrasounds 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.

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.

  • Huang, Guangming; Ouyang, Zheng; Cooks, R. Graham (2009). “High-throughput trace melamine analysis in complex mixtures”. Chemical Communications (5): 556–8. doi:10.1039/b818059h. PMID 19283289.

The Melaminometer 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 ppm level (1 part per million) in food and beverage has been reported due to migration from melamine-containing resins. Small amounts of melamine have also been reported in foodstuff as a metabolite product of cyromazine, an insecticide used on animals and crops.

  • Ishiwata H, Inoue T, Yamazaki T, Yoshihira K (1987). “Liquid chromatographic determination of melamine in beverages”. Journal of the Association of Official Analytical Chemists. 70 (3): 457–460. doi:10.1093/jaoac/70.3.457. PMID 3610957.
  • Sancho, J.V.; Ibáñez, M.; Grimalt, S.; Pozo, Ó.J.; Hernández, F. (2005). “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. 530 (2): 237–243. doi:10.1016/j.aca.2004.09.038. INIST:16514561.

Cyromazine is a triazine insect growth regulator used as an insecticide. It is a cyclopropyl derivative of melamine. Cyromazine works by affecting the nervous system of the immature larval stages of certain insects. In veterinary medicine, cyromazine is used as an ectoparasiticide.[citation needed] 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.” 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.”

Pest control: Insecticides

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

Member states of the European Union are required under Commission Decision 2008/757/EC 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 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.

  • Baselt RC (2014). Disposition of toxic drugs and chemicals in man. Seal Beach, Ca.: Biomedical Publications. pp. 1213–1214. ISBN 978-0-9626523-9-4.

Melamine on metal surfaces

It is reported that melamine molecules adsorbed on gold or silver 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 and DFT methods.

See also

Cyanamide Production

Cyanamide is produced by hydrolysis of calcium cyanamide, which in turn is prepared from calcium carbide via the Frank-Caro process.

CaCN2 + H2O + CO2 → CaCO3 + H2NCN

The conversion is conducted on slurries.

  • Kurzer, Frederick; Lawson, Alexander (1954). “Methylisourea Hydrochloride”. Organic Syntheses. 34: 67. doi:10.15227/orgsyn.034.0067.

Reactions and uses

Cyanamide can be regarded as a functional single carbon fragment which can react as an electrophile or nucleophile. The main reaction exhibited by cyanamide involves additions of compounds containing an acidic proton. Water, hydrogen sulfide, and hydrogen selenide react with cyanamide to give urea, thiourea, and selenourea, respectively:

H2NCN + H2E → H2NC(E)NH2 (E = O, S, Se)

In this way, cyanamide behaves as a dehydration agent and thus can induce condensation reactions. Alcohols, thiols, and amines react analogously to give alkylisoureas, isothioureas, and guanidines. The anti-ulcer drug cimetidine is generated using such reactivity. Related reactions exploit the bifunctionality of cyanamide to give heterocycles, and this latter reactivity is the basis of several pharmaceutical syntheses such as the aminopyrimidine imatinib, and agrichemicals Amitrol and hexazinone. The hair-loss treatment minoxidil and the anthelmintics albendazole, flubendazole, and mebendazole feature 2-aminoimidazole substructures derived from cyanamide.

Cyanamide is also used in the synthesis of other pharmaceutical drugs including tirapazamine, etravirine, revaprazan, and dasantafil.

The cyanamide anion has the character of a pseudo chalcogen, cyanamide can therefore be regarded as analogue to water or hydrogen sulfide.

A convenient method for the preparation of secondary amines which are not contaminated with primary or tertiary amines is the reaction of cyanamide with alkyl halides to N,N-dialkylcyanamides which can easily be hydrolyzed to dialkylamines and then decarboxylated. Cyanamide adds itself in the presence of N-bromosuccinimide to olefinic double bonds. The addition product is converted by bases to N-Cyanaziridine, cyclized in the presence of acids to imidazolines, which can be further reacted to vicinal diamines by alkaline cleavage.

  • Jonczyk A, Ochal Z, Makosza M (1978). “Reactions of Organic Anions; LXXXV1. Catalytic Two-Phase Alkylation of Cyanamide”. Synthesis. 1978 (12): 882–883. doi:10.1055/s-1978-24922.
  • Ponsold K, Ihn W (1970). “Die Addition von cyanamid und Halogen an Olefine ein neues Verfahren zur Darstellung von vic.-Halogencyanaminen und Aziridinen”. Tetrahedron Lett. 11 (13): 1125–1128. doi:10.1016/S0040-4039(01)97925-0. PMID 5439242.
  • Kohn, Harold; Jung, Sang Hun (1983). “New stereoselective method for the preparation of vicinal diamines from olefins and cyanamide”. Journal of the American Chemical Society. 105 (12): 4106–4108. doi:10.1021/ja00350a068..

Cyanamide is also a versatile synthetic building block for heterocycles: it forms 2-aminobenzimidazole with 1,2-diaminobenzene and it forms with the readily available cyclic enamine 4-(1-cyclohexenyl)morpholine and with elemental sulfur a 2-aminothiazole in good yields.

  • Weiss, Stefan; Michaud, Horst; Prietzel, Horst; Krommer, Helmut (1973). “A New, Simple Synthesis of 2-Aminobenzimidazole”. Angewandte Chemie International Edition in English. 12 (10): 841. doi:10.1002/anie.197308411..
  • S. Hünig, E. Lücke, and W. Brenninger (1961). “1-Morpholino-1-Cyclohexene”. Organic Syntheses: 65. doi:10.15227/orgsyn.041.0065.
  • Gewald, K.; Spies, H.; Mayer, R. (1970). “Zur Reaktion von Enaminen mit Schwefel und Cyanamid” [On the Reaction of Enamines with Sulfur and Cyanamide]. Journal für Praktische Chemie. 312 (5): 776–779. doi:10.1002/prac.19703120507..

Sodium dicyanamide is available in good yield and high purity from cyanamid and cyanogen chloride, which is suitable as an intermediate for the synthesis of active pharmaceutical ingredients. A guanidino group is introduced by reaction of cyanamide with sarcosine In the industrial synthesis of creatine:

reaction equation
  • E. B. Vliet (1925). “Diallylcyanamide”. Organic Syntheses. 5: 45. doi:10.15227/orgsyn.005.0045.
  • Verfahren zur Herstellung von Natrium-Dicyanamid, veröffentlicht am 10. August 2000, Anmelder: SKW Trostberg AG.
  • “Sodium dicyanamide (Na-dicyanamide)”. lonza.com. Archived from the original on 2013-05-23. Retrieved 2019-07-01.
  • Deutsche Offenlegungsschrift DE-OS 10 2006 016 227 A1, Offenlegungsdatum: 11. Oktober 2007, Anmelder: Degussa GmbH.

