Chlorocresol is an antiseptic and preservative compound commonly used in cosmetic and pharmaceutical formulations. It is known for its antimicrobial properties, making it effective in preventing the growth of bacteria, fungi, and other microorganisms in products. Chlorocresol is often included in creams, ointments, lotions, and medical solutions to extend shelf life and maintain product integrity by preventing microbial contamination.
Chemical Composition and Structure
Chlorocresol is a chlorinated derivative of cresol, with the following characteristics:
- Cresol Backbone: Chlorocresol is derived from cresol, which is a phenolic compound with a methyl group and a hydroxyl group on the aromatic ring.
- Chlorination: A chlorine atom is attached to the benzene ring, enhancing its antimicrobial properties and making it more effective as a preservative and antiseptic.
Physical Properties
- Appearance: Chlorocresol is typically a colorless to pale yellow liquid or crystalline powder.
- Odor: It has a faint phenolic, medicinal odor.
- Solubility: It is soluble in alcohol, acetone, and other organic solvents but is only slightly soluble in water.
- Melting Point: Chlorocresol has a melting point around 37–40°C, depending on the form.
- Stability: Chlorocresol is stable under normal conditions of use, but it can degrade under extreme light or heat conditions.
Production Process
- Synthesis: Chlorocresol is synthesized by chlorinating cresol in the presence of a suitable catalyst. This reaction introduces the chlorine atom into the cresol molecule.
- Purification: After synthesis, the compound is purified to remove any unwanted by-products and ensure its effectiveness and safety in formulations.
Applications
Medical Applications
- Antiseptic: Chlorocresol is widely used in medical applications for its antiseptic properties. It helps prevent infections by inhibiting the growth of bacteria and fungi on the skin and in wounds.
- Topical Treatment: It is used in creams, ointments, and other topical formulations to treat skin conditions, including minor cuts, burns, and abrasions.
Cosmetics
- Preservative: Chlorocresol is commonly used as a preservative in skincare and cosmetic products to prevent microbial growth and extend the shelf life of products like lotions, shampoos, and creams.
- Antimicrobial: Helps reduce the risk of infection and skin irritation by keeping products free from harmful microorganisms.
Cosmetic Safety
Restricted cosmetic ingredient as V / 24 a Relevant Item in the Annexes of the European Cosmetics Regulation 1223/2009. Substance or ingredient reported:
Not to be used in products applied on mucous membranes
Maximum concentration in ready for use preparation 0.2%
Industrial Applications
- Pharmaceutical Products: Used in pharmaceutical preparations, such as injectable solutions or topical creams, to maintain sterility and prevent microbial contamination.
- Cosmetic Formulations: Often found in formulations where maintaining product stability and preventing contamination are crucial.
Environmental and Safety Considerations
- Biodegradability: Chlorocresol is not highly biodegradable and can persist in the environment if improperly disposed of.
- Safety Profile: Chlorocresol is generally considered safe for use in cosmetic and medical formulations within regulated concentrations. However, it can cause skin irritation or allergic reactions in some individuals. Prolonged exposure or misuse may lead to more serious side effects.
- Sustainability: The production of chlorocresol involves chemical processes, and while it is effective as a preservative, its environmental impact and sustainability are considerations for future alternatives.
Molecular Formula C7H7ClO
Molecular Weight 142.58 g/mol
CAS 59-50-7
UNII 36W53O7109
EC Number 200-431-6
DTXSID4021717
Synonyms:
.4-Chloro-m-cresol
p-Chloro-m-cresol
4-Chloro-3-methylphenol
References__________________________________________________________________________
Tegazzin V, Scutari E, Treves S, Zorzato F. Chlorocresol, an additive to commercial succinylcholine, induces contracture of human malignant hyperthermia-susceptible muscles via activation of the ryanodine receptor Ca2+ channel. Anesthesiology. 1996 Jun;84(6):1380-5. doi: 10.1097/00000542-199606000-00014.
