Thursday 17 July 2014

Urea / REF / 441 / 2014


Urea or carbamide is an organic compound with the chemical formula CO(NH2). The molecule has two —NH2 groups joined by a carbonyl (C=O) functional group.

Urea serves an important role in the metabolism of nitrogen-containing compounds by animals and is the main nitrogen-containing substance in the urine of mammals. It is a colorless, odorless solid, highly soluble in water and practically non-toxic (LD50 is 15 g/kg for rat). Dissolved in water, it is neither acidic nor alkaline. The body uses it in many processes, the most notable one being nitrogen excretion. Urea is widely used in fertilizers as a convenient source of nitrogen. Urea is also an important raw material for the chemical industry.

The discovery by Friedrich Wöhler in 1828 that urea can be produced from inorganic starting materials was an important conceptual milestone in chemistry, as it showed for the first time that a substance previously known only as a byproduct of life could be synthesized in the laboratory without any biological starting materials, contradicting the widely held doctrine of vitalism.
Related compounds

The terms urea is also used for a class of chemical compounds sharing the same functional group RR'N—CO—NRR', namely a carbonyl group attached to two organic amine residues. Examples include carbamide peroxide, allantoin, and hydantoin. Ureas are closely related to biurets and related in structure to amides, carbamates, carbodiimides, and thiocarbamides.
History

Urea was first discovered in urine in 1727 by the Dutch scientist Herman Boerhaave, though this discovery is often attributed to the French chemist Hilaire Rouelle.

In 1828, the German chemist Friedrich Wöhler obtained urea artificially by treating silver cyanate with ammonium chloride.

    AgNCO + NH4Cl → (NH2)2CO + AgCl

This was the first time an organic compound was artificially synthesized from inorganic starting materials, without the involvement of living organisms. The results of this experiment implicitly discredited vitalism — the theory that the chemicals of living organisms are fundamentally different from those of inanimate matter. This insight was important for the development of organic chemistry. His discovery prompted Wöhler to write triumphantly to Berzelius: "I must tell you that I can make urea without the use of kidneys, either man or dog. Ammonium cyanate is urea." For this discovery, Wöhler is considered by many[who?] the father of organic chemistry.
Physiology

Urea is synthesized in the body of many organisms as part of the urea cycle, either from the oxidation of amino acids or from ammonia. In this cycle, amino groups donated by ammonia and L-aspartate are converted to urea, while L-ornithine, citrulline, L-argininosuccinate, and L-arginine act as intermediates. Urea production occurs in the liver and is regulated by N-acetylglutamate. Urea is then dissolved into the blood (in the reference range of 2.5 to 6.7 mmol/liter) and further transported and excreted by the kidney as a component of urine. In addition, a small amount of urea is excreted (along with sodium chloride and water) in sweat.

Amino acids from ingested food that are not used for the synthesis of proteins and other biological substances are oxidized by the body, yielding urea and carbon dioxide, as an alternative source of energy.[8] The oxidation pathway starts with the removal of the amino group by a transaminase; the amino group is then fed into the urea cycle.

Ammonia (NH3) is another common byproduct of the metabolism of nitrogenous compounds. Ammonia is smaller, more volatile and more mobile than urea. If allowed to accumulate, ammonia would raise the pH in cells to toxic levels. Therefore many organisms convert ammonia to urea, even though this synthesis has a net energy cost. Being practically neutral and highly soluble in water, urea is a safe vehicle for the body to transport and excrete excess nitrogen.

In water, the amine groups undergo slow displacement by water molecules, producing ammonia, ammonium ion, and bicarbonate ion. For this reason, old, stale urine has a stronger odor than fresh urine.
In humans

The handling of urea by the kidneys is a vital part of mammalian metabolism. Besides its role as carrier of waste nitrogen, urea also plays a role in the countercurrent exchange system of the nephrons, that allows for re-absorption of water and critical ions from the excreted urine. Urea is reabsorbed in the inner medullary collecting ducts of the nephrons,[9] thus raising the osmolarity in the medullary interstitium surrounding the thin ascending limb of the loop of Henle, which in turn causes water to be reabsorbed. By action of the urea transporter 2, some of this reabsorbed urea will eventually flow back into the thin ascending limb of the tubule, through the collecting ducts, and into the excreted urine. This mechanism, which is controlled by the antidiuretic hormone, allows the body to create hyperosmotic urine, that has a higher concentration of dissolved substances than the blood plasma. This mechanism is important to prevent the loss of water, to maintain blood pressure, and to maintain a suitable concentration of sodium ions in the blood plasmas.

