1-Hexadecanol

Absorption

Following ingestion at a dose level of 2.0 g/kg in rats, cetyl alcohol was partly absorbed . Administration of 0.2 mg cetyl alcohol in rat by stomach tube indicated good absorption as 63-96 % of radiolabeled cetyl alcohol was detected in the lymph . About 15% of total cetyl alcohol was unchanged during its passage through the mucosal cells of the small intestine but mostly underwent oxidation to palmitic acid . The extent of absorption was reported to be 26% in poultry .

Toxicity

Acute oral LD50 in mouse is 3200 mg/kg and acute dermal LD50 is >2600 mg/kg in rabbit . It is considered to be slightly toxic in humans in case of oral ingestion at doses of 5 g/kg and greater . In a rat study, the effects of toxicity were mainly in the central nervous system (CNS) leading to CNS depression and difficulty in respiration after 7-14 days post-administration via stomach tube . In a subchronic dermal toxicity study of rabbits, topical application of 11.5 % cetyl alcohol was associated with histological findings of keratosis, hyperkeratosis, and papillary projections of the epidermis, all of which are features of exfoliative dermatitis . However it is concluded that there is no evidence of major skin irritation and systemic toxicity of cetyl alcohol. Inhalation of 26 ppm cetyl alcohol vapors in animals caused slight irritation of the mucous membranes of the eyes, nose, throat, and respiratory passages . Cetyl Alcohol was not mutagenic in Salmonella typhimurium LT2 mutant strains in the spot test .

Description

1-Hexadecanol is a waxy white powder or flake form at room temperature, and is insoluble in water and soluble in alcohols and oils. Discovered by Chevrenl in 1913, It is one of the oldest known long-chain alcohol. It can be produced from the reduction of palmitic acid. 1-Hexadecanol may be contained in cosmetic and personal care products such as shampoos, creams and lotions. it is mainly used as an opacifier, emulsifier, and thickening agent that alter the thickness of the liquid, and increase and stabilize the foaming capacity.

Chemical properties

Cetyl alcohol occurs as waxy, white flakes, granules, cubes, or castings. It has a faint characteristic odor and bland taste.

Originator

Hexadecyl alcohol,Esso Res. And Eng. Co.

Occurrence

Reported as a major constituent of spermaceti oil, where it is present chiefy as cetyl palmitate Also reported found in guava, peach, pear, kohlrabi, baked potato, mustard, Parmesan cheese, butter, milk powder, boiled egg, cooked chicken, roasted beef, beef fat, whiskies, tea, starfruit, mango, rice, licorice, kiwifruit, loquat, endive, shrimp, crab, clam, Cape gooseberry and pawpaw

The Uses of 1-Hexadecanol

1-Hexadecanol has been used in preparation of:
(±)-2-methoxyheptadecanoic acid (fatty acid)
high-chain fatty acid esters of 1-hexadecanol, novel organic phase change material for thermal energy storage
hexadecane (alkane) in the presence of membrane fraction of Vibrio furnissii M1

The Uses of 1-Hexadecanol

cetyl alcohol is a versatile ingredient that can serve as an emollient, emulsifier, thickener, binder, foam booster, or emulsion stabilizer, depending on the formulation and need. It is derived from coconut or palm oil as well as being synthetically manufactured. It is considered by some sources to be a non-comedogenic material.

Indications

No therapeutic indications in medicinal products. Indicated to be used as an indirect additive in food contact substances, or an ingredient in commercial or cosmetic products.

