p-Menth-1-en-4-ol

log Kow = 3.26

3.26

2.8

0.926 g/cu cm at 20 °C

0.928-0.934

Slightly soluble in water, soluble in oils

Soluble (in ethanol)

209 °C

88.00 to 90.00 °C. @ 6.00 mm Hg

212 °C (d-isomer)

Warning

H302 (> 99.9%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P264+P265, P270, P271, P272, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P333+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2000 reports by companies from 29 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

H227: Combustible liquid [Warning Flammable liquids]

Chemical: 3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)-

Regulation (EC) No 1831/2003 (amended)

3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)- 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: 17-01-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/21354

Terpinen-4-ol: Does not have an individual approval but may be used under an appropriate group standard

4-Carvomenthenol is a food additive permitted for direct addition to food for human consumption as a synthetic flavoring substance and adjuvant in accordance with the following conditions: a) they are used in the minimum quantity required to produce their intended effect, and otherwise in accordance with all the principles of good manufacturing practice, and b) they consist of one or more of the following, used alone or in combination with flavoring substances and adjuvants generally recognized as safe in food, prior-sanctioned for such use, or regulated by an appropriate section in this part.

Carbon oxides

When heated to decomposition it emits acrid smoke and irritating fumes.

A skin irritant.

/Skin/ Terpineol applied at full strength ...produced moderate irritation.

Use water spray to cool unopened containers.

Wear self-contained breathing apparatus for firefighting if necessary. Use water spray to cool unopened containers

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Wear self-contained breathing apparatus for firefighting if necessary.

SRP: 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 air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

Product: This combustible material may be burned in a chemical incinerator equipped with an afterburner and scrubber. Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Contaminated packaging: Dispose of as unused product. Contaminated packaging: Dispose of as unused product.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapors accumulating to form explosive concentrations. Vapors can accumulate in low areas.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Skin protection: Handle with gloves.

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

This study compared the antimicrobial activity of Melaleuca alternifolia (tea tree) oil with that of some of its components, both individually and in two-component combinations. Minimum inhibitory concentration and time-kill assays revealed that terpinen-4-ol, the principal active component of tea tree oil, was more active on its own than when present in tea tree oil. Combinations of terpinen-4-ol and either gamma-terpinene or p-cymene produced similar activities to tea tree oil. Concentration-dependent reductions in terpinen-4-ol activity and solubility also occurred in the presence of gamma-terpinene. Non-oxygenated terpenes in tea tree oil appear to reduce terpinen-4-ol efficacy by lowering its aqueous solubility. These findings explain why tea tree oil can be less active in vitro than terpinen-4-ol alone and further suggest that the presence of a non-aqueous phase in tea tree oil formulations may limit the microbial availability of its active components.

Terpinen-4-ol (4TRP) is a monoterpenoid alcoholic component of essential oils obtained from several aromatic plants. We investigated the psychopharmacological and electrophysiological activities of 4TRP in male Swiss mice and Wistar rats. 4TRP was administered intraperitoneally (i.p.) at doses of 25 to 200 mg/kg and intracerebroventricularly (i.c.v.) at concentrations of 10, 20, and 40 ng/2 uL. For in vitro experiments, 4TRP concentrations were 0.1mM and 1.0mM. 4TRP (i.p.) inhibited pentylenetetrazol- (PTZ-) induced seizures, indicating anticonvulsant effects. Electroencephalographic recordings showed that 4TRP (i.c.v.) protected against PTZ-induced seizures, corroborating the behavioural results. To determine whether 4TRP exerts anticonvulsant effects via regulation of GABAergic neurotransmission, we measured convulsions induced by 3-mercapto-propionic acid (3-MP). The obtained results showed involvement of the GABAergic system in the anticonvulsant action exerted by 4TRP, but flumazenil, a selective antagonist of the benzodiazepine site of the GABAA receptor, did not reverse the anticonvulsant effect, demonstrating that 4TRP does not bind to the benzodiazepine-binding site. Furthermore, 4TRP decreased the sodium current through voltage-dependent sodium channels, and thus its anticonvulsant effect may be related to changes in neuronal excitability because of modulation of these channels.

