Compendium of the most significant studies with reference to properties, intake, effects.

Rütering M, Schmid J, Gansbiller M, Braun A, Kleinen J, Schilling M, Sieber V. Rheological characterization of the exopolysaccharide Paenan in surfactant systems. Carbohydr Polym. 2018 Feb 1;181:719-726. doi: 10.1016/j.carbpol.2017.11.086.

Abstract

Rheology-controlling agents are of importance for numerous products in a variety of industries. Replacement of synthetic chemicals with natural additives is desired in light of current environmental awareness and limited fossil resources. This study investigates the rheological features of Paenan, an exopolysaccharide produced by Paenibacillus polymyxa. Paenan exhibits highly shear-thinning flow behavior at concentrations ≥0.1% in 0.5% NaCl. Because of its pronounced intermolecular network, it forms stable, weak gels, thereby delivering elasticity as well as thixotropy. Application-relevant flow behavior is obtained with 60-65% less polymer as compared to the benchmark commercial products Xanthan and Gellan. In mixtures with surfactants (sodium lauryl ether sulfate, cetrimonium chloride, cocamidopropyl betaine, or lauryl glucoside), Paenan displays outstanding compatibility with every class of surfactant, making it superior to the partially incompatible Xanthan and Gellan. The weak-gel character of Paenan/surfactant systems is retained with three out of four surfactants, rendering Paenan highly interesting for various applications.

Mietz H, Niesen U, Krieglstein GK. The effect of preservatives and antiglaucomatous medication on the histopathology of the conjunctiva. Graefes Arch Clin Exp Ophthalmol. 1994 Sep;232(9):561-5. doi: 10.1007/BF00182000.

Abstract

Background: Topical medication applied chronically for the treatment of glaucoma changes the cellular profile of the conjunctiva. We wanted to determine the role of preservatives, which are usually combined with the drugs, on this effect.

Methods: We applied metipranolol 0.3% and pilocarpine 2% with and without benzalkonium chloride 0.01% and cetrimonium chloride 0.004%, respectively. Twenty-four rabbits, divided into four groups, were treated for 3 months. The complete globes and the adherent bulbar conjunctiva were examined histopathologically and immunohistochemically.

Results: With special stains for collagen, a slight increase of the thickness of subepithelial collagen of the conjunctiva was present in both groups treated with medication and preservative compared with eyes treated with medication alone. This effect was also true for special antibodies for collagen type IV and alpha-smooth muscle actin in the eyes treated with pilocarpine, but not in the eyes treated with metipranolol.

Conclusion: The results suggest that preservatives may have an additional adverse effect on the conjunctiva in addition to the effects of the medications alone.

de Araújo BRS, Linares León JJ. Electrochemical treatment of cetrimonium chloride with boron-doped diamond anodes. A technical and economical approach. J Environ Manage. 2018 May 15;214:86-93. doi: 10.1016/j.jenvman.2018.02.094.

Abstract

This study presents the results of the electrochemical degradation of the emulsifier cetrimonium chloride (CTAC) on a boron-doped diamond (BDD) anode under different current densities and flow rates. Higher values of these parameters result in a more rapid removal. Nevertheless, operation at low current reduces the required applied charge and increases the chemical oxygen demand (COD) removal efficiency, as there is less development of ineffective parasitic reactions. On the other hand, high flow rates reduce the required volumetric applied charge and increase the COD removal current efficiency. In order to assist and enrich the study, an economic analysis has been performed. For short expected plant lifespans, operation at low current is advantageous due to the lower investment required, whereas for longer expected lifespans, the operational costs make the lower current densities less costly. High flow rates are always advantageous from a financial point of view.

Cetyltrimethylammonium chloride better known as Cetrimonium chloride, is a quaternary ammonium compound commonly used as a conditioning agent and preservative in cosmetics and personal care products, particularly in hair care formulations. It is known for its ability to reduce static electricity, soften hair, and enhance detangling, making it a popular ingredient in conditioners, shampoos, and other hair treatments. Cetrimonium chloride is also used for its antimicrobial properties, which help preserve cosmetic products.

Chemical Composition and Structure

Cetrimonium chloride, with the chemical formula C₁₉H₄₂ClN, is a quaternary ammonium salt consisting of a cetyl group (hexadecyl) attached to a nitrogen atom with a positive charge. This positive charge interacts with negatively charged surfaces like hair, making it an effective conditioning agent. The chloride ion serves as a counterion to balance the positive charge of the nitrogen.

Physical Properties

Cetrimonium chloride is typically found as a clear to pale yellow liquid or powder that is soluble in water. It has excellent antistatic and conditioning properties, which make it suitable for improving the feel and manageability of hair. It is commonly used in low concentrations to ensure safe use while providing effective conditioning.

