Nonproprietary Names

USP:Glacial Acetic Acid JP: Glacial Acetic Acid
PhEur:Acetic Acid, Glacial
USP:Glacial Acetic Acid

Synonyms

Acidum aceticum glaciale; E260; ethanoic acid; ethylic acid; methane carboxylic acid; vinegar acid. See also Sections 17 and 18.

Chemical Name and CAS Registry Number

Ethanolic acid [64-19-7]

Empirical Formula and Molecular Weight

C2H4O2 60.05

Structural Formula

Functional Category

Acidifying agent. 7 Applications in Pharmaceutical Formulations or Technology Glacial and diluted acetic acid solutions are widely used as acidifying agents in a variety of pharmaceutical formulations and food preparations. Acetic acid is used in pharmaceutical products as a buffer system when combined with an acetate salt such as sodium acetate. Acetic acid is also claimed to have some antibacterial and antifungal properties.

Description

Glacial acetic acid occurs as a crystalline mass or a clear, colorless volatile solution with a pungent odor.

Pharmacopeial Specifications

See Table I. Table I: Pharmacopeial specifications for glacial acetic acid. Test JP XV PhEur 6.0 USP 32 Identification Characters Freezing point þ þ514.58C þ þ 514.88C þ — 515.68C Nonvolatile matter 41.0 mg 40.01% 41.0 mg Sulfate Chloride Heavy metals þ þ410 ppm þ þ 45 ppm þ þ 45 ppm Iron — 45 ppm — Readily oxidizable impurities þ599.0% 99.5–100.5þ % 99.5–100.5þ % Assay

Typical Properties

Acidity/alkalinity pH = 2.4 (1M aqueous solution); pH = 2.9 (0.1M aqueous solution); pH = 3.4 (0.01M aqueous solution). Boiling point 1188C Dissociation constant pKa = 4.76 Flash point 398C (closed cup); 578C (open cup). Melting point 178C Refractive index n 20D = 1.3718 Acetic Acid, Glacial Solubility Miscible with ethanol, ether, glycerin, water, and other fixed and volatile oils. Specific gravity 1.045

Stability and Storage Conditions

Acetic acid should be stored in an airtight container in a cool, dry place.

Incompatibilities

Acetic acid reacts with alkaline substances.

Method of Manufacture

Acetic acid is usually made by one of three routes: acetaldehyde oxidation, involving direct air or oxygen oxidation of liquid acetaldehyde in the presence of manganese acetate, cobalt acetate, or copper acetate; liquid-phase oxidation of butane or naphtha; methanol carbonylation using a variety of techniques.

Safety

Acetic acid is widely used in pharmaceutical applications primarily to adjust the pH of formulations and is thus generally regarded as relatively nontoxic and nonirritant. However, glacial acetic acid or solutions containing over 50% w/w acetic acid in water or organic solvents are considered corrosive and can cause damage to skin, eyes, nose, and mouth. If swallowed glacial acetic acid causes severe gastric irritation similar to that caused by hydrochloric acid.(1) Dilute acetic acid solutions containing up to 10% w/w of acetic acid have been used topically following jellyfish stings.(2) Dilute acetic acid solutions containing up to 5% w/w of acetic acid have also been applied topically to treat wounds and burns infected with Pseudomonas aeruginosa.(3) The lowest lethal oral dose of glacial acetic acid in humans is reported to be 1470mg/kg.(4) The lowest lethal concentration on inhalation in humans is reported to be 816ppm.(4) Humans, are, however, estimated to consume approximately 1g/day of acetic acid from the diet. LD50 (mouse, IV): 0.525g/kg(4) LD50 (rabbit, skin): 1.06g/kg LD50 (rat, oral): 3.31g/kg

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Acetic acid, particularly glacial acetic acid, can cause burns on contact with the skin, eyes, and mucous membranes. Splashes should be washed with copious quantities of water. Protective clothing, gloves, and eye protection are recommended.

Regulatory Status

GRAS listed. Accepted as a food additive in Europe. Included in the FDA Inactive Ingredients Database (injections, nasal, ophthalmic, and oral preparations). Included in parenteral and nonparenteral preparations licensed in the UK. 17 Related Substances Acetic acid; artificial vinegar; dilute acetic acid. Acetic acid Comments A diluted solution of glacial acetic acid containing 30–37% w/w of acetic acid. See Section 18. Artificial vinegar Comments A solution containing 4% w/w of acetic acid. Dilute acetic acid Comments A weak solution of acetic acid which may contain between 6–10% w/w of acetic acid. See Section 18.

Comments

In addition to glacial acetic acid, many pharmacopeias contain monographs for diluted acetic acid solutions of various strengths. For example, the USP32–NF27 has a monograph for acetic acid, which is defined as an acetic acid solution containing 36.0–37.0% w/w of acetic acid. Similarly, the BP 2009 contains separate monographs for glacial acetic acid, acetic acid (33%), and acetic acid (6%). Acetic acid (33%) BP 2009 contains 32.5–33.5% w/w of acetic acid. Acetic acid (6%) BP 2009 contains 5.7–6.3% w/w of acetic acid. The JP XV also contains a monograph for acetic acid that specifies that it contains 30.0–32.0% w/w of acetic acid. A specification for glacial acetic acid is contained in the Food Chemicals Codex (FCC).(5) The EINECS number for acetic acid is 200-580-7. The PubChem Compound ID (CID) for glacial acetic acid is 176. 19 Specific References 1 Sweetman SC, ed. Martindale: The Complete Drug Reference, 36th edn. London: Pharmaceutical Press, 2009; 2244–2245. 2 Fenner PJ, Williamson JA. Worldwide deaths and severe envenomation from jellyfish stings. Med J Aust 1996; 165: 658–661. 3 Milner SM. Acetic acid to treat Pseudomonas aeruginosa in superficial wounds and burns. Lancet 1992; 340: 61. 4 Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004; 15–16. 5 Food Chemicals Codex, 6th edn. Bethesda, MD: United States Pharmacopeia, 2008; 12.

General References

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Author

WG Chambliss.

Date of Revision

23 March 2009.