The equivalent nitrogen content (in gram) of urea (in mmol) can be estimated by the conversion factor 0.028 g/mmol. Furthermore, 1 gram of nitrogen is roughly equivalent to 6.25 grams of protein, and 1 gram of protein is roughly equivalent to 5 grams of muscle tissue. In situations such as muscle wasting, 1 mmol of excessive urea in the urine (as measured by urine volume in litres multiplied by urea concentration in mmol/l) roughly corresponds to a muscle loss of 0.67 gram.
In other species

In aquatic organisms the most common form of nitrogen waste is ammonia, whereas land-dwelling organisms convert the toxic ammonia to either urea or uric acid. Urea is found in the urine of mammals and amphibians, as well as some fish. Birds and saurian reptiles have a different form of nitrogen metabolism that requires less water, and leads to nitrogen excretion in the form of uric acid. It is noteworthy that tadpoles excrete ammonia but shift to urea production during metamorphosis. Despite the generalization above, the urea pathway has been documented not only in mammals and amphibians but in many other organisms as well, including birds, invertebrates, insects, plants, yeast, fungi, and even microorganisms.
Production

Urea is produced on an industrial scale: In 2012, worldwide production capacity was approximately 184 million tonnes.
Industrial methods

For use in industry, urea is produced from synthetic ammonia and carbon dioxide. As large quantities of carbon dioxide are produced during the ammonia manufacturing process as a byproduct from hydrocarbons (predominantly natural gas, less often petroleum derivatives), or occasionally from coal, urea production plants are almost always located adjacent to the site where the ammonia is manufactured. Although natural gas is both the most economical and the most widely available ammonia plant feedstock, plants using it do not produce quite as much carbon dioxide from the process as is needed to convert their entire ammonia output into urea. In recent years new technologies such as the KM-CDR process have been developed to recover supplementary carbon dioxide from the combustion exhaust gases produced in the fired reforming furnace of the ammonia synthesis gas plant, allowing operators of stand-alone nitrogen fertilizer complexes to avoid the need to handle and market ammonia as a separate product and also to reduce their 'greenhouse gas' emissions to the atmosphere.
Synthesis

The basic process, developed in 1922, is also called the Bosch–Meiser urea process after its discoverers. The various commercial urea processes are characterized by the conditions under which urea formation takes place and the way in which unconverted reactants are further processed. The process consists of two main equilibrium reactions, with incomplete conversion of the reactants. The first is carbamate formation: the fast exothermic reaction of liquid ammonia with gaseous carbon dioxide (CO2) at high temperature and pressure to form ammonium carbamate (H2N-COONH4):

    2NH3 + CO2 is in equilibrium with H2N-COONH4

The second is urea conversion: the slower endothermic decomposition of ammonium carbamate into urea and water:

    H2N-COONH4 is in equilibrium with (NH2)2CO + H2O

The overall conversion of NH3 and CO2 to urea is exothermic, the reaction heat from the first reaction driving the second. Like all chemical equilibria, these reactions behave according to Le Chatelier's principle, and the conditions that most favour carbamate formation have an unfavourable effect on the urea conversion equilibrium. The process conditions are, therefore, a compromise: the ill-effect on the first reaction of the high temperature (around 190̂̂°C) needed for the second is compensated for by conducting the process under high pressure (140–175 bar), which favours the first reaction. Although it is necessary to compress gaseous carbon dioxide to this pressure, the ammonia is available from the ammonia plant in liquid form, which can be pumped into the system much more economically. To allow the slow urea formation reaction time to reach equilibrium a large reaction space is needed, so the synthesis reactor in a large urea plant tends to be a massive pressure vessel.