Production Process

Cetrimonium chloride is synthesized through a chemical reaction between cetyl alcohol and trimethylamine, resulting in the formation of the quaternary ammonium compound. The final product is purified for use in cosmetic formulations.

Applications

• Hair Conditioners: Cetrimonium chloride is widely used in conditioners, leave-in treatments, and hair masks for its conditioning properties. It helps detangle hair, reduce static, and improve manageability.

• Shampoos: In shampoos, it works as a conditioning agent, leaving the hair feeling softer and smoother after washing.

• Styling Products: It is also found in hair sprays and styling creams, where it helps to control frizz and static while providing a lightweight feel to the hair.

• Preservative: Thanks to its antimicrobial properties, Cetrimonium chloride is sometimes used to help preserve the shelf life of personal care products by preventing microbial growth.

INCI Functions:

Antimicrobial agent. This ingredient is able to suppress or inhibit the growth and replication of a broad spectrum of microorganisms such as bacteria, fungi and viruses by making the stratum corneum temporarily bactericidal and fungicidal.

Antistatic agent. Static electricity build-up has a direct influence on products and causes electrostatic adsorption. The antistatic ingredient reduces static build-up and surface resistivity on the surface of the skin and hair.

Surfactant - Emulsifying agent. Emulsions are thermodynamically unstable and are used to soothe or soften the skin and emulsify, so they need a specific, stabilising ingredient. This ingredient forms a film, lowers the surface tension and makes two immiscible liquids miscible. A very important factor affecting the stability of the emulsion is the amount of the emulsifying agent. Emulsifiers have the property of reducing the oil/water or water/oil interfacial tension, improving the stability of the emulsion and also directly influencing the stability, sensory properties and surface tension of sunscreens by modulating the filmometric performance.

Preservative. Any product containing organic, inorganic compounds, water, needs to be preserved from microbial contamination. Preservatives act against the development of harmful microorganisms and against oxidation of the product.

Cosmetic safety

Restricted cosmetic ingredient as V/44 a Relevant Item in the Annexes of the European Cosmetics Regulation 1223/2009. Substance or ingredient reported: Alkyl (C12-C22) trimethyl ammonium bromide and chloride. Maximum concentration in ready for use preparation    0.1%

Health and Safety Considerations

Safety in Use
Cetrimonium chloride is considered safe for use in cosmetic products when used within recommended concentrations. In the European Union, it is allowed at a maximum concentration of 0.1% in leave-on products and 1.0% in rinse-off products. It is generally well-tolerated by most users, although some individuals with sensitive skin or scalp may experience mild irritation.

Allergic Reactions
While allergic reactions to Cetrimonium chloride are uncommon, it may cause mild irritation, particularly for people with sensitive skin or when used in high concentrations. Patch testing is recommended for individuals with known sensitivities to ingredients in hair care products.

Toxicity and Carcinogenicity
There is no evidence suggesting that Cetrimonium chloride is carcinogenic or toxic at the concentrations approved for cosmetic use. It has undergone safety evaluations and is considered safe for use in personal care products when formulated within regulatory guidelines.

Environmental and Safety Considerations
As with many quaternary ammonium compounds, Cetrimonium chloride is not readily biodegradable, and its release into the environment should be minimized. Proper waste disposal and environmental safety measures are recommended to avoid potential ecological impact, particularly in aquatic environments.

Regulatory Status
Cetrimonium chloride is regulated by cosmetic safety authorities such as the Cosmetic Ingredient Review (CIR) and is approved for use in the European Union, United States, and other global markets. Its use in cosmetics is subject to concentration limits, particularly in rinse-off and leave-on products, to ensure safety.

Cetrimonium chloride studies

Molecular Formula: C₁₉H₄₂ClN    C₁₉H₄₂N.Cl

Condensed Formula:  CH₃(CH₂)₁₅N(Cl)(CH₃)₃

Molecular Weight: 320.0  g/mol

CAS: 112-02-7    68002-63-1

UNII UC9PE95IBP

EC Number: 203-928-6    268-077-5

DSSTox Substance ID: DTXSID6026901    DTXSID2029402

MDL number  MFCD00011773

PubChem Substance ID 24857608

Beilstein/REAXYS Number:  3657974

Sinonimi: 

• Hexadecyltrimethylammonium chloride solution
• Hexadecyltrimethylammonium chloride
• Palmityltrimethylammonium chloride
• Cetrimonium chloride
• 1-Hexadecanaminium, N,N,N-trimethyl-, chloride
• Cetyltrimethylammonium chloride
• Quaternary ammonium compounds, C14-18-alkyltrimethyl, chlorides
• N,N,N-trimethylhexadecan-1-aminium chloride
• Trimethyl-1-hexadecanaminium chloride
• N-Hexadecyltrimethylammonium chloride
• Adogen 444
• Hexadecyl trimethyl ammonium chloride
• Genamin CTAC
• Cetyl trimethyl ammonium chloride
• Arquad 16
• Trimethylcetylammonium chloride