Artemisia phaeolepis, a perennial herb with a strong volatile odor, grows on the grasslands of Mediterranean region. Essential oil obtained from Artemisia phaeolepis was analyzed by gas chromatography-flame ionization detection and gas chromatography-mass spectrometry. A total of 79 components representing 98.19% of the total oil were identified, and the main compounds in the oil were found to be eucalyptol (11.30%), camphor (8.21%), terpine-4-ol (7.32%), germacrene D (6.39), caryophyllene oxide (6.34%), and caryophyllene (5.37%). The essential oil showed definite inhibitory activity against 10 strains of test microorganisms. Eucalyptol, camphor, terpine-4-ol, caryophyllene, germacrene D and caryophyllene oxide were also examined as the major components of the oil. Camphor showed the strongest antimicrobial activity; terpine-4-ol, eucalyptol, caryophyllene and germacrene D were moderately active and caryophyllene oxide was weakly active. The study revealed that the antimicrobial properties of the essential oil can be attributed to the synergistic effects of its diverse major and minor components.

The combined effect of terpinen-4-ol, the main component of tea tree oil, and capric acid against mycelial growth of Candida albicans and murine oral candidiasis was evaluated in vitro and in vivo. Mycelial growth of C. albicans was estimated by the Cristal violet method. Combination of these compounds revealed a potent synergistic inhibition of growth. Therapeutic efficacy of the combination was evaluated microbiologically in murine oral candidiasis, and its application of the compounds clearly demonstrated therapeutic activity. Based on these results, the combined agent of terpinen-4-ol and capric acid was discussed as a possible candidate for oral candidiasis therapy.

The present study investigated the hypotensive responses to intravenous (i.v.) treatment with the essential oil of Alpinia zerumbet (EOAZ) and its main constituent, terpinen-4-ol (Trp-4-ol), in the experimental model of deoxycorticosterone-acetate (DOCA)-salt hypertensive rat. In both DOCA-salt hypertensive and uninephrectomized, normotensive rats, i.v. bolus injections of EOAZ (1-20 mg/kg) or Trp-4-ol (1-10 mg/kg) decreased mean aortic pressure (MAP) in a dose-related manner. However, hypotensive responses to Trp-4-ol were significantly greater than those evoked by the same doses of EOAZ (1-10 mg/kg). Treatment with DOCA-salt significantly enhanced the maximal percentage decreases in MAP evoked by EOAZ or Trp-4-ol. Likewise, both maximal percentage and absolute decreases in MAP elicited by i.v. injection of the ganglion blocker, hexamethonium (30 mg/kg), were significantly greater in DOCA-salt hypertensive than in control rats. In DOCA-salt hypertensive rats, neither hexamethonium (30 mg/kg, i.v.) nor methylatropine (1 mg/kg, i.v.) pretreatment affected the enhancement of EOAZ-induced hypotension. These results show that i.v. treatment with either EOAZ or Trp-4-ol dose-dependently decreases blood pressure in conscious DOCA-salt hypertensive rats, and this action is enhanced when compared with uninephrectomized controls. This enhancement could be related mainly to an increase in EOAZ-induced vascular smooth muscle relaxation rather than to enhanced sympathetic nervous system activity in this hypertensive model. The data further support our previous hypothesis that hypotensive effects of EOAZ are partially attributed to the actions of Trp-4-ol.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a structure estimation method(2), indicates that 4-terpineol is expected to have high mobility in soil(SRC). Volatilization of 4-terpineol from moist soil surfaces is expected(SRC) given an estimated Henry's Law constant of 3.2X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(2). 4-Terpineol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.04 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Aerobic degradation studies done using batch and continuous digesters resulting in 96% 4-terpineol removal(3) suggest that biodegradation may be an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a structure estimation method(2), indicates that 4-terpineol is not 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 3.2X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 15 and 110 days, respectively(SRC). 4-Terpineol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). According to a classification scheme(4), an estimated BCF of 66(SRC), from its log Kow of 3.26(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Aerobic degradation studies done using batch and continuous digesters resulting in 96% 4-terpineol removal(6) suggest that biodegradation may be 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), 4-terpineol, which has a estimated vapor pressure of 0.04 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 4-terpineol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals and ozone(SRC); the half-lives for these reactions in air are estimated to be 3.7 hours and 38 minutes(SRC), calculated from respective rate constants of 1.0X10-10 and 4.3X10-16 cu cm/molecule-sec at 25 °C(SRC) that were derived using a structure estimation method(2). 4-Terpineol 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).

