rac-(R*)-12-ヒドロキシステアリン酸

SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

A low molecular mass gelator can form soft solids in a variety of organic liquids and vegetable oils. These soft solids are generally called organogels. ...This study /examined organogel prepared/ using 12-hydroxystearic acid (12-HSA) as a gelator for soybean oil and investigated its characteristics as a controlled release formulation for lipophilic compounds. The release rate of ibuprofen, a model lipophilic compound, from organogel decreased with the increase of 12-HSA concentration in the formulation; however, the difference in the concentration of 12-HSA in the formulation did not affect the diffusivity of ibuprofen in the organogel. The erosion constant of organogel in the intestinal tract was examined by using simulated gastric fluid and intestinal fluid. Regardless of 12-HSA concentration in the formulation, organogel is very stable in the simulated gastric fluid. On the other hand, the erosion constant of organogel in the simulated intestinal fluid increased with the decreasing concentration of 12-HSA. Therefore, it is speculated that the difference in the release rate of ibuprofen among organogels with various concentrations of 12-HSA was mainly caused by the difference in the erosion rate. To characterize the organogel effect in vivo, ibuprofen was orally administered to rats in an aqueous suspension or organogel. Ibuprofen concentration in plasma rapidly increased after administration with an aqueous suspension, whereas organogel suppressed the rapid absorption. In conclusion, organogel is clearly useful as an oral controlled release formulation for lipophilic compounds.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 900(SRC), determined from a structure estimation method(2), indicates that 12-hydroxyoctadecanoic acid is expected to have low mobility in soil(SRC). The pKa of 12-hydroxyoctadecanoic acid is 4.75(3), indicating that this compound will almost entirely exist in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the acid exists as an anion and anions do not volatilize(SRC). 12-Hydroxyoctadecanoic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.94X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). 12-Hydroxyoctadecanoic acid degraded 93% of theoretical BOD using activated sludge in the Japanese MITI test(6), suggesting that biodegradation is an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 900(SRC), determined from a structure estimation method(2), indicates that 12-hydroxyoctadecanoic acid is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 4.75(3) indicates 12-hydroxyoctadecanoic acid will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 56(SRC), from an estimated log Kow of 6.41(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is moderate, provided the compound is not metabolized by the organism(SRC). 12-Hydroxyoctadecanoic acid degraded 93% of theoretical BOD using activated sludge in the Japanese MITI test(6), suggesting that biodegradation is an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 12-hydroxyoctadecanoic acid, which has an estimated vapor pressure of 1.94X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase 12-hydroxyoctadecanoic acid may be removed from the air by wet or dry deposition(SRC). 12-Hydroxyoctadecanoic acid does not contain chromophores that absorb at wavelengths >290 nm(3), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

The CIR Expert Panel concluded that the following ingredients are safe in the present practices of use andconcentration described in the safety assessment when formulated to be non-irritating and non-sensitizing, which may be basedon a QRA...Hydroxystearic Acid...

Safe for use in cosmetics, with qualifications

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 12-hydroxyoctadecanoic acid can be estimated to be 900(SRC). According to a classification scheme(2), this estimated Koc value suggests that 12-hydroxyoctadecanoic acid is expected to have low mobility in soil. The estimated pKa of 12-hydroxyoctadecanoic acid is 4.75(3), indicating that this compound will almost entirely exist in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

/HUMAN EXPOSURE STUDIES/ The skin irritation potential of four antiperspirant prototype formulations ... containing 7% hydroxystearic acid was evaluated using 35 healthy adult volunteers between the ages of 8 and 65 years old (33 females; 2 males). The four formulations were applied to the back of each subject (in vertical rows over the scapulae areas) in occlusive and semiocclusive patch tests. Prior to patch application, test sites on the back were wiped with a pad containing 70% isopropyl alcohol. Each formulation was applied to a patch by wiping the antiperspirant stick across the patch approximately five times. The quantity of test material applied per patch application (occlusive and semiocclusive) was in the range of 0.05 to 0.1 g. The semiocclusive patches were applied to the left side of the back three times, each for 48 hours (total of three 48-hour applications per test site). Occlusive patches were applied to the right side of the back (total of three 24-hours applications per test site). Both semiocclusive and occlusive patches were reinforced with strips of tape. Following patch removal, subjects were instructed to rinse the test sites with warm water. Patches were also removed by laboratory personnel, and were not reapplied to anysite that was assigned a score of 2 or greater. Test sites were evaluated for skin irritation within 24 hours after patch removal according to the following scale: 0 (no visible erythema) to 3 (severe erythema, very intense redness). Reactions to semiocclusive patches were scored on days 4, 7, and 10; occlusive patch test reactions were scored on days 4, 6, and 8. ... Semioccluded patches produced reactions in as many as nine of the subjects, whereas occluded patches produced reactions in as many as 17 individuals. Only two reactions were noted in the semioccluded patch controls and only one in the occluded patch controls. Although the formulations reportedly contained the same concentration of Hydroxystearic Acid, there were

