Propionic acid

Absorption

Some propionic acid is oxidized to lactic acid during absorption, but most passes to the liver, which removes nearly all of it from the portal blood . Propionic acid represents 20-25% of absorbed volatile fatty acids .
Propionic acid is rapidly absorbed through the gastrointestinal tract .

Toxicity

As a compound that is typically found naturally in the body, little to no adverse cumulative health effects have been associated with exposure to propionic acid . Medical reports of acute exposures of workers to propionic acid show mild to moderate skin burns, mild eye redness, and one case of a mild cough and asthmatic response .

Description

First described by Johann Gottlieb in 1844, propanoic acid has become one of the most widely used additives in processed foods for human consumption and animal feedstocks. Originally, Gottlieb found the compound among the degradation products of certain sugars. The term – propionic acid – itself has the unique distinction of once being the designation for all fatty acids due to the writings of Jean-Baptiste Dumas, who, in 1847, postulated that all fatty acids were in reality just one compound. While larger chain fatty acids are important components of all living things, propionic acid is the shortest fatty acid that exhibits the classic behaviors of similar compounds.

Chemical properties

Propionic acid, CH3CH2COOH, also known as propanoic acid and methylacetic acid, is a clear, colorless liquid that boils at 140°C (284 OF). It is flammable. It has a pungent odor and is soluble in water and alcohol. The Odor Threshold is 0.16 ppm. Propionic acid is an aliphatic monocarboxylic acid. Propionic acid is used in nickel electroplating solutions,perfumes, artificial flavors, pharmaceuticals, and manufacturing propionates.

Occurrence

Reported found in apple, apple juice, banana, currants, pineapple, raspberry, papaya, onion, sauerkraut, tomato, vinegar, beef, beef broth, beer, blackberry juice, bread, cheese, cherry juice, butter, yogurt, milk, cream, lean and fatty fish, cured pork, cooked beef and mutton, chicken fat, cognac, rum, whiskies, cider, sherry, roasted cocoa bean, cocoa powder, coffee, black currant juice, white currant juice, grape juice, grape musts and port wine, grapefruit juice, grape syrup, orange juice, Valencia orange oil, orange essence, roasted peanuts, pecans, potato chips, honey, soybean, Arctic bramble, coconut meat, cloudberry, mushroom, sesame seed, cardamom, rice, jackfruit, sake, buckwheat, laurel, peated malt, cassava, Bourbon vanilla, oyster, mussels, scallop, Chinese quince and maté.

The Uses of Propionic acid

Propionic Acid is the acid source of the propionates. propionic acid in the liquid form has a strong odor and is corrosive, so it is used as the sodium, calcium, and potassium salts as a preservative. these yield the free acid in the ph range of the food in which they are used. it functions principally against mold. see calcium propionate; sodium propionate.

The Uses of Propionic acid

Propionic acid is used in the productionof propionates used as mold inhibitors andpreservatives for grains and wood chips, inthe manufacture of fruit flavors and perfumebases, and as an esterifying agent.

Indications

Propanoic acid and various direct sodium or calcium salt formulations of the acid are currently most commonly approved and indicated by organizations like the FDA and EMA for use as an antibacterial food additive preservative in animal feed and food for human consumption .
Similarly, although the use of propanoic acid or any of its direct sodium or calcium salt formulations as excipient ingredients in pharmaceuticals is not necessarily a major role for the compound today, sodium propionate was used in some vaginal cream preparations indicated for cervicitis, cervical tears, and/or postcauterization, postcryosurgery, and postconization of the cervix . In such products, the sodium propionate was primarily used to elicit a preservative, bacteriostatic effect while other active ingredients combined in the formulation like urea, benzalkonium chloride, inositol, and methionine and cystine amino acids facilitated debridement, enhanced medication spread, epithelialization promotion, and wound healing, respectively .
Nevertheless, a great variety of propionic acid derivatives exist as separate pharmaceuticals, each with their own unique therapeutic categories, pharmacodynamics, and pharmacokinetics.