Because the urea conversion is incomplete, the product has to be separated from unchanged ammonium carbamate. In early "straight-through" urea plants this was done by letting down the system pressure to atmospheric so as to allow the carbamate to decompose back to ammonia and carbon dioxide. Originally, because it was not economic to recompress the ammonia and carbon dioxide for recycle, the ammonia at least would be used for the manufacture of other products, for example ammonium nitrate or sulfate. (The carbon dioxide would be wasted, as likely as not.) Later process schemes were developed to allow recycling of the unused ammonia and carbon dioxide. This was accomplished by depressurizing the reaction solution in stages (first to 18–25 bar and then to 2–5 bar) and passing it at each stage through a steam-heated "carbamate decomposer", then recombining the resultant carbon dioxide and ammonia in a falling-film "carbamate condenser" and pumping the carbamate solution into the previous stage.
The stripping concept

There are two main disadvantages to the "total recycle" concept just outlined. The first is the complexity of the flow scheme and, consequently, the amount of process equipment needed; the second is the amount of water recycled in the carbamate solution, which has an adverse effect on the equilibrium in the urea conversion reaction and thus on the overall efficiency of the plant. The stripping concept, developed in the early 1960s by Stamicarbon in The Netherlands, addressed both problems. It also improved heat recovery and reuse in the process.

The position of the equilibrium in the carbamate formation/decomposition depends on the product of the partial pressures of the reactants. In the total recycle processes carbamate decomposition is promoted by reducing the overall pressure, which reduces the partial pressure of both ammonia and carbon dioxide. But it is possible to achieve a similar effect without lowering the overall pressure by suppressing the partial pressure of just one of the reactants. Instead of being fed directly to the reactor along with the ammonia, as in the total recycle process, in the stripping process the carbon dioxide gas is first routed through a stripper (a carbamate decomposer operating under the full system pressure which is configured to provide maximum gas-liquid contact), flushing out free ammonia and thus reducing its partial pressure over the liquid surface, and carrying it directly to a carbamate condenser (also operating at full system pressure), from which reconstituted ammonium carbamate liquor passes directly to the reactor. That allows the medium-pressure stage of the total recycle process to be omitted altogether.

The stripping concept proved to be such a major advance that competitors such as Snamprogetti – now Saipem – (Italy), the former Montedison (Italy), Toyo Engineering Corporation (Japan) and Urea Casale (Switzerland) all developed their own versions of it. Today effectively all new urea plants use the principle, and many total recycle urea plants have been converted to stripping processes. No radical alternative to it has been proposed; the main thrust of technological development today, in response to industry demands for ever larger individual plants, is directed at reconfiguring and reorientating major items in the plant to reduce their size and the overall height of the plant, as well as at meeting ever more challenging environmental performance targets.
Side reactions

It is fortunate that the urea conversion reaction is a slow one, because if it were not it would go into reverse in the stripper. As it is, the succeeding stages of the process must be designed to minimize residence times, at least until the temperature has been reduced to the point where the reversion reaction is very slow.

Two reactions produce impurities. Biuret is formed when two molecules of urea combine with the loss of a molecule of ammonia.

    2NH2CONH2 → H2NCONHCONH2 + NH3

Normally this reaction is suppressed in the synthesis reactor by maintaining an excess of ammonia, but after the stripper it will occur until the temperature is reduced. Biuret is undesirable in fertilizer urea because it is toxic to crop plants, although to what extent depends on the nature of the crop and the method of application of the urea.[18] (Biuret is actually welcome in urea when is used as a cattle feed supplement.)