Background

Cetyl alcohol, also known as 1-hexadecanol or n-hexadecyl alcohol, is a 16-C fatty alcohol with the chemical formula CH3(CH2)15OH. It can be produced from the reduction of palmitic acid. Cetyl alcohol is present in a waxy white powder or flake form at room temperature, and is insoluble in water and soluble in alcohols and oils . Discovered by Chevrenl in 1913, cetyl alcohol is one of the oldest known long-chain alcohol . It may be contained in cosmetic and personal care products such as shampoos, creams and lotions. Mainly it is used as an opacifier, emulsifier, and thickening agent that alter the thickness of the liquid, and increase and stabilize the foaming capacity. Due to its water-binding property, cetyl alcohol is commonly used as an emollient that prevents drying and chapping of the skin . According to the FDA Code of Federal Regulations, cetyl alcohol is a safe synthetic fatty acid in food and in the synthesis of food components under the condition that it contain not less than 98 percent of total alcohols and not less than 94 percent of straight chain alcohols . Cetyl alcohol is also listed in the OTC ingredient list as a skin protectant for skin irritations caused by poison ivy, oak, sumac, and insect bites or stings . Cetyl alcohol is reported to be a mild skin or eye irritant.

Definition

ChEBI: 1-Hexadecanol is a long chain fatty alcohol that is hexadecane substituted by a hydroxy group at position 1. It is a synthetic, solid, fatty alcohol and nonionic surfactant. It is used as an emulsifying agent in pharmaceutical preparations.

Production Methods

Cetyl alcohol may be manufactured by a number of methods such as esterification and hydrogenolysis of fatty acids or by catalytic hydrogenation of the triglycerides obtained from coconut oil or tallow. Cetyl alcohol may be purified by crystallization and distillation.

Therapeutic Function

Pharmaceutic aid

Synthesis Reference(s)

The Journal of Organic Chemistry, 42, p. 512, 1977 DOI: 10.1021/jo00423a025
Synthetic Communications, 25, p. 1901, 1995 DOI: 10.1080/00397919508015865
Tetrahedron Letters, 24, p. 4485, 1983 DOI: 10.1016/S0040-4039(00)85933-X

General Description

1-Hexadecanol is a free fatty acid alcohol generally used as an emulsifier, emollient, opacifier and surfactant in cosmetics formulations.

Flammability and Explosibility

Not classified

Pharmacokinetics

Cetyl alcohol exhibits skin protect properties against skin irritations caused by bites, rashes and stings. The inhibitory action of cetyl alcohol against the growth of Mycoplasma gallisepticum and Mycopiasma pneumoniae has been reported .

Safety

Cetyl alcohol is mainly used in topical formulations, although it has also been used in oral and rectal preparations.
Cetyl alcohol has been associated with allergic delayed-type hypersensitivity reactions in patients with stasis dermatitis. Crosssensitization with cetostearyl alcohol, lanolin, and stearyl alcohol has also been reported. It has been suggested that hypersensitivity may be caused by impurities in commercial grades of cetyl alcohol since highly refined cetyl alcohol (99.5%) has not been associated with hypersensitivity reactions.
LD₅₀ (mouse, IP): 1.6 g/kg
LD₅₀ (mouse, oral): 3.2 g/kg
LD₅₀ (rat, IP): 1.6 g/kg
LD₅₀ (rat, oral): 5 g/kg

Metabolism

Following ingestion at a dose level of 2.0 g/kg in rats, cetyl alcohol was partly metabolized to palmitic acid . After administration of 0.2 mg cetyl alcohol in rat by stomach tube, cetyl alcohol was mostly oxidized to palmitic acid and incorporated into triglycerides and phospholipids during its passage through the mucosal cells of the small intestine .

storage

Cetyl alcohol is stable in the presence of acids, alkalis, light, and air; it does not become rancid. It should be stored in a well-closed container in a cool, dry place.

Purification Methods

Crystallise the alcohol from aqueous EtOH or from cyclohexane. Alternatively purify it by zone refining. The purity can be checked by gas chromatography. [Beilstein 1 H 429, 1 I 219, 1 II 466, 1 III 1815, 1 IV 1876.]

Incompatibilities

Incompatible with strong oxidizing agents. Cetyl alcohol is responsible for lowering the melting point of ibuprofen, which results in sticking tendencies during the process of film coating ibuprofen crystals.

Regulatory Status

Included in the FDA Inactive Ingredients Database (ophthalmic preparations, oral capsules and tablets, otic and rectal preparations, topical aerosols, creams, emulsions, ointments and solutions, and vaginal preparations). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Nonmedicinal Ingredients.