4-Terpineol was identified, not quantified, in the volatile emissions of raw earth almonds(1), Frankfurter sausages(2), edible Korean chamchwi (Aster scaber Thunb)(3), apricots(4), pine needle tea(5), roasted filberts(6), and nectarines(7). 4-Terpineol was detected in fresh-squeezed unpasteurized orange juice from five of six different cultivars at 0.071-0.20 ppm(8). 4-Terpineol has been detected in beer, wine and spirits(9).

IDENTIFICATION AND USE: 1-Terpinen-4-ol is colorless to pale yellow liquid with pine odor. It is found in more than 200 derivatives from leaves, herbs, and flowers. It is used in artificial geranium and pepper oils and in perfumery for creating herbaceous and lavender notes. It is also used as experimental medication and topical antimicrobial. HUMAN EXPOSURE AND TOXICITY: Terpinen-4-ol can induce human leukemic MOLT-4 cell apoptosis via both intrinsic and extrinsic pathways. It suppress the production of superoxide by monocytes, but not neutrophils, suggesting the potential for selective regulation of cell types by these components during inflammation. In addition, the water-soluble components of tea tree oil can suppress pro-inflammatory mediator production by activated human monocytes. ANIMAL STUDIES: Oral LD50's range from 1.0 to 4.3 g/kg in rodents. A single study of dermal toxicity in rabbits reported a LD50 of >3 g/kg.

Pineapple guava contained 4-terpineol at 0.03 ug/g(1). 4-Terpineol has been identified as a volatile emission from big sagebrush and choke cherry trees(2). 4-Terpineol was identified as a volatile component of fresh ginger root(3). 4-Terpineol was found to be 7.32% of the essential oil of the perennial herb Artemisia phaeolepis; plants were collected from Qassim, Saudi Arabia(4). 4-Terpineol has been reported in the oil of Cupressus macrocarpa lavender, Spanish origanum, Ledum palustre, Eucalyptus australiana, Eucalyptus dives, Xanthoxylum rhetsa and camphor oil(5). It has been found in fresh apple, apricots, orange juice, peel oils of orange, lemon, grapefruit, tangerines, anise, cinnamon, ginger and nutmeg(5).

4-Terpineol detections in plants(1).[Table#8246]

4-Terpineol was detected in wastewater effluent at unreported concentrations from plastics and synthetics industries(1). 4-Terpineol was detected in a final effluent sample collected Apr 17, 1980 from a publicly owned water treatment plant in Addison, IL at an unreported concentration; grab samples from 9 other sites in Illinois did not contain detectable concentrations of 4-terpineol(2). 4-Terpineol was detected in effluent from two kraft pulp mill waste waters receiving secondary treatment in aerated lagoons(3). 4-Terpineol was detected at unreported concentrations in head space analyses of kitchen waste exudate(4) and garden waste exudate(5) collected in Denmark. 4-Terpineol was detected in the primary clarifier effluent from a Finnish bleached kraft pulp mill(6). 4-Terpineol was detected in 4 of 9 aerated lagoon discharge samples at a mean and range of 50 and 10-100 ug/L, respectively; samples were collected from softwood bleached kraft pulp mills located across Canada during winter 1980-1981(7).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 4-terpineol can be estimated to be 80(SRC). According to a classification scheme(2), this estimated Koc value suggests that 4-terpineol is expected to have high mobility in soil.

4-Terpineol occurs naturally in many plants and plant volatiles including; guava(1), big sagebrush and choke cherry trees(2), ginger root(3), Artemisia phaeolepis(4), lavender(5), Eucalyptus(5), apple(5), apricots(5), orange(5), lemon(5), grapefruit(5), tangerines(5), anise(5), cinnamon(5) and nutmeg(5).