What are the applications of Application

Propionic acid solution is an eluent and buffer component in chromatography applications

Background

Sodium propionate is the sodium salt of propionic acid that exists as colorless, transparent crystals or a granular crystalline powder. It is considered generally recognized as safe (GRAS) food ingredient by FDA, where it acts as an antimicrobial agent for food preservation and flavoring agent. Its use as a food additive is also approved in Europe. Sodium propionate is is prepared by neutralizing propionic acid with sodium hydroxide. Sodium propionate was previously approved in Canada as an active ingredient in Amino-Cerv (used to treat inflammation or injury of the cervix).

Definition

ChEBI: Propionic acid is a short-chain saturated fatty acid comprising ethane attached to the carbon of a carboxy group. It has a role as an antifungal drug. It is a short-chain fatty acid and a saturated fatty acid. It is a conjugate acid of a propionate.

Production Methods

Propionic acid can be obtained from wood pulp waste liquor by fermentation. It can also be prepared from ethylene, carbon monoxide and steam; from ethanol and carbon monoxide using boron trifluoride catalyst; from natural gas; or as a by-product in the pyrolysis of wood. Very pure propionic acid can be obtained from propionitrile. Propionic acid can be found in dairy products in small amounts.

Biotechnological Production

Generally, propionic acid is produced via petrochemical routes. However, fermentative processes are interesting for food-grade production, although the price of biotechnologically produced propionic acid may be twice that of petrochemistry- based propionic acid. The microbial production of propionic acid is done with propionibacteria (e.g. Propionibacterim freudenreichii) . Several fermentation methods have been studied. For example, an extractive fermentation is suggested to avoid low productivity and yields caused by product inhibition . With this technique, a product concentration of 75 g.L-1 propionic acid, a yield of 0.66 g propionic acid per gram lactose, and a productivity of approximately 1 g.L-1.h-1 are reached .
Different substrates, such as glycerol , wheat flour , or mixtures of glycerol and glucose , have been analyzed to reduce costs. Also, techniques of cell immobilization show promising results . Fibrous-bed reactor systems show the highest product concentrations: up to 106 g.L-1 propionic acid and a yield of 0.56 g propionic acid per gram glycerol. In recent years, metabolic engineering has been used to improve the acid tolerance and to reduce byproduct formation . 104 H. Quitmann et al.
For example, the acetate kinase gene has been inactivated by mutation of Propionibacterium acidipropionici . Additionally, an adaptive evolution has been carried out. As result, the productivity was enhanced by approximately 50 %, up to 0.25 g.L-1.h-1 and a yield of 0.59 g propionic acid per gram glycerol, using immobilized cells adapted to high acid concentration.

Taste threshold values

Taste characteristics at 60 ppm: acidic, dairy with a pronounced fruity lift.

General Description

Propionic acid is a clear oily aqueous liquid with a pungent rancid odor. Burns skin and the vapors irritate mucous membranes. Corrosive to most metals and tissue. Density 8.3 lb / gal.

Air & Water Reactions

Dilution with water causes release of heat.

Reactivity Profile

Propionic acid reacts as an acid to neutralize bases in exothermic reactions. Burns when exposed to heat, flame or oxidizers. When heated to decomposition emits acrid smoke and irritating fumes [Lewis, 3rd ed., 1993, p. 1090].

Hazard

Moderate fire risk. Strong eye, skin and upper respiratory tract irritant.

Health Hazard

Propionic acid is a toxic and corrosive liquid. Contact with the eyes can result ineye injury. Skin contact may cause burns.Acute exposures to its vapors can causeeye redness, mild to moderate skin burns,and mild coughing (ACGIH 1986). Ingestionof high amounts of this acid may producecorrosion of the mouth and gastrointestinaltract in humans. Other symptoms includevomiting, diarrhea, ulceration, and convulsions. Oral LD50 value in rats is about3500–4300 mg/kg. The LD50 value by skinabsorption in rabbits is 500 mg/kg..

Fire Hazard

Flammable/combustible material. May be ignited by heat, sparks or flames. Vapors may form explosive mixtures with air. Vapors may travel to source of ignition and flash back. Most vapors are heavier than air. They will spread along ground and collect in low or confined areas (sewers, basements, tanks). Vapor explosion hazard indoors, outdoors or in sewers. Runoff to sewer may create fire or explosion hazard. Containers may explode when heated. Many liquids are lighter than water.