/CASE REPORTS/ A 34-year-old male experienced severe allergic contact dermatitis from 12-hydroxystearic acid in a lip balm and from hydrogenated castor oil in an underarm deodorant. He also had a positive patch-test reaction to bis-diglyceryl polyacyladipate-2, which is present in the implicated lip balm and which itself contains 12-hydroxystearic acid. He was also incidentally found to have contact allergy to ricinoleic acid and castor oil. Ricinoleic acid is the principal fatty acid in castor oil, whereas 12-hydroxystearic acid is the principal fatty acid in hydrogenated castor oil. These two fatty acids are each 18-carbon 12-hydroxylated fatty acids, differing only in degree of saturation. The lack of patch-test reactivity to the analogous nonhydroxylated fatty acids, stearic acid (C18:0), and oleic acid (C18:1) indicates that 12-hydroxylation was required for allergenicity in this patient. In addition, serial dilution testing demonstrated that saturation of the hydroxylated C18 fatty acid enhanced its allergenicity.

AEROBIC: 12-Hydroxyoctadecanoic acid, present at 100 mg/L, reached 93% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/L in the Japanese MITI test(1), suggesting that biodegradation may be an important environmental fate process(SRC).

An estimated BCF of 56 was calculated in fish for 12-hydroxyoctadecanoic acid(SRC), using an estimated log Kow of 6.41(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC), provided the compound is not metabolized by the organism(SRC).

An estimated pKa of 4.75(1) indicates 12-hydroxyoctadecanoic acid will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(SRC). Volatilization from moist soil is not expected because the acid exists as an anion and anions do not volatilize(SRC). 12-Hydroxyoctadecanoic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.94X10-8 mm Hg(SRC), determined from a fragment constant method(2).

/LABORATORY ANIMALS: Acute Exposure/ The primary autoxidation products of polyunsaturated fatty acids are known to stimulate DNA synthesis and induce ornithine decarboxylase activity in colonic mucosa. ... The present study ... determined the structural features of the oxidized fatty acids necessary for the stimulation of these two components of mitogenesis. Compounds were instilled intrarectally in either aqueous or mineral oil vehicles and 3 hr later (ornithine decarboxylase activity) or 12 hr later (tritiated thymidine incorporation), the animals were killed and the colonic mucosa harvested for measurement of the two parameters of cell proliferation. Hydroperoxy and hydroxy fatty acids derived from oleate and stearate were studied. Ricinoleic acid and the alpha,beta-unsaturated ketone derived from oleic acid were also investigated. The minimal requirement for stimulation of cell proliferation is the presence of an oxidized functionally adjacent to a carbon-carbon double bond. All active compounds studied were roughly equipotent, which suggests a common mediator may be involved. These results imply that, in addition to biliary steroids, the autoxidation products of unsaturated fatty acids may play a role in the enhancement of tumorigenesis by high levels of dietary fat. Furthermore, the data suggest a possible mechanism of action for the active compounds. /Hydroxy fatty acid from stearate/

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ The subchronic (90-day) oral toxicity of hydrogenated castor oil was evaluated using weanling female rats (weights not stated). ... The fatty acid composition of the test substance was as follows: 86.5% 12-hydroxystearic acid, 10.3% nonoxygenated acids, and 3.2% 12-ketostearic acid. The rats were divided into groups of three and fed diets containing 5, 10, and 20% hydrogenated castor oil, respectively, for 90 days. Thus, the content of 12-Hydroxystearic acid in each diet was as follows: 5% diet (4.3% 12-hydroxystearic acid), 10% diet (8.7% 12-hydroxystearic acid) and 20% diet (17.3% 12-Hydroxystearic acid). The control group was fed a commercial rat diet. At necropsy, organ weights were recorded and numerous tissues were preserved for microscopic examination. Blood samples were obtained for hematological evaluation prior to necropsy. The only abnormality noted in this study was a reduced growth rate in rats fed diets containing 8.7 and 17.3% 12-hydroxystearic acid.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Sarcomas were elicited in mice at the site of repeated sc injections with 12-hydroxystearic acid.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... The carcinogenicity of 12-hydroxystearic acid was evaluated using the pulmonary tumor induction technique. The test substance was dissolved in 0.1 mL tricaprylin and injected intraperitoneally (ip) into each of nine strain A/He male mice (2 months old). Twelve ip injections were made three times per week for four weeks, and the total dose of 12-Hydroxystearic Acid that was administered was 60 mg. At 20 weeks after the last injection, the mice were killed, the lungs were excised and fixed, and the pulmonary nodules counted. A single pulmonary nodule was observed in one mouse and two mice had two pulmonary tumors each (mean = 0.6 lung tumor/animal). A comparison of these results with untreated mice indicated that the frequency of lung tumors was within the spontaneous occurrence.