This synthesis route mostly avoids problematic impurities like chloroacetic acid, iminodiacetic acid, or dihydrotriazine that occur in other routes. The physiological precursor guanidinoacetic is obtained analogously by reacting cyanamide with glycine.

Methods to stabilize cyanamidefmel make it available on an industrial scale. Due to the strong affinity towards self-condensation in alkaline media (see above) solutions of cyanamide are stabilized by the addition of 0.5 wt% of monosodium phosphate as buffer. Solid cyanamide is produced by careful evaporation of the solvent and subsequent addition of a hydrolysis-labile ester of formic acid. The ester absorbs traces of moisture (suppression of urea formation), neutralizes alkalinity (ammonia) and continually releases small amounts of formic acid.

  • Wehrstedt, Klaus-Dieter; Wildner, Werner; Güthner, Thomas; Holzrichter, Klaus; Mertschenk, Bernd; Ulrich, Armin (2009-10-30). “Safe transport of cyanamide”. Journal of Hazardous Materials. 170 (2–3): 829–835. doi:10.1016/j.jhazmat.2009.05.043. ISSN 0304-3894. PMID 19505756

Agricultural use

Cyanamide, under the trade name Dormex, is a common agricultural rest-breaking agent applied in spring to stimulate uniform opening of buds, early foliation and bloom. Cyanamide can effectively compensate for the moderate lack of chilling units accumulated in the previous autumn and save the harvest that would otherwise be lost. It is particularly effective for woody plants such as blueberries, grapes, apples, peaches and kiwifruit. Most recently the product was approved for use on almonds and pistachios in the USA. Overdosage, high concentration and error in timing of application can damage the buds (especially of peach trees). Growers may avoid damage by applying 30 days prior to bud break according to the label.

Dormancy and rest-breaking agents

In plant physiology, dormancy is a period of arrested plant growth. It is a survival strategy exhibited by many plant species, which enables them to survive in harsh conditions and climates where part of the year is unsuitable for growth, such as winter or dry seasons.

Many plant species that exhibit dormancy have a biological clock that tells them when to slow activity and to prepare soft tissues for a period of freezing temperatures or water shortage. On the other hand, dormancy can be triggered after a normal growing season by decreasing temperatures, shortened day length, and/or a reduction in rainfall.

Chemical treatment on dormant plants has been proven to be an effective method to break dormancy, particularly in woody plants such as grapes, berries, apples, peaches, and kiwis.

The names of the genes in up panels are shown in ovals, and in low panel are shown in the capsule shapes (see the text for further details). DMAPP: dimethylallyl pyrophosphate; iPRMP: isopentenyladenosine-5-monophosphate; tZRMP, trans-zeatin riboside 5′-monophosphate; cZRMP, cis-zeatin riboside 5′-monophosphate; iP, N6-(Δ2-isopentenyl)adenine; tZ: trans-zeatin; cZ: cis-zeatin; Ade: adenine; IPT, isopentenyltransferases; tRNA-IPT, tRNA-isopentenyltransferase; CYP735A, cytochrome P450 monooxygenase; LOG, LONELY GUY; GT, glycosyltransferase; CKX, cytokinin oxidase/dehydrogenase; ABCG, g subfamily ATP-binding cassette; PUP, purine permeases; ENT, equilibrative nucleoside transporters; HKs, histidine kinase; HPTs, histidine phosphotransfer proteins; ARR, response regulator, CRF, cytokinin response factor. Other abbreviations are as defined in the text Wu, W., Du, K., Kang, X. et al. The diverse roles of cytokinins in regulating leaf development. Hortic Res 8, 118 (2021). https://doi.org/10.1038/s41438-021-00558-3
Schematic representation of the mechanisms of blueberry bud break after HC treatment. Red/green indicates metabolites whose relative content increases/decreases after HC treatment compared with CK.
Schematic representation of the mechanisms of blueberry bud break after HC treatment. Red/green indicates metabolites whose relative content increases/decreases after HC treatment compared with CK. Wang, H.; Xia, X.; An, L. Metabolomics Analysis Reveals the Mechanism of Hydrogen Cyanamide in Promoting Flower Bud Break in Blueberry. Agronomy 2021, 11, 102. https://doi.org/10.3390/agronomy11010102

Specifically, hydrogen cyanamide stimulates cell division and growth in dormant plants, causing buds to break when the plant is on the edge of breaking dormancy.[citation needed] 

Slight injury of cells may play a role in the mechanism of action. The injury is thought to result in increased permeability of cellular membranes.[citation needed] 

The injury is associated with the inhibition of catalase, which in turn stimulates the pentose phosphate cycle. Hydrogen cyanamide interacts with the cytokinin metabolic cycle, which results in triggering a new growth cycle.[citation needed] 

Liang, D., Huang, X., Shen, Y. et al. Hydrogen cyanamide induces grape bud endodormancy release through carbohydrate metabolism and plant hormone signaling. BMC Genomics 20, 1034 (2019). https://doi.org/10.1186/s12864-019-6368-8

Catalase

A 50% aqueous solution of cyanamide is also used as a biocide (disinfectant) particularly in pig farming, because it effectively kills salmonella and shigella and fights flies in all stages of development.

Environmental aspects

Cyanamide degrades via hydrolysis to urea, an excellent fertilizer. Fungi, like Myrothecium verrucaria, accelerate this process utilizing the enzyme cyanamide hydratase.

  • Stransky H, Amberger A (1973). “Isolierung und eigenschaften einer Cyanamid-hydratase (E.C.-Gruppe 4. 2.1.) aus Myrothecium verrucaria Alb. u. Schw” [Isolation and properties of a cyanamide hydratase (EC 4.2.1) from Myrothecium verrucaria]. Z. Pflanzenphysiol. 70: 74–87. doi:10.1016/S0044-328X(73)80049-2.

Cyanamide functional group

Cyanamide is the name for a functional group with the formula NCNRR’ where R and R’ can be a variety of groups. These compounds are called cyanamides. One example is naphthylcyanamide, C10H7N(H)CN Some cyanamides are prepared by alkylation of calcium cyanamide. Others, such as the naphthyl derivative, are produced indirectly.

Cyanamide in space

Due to its high permanent dipole moment (i.e., 4.32 ± 0.08 D), cyanamide was detected in spectral emissions coming from the Sgr B2 molecular cloud (T < 100 K) through its microwave transitions as the first known interstellar molecule containing the NCN frame.

  • Tyler, J.K.; Sheridan, J.; Costain, C.C. (August 1972). “The microwave spectra of cyanamide”. Journal of Molecular Spectroscopy. 43 (2): 248–261. doi:10.1016/0022-2852(72)90021-5.
  • Turner, B. E.; Liszt, H. S.; Kaifu, N.; Kisliakov, A. G. (November 1975). “Microwave detection of interstellar cyanamide”. The Astrophysical Journal. 201: L149. Bibcode:1975ApJ…201L.149T. doi:10.1086/181963

Safety

It is used as an alcohol-deterrent drug in Canada, Europe, and Japan.