Flammability and Explosibility

Flammable

Pharmaceutical Applications

Propionic acid is primarily used as an antioxidant and antimicrobial preservative in foods, and in oral and topical pharmaceutical applications. It is also used as an esterifying agent.

Pharmacokinetics

As a naturally occurring carboxylic acid, propionic acid typically undergoes metabolism via conversion to propionyl coenzyme A (propionyl-CoA), which is part of the usual metabolic pathway that carboxylic acids participate within in the human body . Most of propionic acid's antibacterial and preservative activities subsequently stem from this metabolic pathway as the metabolic fate of propionates varies in different microorganisms, resulting in antimicrobial mechanisms of action that may revolve around differing propionate metabolites causing competition, inhibition, and/or interference effects along other metabolic pathways in the various microorganisms affected .
In the human body, however, propionic acid is generally metabolized with little ill effect and ultimately becomes a chemical intermediate in the citric acid cycle .

Clinical Use

Propionic acid is an antifungal agent that is nonirritatingand nontoxic. After application, it is present in perspiration in low concentration ( 0.01%). Salt forms with sodium,potassium, calcium, and ammonium are also fungicidal.Propionic acid is a clear, corrosive liquid with a characteristicodor. It is soluble in water and alcohol. Thesalts are usually used because they are nonvolatile andodorless.

Safety Profile

Poison by intraperitoneal route. Moderately toxic by ingestion, skin contact, and intravenous routes. A corrosive irritant to eyes, skin, and mucous membranes. Flammable liquid. Highly flammable when exposed to heat, flame, or oxidizers. To fight fire, use alcohol foam. When heated to decomposition it emits acrid smoke and irritating fumes.

Safety

Propionic acid is generally regarded as a nontoxic and nonirritant material when used in low levels as an excipient. Up to 1% may be used in food applications (up to 0.3% in flour and cheese products). Propionic acid is readily metabolized.
The pure form of propionic acid is corrosive and will cause burns to any area of contact. Both liquid and vapor forms are flammable. Concentrated propionic acid is harmful if swallowed, inhaled or absorbed through the skin. See also Sodium Propionate.
(mouse, IV): 0.63 g/kg
(rabbit, skin): 0.5 g/kg
(rat, oral): 2.6 g/kg

Synthesis

Commercial processes produce propionic acid by chemical synthesis and in small quantities by bacterial fermentation. Industrially Propionic acid is produced by hydrocarboxylation of ethylene in presence nickel carbonyl as a catalyst.

Potential Exposure

Propionic acid is used in the manufac- ture of inorganic propionates and propionate esters which are used as mold inhibitors, electroplating additives; emul- sifying agents; flavors and perfumes. It is an intermediate in pesticide manufacture, pharmaceutic manufacture; and in the production of cellulose propionate plastics. Also used as grain preservative.

Carcinogenicity

Rats fed high levels of propionic acid (4%) in a powdered diet developed forestomach neoplasia, which was believed to have arisen from sustained high levels of cellular proliferation. When administered at 4% in the diet as a pellet rather than as a powder, cellular hyperplasia and the associated severe inflammatory response were absent. In another study whereWistar ratswere fed 75%bread containing5%of the salt, sodiumpropionate rather than the acid for 1 year, no histopathology of the forestomach was reported. This suggests that the form of chemical (salt versus free acid), as well as the type of diet, is also an important factor in eliciting this effect. Harrison notes that a variety of chemicals, chemical and mechanical irritants, parasites, and dietary deficiencies cause forestomach tumors in rats. The predictive value of this finding in humans is, therefore, problematic because humans have no forestomach and food transit times are much faster. Interestingly, propionic acid inhibited the growth of the human adenocarcinoma cell line HT29 derived from similar epithelial tissue of human colon cancer patients, whereas other short-chain fatty acids, such as acetate, enhance transformation.