/ALTERNATIVE and IN VITRO TESTS/ Terpinen-4-ol is a terpene found in the rhizome of Plai (Zingiber montanum (Koenig) Link ex Dietr.). In this study apoptogenic activity and mechanisms of cell death induced by terpinen-4-ol were investigated in the human leukemic MOLT-4 cell line. Terpinen-4-ol exhibited cytotoxicity in MOLT-4 cells, with characteristic morphological features of apoptosis by Wright's staining. The mode of cell death was confirmed to be apoptosis by flow cytometric analysis after staining with annexin V-FITC and propidium iodide. A sub-G1 peak in DNA histograms of cell cycle assays was observed. Terpinen-4-ol induced-MOLT-4 cell apoptosis mediated through an intrinsic pathway involving the loss of mitochondrial transmembrane potential (MTP) and release of cytochrome c into the cytosol. In addition, terpinen-4-ol also induced apoptosis via an extrinsic pathway by caspase-8 activation resulting in the cleavage of cytosolic Bid. Truncated-Bid (tBid) translocated to mitochondria and activated the mitochondrial pathway in conjunction with down-regulation of Bcl-2 protein expression. Caspase-3 activity also increased. In conclusion, terpinen-4-ol can induce human leukemic MOLT-4 cell apoptosis via both intrinsic and extrinsic pathways.

/ALTERNATIVE and IN VITRO TESTS/ To evaluate the regulatory properties of the essential oil of Melaleuca alternifolia (tea tree oil) on the production of oxygen derived reactive species by human peripheral blood leukocytes activated in vitro. The ability of tea tree oil to reduce superoxide production by neutrophils and monocytes stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP), lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) was examined. The water-soluble fraction of tea tree oil had no significant effect on agonist-stimulated superoxide production by neutrophils, but significantly and dose-dependently suppressed agonist-stimulated superoxide production by monocytes. This suppression was not due to cell death. Chemical analysis identified the water-soluble components to be terpinen-4-ol, alpha-terpineol and 1,8-cineole. When examined individually, terpinen-4-ol significantly suppressed fMLP- and LPS- but not PMA-stimulated superoxide production; alpha-terpineol significantly suppressed fMLP-, LPS- and PMA-stimulated superoxide production; 1,8-cineole was without effect. Tea tree oil components suppress the production of superoxide by monocytes, but not neutrophils, suggesting the potential for selective regulation of cell types by these components during inflammation.

/ALTERNATIVE and IN VITRO TESTS/ To evaluate potential antiinflammatory properties of tea tree oil, the essential oil steam distilled from the Australian native plant, Melaleuca alternifolia. The ability of tea tree oil to reduce the production in vitro of tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-1beta, IL-8, IL-10 and prostaglandin E2 (PGE2) by lipopolysaccharide (LPS)-activated human peripheral blood monocytes was examined. Tea tree oil emulsified by sonication in a glass tube into culture medium containing 10% fetal calf serum (FCS) was toxic for monocytes at a concentration of 0.016% v/v. However, the water soluble components of tea tree oil at concentrations equivalent to 0.125% significantly suppressed LPS-induced production of TNFalpha, IL-1beta and IL-10 (by approximately 50%) and PGE2 (by approximately 30%) after 40 h. Gas chromatography/mass spectrometry identified terpinen-4-ol (42 %), a-terpineol (3 %) and 1,8-cineole (2%, respectively, of tea tree oil) as the water soluble components of tea tree oil. When these components were examined individually, only terpinen-4-ol suppressed the production after 40 h of TNFalpha, IL-1beta, IL-8, IL-10 and PGE2 by LPS-activated monocytes. The water-soluble components of tea tree oil can suppress pro-inflammatory mediator production by activated human monocytes. /Tea tree oil/

AEROBIC: Utilizing both batch and continuous digesters, 96% removal of 4-terpineol (initial concentration of 0.50 ppm) was reported when it was incubated for 168-192 hr under aerobic conditions using sewage inoculum in a biological treatment study(1).

