Chlorocresol

• BPChlorocresol
• Ph. Eur.Chlorocresol
• USP–NFChlorocresol

4-chloro-m-cresol; p-chloro-m-cresol; chlorocresolum; 2-chloro-5-hydroxytoluene; PCMC; Preventol CMK

4-Chloro-3-methylphenol · [59-50-7]

UNII 36W53O7109 · PubChem CID 1732

C7H7ClO · 142.58

Antimicrobial preservative

Typical concentrations: 0.1–0.2% · Dosage forms: Semi-solid, Sterile (parenteral/ophthalmic)

A phenolic antimicrobial preservative used mainly in topical creams and emulsions, typically at about 0.1% w/v (up to about 0.2%), and at about 0.1% in some multidose injections. It is not suitable for eye drops because it irritates the eye. At higher concentrations it is used as a disinfectant.

Colourless or almost white crystals or crystalline powder with a characteristic phenolic odour.

Melting point

about 64–67 °C

Boiling point

about 235 °C

pKa

about 9.6

Solubility

slightly soluble in water (about 1 in 260 at 20 °C, more soluble in hot water); very soluble in ethanol; freely soluble in fixed oils; dissolves in alkali hydroxide solutions

Antimicrobial spectrum

bacteria (Gram-positive and Gram-negative) and fungi; more active in acidic than in alkaline solution

Stable at room temperature. Aqueous solutions may be sterilised by autoclaving but slowly become yellow on exposure to light and air. Store in a well-closed container, protected from light, in a cool, dry place.

Its activity is reduced by non-ionic surfactants such as polysorbate 80 and by methylcellulose, through micellar solubilisation and binding, and by partitioning into the oil phase of emulsions. It is sorbed by rubber closures and some plastics. It is also reported to be incompatible with calcium chloride, codeine phosphate, diamorphine hydrochloride, papaverine hydrochloride and quinine hydrochloride, and it discolours with iron salts.

Prepared by chlorination of m-cresol, followed by purification.

Used mainly in topical preparations, where it is generally well tolerated at preservative levels, although it can irritate the skin and has caused allergic contact dermatitis, with cross-sensitivity to related phenols. It must not be used in products for intrathecal, intracisternal or epidural injection.

Observe normal precautions for the quantity handled. Chlorocresol is irritant and corrosive to the skin and eyes in concentrated form; wear eye protection and gloves and avoid inhaling the dust or vapour.

Included in non-parenteral medicines and some parenteral medicines licensed in the UK and Europe, and permitted as a preservative in cosmetics in the EU within set limits.

Cresol; metacresol; chloroxylenol; phenol.

Because chlorocresol is lipophilic, much of it partitions into the oil phase of creams and into surfactant micelles, so the free aqueous concentration may be well below the nominal amount; confirm efficacy with a preservative effectiveness test. It dissolves faster in warm water.