Isocyanic acid results from the thermal decomposition of ammonium cyanate, with which urea is interchangeable:

    NH2CONH2 → NH4NCO → HNCO + NH3

This reaction is at its worst when the urea solution is heated at low pressure, which happens when the solution is concentrated for prilling or granulation (see below). The reaction products mostly volatilize into the overhead vapours and recombine when these are condensed to form urea again, which contaminates the process condensate.
Corrosion

Ammonium carbamate solutions are notoriously corrosive towards metallic materials of construction, even the more resistant forms of stainless steel, especially in the hottest parts of the plant such as the stripper. Traditionally corrosion has been minimized (although not eliminated) by continuously injecting a minor amount of oxygen (as air) into the plant to establish and maintain a passive oxide layer on exposed stainless steel surfaces. But because the carbon dioxide feed is recovered from ammonia synthesis gas it contains traces of hydrogen which can mingle with the passivation air to form an explosive mixture if allowed to accumulate in the plant. In the mid 1990s two duplex (ferritic-austenitic) stainless steels were introduced (DP28W, jointly developed by Toyo Engineering and Sumitomo Metals Industries  and Safurex, jointly developed by Stamicarbon and Sandvik Materials Technology (Sweden)  which have allowed the amount of passivation oxygen to be drastically reduced and can, in theory, operate without oxygen at all.

Saipem now uses either zirconium stripper tubes or bimetallic tubes comprising a titanium body (which is cheaper but less erosion-resistant) to which is metallurgically bonded an internal lining of zirconium. These tubes are fabricated by ATI Wah Chang (USA), a leading specialist in refractory and 'reactive' metals, using its Omegabond technique.
Finishing

Urea can be produced as prills, granules, pellets, crystals, and solutions.
Solid forms

For its main use as a fertilizer urea is mostly marketed in solid form, either as prills or granules. The advantage of prills is that, in general, they can be produced more cheaply than granules and that the technique was firmly established in industrial practice long before a satisfactory urea granulation process was commercialized. However, on account of the limited size of particles that can be produced with the desired degree of sphericity and their low crushing and impact strength, the performance of prills during bulk storage, handling and use is generally (although not always!) considered inferior to that of granules.

High-quality compound fertilizers containing nitrogen co-granulated with other components such as phosphates have been produced routinely since the beginnings of the modern fertilizer industry, but on account of the low melting point and hygroscopic nature of urea it took courage to apply the same kind of technology to granulate urea on its own. But at the end of the 1970s three companies began to develop fluidized-bed granulation. The first in the field was Nederlandse Stikstof Maatschappij, which later became part of Hydro Agri (now Yara International). Yara eventually sold this technology to Uhde GmbH, whose Uhde Fertilizer Technology (UFT) subsidiary now markets it. Around the same time Toyo Engineering Corporation developed its spouted-bed process, comprising a fluidized bed deliberately agitated to produce turbulent ebullation. Stamicarbon also undertook development work on its own fluidized-bed granulation system, using film sprays rather than atomizing sprays to introduce the urea melt, but shelved it until the 1990s, when there was for a time considerable doubt about the commercial future of the Hydro (UFT) process. As a result, the Stamicarbon technology is now commercialized and highly successful. More recently, Urea Casale has introduced a fluidized-bed granulation system with a difference: the urea is sprayed in laterally from the side walls of the granulator instead of from the bottom so that the bed organizes into two cylindrical masses contrarotating on parallel longitudinal axes. The raw product is stated to be so uniform that screens are unnecessary.

Surprisingly, perhaps, considering the product particles are anything but spherical, pastillation using a Rotoform steel-belt pastillator is beginning to gain ground as a urea particle-forming process as a result of development work by Stamicarbon in collaboration with Sandvik Process Systems (Germany). Single-machine capacity is limited to 175 t/d, but the machines are simple and need little maintenance, specific power consumption is much lower than for granulation, and the product is very uniform. The robustness of the product appears to make up for its very non-spherical shape.
UAN solutions

In admixture, the combined solubility of ammonium nitrate and urea is so much higher than that of either component alone that it is possible to obtain a stable solution (known as UAN) with a total nitrogen content (32%) approaching that of solid ammonium nitrate (33.5%), though not, of course, that of urea itself (46%). Given the ongoing safety and security concerns surrounding fertilizer-grade solid ammonium nitrate, UAN provides a considerably safer alternative without entirely sacrificing the agronomic properties that make ammonium nitrate more attractive than urea as a fertilizer in areas with short growing seasons. It is also more convenient to store and handle than a solid product and easier to apply accurately to the land by mechanical means.
Laboratory preparation

Ureas in the more general sense can be accessed in the laboratory by reaction of phosgene with primary or secondary amines, proceeding through an isocyanate intermediate. Non-symmetric ureas can be accessed by reaction of primary or secondary amines with an isocyanate.

