Eugenol

Pharmaceuticals

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Analgesics and anti-inflammatories

Cosmetics ingredient -> Base; Emulsifier; Flavor; Fragrance; Moisturizing/Humectant; Other (Specify)

Denaturant; Tonic

Fragrance Ingredient (Eugenol) -> IFRA transparency List

Fragrance

Agrochemicals -> Pesticide active substances

Active substance -> EU Pesticides database: Approved

log Kow = 2.49

2.270

2.49

Odor of cloves

Warm, spicy, floral

1.0652 at 68 °F (NTP, 1992) - Denser than water; will sink

1.0652 g/cu cm at 20 °C

1.064-1.070

This chemical does not meet GHS hazard criteria for 0.2% (5 of 2820) of reports.

Warning

H302 (17.3%): Harmful if swallowed [Warning Acute toxicity, oral]

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

Aggregated GHS information provided per 2820 reports by companies from 27 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

Chemical: Phenol, 2-methoxy-4-(2-propenyl)-

Hazard Traits - Fragrance Allergen

Regulation (EC) No 1831/2003 (amended)

Phenol, 2-methoxy-4-(2-propen-1-yl)- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Phenol, 2-methoxy-4-(2-propen-1-yl)- 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)

2007/442/EC, Dossier complete 2011/266/EU, Reg. (EU) 2018/155, Reg. (EU) 2023/1757, Reg. (EU) No 546/2013

Status: Active Update: 13-10-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/13694

SYMPTOMS: This compound is a primary irritant and sensitizer and can cause contact dermatitis. Irritation of the skin, eyes and respiratory tract occurs. Ingestion of this compound may cause gastroenteritis, vomiting and gastric secretion of mucin. It may also cause abdominal burning, nausea, diarrhea and convulsions. Ingestion of large amounts can cause liver damage and gastrointestinal damage. Inhalation of this compound can lead to bronchial irritation, dizziness, and rapid and shallow breathing. Skin contact may cause an inflammatory reaction on the skin. Prolonged or repeated skin contact may cause allergic dermatitis. Eye contact may cause burns. Skin sensitization may also occur. Symptoms of exposure to this type of compound include intense irritation of all tissues, circulatory collapse, dysuria, hematuria, unconsciousness, tachycardia, pulmonary edema, bronchial pneumonia, abortion and irreversible renal damage.

A contact skin allergen present in cosmetics and foods; [Marks, p. 172] Occupational asthma confirmed in a hairdresser; [Malo] Toxic by ingestion: metabolic acidosis, proteinuria, hepatotoxicity, CNS depression, ataxia, and convulsions; [HSDB] Generally regarded as safe (GRAS) for use in foods; [FDA] A primary irritant; May cause skin sensitization and contact dermatitis; [CAMEO] Safe when used as a flavoring agent in food; Acceptable daily intake (ADI) of 0-2.5 mg/kg; [JECFA] Mildly irritating to human skin; [RTECS]

Substance added directly to human food affirmed as generally recognized as safe (GRAS).

Synthetic flavoring substances and adjuvants /for animal drugs, feeds, and related products/ that are generally recognized as safe for their intended use, within the meaning of section 409 of the Act. Eugenol is included on this list.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: Eugenol is included in external analgesic drug products and skin protectant drug products.

Zinc oxide-eugenol is a device composed of zinc oxide-eugenol intended to serve as a temporary tooth filling or as a base cement to affix a temporary tooth filling, to affix dental devices such as crowns or bridges, or to be applied to a tooth to protect the tooth pulp.

Exemptions for pesticides of a character not requiring FIFRA regulation. The pesticides or classes of pesticides listed in this section have been determined to be of a character not requiring regulation under FIFRA, and are therefore exempt from all provisions of FIFRA when intended for use, and used, only in the manner specified. Eugenol is included on this list.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer saftey standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. Eugenol is found on List D. Case No: 4038; Pesticide type: insecticide; Case Status: Pesticides in the case have been exempted from regulation under FIFRA Section 25 (b).; Active ingredient (AI): eugenol; AI Status: OPP has completed a Reregistration Eligibility Decision (RED) for the case/AI.

2 - Materials that, under emergency conditions, can cause temporary incapacitation or residual injury.

2 - Materials that must be moderately heated or exposed to relatively high ambient temperatures before ignition can occur. Materials would not under normal conditions form hazardous atmospheres with air, but under high ambient temperatures or under moderate heating could release vapor in sufficient quantities to produce hazardous atmospheres with air.

0 - Materials that in themselves are normally stable, even under fire conditions.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, FIRST REMOVE ALL SOURCES OF IGNITION. Then, use absorbent paper to pick up all liquid spill material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity 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 and plant life; and conformance with environmental and public health regulations.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Mice treated with eugenol (400-600 mg/kg, orally) in combination with an inhibitor of glutathione synthesis, buthionine sulfoximine (1 hr before eugenol, 4 mmol/kg, ip) developed hepatotoxicity characterized by increases in relative liver weight and serum glutamic-pyruvic transaminase, hepatic congestion, and centrilobular necrosis of hepatocytes. Eugenol (up to 600 mg/kg) alone produced no hepatotoxicity. Drug metabolism inhibitors such as carbon disulfide, methoxsalen, and piperonyl butoxide prevented or significantly reduced the hepatotoxic effect of eugenol given in combination with buthionine sulfoximine.

