도코사놀

Cosmetic ingredients (Behenyl Alcohol) -> CIR (Cosmetic Ingredient Review)

Emollient

Slightly soluble in ether; very soluble in ethanol, methanol, petroleum ether; soluble in chloroform

Insoluble in water

1.96e-05 g/L

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

This chemical does not meet GHS hazard criteria for 79.6% (425 of 534) of all reports.

Warning

H319 (16.1%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

P264+P265, P273, P280, P305+P351+P338, P337+P317, P391, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 534 reports by companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chemical: 1-Docosanol

1-Docosanol is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 1-Docosanol are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 17-05-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/14378

1-Docosanol: Does not have an individual approval but may be used under an appropriate group standard

Aliphatic alcohols are metabolized and eliminated efficiently; Not skin sensitizers; May have low-grade liver effects; CNS depression seen in shorter chain alcohols, e.g., 1-hexanol and 1-octanol; [Reference #1] May cause irritation; [MSDSonline]

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed over-the-counter drug products, incl docosanol, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

-Ouabain to heart is inhibited by long-chain fatty acids and alcohols; [J. Mol Cell Cardiol 12(9) 847 (1980)] Long-chain fatty acids and alcohols inhibit specific binding of (3)H-labeled ouabain to a particulate fraction from dog heart. The magnitude of inhibition increased with chain length, reaching max with lauric acid, myristoleic acid, and decanol in a series of saturated fatty acids, unsaturated fatty acids, and alcohols, respectively, followed by a decline with longer chain members of homologous series.[KIM RS, LABELLA FS; SPECIFIC BINDING OF

... The anti-HSV activity of acyclovir (ACV) was synergistically enhanced by treatment of cells with docosanol as judged by inhibition of progeny virus production and plaque formation. This drug interaction between ACV and docosanol was observed with laboratory strains of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), oral and genital clinical isolates of HSV, cytomegalovirus (CMV), and varicella zoster virus (VZV). Near optimal concentrations of docosanol plus ACV inhibited HSV replication >99% more than either drug alone, including emergence of ACV-resistant variants. The response was observed with African Green Monkey kidney cells, normal human foreskin cells, and normal human lung cells. Treatment of cells with docosanol also synergistically intensified the inhibition of HSV production by trifluorothymidine (TFT), adenine arabinoside (Ara-A), and ribavirin. An additive anti-HSV effect was observed with docosanol and phosphonoformate (PFA). No evidence was found for either synergistic inhibition of cellular DNA synthesis or induction of overt cellular toxicity when docosanol was combined with ACV, TFT, Ara-A, ribavirin, PFA, 8-azaguanine, or 5-fluorouracil.

Studies of the influence of fatty acids, which were the component of intestinal mucosal lipids, on the permeability of several drugs across bilayer lipid membranes generated from egg phosphatidylcholine and intestinal lipid have been pursued. The permeability coefficients of p-aminobenzoic acid, salicylic acid and p-aminosalicylic acid (anionic-charged drug) increased when fatty acids such as lauric, stearic, oleic, linoleic and linolenic acid were incorporated into the bilayer lipid membranes generated from phosphatidylcholine. In the presence of methyl linoleate and oleyl alcohol, no enhancing effect on p-aminobenzoic acid transfer was obtained. The effect of fatty acids was more marked at pH 6.5 than at pH 4.5. In contrast, upon the addition of fatty acids to intestinal lipid membranes which originally contained fatty acids, the permeability coefficient of p-aminobenzoic acid tended to decrease, though the permeability through intestinal lipid membranes was larger than that of phosphatidylcholine membranes. The permeability of p-aminobenzoic acid across bilayer lipid membranes from intestinal phospholipids was significantly decreased to about equal that of phosphatidylcholine membranes, and reverted to the value of intestinal lipid membranes when fatty acids were added to intestinal phospholipids. It seemed reasonable to assume that free fatty acids in the intestinal neutral lipid fraction could contribute to the increase in the permeability of p-aminobenzoic acid. On the basis of above results, possible mechanisms for good absorbability of weakly acidic drugs from the intestine are discussed.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1.5X10+5(SRC), determined from a structure estimation method(2), indicates that 1-docosanol is expected to be immobile in soil(SRC). Volatilization of 1-docosanol from moist soil surfaces may be expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.6X10-3 atm-cu m/mole(SRC), using a fragment constant estimation method(3). 1-Docosanol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.1X10-8 mm Hg(SRC), determined from a fragment constant method(4). However, adsorption to soil is expected to attenuate volatilization(SRC). 1-Docosanol is expected to biodegrade rapidly based upon estimates from the chemical structure(5).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1.5X10+5(SRC), determined from a structure estimation method(2), indicates that 1-docosanol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 1.6X10-3 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 6 hours and 7.5 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life of 1-docosanol from a model pond is 2 years if adsorption is considered(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from an estimated log Kow of 9.7(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low(SRC). 1-Docosanol is expected to biodegrade rapidly based upon estimates from the chemical structure(9).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 1-docosanol, which has an estimated vapor pressure of 6.1X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 1-docosanol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 12 hours(SRC), calculated from its rate constant of 3.2X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase 1-docosanol may be removed from the air by wet or dry deposition(SRC).