12-Hydroxyoctadecanoic acid is not expected to undergo hydrolysis in the environment due to its lack of functional groups that hydrolyze under environmental conditions(1). 12-Hydroxyoctadecanoic acid does not contain chromophores that absorb at wavelengths >290 nm(1), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Chemical: Octadecanoic acid, 12-hydroxy-

Octadecanoic acid, 12-hydroxy- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Octadecanoic acid, 12-hydroxy- 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: 01-02-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/15245

Octadecanoic acid, 12-hydroxy-: Does not have an individual approval but may be used under an appropriate group standard

CIR ingredient: Hydroxystearic Acid

Used in lithium greases; as a chemical intermediate; as a defoamer in foods; as an ingredient in cosmetics; [HSDB]

Hydroxystearic acid is used as a surfactant-cleansing agent in cosmetic products.

12-Hydroxystearic acid has been used as a textile lubricant and as a saponifiable base for greases. 12-Hydroxystearic acid-polyethylene glycol block polymers have been approved by FDA for use as surfactants, for dispersions of polyacrylamide retention and draining aids, employed prior to the sheet forming operation in the manufacture of paper and paperboard that come in contact with aqueous and fatty foods.

Lithium greases; chemical intermediates

Used for skin and hair-cleaning purposes and as emulsifiers in cosmetics.

(1979) No Data

(1981) No Data

(1979) No Data

(1981) No Data

2023: 8,500,000 - <10,000,000 lb；2022: 4,000,000 - <5,500,000 lb；2021: 8,500,000 - <10,000,000 lb；2020: 10,000,000 - <50,000,000 lb

(1979) No Data

(1982) AT LEAST 2.27X10+6 G (SODIUM SALT)

Octadecanoic acid, 12-hydroxy- is listed as a High Production Volume (HPV) chemical (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).

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#5376]

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: Octadecanoic acid, 12-hydroxy-. Aggregated National Production Volume: < 500,000 lbs.

12-Hydroxystearic acid may be synthesized as follows: 2-hexylcyclododecanone is oxidized with a mixture of peracetic and permaleic acids in methylene chloride to form the lactone of Hydroxystearic acid. Alkaline hydrolysis of the lactone leads to the production of Hydroxystearic acid. Acylcyclododecanones, such as 2-hexylcyclododecanone, can be obtained by the addition of cyclododecanone at the double bond of the respective 1-alkene. This reaction occurs through a radical-chain mechanism; organic peroxides are used as initiators. The catalytic hydrogenation of castor oil to 12-Hydroxystearic acid has also been reported.

It is produced by hydrogenation of ricinoleic acid.

Fractional distillation of hydrolyzed hydrogenated castor oil.

EPA Safer Chemical Functional Use Classes -> Surfactants

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

Cosmetics -> Emulsifying; Cleansing; Surfactant

Petroleum Lubricating Oil and Grease Manufacturing；Paint and Coating Manufacturing；All Other Chemical Product and Preparation Manufacturing；Not Known or Reasonably Ascertainable

Octadecanoic acid, 12-hydroxy-: ACTIVE

Cosmetic oil bases are prepared with 12-hydroxystearic acid oligoesters which are produced by esterification of 12-hydroxystearic acid.

The synthesis of four sugar-based surfactants derived from glucose and (R)-12-hydroxystearic acid is described. The surfactants have a hydroxy group in the hydrophobic part, which is either free or acylated using acetyl chloride, hexanoyl chloride, or myristoyl chloride. Three of the synthesized surfactants are water-soluble and are evaluated with respect to their critical micelle concentrations and hemolytic activities. The fourth surfactant has limited water solubility and is not further included in the study. The investigated surfactants are all hemolytic close to their respective critical micelle concentration indicating that their use in parenteral formulations may be limited. Nevertheless, surfactants having the proposed structure appear as promising alternatives to existing solubilizing agents for pharmaceutical applications.