Cyanamide has a modest toxicity in humans. Workplace exposure to hydrogen cyanamide sprays or exposure in people living in the vicinity of spraying have been reported as causing respiratory irritation, contact dermatitis, headache, and gastrointestinal symptoms of nausea, vomiting, or diarrhea.

Calcium cyanamide

Calcium cyanamide, also known as Calcium carbondiamide, Calcium cyan-2°-amide or Calcium cyanonitride is the inorganic compound with the formula CaCN2. It is the calcium salt of the cyanamide (CN2−2) anion. This chemical is used as fertilizer and is commercially known as nitrolime. It was first synthesized in 1898 by Adolph Frank and Nikodem Caro (Frank–Caro process).

The Frank–Caro process, also called cyanamide process, is the nitrogen fixation reaction of calcium carbide with nitrogen gas in a reactor vessel at about 1,000 °C. The reaction is exothermic and self-sustaining once the reaction temperature is reached. Originally the reaction took place in large steel cylinders with an electrical resistance element providing initial heat to start the reaction. Modern production uses rotating ovens. The synthesis produces a solid mixture of calcium cyanamide (CaCN2), also known as nitrolime, and carbon.

CaC2 + N2 → CaCN2 + C

The Frank–Caro process was the first commercial process that was used worldwide to fix atmospheric nitrogen. The product was used as fertilizer and commercially known as Lime-Nitrogen. Nitrolim or Kalkstickstoff in German.[“Muscle Shoals Alabama” (PDF). Historic American Engineering Record. Archived from the original (PDF) on 2014-02-22. Retrieved 2014-02-18.] The method was developed by the German chemists Adolph Frank and Nikodem Caro between 1895 and 1899. In its first decades, the world market for inorganic fertilizer was dominated by factories utilizing the cyanamide process.

The first full-scale factories were established in 1905 in Piano d´Orta (Italy) and Westeregeln (Germany). From 1908 the Frank–Caro process was used at North Western Cyanamide Company at Odda, Norway. With an annual production capacity of 12,000 ton from 1909, the factory at Odda was by far the largest in the world. At this time, first phase factories were established in Briançon (France), Martigny (Switzerland), Bromberg (Prussia/Poland) and Knapsack (Germany). The cyanamide factory at Odda ceased operation in 2002. It is still intact and is a Norwegian candidate to the UNESCO World Heritage List.[“Rjukan/Notodden and Odda/Tyssedal Industrial Heritage Sites, Hydro Electrical Powered Heavy Industries with associated Urban Settlements (Company Towns) and Transportation System”. UNESCO. Retrieved 2010-06-29.]

See also

In the 1920s the more energy-efficient Haber process gradually took over. In 1945 the production of calcium cyanamide reached a peak of an estimated 1.5 million tons a year.[ “Discovery of the Commercial Processes for Making Calcium Carbide and Acetylene”. National Historic Chemical Landmarks. American Chemical Society. Archived from the original on February 23, 2013. Retrieved June 25, 2012.]

In their search for a new process for producing cyanides for cyanide leaching of gold, Frank and Caro discovered the ability of alkaline earth carbides to absorb atmospheric nitrogen at high temperatures.

  • Deutsches Reichspatent DRP 88363, “Verfahren zur Darstellung von Cyanverbindungen aus Carbiden”, Erfinder: A. Frank, N. Caro, erteilt am 31. März 1895.

Fritz Rothe, a colleague of Frank and Caro, succeeded in 1898 in overcoming problems with the use of calcium carbide and clarified that at around 1,100 °C not calcium cyanide but calcium cyanamide is formed in the reaction. In fact, the initial target product sodium cyanide can also be obtained from calcium cyanamide by melting it with sodium chloride in the presence of carbon:

CaCN2 + 2 NaCl + C → 2 NaCN + CaCl2

  • H.H. Franck, W. Burg, Zeitschrift für Elektrochemie und angewandte physikalische Chemie, 40(10), 686-692 (Oktober 1934).

Frank and Caro developed this reaction for a large-scale, continuous production process. The process was particularly challenging due to the equipment requirements required by the high temperatures during the initial igniter step. This process requires meticulous temperature control since the melting point of calcium cyanamide is only about 120°C lower than the boiling point of sodium chloride.

In 1901, Ferdinand Eduard Polzeniusz patented a process that converts calcium carbide to calcium cyanamide in the presence of 10% calcium chloride at 700 °C. The advantage of lowering the reaction temperature by about 400 °C, however, must be weighed against the high amount of calcium chloride required and the discontinuous process control. Nevertheless, both processes (the Rothe–Frank–Caro process and the Polzeniusz-Krauss process) played a role in the first half of the 20th century. In the record year 1945, a total of approx. 1.5 million tonnes were produced worldwide using both processes. Frank and Caro also noted the formation of ammonia from calcium cyanamide.

CaCN2 + 3 H2O → 2 NH3 + CaCO3

Albert Frank recognized the fundamental importance of this reaction as a breakthrough in the provision of ammonia from atmospheric nitrogen and in 1901 recommended calcium cyanamide as a nitrogen fertilizer. Between 1908 and 1919, five calcium cyanamide plants with a total capacity of 500,000 tonnes per year were set up in Germany, and one in Switzerland.

It was at the time the cheapest nitrogen fertilizer with additional efficacy against weeds and plant pests and had great advantages over conventional nitrogen fertilizers. However, the large-scale implementation of ammonia synthesis via the Haber process became a serious competitor to the very energy-intensive Frank Caro process. As urea (formed via the Haber–Bosch process) was significantly more nitrogen-rich (46% compared to ca. 20% nitrogen content) cheaper and faster acting, the role of calcium cyanamide was gradually reduced to a multifunctional nitrogen fertilizer in niche applications. Other reasons for its loss of popularity were its dirty-black color, dusty appearance and irritating properties, as well as its inhibition of an alcohol-degrading enzyme which causes temporary accumulation of acetaldehyde in the body leading to dizziness, nausea, and alcohol flush reaction when alcohol is consumed around the time of bodily exposure.

Production

Calcium cyanamide is prepared from calcium carbide. The carbide powder is heated at about 1000 °C in an electric furnace into which nitrogen is passed for several hours.

The product is cooled to ambient temperatures and any unreacted carbide is leached out cautiously with water.

CaC2 + N2 → CaCN2 + C (ΔHof = –69.0 kcal/mol at 25 °C)

It crystallizes in hexagonal crystal system with space group R3m and lattice constants a = 3.67 Å, c = 14.85 Å.