1-Docosanol emission rates from wood smoke were calculated as 0.9 ug/g, 0.2 ug/g, and 4.3 ug/g from oak, eucalyptus and pine, respectively(1). 1-Docosanol emission rate from road dust samples was 6.0 ug/g(2). 1-Docosanol emission rate from pine wood (Pinus elliottii) smoke was measured at 66 ng/g of burnt wood(3).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 1-docosanol can be estimated to be 1.5X10+5(SRC). According to a classification scheme(2),this estimated Koc value suggests that 1-docosanol is expected to be immobile in soil.

URBAN/SUBURBAN: 1-Docosanol was found in California at atmospheric concentrations of 6.6 ng/cu m and 9.3 ng/cu m in Bakersfield and Fresno, respectively(1).

RURAL/REMOTE: 1-Docosanol was found at an atmospheric concentration of 0.5 ng/cu m in Kern Wildlife Refuge, California(1).

1-Docosanol's production and use in synthetic fibers, lubricants and as an evaporation retardant on water surfaces(1) may result in its release to the environment through various waste streams(SRC). 1-Docosanol has also been identified in wood smoke(2), green leaf composite(3), dead leaves(3), paved road dust(3), and cigarettes(3).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed over-the-counter drug products, incl docosanol, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

D06BB11

D - Dermatologicals

QD - Dermatologicals

Docosanol is a saturated 22-carbon aliphatic alcohol which exhibits antiviral activity against many lipid enveloped viruses including herpes simplex virus (HSV). Docosanol speeds the healing of cold sores and fever blisters on the face or lips. It also relieves the accompanying symptoms, including tingling, pain, burning, and itching. Docosanol cannot, however, prevent cold sores or fever blisters from appearing.

Docosanol works by inhibiting fusion between the human cell plasma membrane and the herpes simplex virus (HSV) envelope, thereby preventing viral entry into cells and subsequent viral replication. Unlike other cold-sore antivirals, docosanol does not act directly on the virus, and as such it is unlikely it will produce drug resistant mutants of HSV.

n-Docosanol-treated cells resist infection by a variety of lipid-enveloped viruses including the herpesviruses. Previous studies of the mechanism of action demonstrated that n-docosanol inhibits an event prior to the expression of intermediate early gene products but subsequent to HSV attachment. The studies reported here indicate that n-docosanol inhibits fusion of the HSV envelope with the plasma membrane. Evidence suggests that antiviral activity requires a time-dependent metabolic conversion of the compound. Cellular resistance to infection declines after removal of the drug with a t1/2 of approximately 3 h. Reduced expression of viral genes in n-docosanol-treated cells was confirmed by a 70% reduction in expression of a reporter gene regulated by a constitutive promoter inserted into the viral genome. Inhibited release in treated cells of virion-associated regulatory proteins--an immediate post entry event--was indicated by a 75% reduction in the expression of beta-galactosidase in target cells carrying a stably transfected lacZ gene under control of an HSV immediate--early promoter. Finally, the fusion-dependent dequenching of a lipophilic fluorescent probe, octadecyl rhodamine B chloride, inserted into the HSV envelope was significantly inhibited in treated cells. Inhibition of fusion between the plasma membrane and the HSV envelope, and the subsequent lack of replicative events, may be the predominant mechanism for the anti-HSV activity of n-docosanol.

