Triacetin

Description

Triacetin (C8H14O6), also known as 1,2,3-propanetriol triacetate or glyceryl triacetate, is the triester of glycerin and acetic acid. Triacetin can be prepared by heating glycerin with acetic anhydride alone or in finely divided potassium hydrogen sulfate. It can also be prepared by the reaction of oxygen with a liquid-phase mixture of allyl acetate and acetic acid using a bromide salt as a catalyst.

Chemical properties

Triacetin is a colourless, viscous liquid with a slightly fatty odour. It has a very faint, fruity odour. It has a mild, sweet taste that is bitter above 0.05%. Slightly soluble in water; very soluble in alcohol, ether, and other organic solvents. Combustible.

Originator

Enzactin,Ayerst,US,1957

Occurrence

Reported found in papaya.

The Uses of Triacetin

Triacetin is a colourless, oily liquid with a slightly fatty odour and bitter taste. It is soluble in water and is miscible with alcohol and ether. It functions in foods as a humectant and solvent. Triacetin, a component of cigarette filters, induced a contact dermatitis in a worker at a cigarette manufacturers. It could be used as a fixative in perfumery, solvent in the manufacture of celluloid, and photographic films. Technical triacetin (a mixture of mono-, di-, and small quantities of triacetin) is used as a solvent for basic dyes, particularly indulines and tannin in dyeing.

Definition

ChEBI: A triglyceride obtained by acetylation of the three hydroxy groups of glycerol. It has fungistatic properties (based on release of acetic acid) and has been used in the topical treatment of minor dermatophyte infections.

Production Methods

Triacetin is prepared by the esterification of glycerin with acetic anhydride.

Preparation

By direct reaction of glycerol with acetic acid in the presence of Twitchell’s reagent, or in benzene solution of glycerol and boiling acetic acid in the presence of a cationic resin (Zeo-Karb H) pretreated with dilute H2SO4.

Manufacturing Process

200 grams of allyl acetate, 450 grams of glacial acetic acid and 3.71 grams of cobaltous bromide were charged to the reactor and the mixture was heated to 100°C. Pure oxygen was then introduced into the reactor below the surface of the liquid reaction mixture at the rate of 0.5 standard cubic feet per hour. Initially, all of the oxygen was consumed, but after a period of time oxygen introduced into the mixture passed through unchanged. During the course of the reaction, a small quantity of gaseous hydrogen bromide (a total of 1.9 grams) was introduced into the reaction zone, along with the oxygen. The reaction was allowed to continue for 6 hours following which the reaction mixture was distilled. Essentially complete conversion of the allyl acetate took place. A yield of 116 grams of glycerol triacetate was obtained, this being accomplished by distilling the glycerol triacetate overhead from the reaction mixture, at an absolute pressure of approximately 13 mm of mercury.

Therapeutic Function

Topical antifungal

Taste threshold values

Sweet and creamy with an oily mouthfeel.

General Description

Triacetin is a triester of glycerin and acetic acid that occurs naturally in papaya. It is mainly used as a synthetic flavoring agent in ice-creams, nonalcoholic beverages and baked goods.

Pharmaceutical Applications

Triacetin is mainly used as a hydrophilic plasticizer in both aqueous and solvent-based polymeric coating of capsules, tablets, beads, and granules; typical concentrations used are 10–35% w/w.
Triacetin is used in cosmetics, perfumery, and foods as a solvent and as a fixative in the formulation of perfumes and flavors.

Contact allergens

Triacetin is a component of cigarette filters, which induced a contact dermatitis in a worker at a cigarette manufactory.

Clinical Use

Glyceryl triacetate (Enzactin, Fungacetin) is a colorless, oilyliquid with a slight odor and a bitter taste. The compound issoluble in water and miscible with alcohol and most organicsolvents.
The activity of triacetin is a result of the acetic acid releasedby hydrolysis of the compound by esterases presentin the skin. Acid release is a self-limiting process becausethe esterases are inhibited below pH 4.

Safety Profile

Poison by ingestion. Moderately toxic by intraperitoneal, subcutaneous, and intravenous routes. An eye irritant. Combustible when exposed to heat, flame, or powerful oxidizers. To fight fire, use alcohol foam, water, CO2, dry chemical. When heated to decomposition it emits acrid smoke and irritating fumes.

Safety

Triacetin is used in oral pharmaceutical formulations and is generally regarded as a relatively nontoxic and nonirritant material at the levels employed as an excipient.
LD50 (dog, IV): 1.5 g/kg
LD50 (mouse, IP): 1.4 g/kg
LD50 (mouse, IV): 1.6 g/kg
LD50 (mouse, oral): 1.1 g/kg
LD50 (mouse, SC): 2.3 g/kg
LD50 (rabbit, IV): 0.75 g/kg
LD50 (rat, IP): 2.1 g/kg
LD50 (rat, oral): 3 g/kg
LD50 (rat, SC): 2.8 g/kg

in vitro

Litton Bionetics, Inc. (1976) evaluated the mutagenic potential of Triacetin in a plate test using Salmonella typhimurium strains TA1535, TA1537, and TA1538 with and without metabolic activation. Test concentrations were 0.0013%, 0.00065%, and 0.000325% and the solvent was dimethyl sulfoxide (DMSO). A negative control (solvent) and appropriate positive controls were used and gave expected results. Triacetin was not mutagenic with or without metabolic activation.
Unichema Chemie B.V. (1994) reported that Triacetin was not mutagenic at 50 to 5000 μg/plate in an Ames test using S. typhimurium strains TA1535, TA1537, TA98, and TA100 with and without metabolic activation.

in vivo

The mutagenic potential of Triacetin was determined using adult Drosophila melanogaster (Efremova 1962). A dose of 0.2 to 0.3 mg Triacetin had a spontaneous mutation rate of approximately one mutation per 750 chromosomes.

Side Effects

Triacetin was not toxic to animals in acute oral or dermal exposures, nor was it toxic in short-term inhalation or parenteral studies, as well as subchronic feeding and inhalation studies. Triacetin was, at most, slightly irritating to guinea pig skin. However, in one study, it caused erythema, slight edema, alopecia, and desquamation, and did cause some irritation in rabbit eyes. Triacetin was not sensitizing in guinea pigs.

storage

Triacetin is stable and should be stored in a well-closed, nonmetallic container, in a cool, dry place.

Incompatibilities

Triacetin is incompatible with metals and may react with oxidizing agents. Triacetin may destroy rayon fabric.

Regulatory Status

GRAS listed. Accepted in Europe as a food additive in certain applications. Included in the FDA Inactive Ingredients Database (oral capsules and tablets and gels). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.