  • F. Brezina, J. Mollin, R. Pastorek, Z. Sindelar. Chemicke tabulky anorganickych sloucenin (Chemical tables of inorganic compounds). SNTL, 1986.
  • Vannerberg, N.G. “The crystal structure of calcium cyanamide” Acta Chemica Scandinavica (1-27,1973-42,1988) (1962) 16, p2263-p2266

Uses

The main use of calcium cyanamide is in agriculture as a fertilizer. In contact with water, it decomposes and liberates ammonia:

CaCN2 + 3 H2O → 2 NH3 + CaCO3

It was used to produce sodium cyanide by fusing with sodium carbonate:

CaCN2 + Na2CO3 + 2 C → 2 NaCN + CaO + 2 CO

Sodium cyanide is used in cyanide process in gold mining. It can also be used in the preparation of calcium cyanide and melamine.

Through hydrolysis in the presence of carbon dioxide, calcium cyanamide produces cyanamide:[clarification needed]

CaCN2 + H2O + CO2 → CaCO3 + H2NCN

The conversion is conducted in slurries. For this reason, most commercial calcium cyanamide is sold as an aqueous solution.

Thiourea can be produced by the reaction of hydrogen sulfide with calcium cyanamide in the presence of carbon dioxide.

Calcium cyanamide is also used as a wire-fed alloy in steelmaking to introduce nitrogen into the steel.

Safety

The substance can cause alcohol intolerance, before or after the consumption of alcohol.

American Cyanamid Company

American Cyanamid Company was a leading American conglomerate that became one of the nation’s top 100 manufacturing companies during the 1970s and 1980s, according to the Fortune 500 listings at the time.[citation needed] It started in fertilizer, but added many other lines of business. It merged with American Home Products in 1994. The combined company sold off most of its lines of business except pharmaceuticals, adopted the name of its remaining Wyeth division, and was bought by Pfizer in 2009, becoming defunct as a separate concern.

History

The company was founded by engineers Frank S. Washburn and Charles H. Baker in New York City in 1907, to capitalize on a German patent they had licensed for the manufacture of nitrogen products for fertilizer. The company’s name is derived from the chemical calcium cyanamide, the fertilizer they would manufacture. They soon set up headquarters in Nashville, investing a million dollars in several corporations underpinning the manufacturing operation to be set up in nearby Muscle Shoals, Alabama (sometimes called Mussel Shoals), 120 miles from Nashville, on the Tennessee River. These planned operations included an electric power generating company (Mussel Shoals Hydro-electric) a utility company to distribute the electricity that would power the chemical plant, and the Cyanamid manufacturing plant. Washburn was President and located in Nashville, while Baker was Vice President and remained in New York. Cynamide plants were also planned for Niagara Falls, Ontario and Georgia. By 1908 the company was incorporated in Maine. The Canadian plant was the first in operation in 1910, and was to be followed by the Alabama plant.

However, the development of United States manufacturing was suspended when they were denied the construction of a dam for the hydroelectric generation station. Instead, United States offices of the company imported product from its Canadian plant. The company abandoned its Nashville headquarters in 1915 and relocated them to New York City. At the same time, it was trying to raise political support, both grass-roots and via lobbying, to implement the Alabama power generation plan, and as it began to face competition for the American market.

In 1917, Cyanamid purchased the Ammo-Phosphate Corporation, which owned a fertilizer plant in Linden, New Jersey manufacturing ammonium phosphate.

During World War I, the company shifted its nitrogen production from fertilizer to explosives. With offers of free use of patents and processes, along with personnel and equipment, it enticed the United States government to approve and pay for its original plans for the Alabama plant, with some modifications, to help with the war effort. A separate company, the Air Nitrates Corporation, was set up for this government contract to build and operate the plant for the duration of the war, with Cyanamid earning some fees and to later inherit the plant for the fertilizer business. This raised concerns of cronyism, but the critics were outnumbered by local supporters in Congress. However, when the war ended, the first stage of the plant had only just begun limited production. A few months later, the Justice Department began an investigation into the contract and possible graft.

Washburn died October 9, 1922. At the time, the government still owned the Muscle Shoals plants. A year later, a number of interests were competing to buy or lease it, including Air Nitrates/American Cynamid, General Electric, and Henry Ford. However by 1926, the list of bidders was far different as the Senate debated the merits of Air Nitrates in a joint venture with Union Carbide, the local power companies (who were most interested in the generating station), and a New York financial consortium. In the end, after much lobbying and debate, none of the bids were accepted. The government elected to run the plants itself, balancing the regional power requirements against farming needs for inexpensive fertilizer.

The company grew to over 100,000 employees worldwide, and had over 200,000 shareholders by the mid-1970s. Its stock was traded on the New York Stock Exchange under the symbol ACY. It was repeatedly reorganized after the mid-1990s, merged with other firms, and saw brands and divisions sold or spun off. The bulk of the former company is now part of Pfizer, with smaller portions belonging to BASF, Procter & Gamble and other firms.

Product lines

Although originally a manufacturer of agricultural chemicals, the company broadened its product lines into many types of industrial chemicals and specialty chemicals. The company then diversified into synthetic fibers, pharmaceuticals, surgical products, plastics, and inorganic pigments before World War II; and later added, by acquisitions, cosmetic and toiletry products, perfumes, building products, home building, and several smaller product categories following World War II.

From 1931 to 1943 American Cyanamid produced the pesticide Zyklon B under license.

Zyklon B (German: [translated Cyclone B) was the trade name of a cyanide-based pesticide invented in Germany in the early 1920s. It consisted of hydrogen cyanide (prussic acid), as well as a cautionary eye irritant and one of several adsorbents such as diatomaceous earth. The product is notorious for its use by Nazi Germany during the Holocaust to murder approximately 1.1 million people in gas chambers installed at Auschwitz-Birkenau, Majdanek, and other extermination camps. [A total of around 6 million Jews were murdered during the Holocaust. Evans, Richard J. (2008). The Third Reich At War. New York: Penguin Books. ISBN 978-0-14-311671-4.]

Hydrogen cyanide, a poisonous gas that interferes with cellular respiration, was first used as a pesticide in California in the 1880s. Research at Degesch of Germany led to the development of Zyklon (later known as Zyklon A), a pesticide that released hydrogen cyanide upon exposure to water and heat. It was banned after World War I, when Germany used a similar product as a chemical weapon. Degussa purchased Degesch in 1922. Their team of chemists, which included Walter Heerdt [de] and Bruno Tesch, devised a method of packaging hydrogen cyanide in sealed canisters along with a cautionary eye irritant and one of several adsorbents such as diatomaceous earth. The new product was also named Zyklon, but it became known as Zyklon B to distinguish it from the earlier version. Uses included delousing clothing and fumigating ships, warehouses, and trains.

The Nazis started using Zyklon B in extermination camps in early 1942 to murder prisoners during the Holocaust. Tesch, as well as his deputy executive, Karl Weinbacher, were executed in 1946 for knowingly selling the product to the SS for use on humans. Hydrogen cyanide is now rarely used as a pesticide but still has industrial applications. Firms in several countries continue to produce Zyklon B under alternative brand names, including Detia-Degesch, the successor to Degesch, who renamed the product Cyanosil in 1974.