References________________________________________________________________

Terol A, Gómez-Mingot M, Maestre SE, Prats S, Luis Todolí J, Paredes E. Simple and rapid analytical method for the simultaneous determination of cetrimonium chloride and alkyl alcohols in hair conditioners. Int J Cosmet Sci. 2010 Feb;32(1):65-72. doi: 10.1111/j.1468-2494.2009.00553.x.

Abstract. A simple method for the simultaneous determination of a cationic surfactant (cetrimonium chloride) and four non-ionic surfactants (1-tetradecanol, 1-hexadecanol, 1-octadecanol and 1-eicosanol) has been developed. Direct extraction of the analytes from the sample with methanol and a subsequent separation using reversed-phase high-performance liquid chromatography with refractive index detection are the steps followed in the procedure. The column used was a Luna C18 and the mobile phase consisted of a 0.1 M KClO(4) solution prepared on a 95:5 mixture of methanol and water. This solution was adjusted to pH 2.8 with phosphoric acid. Recoveries close to 100% were obtained in spiked commercial hair conditioner samples for the surfactants assayed using this method. Limits of detection were 10.4, 16.7 and 22.9 mg kg(-1) of cetrimonium chloride, 1-hexadecanol, 1-hexadecanol and 1-1-octadecanol respectively. The methodology was successfully applied to nine commercial hair conditioners of several types and different brands. All hair conditioners but one contained at least two of the surfactants included in this study.

Okeke CAV, Khanna R, Ehrlich A. Quaternary Ammonium Compounds and Contact Dermatitis: A Review and Considerations During the COVID-19 Pandemic. Clin Cosmet Investig Dermatol. 2023 Jun 30;16:1721-1728. doi: 10.2147/CCID.S410910. PMID: 37409071; PMCID: PMC10319159.

Becker, L. C., Bergfeld, W. F., Belsito, D. V., Hill, R. A., Klaassen, C. D., Liebler, D., ... & Andersen, F. A. (2012). Safety assessment of trimoniums as used in cosmetics. International journal of toxicology, 31(6_suppl), 296S-341S.

Abstract. Quaternary ammonium salts, including alkyl chain, alkanol, and polymer derivatives (trimoniums) are used in cosmetics mainly as surfactant-cleansing agents, hair-conditioning agents, and antistatic agents.  The Cosmetic Ingredient Review Expert Panel reviewed the relevant animal and human data and noted gaps in the available safety data for some of the trimomiums.  The available data on many of the trimoniums are sufficient, however, and similar structural activity relationships, functions in cosmetics, and cosmetic product usage supported extending these data to the entire group.  These ingredients were determined to be safe in the present practices of use and concentration when formulated to be nonirritating.

Agredo, P., Rave, M. C., Echeverri, J. D., Romero, D., & Salamanca, C. H. (2019). An evaluation of the physicochemical properties of stabilized oil-in-water emulsions using different cationic surfactant blends for potential use in the cosmetic industry. Cosmetics, 6(1), 12.

Abstract. One of the most complex problems in hair care formulations is the duality of the surfactants used. In this regard, such surfactants must be cationic so as to interact with the negatively charged cuticle surface of hair. However, these interdependencies typically lead to non-ideal values for the required hydrophilic–lipophilic balance (HLB) in the oil phase. This study was designed to evaluate the physicochemical properties of several oil-in-water emulsion prototypes for the potential use in hair conditioners. Here, a base formulation was utilized, incorporating binary mixtures of cationic surfactants in different proportions. The cationic surfactants employed were hydroxyethyl-behenamidopropyl-diammonium chloride, behentrimonium methosulphate, cetrimonium chloride, and (iv) Polyquaterniumpolyquaternium-70. The surfactants were evaluated for their capability to decrease the surface tension in an aqueous solution through contact angle measurements between the oily phase and the aqueous phase. The required HLB of the oil phase was also determined. The emulsification process was developed using standard preparation methods. For three months, the prototypes with high viscosity were packed in containers and stored in a stability chamber at accelerated conditions (40 ± 2 °C and 75 ± 5% RH). During this time, the size, size polydispersity, zeta potential, viscosity, rheological profile, and creaming index were all evaluated monthly. The results showed a slight change in the physical stability of the prototypes, where the droplet size increased moderately, however, did little to destabilize the formulations. This suggests that the mixtures of cationic surfactants used could be useful for technological developments in hair conditioning products.