Also, urea is produced when phosgene reacts with ammonia:

    COCl2 + 4 NH3 → (NH2)2CO + 2 NH4Cl

Historical process

Urea was first noticed by Hermann Boerhaave in the early 18th century from evaporates of urine. In 1773, Hilaire Rouelle obtained crystals containing urea from human urine by evaporating it and treating it with alcohol in successive filtrations.This method was aided by Carl Wilhelm Scheele's discovery that urine treated by concentrated nitric acid precipitated crystals. Antoine François, comte de Fourcroy and Louis Nicolas Vauquelin discovered in 1799 that the nitrated crystals were identical to Rouelle's substance and invented the term "urea." Berzelius made further improvements to its purification and finally William Prout, in 1817, succeeded in obtaining and determining the chemical composition of the pure substance. In the evolved procedure, urea was precipitated as urea nitrate by adding strong nitric acid to urine. To purify the resulting crystals, they were dissolved in boiling water with charcoal and filtered. After cooling, pure crystals of urea nitrate form. To reconstitute the urea from the nitrate, the crystals are dissolved in warm water, and barium carbonate added. The water is then evaporated and anhydrous alcohol added to extract the urea. This solution is drained off and allowed to evaporate resulting in pure urea.
Chemical properties
Molecular and crystal structure

The urea molecule is planar in the crystal structure, but the geometry around the nitrogens is pyramidal in the gas-phase minimum-energy structure. In solid urea, the oxygen center is engaged in two N-H-O hydrogen bonds. The resulting dense and energetically favourable hydrogen-bond network is probably established at the cost of efficient molecular packing: The structure is quite open, the ribbons forming tunnels with square cross-section. The carbon in urea is described as sp2 hybridized, the C-N bonds have significant double bond character, and the carbonyl oxygen is basic compared to, say, formaldehyde. Urea's high aqueous solubility reflects its ability to engage in extensive hydrogen bonding with water.

By virtue of its tendency to form a porous frameworks, urea has the ability to trap many organic compounds. In these so-called clathrates, the organic "guest" molecules are held in channels formed by interpenetrating helices composed of hydrogen-bonded urea molecules. This behaviour can be used to separate mixtures, e.g. in the production of aviation fuel and lubricating oils, and in the separation of hydrocarbons.

As the helices are interconnected, all helices in a crystal must have the same molecular handedness. This is determined when the crystal is nucleated and can thus be forced by seeding. The resulting crystals have been used to separate racemic mixtures.
Reactions

Urea reacts with alcohols to form urethanes. Urea reacts with malonic esters to make barbituric acids.
Uses
Agriculture

More than 90% of world industrial production of urea is destined for use as a nitrogen-release fertilizer. Urea has the highest nitrogen content of all solid nitrogenous fertilizers in common use. Therefore, it has the lowest transportation costs per unit of nitrogen nutrient. The standard crop-nutrient rating (NPK rating) of urea is 46-0-0.

Many soil bacteria possess the enzyme urease, which catalyzes the conversion of the urea to ammonia or ammonium ion and bicarbonate ion, thus urea fertilizers are very rapidly transformed to the ammonium form in soils. Among soil bacteria known to carry urease, some ammonia-oxidizing bacteria (AOB), such as species of Nitrosomonas, are also able to assimilate the carbon dioxide released by the reaction to make biomass via the Calvin Cycle, and harvest energy by oxidizing ammonia (the other product of urease) to nitrite, a process termed nitrification. Nitrite-oxidizing bacteria, especially Nitrobacter, oxidize nitrite to nitrate, which is extremely mobile in soils because of its negative charge and is a major cause of water pollution from agriculture. Ammonium and nitrate are readily absorbed by plants, and are the dominant sources of nitrogen for plant growth. Urea is also used in many multi-component solid fertilizer formulations. Urea is highly soluble in water and is, therefore, also very suitable for use in fertilizer solutions (in combination with ammonium nitrate: UAN), e.g., in 'foliar feed' fertilizers. For fertilizer use, granules are preferred over prills because of their narrower particle size distribution, which is an advantage for mechanical application.