Hydrogen cyanide is a poisonous gas that interferes with cellular respiration. Cyanide prevents the cell from producing adenosine triphosphate (ATP) by binding to one of the proteins involved in the electron transport chain. This protein, cytochrome c oxidase, contains several subunits and has ligands containing iron groups. The cyanide component of Zyklon B can bind at one of these iron groups, heme a3, forming a more stabilized compound through metal-to-ligand pi bonding. As a result of the formation of this new iron–cyanide complex, the electrons that would situate themselves on the heme a3 group can no longer do so. Instead, these electrons destabilize the compound; thus, the heme group no longer accepts them. Consequently, electron transport is halted, and cells can no longer produce the energy needed to synthesize ATP.[Nelson, David L.; Cox, Michael M. (2000). Lehninger Principles of Biochemistry. New York: Worth Publishers. ISBN 1-57259-153-6.] Death occurs in a human being weighing 68 kilograms (150 lb) within two minutes of inhaling 70 mg of hydrogen cyanide.[“Environmental and Health Effects”. International Cyanide Management Institute. Archived from the original on 30 November 2012. Retrieved 10 February 2017.][Hayes, Peter (2004). From Cooperation to Complicity: Degussa in the Third Reich. Cambridge; New York; Melbourne: Cambridge University Press. ISBN 0-521-78227-9.]

Hydrogen cyanide, discovered in the late 18th century, was used in the 1880s for the fumigation of citrus trees in California. Its use spread to other countries for the fumigation of silos, goods wagons, ships, and mills. Its light weight and rapid dispersal meant its application had to take place under tents or in enclosed areas.[Hayes, Peter (2004). From Cooperation to Complicity: Degussa in the Third Reich. Cambridge; New York; Melbourne: Cambridge University Press. ISBN 0-521-78227-9.] Research by Fritz Haber of the Kaiser Wilhelm Institute for Physical Chemistry and Electrochemistry led to the founding in 1919 of Deutsche Gesellschaft für Schädlingsbekämpfung mbH (Degesch), a state-controlled consortium formed to investigate military use of the chemical. Chemists at Degesch added a cautionary eye irritant to a less volatile cyanide compound which reacted with water in the presence of heat to become hydrogen cyanide. The new product was marketed as the pesticide Zyklon (cyclone). As a similar formula had been used as a weapon by the Germans during World War I, Zyklon was soon banned.[Hayes, Peter (2004). From Cooperation to Complicity: Degussa in the Third Reich. Cambridge; New York; Melbourne: Cambridge University Press. ISBN 0-521-78227-9.]

Deutsche Gold- und Silber-Scheideanstalt (German Gold and Silver Refinery; Degussa) became sole owners of Degesch in 1922. There, beginning in 1922, Walter Heerdt [de], Bruno Tesch, and others worked on packaging hydrogen cyanide in sealed canisters along with a cautionary eye irritant and adsorbent stabilizers such as diatomaceous earth. [Cautionary eye irritants used included chloropicrin and cyanogen chloride. Christianson, Scott (2010). The Last Gasp: The Rise and Fall of the American Gas Chamber. Berkeley: University of California Press. ISBN 978-0-520-25562-3.]

The new product was also labelled as Zyklon, but it became known as Zyklon B to distinguish it from the earlier version.[Hayes, Peter (2004). From Cooperation to Complicity: Degussa in the Third Reich. Cambridge; New York; Melbourne: Cambridge University Press. ISBN 0-521-78227-9.] Heerdt was named the inventor of Zyklon B in the Degesch patent application (number DE 438818) dated 20 June 1922. The Deutsches Patent- und Markenamt awarded the patent on 27 December 1926.[DE patent 438818, Heerdt, Dr Walter, “Verfahren zur Schaedlingsbekaempfung”, issued 27 December 1926, assigned to Deutsche Gesellschaft für Schädlingsbekämpfung mbH.] Beginning in the 1920s, Zyklon B was used at U.S. Customs facilities along the Mexican border to fumigate the clothing of border crossers.[Cockburn, Alexander (21 June 2007). “Zyklon B on the US Border”. The Nation. Retrieved 14 July 2021.][Burnett, John (January 28, 2006). “The Bath Riots: Indignity Along the Mexican Border”. NPR. Retrieved May 6, 2017.]

Corporate structure and marketing

In 1930, Degussa ceded 42.5 percent ownership of Degesch to IG Farben and 15 percent to Th. Goldschmidt AG, in exchange for the right to market pesticide products of those two companies through Degesch. Degussa retained managerial control.[Hayes, Peter (2004). From Cooperation to Complicity: Degussa in the Third Reich. Cambridge; New York; Melbourne: Cambridge University Press. ISBN 0-521-78227-9.]

While Degesch owned the rights to the brand name Zyklon and the patent on the packaging system, the chemical formula was owned by Degussa. Schlempe GmbH, which was 52 percent owned by Degussa, owned the rights to a process to extract hydrogen cyanide from waste products of sugar beet processing. This process was performed under license by two companies, Dessauer Werke and Kaliwerke Kolin, who also combined the resulting hydrogen cyanide with stabilizer from IG Farben and a cautionary agent from Schering AG to form the final product, which was packaged using equipment, labels, and canisters provided by Degesch.[Hayes, Peter (2004). From Cooperation to Complicity: Degussa in the Third Reich. Cambridge; New York; Melbourne: Cambridge University Press. ISBN 0-521-78227-9.] The finished goods were sent to Degesch, who forwarded the product to two companies that acted as distributors: Heerdt-Linger GmbH (Heli) of Frankfurt and Tesch & Stabenow (Testa) of Hamburg. Their territory was split along the Elbe river, with Heli handling clients to the west and south, and Testa those to the east.[Christianson, Scott (2010). The Last Gasp: The Rise and Fall of the American Gas Chamber. Berkeley: University of California Press. ISBN 978-0-520-25562-3.] Degesch owned 51 percent of the shares of Heli, and until 1942 owned 55 percent of Testa.[Hayes, Peter (2004). From Cooperation to Complicity: Degussa in the Third Reich. Cambridge; New York; Melbourne: Cambridge University Press. ISBN 0-521-78227-9.]