Abstract. Background: A defect in the ryanodine (Ry1) receptor Ca2+ channel has been implicated as one of the possible underlying causes of malignant hyperthermia (MH), a pharmacogenetic disorder characterized by sustained muscle contracture. The disease is triggered by common halogenated anesthetics and skeletal muscle relaxants, such as succinylcholine. This study tested whether the functional properties of the Ry1 receptor Ca2+ channel are affected by chlorocresol, a preservative added to a commercial preparation of succinylcholine (Midarine) and other parenteral compounds. Methods: In vitro contracture testing was carried out on muscle biopsies from malignant hyperthermia-susceptible (MHS) and -negative (MHN) individual according to the protocol of the European MH group. Ca2+ flux studies on isolated rabbit sarcoplasmic reticulum fractions were measured spectrophotometrically by following the A710-790 of the Ca2+ indicator antipyrylazo III. Results: Chlorocresol causes muscle contracture in MHS muscles at a concentration of 25-50 microM and potentiates the caffeine contracture response in human MHS muscles. Sub-threshold (20 microM) concentrations of chlorocresol increase both the Kd and the Vmax of caffeine-induced Ca2+ release from isolated rabbit terminal cisternae. Conclusions: These data suggest that, in muscle from MHS individuals, the enhanced Ca2+ released from the sarcoplasmic reticulum may not be due to the effect of succinylcholine alone but rather to the action of the preservative chlorocresol added to the drug.
Burry JN, Kirk J, Reid J, Turner T. Chlorocresol sensitivity. Contact Dermatitis. 1975;1(1):41-2. doi: 10.1111/j.1600-0536.1975.tb05309.x.
Abstract. Contact allergic sensitivity may follow the use of chlorocresol incorporated as a preservative into both betamethasone cream and aqueous cream, which are commonly prescribed as a mixture in South Australia. In several cases, although the clinical courses indicated sensitivity to chlorocresol, patch test reactions to this chemical were negative. In these cases positive patch test reactions to chloroxylenol, a chemical closely related to chlorocresol, confirmed the diagnoses.
Bloomfield MS, Prebble KA. The determination of the preservative, chlorocresol, in a pharmaceutical formulation by flow injection analysis. J Pharm Biomed Anal. 1992 Oct-Dec;10(10-12):775-8. doi: 10.1016/0731-7085(91)80079-o.
Abstract. A flow injection analysis (FIA) procedure is described for the determination of chlorocresol in a parenteral pharmaceutical formulation. The product is directly injected into a carrier stream of water and subsequently reacted with a reagent stream of nitrous acid. The resulting brown nitro-derivative is determined spectrophotometrically at 400 nm. The method has been validated and should be applicable to chlorocresol in other pharmaceutical products and to compounds containing a phenolic ring, assuming absence of matrix interference.
Ben-Abraham R, Krivosic-Horber RM, Haudcoeur G, Perel A, Adnet PJ. Effect of chlorocresol vs caffeine on muscle contracture in malignant hyperthermia susceptible patients. Harefuah. 1997 Jun 15;132(12):839-41, 911.
Abstract. The phenotype of susceptibility to malignant hyperthermia (MHS); can only be detected reliably by the in vitro caffeine-halothane contracture test (CHCT). Enhanced sensitivity of the calcium-induced calcium release mechanism is responsible for the exaggerated contracture response of skeletal muscle fibers from MHS patients to halothane and caffeine. Chlorocresol was demonstrated to be a potent activator of Ca++ release from skeletal muscle sarcoplasmic reticulum. This effect is probably mediated through action on a ryanodine sensitive Ca++ release channel known to be more sensitive in MH. We studied the effect of chlorocresol on the mechanical contracture response of skeletal muscle from patients presenting for the in vitro CHCT. Chlorocresol induces contracture response in a concentration 1/200 of that of caffeine in muscle strips from MH patients. By adding chlorocresol to the protocol of the CHCT, there is clearer discrimination between the responses of MH patients and normal subjects can be achieved.
Chlorocresol 
Chlorine atom