The most common impurity of synthetic urea is biuret, which impairs plant growth.

Urea is usually spread at rates of between 40 and 300 kg/ha but rates vary. Smaller applications incur lower losses due to leaching. During summer, urea is often spread just before or during rain to minimize losses from volatilization (process wherein nitrogen is lost to the atmosphere as ammonia gas). Urea is not compatible with other fertilizers.

Because of the high nitrogen concentration in urea, it is very important to achieve an even spread. The application equipment must be correctly calibrated and properly used. Drilling must not occur on contact with or close to seed, due to the risk of germination damage. Urea dissolves in water for application as a spray or through irrigation systems.

In grain and cotton crops, urea is often applied at the time of the last cultivation before planting. In high rainfall areas and on sandy soils (where nitrogen can be lost through leaching) and where good in-season rainfall is expected, urea can be side- or top-dressed during the growing season. Top-dressing is also popular on pasture and forage crops. In cultivating sugarcane, urea is side-dressed after planting, and applied to each ratoon crop.

In irrigated crops, urea can be applied dry to the soil, or dissolved and applied through the irrigation water. Urea will dissolve in its own weight in water, but it becomes increasingly difficult to dissolve as the concentration increases. Dissolving urea in water is endothermic, causing the temperature of the solution to fall when urea dissolves.

As a practical guide, when preparing urea solutions for fertigation (injection into irrigation lines), dissolve no more than 3 g urea per 1 L water.

In foliar sprays, urea concentrations of 0.5% – 2.0% are often used in horticultural crops. Low-biuret grades of urea are often indicated.

Urea absorbs moisture from the atmosphere and therefore is typically stored either in closed/sealed bags on pallets or, if stored in bulk, under cover with a tarpaulin. As with most solid fertilizers, storage in a cool, dry, well-ventilated area is recommended.
Chemical industry

Urea is a raw material for the manufacture of two main classes of materials: urea-formaldehyde resins and urea-melamine-formaldehyde used in marine plywood.
Explosive

Urea can be used to make urea nitrate, a high explosive that is used industrially and as part of some improvised explosive devices. It is a stabilizer in nitrocellulose explosives.
Automobile systems

Urea is used in SNCR and SCR reactions to reduce the NOx pollutants in exhaust gases from combustion from Diesel, dual fuel, and lean-burn natural gas engines. The BlueTec system, for example, injects water-based urea solution into the exhaust system. The ammonia produced by the hydrolysis of the urea reacts with the nitrogen oxide emissions and is converted into nitrogen and water within the catalytic converter.
Niche

    A component of animal feed, providing a relatively cheap source of nitrogen to promote growth
    A non-corroding alternative to rock salt for road de-icing, and the hardening of ski-resort terrain park take-offs and landings
    A flavor-enhancing additive for cigarettes
    A main ingredient in hair removers such as Nair and Veet
    A browning agent in factory-produced pretzels
    An ingredient in some skin cream,[40] moisturizers, hair conditioners
    A reactant in some ready-to-use cold compresses for first-aid use, due to the endothermic reaction it creates when mixed with water
    A cloud seeding agent, along with other salts
    A flame-proofing agent, commonly used in dry chemical fire extinguisher charges such as the urea-potassium bicarbonate mixture
    An ingredient in many tooth whitening products
    An ingredient in dish soap
    Along with ammonium phosphate, as a yeast nutrient, for fermentation of sugars into ethanol
    A nutrient used by plankton in ocean nourishment experiments for geoengineering purposes
    As an additive to extend the working temperature and open time of hide glue
    As a solubility-enhancing and moisture-retaining additive to dye baths for textile dyeing or printing

Laboratory uses

Urea in concentrations up to 10 M is a powerful protein denaturant as it disrupts the noncovalent bonds in the proteins. This property can be exploited to increase the solubility of some proteins. A mixture of urea and choline chloride is used as a deep eutectic solvent, a type of ionic liquid.

