Acetic Acid, Glacial

1 Nonproprietary Names

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

2 Synonyms
Acidum aceticum glaciale; E260; ethanoic acid; ethylic acid;
methane carboxylic acid; vinegar acid.

3 Chemical Name and CAS Registry Number
Ethanolic acid [64-19-7]

4 Empirical Formula and Molecular Weight
C2H4O2 60.05

Functional Category

Acidifying agent.

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

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 is 1188C

Dissociation constant pKa = 4.76
Flash point 398C (closed cup); 578C (open cup).
Melting point 178C
Refractive index n D
20 = 1.3718
Solubility Miscible with ethanol, ether, glycerin, water, and other fixed and volatile oils.
Specific gravity is 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 1470 mg/kg.

(4) The lowest lethal concentration on inhalation in humans is reported to be 816 ppm.Humans, are, however, estimated to consume approximately 1 g/day of acetic acid from the diet.

LD50 (mouse, IV): 0.525 g/kg(4)
LD50 (rabbit, skin): 1.06 g/kg
LD50 (rat, oral): 3.31 g/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.

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.

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.


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). The EINECS number for acetic acid is 200-580-7. The PubChem Compound ID (CID) for glacial acetic acid is 176.