Cresol

• JPCresol
• Ph. Eur.Cresol, Crude
• USP–NFCresol

cresylic acid; hydroxytoluene; methylphenol; tricresol; mixture of o-, m- and p-cresol

Methylphenol (mixture of isomers) · [1319-77-3]

C7H8O · 108.14

Antimicrobial preservative

Typical concentrations: 0.15–0.3% · Dosage forms: Sterile (parenteral/ophthalmic)

Used as an antimicrobial preservative in injections, typically at about 0.15–0.3% w/v; the single isomer m-cresol (metacresol) is the preservative in many insulin and peptide products. At much higher concentrations, mostly as saponated cresol solutions, it has been used as a disinfectant, but this use has largely been replaced by less toxic agents.

A colourless, yellowish, pale brownish-yellow or pinkish liquid with a strong phenolic, creosote-like odour. It darkens on ageing and on exposure to light and air. Crude cresol is a mixture of the three isomers obtained from coal tar or petroleum.

Distillation range

not less than 90% distils between 195 and 205 °C

Specific gravity

about 1.030–1.038

pKa

about 10.1 (m-cresol)

Solubility

soluble about 1 in 50 of water; miscible with ethanol, ether and glycerol; soluble in fixed oils and in solutions of alkali hydroxides

Antimicrobial activity

bactericidal against vegetative bacteria and moderately active against fungi; poorly active against spores

Darkens with age and on exposure to light and air. Store in an airtight container, protected from light, in a cool, dry place.

Incompatible with strong oxidising agents. Its antimicrobial activity is reduced by nonionic surfactants such as polysorbates, and it can be lost by sorption into rubber closures and some plastics. Iron salts cause discolouration.

Obtained from coal tar or from petroleum by fractional distillation, or produced synthetically, for example by methylation of phenol or from toluene. Pharmaceutical metacresol is a purified single isomer.

Concentrated cresol is corrosive to skin and mucous membranes and is toxic if swallowed or absorbed through the skin, causing central nervous system depression and liver and kidney damage. At the concentrations used as a preservative in injections it is generally well tolerated, although injection-site reactions and hypersensitivity to metacresol have been reported.

Cresol is corrosive and readily absorbed through the skin. Wear chemical-resistant gloves, eye protection and a face shield, and handle in a well-ventilated area or fume cupboard.

Included in the FDA Inactive Ingredient Database (intramuscular, intravenous and subcutaneous injections) and in parenteral medicines licensed in Europe.

Chlorocresol; metacresol; phenol; thymol.

In insulin products metacresol and phenol also stabilise the hexameric form of insulin, so their level affects product stability as well as preservation. Preservative efficacy should be confirmed by a pharmacopoeial antimicrobial effectiveness test in the final container.