Urea can in principle serve as a hydrogen source for subsequent power generation in fuel cells. Urea present in urine/wastewater can be used directly (though bacteria normally quickly degrade urea.) Producing hydrogen by electrolysis of urea solution occurs at a lower voltage (0.37V) and thus consumes less energy than the electrolysis of water (1.2V).

Urea in concentrations up to 8 M can be used to make fixed brain tissue transparent to visible light while still preserving fluorescent signals from labeled cells. This allows for much deeper imaging of neuronal processes then previously obtainable using conventional one photon or two photon confocal microscopes.
Medical use

Urea-containing creams are used as topical dermatological products to promote rehydration of the skin. Urea 40% is indicated for psoriasis, xerosis, onychomycosis, ichthyosis, eczema, keratosis, keratoderma, corns, and calluses. If covered by an occlusive dressing, 40% urea preparations may also be used for nonsurgical debridement of nails. Urea 40% "dissolves the intercellular matrix" of the nail plate. Only diseased or dystrophic nails are removed, as there is no effect on healthy portions of the nail.[citation needed] This drug is also used as an earwax removal aid.[citation needed]

Urea can also be used as a diuretic. It was first used as a diuretic by a Dr. W. Friedrich in 1892.  In a 2010 study of ICU patients in Belgium, urea was used as a diuretic to treat euvolemic hyponatremia and was found to be a safe, inexpensive and simple treatment.

Certain types of instant cold packs (or ice packs) contain water and separated urea crystals. Rupturing the internal water bag starts an endothermic reaction and allows the pack to be used to reduce swelling.[citation needed]

Like saline, urea injection is used to perform abortion.[citation needed]

Urea is the main component of an alternative medicinal treatment referred to as urine therapy.[citation needed]

The blood urea nitrogen (BUN) test is a measure of the amount of nitrogen in the blood that comes from urea. It is used as a marker of renal function, though it is inferior to other markers such as creatinine because blood urea levels are influenced by other factors such as diet and dehydration.

Urea labeled with carbon-14 or carbon-13 is used in the urea breath test, which is used to detect the presence of the bacteria Helicobacter pylori (H. pylori) in the stomach and duodenum of humans, associated with peptic ulcers. The test detects the characteristic enzyme urease, produced by H. pylori, by a reaction that produces ammonia from urea. This increases the pH (reduces acidity) of the stomach environment around the bacteria. Similar bacteria species to H. pylori can be identified by the same test in animals such as apes, dogs, and cats (including big cats).
Analysis

Urea is readily quantified by a number of different methods, such as the diacetyl monoxime colorimetric method, and the Berthelot reaction (after initial conversion of urea to ammonia via urease). These methods are amenable to high throughput instrumentation, such as automated flow injection analyzers[47] and 96-well micro-plate spectrophotometers.


Safety

Urea can be irritating to skin, eyes, and the respiratory tract. Repeated or prolonged contact with urea in fertilizer form on the skin may cause dermatitis.[citation needed]

High concentrations in the blood can be damaging. Ingestion of low concentrations of urea, such as are found in typical human urine, are not dangerous with additional water ingestion within a reasonable time-frame. Many animals (e.g., dogs) have a much more concentrated urine and it contains a higher urea amount than normal human urine; this can prove dangerous as a source of liquids for consumption in a life-threatening situation (such as in a desert).

Urea can cause algal blooms to produce toxins, and its presence in the runoff from fertilized land may play a role in the increase of toxic blooms.

The substance decomposes on heating above melting point, producing toxic gases, and reacts violently with strong oxidants, nitrites, inorganic chlorides, chlorites and perchlorates, causing fire and explosion.

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