4-Carvomenthenol is a food additive permitted for direct addition to food for human consumption as a synthetic flavoring substance and adjuvant in accordance with the following conditions: a) they are used in the minimum quantity required to produce their intended effect, and otherwise in accordance with all the principles of good manufacturing practice, and b) they consist of one or more of the following, used alone or in combination with flavoring substances and adjuvants generally recognized as safe in food, prior-sanctioned for such use, or regulated by an appropriate section in this part.

(R)-Terpinen-4-ol was mixed in an artificial diet at a concentration of 1 mg/g of diet, and the diet was fed to the last instar larvae of common cutworm (Spodoptera litura). Metabolites were recovered from frass and analyzed spectroscopically. (R)-Terpinen-4-ol was transformed mainly to (R)-p-menth-1-en-4,7-diol. Similarly, (S)-terpinen-4-ol was transformed mainly to (S)-p-menth-1-en-4,7-diol. The C-7 position (allylic methyl group) of (R)- and (S)-terpinen-4-ol was preferentially oxidized.

We examined the in vitro metabolism of (+)-terpinen-4-ol by human liver microsomes and recombinant enzymes. The biotransformation of (+)-terpinen-4-ol was investigated by gas chromatography-mass spectrometry (GC-MS). (+)-Terpinen-4-ol was found to be oxidized to (+)-(1R,2S,4S)-1,2-epoxy-p-menthan-4-ol, (+)-(1S,2R,4S)-1,2-epoxy-p-menthan-4-ol, and (4S)-p-menth-1-en-4,8-diol by human liver microsomal P450 enzymes. The identities of (+)-terpinen-4-ol metabolites were determined through the relative abundance of mass fragments and retention times on GC-MS. Of 11 recombinant human P450 enzymes tested, CYP1A2, CYP2A6, and CYP3A4 were found to catalyze the oxidation of (+)-terpinen-4-ol. Based on several lines of evidence, CYP2A6 and CYP3A4 were determined to be major enzymes involved in the oxidation of (+)-terpinen-4-ol by human liver microsomes. First, of the 11 recombinant human P450 enzymes tested, CYP1A2, CYP2A6 and CYP3A4 catalyzed oxidation of (+)-terpinen-4-ol. Second, oxidation of (+)-terpinen-4-ol was inhibited by (+)-menthofuran and ketoconazole, inhibitors known to be specific for these enzymes. Finally, there was a good correlation between CYP2A6 and CYP3A4 activities and (+)-terpinen-4-ol oxidation activities in the 10 human liver microsomes.

The terpenes disturb lipid arrangement in the intercellular region of the stratum corneum (SC) that leads to the increased permeability of the skin. This effect is used in technology of transdermal drug forms and depends on physicochemical properties of terpenes and their amounts penetrated to the stratum corneum; however terpenes do not need penetrate into viable skin tissue and this event is not even desired. To correlate skin absorption and elimination kinetics of four cyclic terpenes, namely alpha-pinene, beta-pinene, eucalyptol and terpinen-4-ol, applied as neat substance with their physicochemical properties. The terpenes were applied onto the human skin in vitro, and after 1-4 h their content in the separated by a tape-stripping method stratum corneum layers and in the epidermis/dermis was determined using GC. Similarly, the amounts of terpenes in the skin were analysed during 4 h following 1 h absorption. The fastest and progressive penetration into all skin layers was observed for terpinen-4-ol. All studied terpenes are absorbed in the viable epidermis/dermis, however penetration into this layers is time-dependent process, constantly increasing during 4 h. Like for stratum corneum, the largest cumulation in epidermis/dermis was observed for terpinen-4-ol. The elimination of terpenes from the stratum corneum was fast, especially in deeper layers, and much faster if the initial cumulation was small. Investigated cyclic terpenes represent different penetration and elimination characteristics and do not permeate across the skin to the acceptor medium due to large cumulation in the skin tissue. The penetration of terpenes into stratum corneum is greater if their log P-value is close to 3.