Environmental Fate

The widespread use of propionic acid has led to its detection in waste streams and groundwater. It is a degradation product of longer chain fatty acids, and has been detected in waste streams following olive oil production and other processes. Additionally, propionic acid has been qualitatively detected as a volatile component of cooked potatoes and meats as well as in other foods and beverages, including dairy products. Propionic acid is a major component of the gas phase of the smoke of unfiltered cigarettes, with quantities estimated at 100–300 mg per cigarette.
In a direct fashion, propionic acid is released to the environment through effluents from the manufacture, use, and disposal of coal-derived and shale oil liquid fuels as well as through wood-preserving chemical waste byproducts. Textile mills and sewage treatment facilities may also be sources of propionic acid-containing waste. Landfills and hazardous waste sites can leach propionic acid to groundwater supplies.
Propionic acid can exist as a vapor in the ambient atmosphere with a vapor pressure of 3.53 mmHg at 25 °C, and can be degraded in the atmosphere by reaction with photochemically produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 11 days. Photolysis of propionic acid is not expected to be important, and wet deposition of propionic acid is expected to occur readily as an atmospheric removal process.
Biodegradation is likely to be the most important removal mechanism of propionic acid from both soil and water. In terrestrial environments, propionic acid will exist as a ratio of the free acid and its conjugate base due to its pKa of 4.87. With an estimated HenryK’s law constant of 4.15 ×10^-7 atmm3 mol^-1, it is not expected to volatilize from soil. Its mobility in soil is expected to be high, with an estimated Koc of 36. The high water solubility of propionic acid and its existence as a charged species result in low absorption by particulate and organic matter in aquatic environments.

Metabolism

Propionic acid is first converted to propionyl coenzyme A (propionyl-CoA), however, it directly enter either beta oxidation or the citric acid cycles . As propionic acid has three carbons, propionyl-CoA . In the majority of vertebrates, propionyl-CoA is carboxylated to D-methylmalonyl-CoA, which is then isomerised to L-methylmalonyl-CoA . A vitamin B12-dependent enzyme catalyzes rearrangement of L-methylmalonyl-CoA to succinyl-CoA, which can then be used as a substrate in the citric acid cycle .

storage

Although stable, propionic acid is flammable. It should be stored in an airtight container away from heat and flames.

Shipping

UN1848 Propionic acid, Hazard class: 8; Labels: 8-Corrosive material. UN3463 Propionic acid, with not ＜90% acid by mass, Hazard Class 8; Labels: 8-Corrosive material, 3-Flammable liquid.

Purification Methods

Dry the acid with Na2SO4 or by fractional distillation, then redistil after refluxing with a few crystals of KMnO4. An alternative purification uses conversion to the ethyl ester, fractional distillation and hydrolysis. [Bradbury J Am Chem Soc 74 2709 1952.] Propionic acid can also be heated for 0.5hour with an amount of benzoic anhydride equivalent to the amount of water present (in the presence of CrO3 as catalyst), followed by fractional distillation. [Cham & Israel J Chem Soc 196 1960, Beilstein 2 IV 695.]

Toxicity evaluation

The behavior of propionic acid is largely pH dependent, and it can alter the local pH in areas where it is applied or ingested. It can behave as a moderately strong acid when concentrated, and can be corrosive under such conditions. There has been some evidence that propionic acid inhibits CO2 production from palmitate in fibroblast cells and ureagenesis in rat liver slices. This is perhaps related to fatty degeneration of the liver and hyperammonemia in propionic and methylmalonic acidemia – an autosomal disorder that results from a defect of propionyl coenzyme A carboxylase. In the latter case, symptoms can include vomiting, lethargy, hypotonia, and metabolic ketoacidosis.

Incompatibilities

Propionic acid is a medium strong acid. Incompatible with sulfuric acid, strong bases; ammonia, isocyanates, alkylene oxides; epichlorohydrin. Reacts with bases; strong oxidizers; and amines, causing fire and explo- sion hazard. Attacks many metals forming flammable/ explosive hydrogen gas. It can be salted out of aqueous solutions by the addition of calcium chloride or other salts.

Waste Disposal

Incineration in admixture with flammable solvent.

Regulatory Status

GRAS listed. Accepted for use in Europe as a food additive. In Japan, propionic acid is restricted to use as a flavoring agent.