Prior to World War II Degesch derived most of its Zyklon B profits from overseas sales, particularly in the United States, where it was produced under license by Roessler & Hasslacher prior to 1931 and by American Cyanamid from 1931 to 1943.[Christianson, Scott (2010). The Last Gasp: The Rise and Fall of the American Gas Chamber. Berkeley: University of California Press. ISBN 978-0-520-25562-3.] From 1929, the United States Public Health Service used Zyklon B to fumigate freight trains and clothes of Mexican immigrants entering the United States.[Christianson, Scott (2010). The Last Gasp: The Rise and Fall of the American Gas Chamber. Berkeley: University of California Press. ISBN 978-0-520-25562-3.] Uses in Germany included delousing clothing (often using a portable sealed chamber invented by Degesch in the 1930s) and fumigating ships, warehouses, and trains. By 1943, sales of Zyklon B accounted for 65 percent of Degesch’s sales revenue and 70 percent of its gross profits.[Hayes, Peter (2004). From Cooperation to Complicity: Degussa in the Third Reich. Cambridge; New York; Melbourne: Cambridge University Press. ISBN 0-521-78227-9.]

Use in the Holocaust

Empty Zyklon B canisters found by the Allies at Auschwitz-Birkenau in 1945

In early 1942, the Nazis began using Zyklon B as the preferred killing tool in extermination camps during the Holocaust.[Longerich, Peter (2010). Holocaust: The Nazi Persecution and Murder of the Jews. Oxford; New York: Oxford University Press. ISBN 978-0-19-280436-5.] They used it to murder roughly 1.1 million people in gas chambers at Auschwitz-Birkenau, Majdanek, and elsewhere.[Hayes, Peter (2004). From Cooperation to Complicity: Degussa in the Third Reich. Cambridge; New York; Melbourne: Cambridge University Press. ISBN 0-521-78227-9.][“Auschwitz: Inside the Nazi State. Auschwitz 1940-1945. The Killing Evolution”. PBS. Retrieved 18 December 2019.] Most of the victims were Jews, and by far the majority of murders using this method took place at Auschwitz.[25][Hayes, Peter (2004). From Cooperation to Complicity: Degussa in the Third Reich. Cambridge; New York; Melbourne: Cambridge University Press. ISBN 0-521-78227-9.][Soviet officials initially stated that over 4 million people were killed using Zyklon B at Auschwitz, but this figure was proven to be greatly exaggerated. Steinbacher, Sybille (2005) [2004]. Auschwitz: A History. Munich: Verlag C. H. Beck. ISBN 0-06-082581-2.] 

Distributor Heli supplied Zyklon B to Mauthausen, Dachau, and Buchenwald, and Testa supplied it to Auschwitz and Majdanek; camps also occasionally bought it directly from the manufacturers. Some 56 tonnes of the 729 tonnes sold in Germany in 1942–44 were sold to concentration camps, amounting to about 8 percent of domestic sales. Auschwitz received 23.8 tonnes, of which 6 tonnes were used for fumigation. The remainder was used in the gas chambers or lost to spoilage (the product had a stated shelf life of only three months). Testa conducted fumigations for the Wehrmacht and supplied them with Zyklon B. They also offered courses to the SS in the safe handling and use of the material for fumigation purposes. In April 1941, the German agriculture and interior ministries designated the SS as an authorized applier of the chemical, which meant they were able to use it without any further training or governmental oversight.[Hayes, Peter (2004). From Cooperation to Complicity: Degussa in the Third Reich. Cambridge; New York; Melbourne: Cambridge University Press. ISBN 0-521-78227-9.]

Rudolf Höss at his trial in Poland, 1947

Rudolf Höss, commandant of Auschwitz, said that the use of Zyklon-B to murder prisoners came about on the initiative of one of his subordinates, SS-Hauptsturmführer (captain) Karl Fritzsch, who had used it to murder some Russian POWs in late August 1941 in the basement of Block 11 in the main camp. They repeated the experiment on more Russian POWs in September, with Höss watching.[Browning, Christopher R. (2004). The Origins of the Final Solution : The Evolution of Nazi Jewish Policy, September 1939 – March 1942. Comprehensive History of the Holocaust. Lincoln: University of Nebraska Press. ISBN 0-8032-1327-1.] Block 11 proved unsuitable, as the basement was difficult to air out afterwards and the crematorium (Crematorium I, which operated until July 1942) was some distance away.[Pressac, Jean-Claude; Pelt, Robert-Jan van (1994). “The Machinery of Mass Murder at Auschwitz”. In Gutman, Yisrael; Berenbaum, Michael (eds.). Anatomy of the Auschwitz Death Camp. Bloomington, Indiana: Indiana University Press. pp. 183–245. ISBN 0-253-32684-2.] The site of the murders was moved to Crematorium I, where more than 700 victims could be murdered at once. By the middle of 1942, the operation was moved to Auschwitz II–Birkenau, a nearby satellite camp that had been under construction since October 1941.[Piper, Franciszek (1994). “Gas Chambers and Crematoria”. In Gutman, Yisrael; Berenbaum, Michael (eds.). Anatomy of the Auschwitz Death Camp. Bloomington, Indiana: Indiana University Press. pp. 157–182. ISBN 0-253-32684-2.]

The first gas chamber at Auschwitz II–Birkenau was the “red house” (called Bunker 1 by SS staff), a brick cottage converted to a gassing facility by tearing out the inside and bricking up the windows. It was operational by March 1942. A second brick cottage, called the “white house” or Bunker 2, was converted some weeks later.[Rees, Laurence (2005). Auschwitz: A New History. New York: Public Affairs. ISBN 1-58648-303-X.][Piper, Franciszek (1994). “Gas Chambers and Crematoria”. In Gutman, Yisrael; Berenbaum, Michael (eds.). Anatomy of the Auschwitz Death Camp. Bloomington, Indiana: Indiana University Press. pp. 157–182. ISBN 0-253-32684-2.] According to Höss, Bunker 1 held 800 victims and Bunker 2 held 1,200 victims.[Piper, Franciszek (1994). “Gas Chambers and Crematoria”. In Gutman, Yisrael; Berenbaum, Michael (eds.). Anatomy of the Auschwitz Death Camp. Bloomington, Indiana: Indiana University Press. pp. 157–182. ISBN 0-253-32684-2.] These structures were in use for mass-murder until early 1943.[Steinbacher, Sybille (2005) [2004]. Auschwitz: A History. Munich: Verlag C. H. Beck. ISBN 0-06-082581-2.] At that point, the Nazis decided to greatly increase the gassing capacity of Birkenau. Crematorium II was originally designed as a mortuary with morgues in the basement and ground-level incinerators; they converted it into a killing factory by installing gas-tight doors, vents for the Zyklon B to be dropped into the chamber, and ventilation equipment to remove the gas afterwards.[Steinbacher, Sybille (2005) [2004]. Auschwitz: A History. Munich: Verlag C. H. Beck. ISBN 0-06-082581-2.][The gas chamber also had to be heated, as the Zyklon B pellets would not vaporize into hydrogen cyanide unless the temperature was 27 °C (81 °F) or above. Pressac, Jean-Claude; Pelt, Robert-Jan van (1994). “The Machinery of Mass Murder at Auschwitz”. In Gutman, Yisrael; Berenbaum, Michael (eds.). Anatomy of the Auschwitz Death Camp. Bloomington, Indiana: Indiana University Press. pp. 183–245. ISBN 0-253-32684-2.] Crematorium III was built using the same design. Crematoria IV and V, designed from the beginning as gassing centers, were also constructed that spring. By June 1943, all four crematoria were operational. Most of the victims were murdered using these four structures.[Rees, Laurence (2005). Auschwitz: A New History. New York: Public Affairs. ISBN 1-58648-303-X.]