The purpose of this study was to evaluate the in vitro cutaneous penetration of five terpenes--linalool, linalyl acetate, terpinen-4-ol, citronellol and alpha-pinene--applied in pure essential oils or in dermatological formulations (o/w emulsion, oily solution or hydrogel) containing 0.75 % w/w of the essential oils. Different skin absorption was observed depending on the type of the vehicle and terpenes' log P values. Cutaneous accumulation of terpenes is several times higher when they are applied in pure essential oils than in topical vehicles. Penetration of terpinen-4-ol to the skin was better from an oily solution (approximately 90 ug/cm (2)) than from an emulsion (60 ug/cm (2)). No penetration of linalyl acetate from topical vehicles into viable skin was observed, but also for this terpene penetration to the upper layers of the stratum corneum was 2-times higher when an oily solution was used. In contrast, the cutaneous absorption of linalool was the same from both vehicles (50-60 ug/cm (2)). The skin penetration of alpha-pinene was not traceable when it was applied in an oily solution. Only a small amount (approximately 5 ug/cm (2)) of this terpene was determined in viable skin after application as a hydrogel. Citronellol applied in a hydrogel penetrated into all skin layers in a total amount of 25 ug/cm (2), while no penetration into viable skin layers after application of an oily solution was noted. Only citronellol permeated into the acceptor medium.

This work aimed to evaluate the effect induced by excipients conventionally used for topical dosage forms, namely isopropyl myristate (IPM) or oleic acid (OA) or polyethylene glycol 400 (PEG400) or Transcutol (TR), on the human skin permeability of terpinen-4-ol (T4OL) contained in the pure Tea tree oil. The effect of such excipients was determined by evaluating the absorption of T4OL using human epidermis and the perturbation of the organization of stratum corneum by ATR-FTIR. Among the tested excipients OA enhanced the absorption of T4OL by perturbing the stratum corneum lipid barrier. Other excipients caused a weak enhancement effect and their use should be carefully monitored.

The purpose of this study was to investigate dermal pharmacokinetics of terpinen-4-ol in rats following topical administration of plai oil derived from the rhizomes of Zingiber cassumunar Roxb. Unbound terpinen-4-ol concentrations in dermal tissue were measured by microdialysis. The dermal pharmacokinetic study of terpinen-4-ol was performed under non-occlusive conditions. The oil was topically applied at a dose of 2, 4, and 8 mg/square cm plai oil corresponding to the amount of 1.0, 1.9, and 3.8 mg/square cm terpinen-4-ol, respectively. Following topical application of the oil, terpinen-4-ol rapidly distributed into the dermis and demonstrated linear pharmacokinetics with no changes in the dose-normalized area under the concentration-time curves across the investigated dosage range. The mean percentages of free terpinen-4-ol distributed in the dermis per amount of administered were 0.39 +/- 0.06 %, 0.41 +/- 0.08 %, and 0.30 +/- 0.03 % for 2, 4, and 8 mg/square cm doses, respectively. The dermal pharmacokinetics of terpinen-4-ol could provide information for its further formulation development and therapy schedules.

It is used ... in artificial geranium and pepper oils and in perfumery for creating herbaceous and lavender notes.

In public use since the 1890's. In the United States, use in fragrances amounts for about 1 million lbs/ year.

Reported uses (ppm):

MEDICATION

2023: 87 lb

Non-confidential 2012 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: 3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)-. National Production Volume: 29,751 lb/yr.

1-Terpinen-4-ol is a byproduct in the synthesis of terpineol from terpin hydrate, and occurs in commercial terpineol. Pure 1-terpinen-4-ol can be prepared from terpinolene by photosensitized oxidation, reduction of the resulting 1-methyl-4-isopropenyl-1-cyclohexene-4-hydroperoxide, and selective hydrogenation of the corresponding alcohol.

Prepared from terpin hydrate by the splitting off the elements of water.

One of several terpinenol isomers, depending on the position of the double bond and that of the hydroxyl group, this terpene ... can be isolated by fractional distillation.

Fragrance Ingredients

Flavoring Agents -> JECFA Flavorings Index

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)-: ACTIVE

Found in more than 200 derivatives from leaves, herbs, and flowers.