Docosanol reduces viral replication and activity by effectively inhibiting the fusion between the plasma membrane and the herpes simplex virus envelope.

The 22-carbon fatty alcohol, n-docosanol, exhibits in vitro antiviral activity against several lipid-enveloped viruses including herpes simplex viruses 1 and 2 by a mechanism that interferes with normal viral entry into target cells. We previously reported that mammalian cells incorporate significant quantities of radiolabeled n-docosanol. Herein, we report that cells extensively metabolize the internalized fatty alcohol. This is evidenced by incorporation of up to 60% of cell-associated radiolabel into phospholipids that copurify with phosphatidylcholine and phosphatidylethanolamine. Analysis by chemical (Vitride) reduction suggests that a significant portion of n-docosanol is oxidized to n-docosanoic acid and then incorporated as an acyl group on polar lipids. A measurable amount of radiolabel, however, is resistant to Vitride reduction, consistent with incorporation of n-docosanol into ether lipids. The rate and extent of metabolic conversion of n-docosanol vary with the cell type and surfactant used to suspend the compound. Furthermore, the anti-HSV activity of n-docosanol is quantitatively proportional to the amount of metabolism observed. These findings suggest that the anti-HSV activity of n-docosanol involves cellular uptake and metabolism of the drug.

A mixture of cis-9[1(-14)C] octadecenol and [1(-14)C] docosanol was injected into the brains of 19-day-old rats. Both alcohols were metabolized by the brain but at different rates; each was oxidized to the corresponding fatty acid. Substantial amounts of radioactivity were incorporated into 18:1 alkyl and alk-1-enyl moieties of the ethanolamine phosphoglycerides and into 18:1 alkyl moieties of the choline phosphoglycerides.

Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.

Topical absorption has been shown to be minimal under conditions reflecting normal clinical use.

Absorption of docosanol has been shown to be minimal under conditions reflecting normal clinical use. Of 209 plasma samples taken from ten subjects 24 hours after a multi-day test, only one had a docosanol level above the quantitation limits (19 nanograms/mL).

Long chain alcohols were detected in developing rat brain at their highest level of 0.0109% of the total lipids at the age of 10 days and decreased to 0.0036% at the age of 40 days. They consited mainly of hexadecanol, octadecanol, octadecenol, eicosanol, docosanol, and tetracosanol.

A mixture of cis-9[1(-14)C] octadecenol and [1(-14)C] docosanol was injected into the brains of 19-day-old rats, and incorporation of radioactivity into brain lipids was determined after 3, 12, and 24 hr. Both alcohols were metabolized by the brain but at different rates; each was oxidized to the corresponding fatty acid, but oleic acid was more readily incorporated into polar lipids. Substantial amounts of radioactivity were incorporated into 18:1 alkyl and alk-1-enyl moieties of the ethanolamine phosphoglycerides and into 18:1 alkyl moieties of the choline phosphoglycerides. Even after the disappearance of the 18:1 alcohol from the substrate mixture (12 hr), the 22:0 alcohol was not used to any measurable extent for alkyl and alk-1-enylglycerol formation.

CIR ingredient: Behenyl Alcohol

Used in synthetic fibers and lubricants and as an evaporation retardant on water surfaces; [HSDB] Used to treat benign prostatic hypertrophy; [Merck Index]

Synthetic fibers, lubricants, evaporation retardant on water surfaces

Antiherpesvirus agents /From table/ /Docosanol/

2023: 1,000,000 - <2,500,000 lb

This chemical is listed as a High Production Volume (HPV) (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).

(1986) >1 million-10 million pounds

(1990) >1 million-10 million pounds

(1994) >1 million-10 million pounds

For more U.S. Production (Complete) data for 1-DOCOSANOL (6 total), please visit the HSDB record page.

Grade: Technical, 99%

Trade name (USA): ABREVA /From table/ /Docosanol/

... Approved by the US FDA as a 10 % over-the-counter cream /Docosanol

Topical: Cream: 10% Abreva, (GlaxoSmithKline).

EPA Safer Chemical Functional Use Classes -> Emollients

Safer Chemical Classes -> Green circle - The chemical has been verified to be of low concern

Fragrance Ingredients

Cosmetics -> Emollient

Wholesale and Retail Trade

1-Docosanol: ACTIVE