The Nazis began shipping large numbers of Jews from all over Europe to Auschwitz in the middle of 1942. Those who were not selected for work crews were immediately gassed.[Pressac, Jean-Claude; Pelt, Robert-Jan van (1994). “The Machinery of Mass Murder at Auschwitz”. In Gutman, Yisrael; Berenbaum, Michael (eds.). Anatomy of the Auschwitz Death Camp. Bloomington, Indiana: Indiana University Press. pp. 183–245. ISBN 0-253-32684-2.] Those selected to die generally comprised about three-quarters of the total and included almost all children, women with small children, all the elderly, and all those who appeared on brief and superficial inspection by an SS doctor not to be completely fit.[Levy, Alan (2006) [1993]. Nazi Hunter: The Wiesenthal File (Revised 2002 ed.). London: Constable & Robinson. ISBN 978-1-84119-607-7.] The victims were told that they were to undergo delousing and a shower. They were stripped of their belongings and herded into the gas chamber.[Piper, Franciszek (1994). “Gas Chambers and Crematoria”. In Gutman, Yisrael; Berenbaum, Michael (eds.). Anatomy of the Auschwitz Death Camp. Bloomington, Indiana: Indiana University Press. pp. 157–182. ISBN 0-253-32684-2.]

A special SS bureau known as the Hygienic Institute delivered the Zyklon B to the crematoria by ambulance. The actual delivery of the gas to the victims was always handled by the SS, on the order of the supervising SS doctor. After the doors were shut, SS men dropped Zyklon B pellets through vents in the roof or holes in the side of the chamber. The victims were dead within 20 minutes. Johann Kremer, an SS doctor who oversaw gassings, testified that the “shouting and screaming of the victims could be heard through the opening and it was clear that they fought for their lives”.[Piper, Franciszek (1994). “Gas Chambers and Crematoria”. In Gutman, Yisrael; Berenbaum, Michael (eds.). Anatomy of the Auschwitz Death Camp. Bloomington, Indiana: Indiana University Press. pp. 157–182. ISBN 0-253-32684-2.]

Sonderkommandos (special work crews forced to work at the gas chambers) wearing gas masks then dragged the bodies from the chamber. The victims’ glasses, artificial limbs, jewelry, and hair were removed, and any dental work was extracted so the gold could be melted down. If the gas chamber was crowded, which they typically were, the corpses were found half-squatting, their skin discolored pink with red and green spots, with some foaming at the mouth or bleeding from their ears. The corpses were burned in the nearby incinerators, and the ashes were buried, thrown in the river, or used as fertilizer. With the Soviet Red Army approaching through Poland, the last mass gassing at Auschwitz took place on 30 October 1944.[Piper, Franciszek (1994). “Gas Chambers and Crematoria”. In Gutman, Yisrael; Berenbaum, Michael (eds.). Anatomy of the Auschwitz Death Camp. Bloomington, Indiana: Indiana University Press. pp. 157–182. ISBN 0-253-32684-2.] In November 1944, Reichsführer-SS Heinrich Himmler, head of the SS, ordered gassing operations to cease throughout the Reich.[Steinbacher, Sybille (2005) [2004]. Auschwitz: A History. Munich: Verlag C. H. Beck. ISBN 0-06-082581-2.]

Legacy

Interior of Majdanek gas chamber, showing Prussian blue residue

After World War II ended in 1945, Bruno Tesch and Karl Weinbacher of Tesch & Stabenow were tried in a British military court and executed for knowingly providing Zyklon B to the SS for use on humans.[Shirer, William L. (1960). The Rise and Fall of the Third Reich. New York: Simon & Schuster. ISBN 978-0-671-62420-0.] Gerhard Peters, who served as principal operating officer of Degesch and Heli and also held posts in the Nazi government, served two years and eight months in prison as an accessory before being released due to amendments to the penal code.[Hayes, Peter (2004). From Cooperation to Complicity: Degussa in the Third Reich. Cambridge; New York; Melbourne: Cambridge University Press. ISBN 0-521-78227-9.]

Use of hydrogen cyanide as a pesticide or cleaner has been banned or restricted in some countries.[United Nations Department of Economic and Social Affairs (2002). Consolidated List of Products Whose Consumption And/or Sale Have Been Banned, Withdrawn, Severely Restricted Or Not Approved by Governments: Chemicals. United Nations Publications. ISBN 978-92-1-130219-6.] Most hydrogen cyanide is used in industrial processes, made by companies in Germany, Japan, the Netherlands and the US.[Dzombak, David A.; Ghosh, Rajat S.; Wong-Chong, George M. (2005). Cyanide in Water and Soil: Chemistry, Risk, and Management. Boca Raton: CRC Press. ISBN 978-1-4200-3207-9.][United Nations Department of Economic and Social Affairs (2002). Consolidated List of Products Whose Consumption And/or Sale Have Been Banned, Withdrawn, Severely Restricted Or Not Approved by Governments: Chemicals. United Nations Publications. ISBN 978-92-1-130219-6.] Degesch resumed production of Zyklon B after the war. The product was sold as Cyanosil in Germany and Zyklon in other countries. It was still produced as of 2008.[“Bekanntmachung der geprüften und anerkannten Mittel und Verfahren zur Bekämpfung von tierischen Schädlingen nach §18 Infektionsschutzgesetz” [Notice of tested and approved means and procedures for combating animal pests according to §18, Infection Protection Act] (PDF). Bundesgesundheitsblatt: Bundesgesundheitsbl – Gesundheitsforsch – Gesundheitsschutz (in German). Bundesamtes für Verbraucherschutz und Lebensmittelsicherheit. 51. 20 June 2008. Archived from the original (PDF) on 23 February 2016. Retrieved 22 May 2018.] Degussa sold Degesch to Detia-Freyberg GmbH in 1986. The company is now called Detia-Degesch.[Hayes, Peter (2004). From Cooperation to Complicity: Degussa in the Third Reich. Cambridge; New York; Melbourne: Cambridge University Press. ISBN 0-521-78227-9.] Up until around 2015, a fumigation product similar to Zyklon B was in production by Lučební závody Draslovka of the Czech Republic, under the trade name Uragan D2. Uragan means “hurricane” or “cyclone” in Czech.[“Uragan D2” (in Czech). Lučební závody Draslovka a.s. Kolín. Archived from the original on 17 July 2015. Retrieved 7 July 2018.]

