removers such as nair and veet a browning agent in factory-produced pretzels an ingredient in some skin cream, moisturizers, hair conditioners, and shampoos 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 diammonium 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 as an optical parametric oscillator in nonlinear optics physiology amino acids from ingested food that are used for the synthesis of proteins and other biological substances — or produced from catabolism of muscle protein — are oxidized by the body as an alternative source of energy, yielding urea and carbon dioxide. the oxidation pathway starts with the removal of the amino group by a transaminase; the amino group is then fed into the urea cycle. the first step in the conversion of amino acids from protein into metabolic waste in the liver is removal of the alpha-amino nitrogen, which results in ammonia. because ammonia is toxic, it is excreted immediately by fish, converted into uric acid by birds, and converted into urea by mammals. ammonia (nh3) is a 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. 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/l) 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. 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. humans the cycling of and excretion 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 reabsorption of water and critical ions from the excreted urine. urea is reabsorbed in the inner medullary collecting ducts of the nephrons, thus raising the osmolarity in the medullary interstitium surrounding the thin descending limb of the loop of henle, which makes the water reabsorb. by action of the urea transporter 2, some of this reabsorbed urea eventually flows back into the thin descending limb of the tubule, through the collecting ducts, and into the excreted urine. the body uses this mechanism, which is controlled by the antidiuretic hormone, to create hyperosmotic urine — i.e., urine with a higher concentration of dissolved substances than the blood plasma. this mechanism is important to prevent the loss of water, maintain blood pressure, and maintain a suitable concentration of sodium ions in the blood plasma. the equivalent nitrogen content (in grams) 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. 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. 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. adverse effects 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. 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. camels, rodents or dogs) have a much more concentrated urine which may contain a higher urea amount than normal human urine. 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. history urea was first discovered in urine in 1727 by the dutch scientist herman boerhaave, although this discovery is often attributed to the french chemist hilaire rouelle as well as william cruickshank. boerhaave used the following steps to isolate urea: boiled off water, resulting in a substance similar to fresh cream used filter paper to squeeze out remaining liquid waited a year for solid to form under an oily liquid removed the oily liquid dissolved the solid in water used recrystallization to tease out the urea in 1828, the german chemist friedrich wöhler obtained urea artificially by treating silver cyanate with ammonium chloride. agnco + cl → co(nh2)2 + 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 jöns jakob berzelius: "i must tell you that i can make urea without the use of kidneys, either man or dog. ammonium cyanate is urea." in fact, his second sentence was incorrect. ammonium cyanate +− and urea co(nh2)2 are two different chemicals with the same empirical formula con2h4, which are in chemical equilibrium heavily favoring urea under standard conditions. regardless, with his discovery, wöhler secured a place among the pioneers of organic chemistry. historical preparation urea was first noticed by herman 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 evaporated, leaving pure urea. laboratory preparation ureas in the more general sense can be accessed in the laboratory by reaction of phosgene with primary or secondary amines: cocl2 + 4 rnh2 → (rnh)2co + 2 +cl− these reactions proceed through an isocyanate intermediate. non-symmetric ureas can be accessed by the reaction of primary or secondary amines with an isocyanate. urea can also be produced by heating ammonium cyanate to 60 °c. +− → (nh2)2co industrial production in 2020, worldwide production capacity was approximately 180 million tonnes. 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 of burning hydrocarbons to generate heat (predominantly natural gas, and less often petroleum derivatives or coal), urea production plants are almost always located adjacent to the site where the ammonia is manufactured. synthesis urea plant using ammonium carbamate briquettes, fixed nitrogen research laboratory, ca. 1930 the basic process, patented in 1922, is called the bosch–meiser urea process after its discoverers carl bosch and wilhelm meiser. 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 (+−): 2 nh3 + co2 ⇌ +− (δh = −117 kj/mol at 110 atm and 160 °c) the second is urea conversion: the slower endothermic decomposition of ammonium carbamate into urea and water: +− ⇌ co(nh2)2 + h2o (δh = +15.5 kj/mol at 160–180 °c) the overall conversion of nh3 and co2 to urea is exothermic, with the reaction heat from the first reaction driving the second. the conditions that favor urea formation (high temperature) have an unfavorable effect on the carbamate formation equilibrium. the process conditions are a compromise: the ill-effect on the first reaction of the high temperature (around 190 °c) needed for the second is compensated for by conducting the process under high pressure (140–175 bar), which favors the first reaction. although it is necessary to compress gaseous carbon dioxide to this pressure, the ammonia is available from the ammonia production 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. reactant recycling because the urea conversion is incomplete, the urea must be separated from the unconverted reactants, including the ammonium carbamate. various commercial urea processes are characterized by the conditions under which urea forms and the way that unconverted reactants are further processed. conventional recycle processes in early "straight-through" urea plants, reactant recovery (the first step in "recycling") was done by letting down the system pressure to atmospheric to let the carbamate 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 such as ammonium nitrate or ammonium sulfate, and the carbon dioxide was usually wasted. later process schemes made recycling unused ammonia and carbon dioxide practical. this was accomplished by the "total recycle process", developed in the 1940's to 1960's and now called the "conventional recycle process". it proceeds 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 resulting carbon dioxide and ammonia in a falling-film carbamate condenser and pumping the carbamate solution back into the urea reaction vessel. stripping recycle process the "conventional recycle process" for recovering and reusing the reactants has largely been supplanted by a stripping process, developed in the early 1960s by stamicarbon in the netherlands, that operates at or near the full pressure of the reaction vessel. it reduces