Cyanamid’s pharmaceutical division included “Lederle Laboratories”, maker of Piperacillin, an antibiotic drug used as a penicillin substitute; Centrum, a multivitamin supplement; Stresstabs vitamins; and Orimune, an oral polio vaccine.

Davis & Geck was the company’s medical device operation, organized under Lederle. Its Consumer Products division included “Shulton” products, primarily Old Spice cologne and after-shave lotion, Breck shampoo, and Pine-Sol household cleaner. A variety of fine fragrance products were made and sold by Shulton under license, including products under labels Nina Ricci, Pierre Cardin, Tabac, and others. “Melmac” was Cyanamid’s trademark for plastic kitchenware, although it was produced and marketed by other firms under license.

Legal issues

Cyanamid was involved in the tetracycline litigation.

The discovery of tetracycline engendered an enormous amount of litigation. In late 1958, the U.S. government charged Pfizer and American Cyanamid with price fixing in connection with tetracycline. [“Government: Dissent on the Wonder Drugs,” Aug. 11, 1958, [1] and Pub Policy: Pricing Fixing.] That and other related litigation lasted until 1982. Often, the series of cases is referred to as the “antibiotics litigation.”

The focal point of the case was the two companies’ settlement of an interference proceeding before the PTO (the U.S. Patent and Trademark Office) over the priority of their respective applications for tetracycline. Under the settlement, American Cyanamid, which had acquired Heyden Chemicals‘s pending tetracycline application, conceded the priority of Pfizer’s application, withdrew its own application and exchanged cross licenses with Pfizer. According to the indictment of American Cyanamid, Bristol Myers, Pfizer, and Cyanamid knew that tetracycline represented a threat to the continuation of their dominant positions and unreasonably high profits. To keep that threat in check, the indictment alleges, Cyanamid bought out Heyden’s rights to the development and agreed to help Pfizer get the tetracycline patent. In return, charges the Justice Department, Pfizer licensed Cyanamid to produce the drug. Later, to avoid a court fight that might have nullified the patent, Pfizer and Cyanamid let Bristol-Myers in. [“Public Policy: Antitrust and & Antibiotics, August 25, 1961. [2]]

The Federal Trade Commission found that the cross-license, combined with the fact that Pfizer had withheld information that it knew or should have known was relevant to the patentability of tetracycline, constituted an attempt by Pfizer and American Cyanamid to share in an unlawful monopoly. [Cacciapaglia and Rockman, “Proposed Drug Industry Antitrust Act–Patents, Pricing, and the Public “ 30 Geo. Wash. L. Rev. 875, 894 (1961-1962); Kennedy, “Patent and Antitrust Policy–Acquisition of Patents by Fraud or by Unfair or Deceptive Acts or Practices,” 35 George Washington Law Review 512, 531 (1966-1967) For an early discussion, see Costello, “The Tetracycline Conspiracy: Structure, Conduct and Performance in the Drug Industry,” Antitrust L. & Economic Rev. 12 (1967-1968)] Ultimately, the government lost. [State of North Carolina v. Chas Pfizer & Co Inc. 537 F. 2d 67 (4th Cir. 1976).]

The government also sought to cancel the Pfizer patent on tetracycline, alleging fraud and the concealment of information that would have been relevant to the patent examiner. The government lost the final appeal of that case in 1982. [U.S. v. Pfizer,, 676 F.2d 51 (1982).]

See also

In its last years, the company was involved in numerous legal issues related to its earlier environmental pollution. During the 1970s, tens of millions of dollars were spent on effluent treatment – such as a $15-million tertiary water treatment plant in Bound Brook, New Jersey, which returned to the Raritan River water that was cleaner than the river itself, due to the river having been directly polluted by American Cyanamid, which had pumped toxic, undiluted liquid waste into the river for decades prior. Tens of millions more were spent in efforts to clean up large wastewater pools which had decades of accumulation of toxic, carcinogenic, and teratogenic chemicals. These are considered by the U.S. Environmental Protection Agency (EPA) to be among the most toxic chemical waste sites in the U.S. Cyanamid merged with American Home Products in 1994, and AHP changed its name to Wyeth which was then purchased by Pfizer in 2009. Responsibility for the clean-up of these sites remained with the site owner during these corporate transitions. Remediation began at Bound Brook in 2007 and Pfizer took over the site in 2009.

The 575-acre Superfund site at Bound Brook-Bridgewater had a history of flooding. It was flooded in the 1930s and again in August 1971 during Hurricane Doria, at which time the plant sustained major damage to its facilities and equipment. In 2011, during Hurricane Irene the site once again flooded, but by this time all manufacturing had ended and all buildings had been torn down. However, impounds and wastesites remained with consequent leakage of benzene and numerous other chemicals into the Raritan River and adjacent land, apparently including residential sites. Subsequent testing showed no evident danger to humans, but the calamity intensified the extensive cleanup work already underway and the EPA announced another remediation plan for the site in September 2012.

In the United Kingdom, the company was involved in a well-known legal case, American Cyanamid Co. (No.1) v Ethicon Ltd. (1975), which set the test for awarding an interim injunction in England and Wales and set down what became known to lawyers as the American Cyanamid principles. The American Cyanamid principles are also applied under public procurement law when the high court determines whether to lift the automatic suspension of the power to award a public contract when an application has been made to the court to challenge the lawfulness of a proposed contract award.

Acquisition and breakup

The company merged with American Home Products (AHP) in 1994. At that time, the purchase price, $9.5 billion, made it the second-largest industrial acquisition in U.S. history to that point. American Home Products eventually changed its name to Wyeth Corporation (one of its subsidiaries), and in 2009 Wyeth merged with Pfizer, becoming a subsidiary of the world’s largest pharmaceutical company.

After the AHP acquisition, the Cyanamid conglomerate was disassembled over a period of years. The Pigments division was sold to National Lead Company. The Old Spice product line, and some others, were sold to Procter and Gamble. Formica Corporation was taken private in a management buyout, and later went through a series of ownership changes, and is owned by Fletcher Building, headquartered in New Zealand.

The $1.7 billion agricultural business was sold in 2000 to the German chemical giant BASF, raising BASF agricultural sales to $3.6 billion (1999 pro-forma), making it one of the top three agricultural companies in the world.

Most of the chemical businesses of American Cyanamid are operated by a spun-off successor company known as Cytec. Cytec was acquired by Solvay Group in December 2015 to form the Cytec Solvay Group based in Brussels, Belgium.

The American Cyanamid compound in Wayne, New Jersey later served as the headquarters of Toys “R” Us.

See also

General sources

References

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External links

Calcium compounds
Agents used in chemical warfare incapacitation riot control
IG Farben
Peroxisomal and lysosomal proteins
Oxidoreductases: peroxidases (EC 1.11)
Enzymes
Techniques in clinical microbiology

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