The present study was undertaken to evaluate the chemopreventive potential of eugenol alone and in combination with a chemotherapeutic agent such as gemcitabine. Eugenol showed dose-dependent selective cytotoxicity toward HeLa cells in comparison to normal cells, pointing to its safe cytotoxicity profile. A combination of eugenol and gemcitabine induced growth inhibition and apoptosis at lower concentrations, compared with the individual drugs. The analysis of the data using a combination index showed combination index values of <1 indicating strong synergistic interaction. The combination thus may enhance the efficacy of gemcitabine at lower doses and minimize the toxicity on normal cells. In addition, the expression analysis of genes involved in apoptosis and inflammation revealed significant downregulation of Bcl-2, COX-2, and IL-1beta on treatment with eugenol. Thus, the results suggest that eugenol exerts its anticancer activities via apoptosis induction and anti-inflammatory properties and also provide the first evidence demonstrating synergism between eugenol and gemcitabine, which may enhance the therapeutic index of prevention and/or treatment of cervical cancer.

The biochemical mechanisms underlying the increased toxicity of several plant essential oils (thymol, eugenol, pulegone, terpineol, and citronellal) against fourth instar of Aedes aegypti L. when exposed simultaneously with piperonyl butoxide (PBO) were examined. Whole body biotransformational enzyme activities including cytochrome P450-mediated oxidation (ethoxyresorufin O-dethylase (EROD)), glutathione S-transferase (GST), and beta-esterase activity were measured in control, essential oil-exposed only (single chemical), and essential oil + PBO (10 mg/liter) exposed larvae. At high concentrations, thymol, eugenol, pulegone, and citronellal alone reduced EROD activity by 5-25% 16 h postexposure. Terpineol at 10 mg/liter increased EROD activity by 5 +/- 1.8% over controls. The essential oils alone reduced GST activity by 3-20% but PBO exposure alone did not significantly affect the activity of any of the measured enzymes. All essential oils in combination with PBO reduced EROD activity by 58-76% and reduced GST activity by 3-85% at 16 hr postexposure. This study indicates a synergistic interaction between essential oils and PBO in inhibiting the cytochrome P450 and GST detoxification enzymes in Ae. aegypti.

... Swiss albino mice were administered different doses of eugenol (75,150 and 300 mg/kg) before exposure to 1.5 Gy of gamma radiation. The micronucleus test was carried out to determine the genetic damage in bone marrow. Our results demonstrated significant reduction in the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) with all three eugenol doses. Eugenol (150 mg/kg) was also tested against different doses of radiation (0.5, 1, 1.5, and 2 Gy) and was found to afford significant radioprotection. Reduction in the incidence of MnPCEs could be noticed up to 72 hr postirradiation (1.5 Gy). Moreover, the level of peroxidative damage and the specific activities of lactate dehydrogenase (LDH) and methylglyoxalase I (Gly I) were observed in the liver of mice treated with eugenol for seven days in comparison to untreated mice.

For more Interactions (Complete) data for EUGENOL (7 total), please visit the HSDB record page.

The low concentrations of eugenol and clove extracts used topically and in herbal products have not been convincingly linked to instances of liver injury, either in the form of serum enzyme elevations or clinically apparent liver injury. In high doses, however, eugenol appears to be a direct cytotoxin and several instances of severe acute liver and kidney injury have been reported after accidental overdose of eugenol containing herbal products, largely in children. Overdoses have been marked by the onset of agitation, decrease in consciousness and coma arising within hours on ingestion (10-30 mL of clove oil). There is typically an accompanying acidosis, respiratory depression and severe hypoglycemia requiring ventilation and intravenous glucose. Liver injury arises 12 to 24 hours after ingestion with marked elevations in serum aminotransferase levels and early coagulation abnormalities. Signs of hepatic failure arise rapidly, and jaundice can develop and deepen. The overall clinical presentation is typical of acute hepatic necrosis and similar to that of acetaminophen, iron or copper overdose. The liver injury generally worsens for several days but then rapidly improves and ultimately resolves within 1 to 3 weeks. Renal dysfunction may also occur but rarely requires intervention or dialysis. Long term injury or effects have not been described. Cases described in the literature have been in infants who swallowed clove oil being used by parents.

LC50 Oncorhynchus kisutch (Coho salmon, juvenile approximately 2-3 months old) 67.6 mg/L/24, 48, 72 hr; 66.1 mg/L/96 hr; static, 15 +/-1 °C, mean hardness 95 mg/L CaCO3, average fish loading density was 0.4 (0.3-0.5) g/L, within a bioassay test volume of 20 L.

LC50 Oncorhynchus mykiss (Rainbow trout, juvenile approximately 2-3 months old) 61.5 mg/L/24 hr; 60.8 mg/L/48, 72, 96 hr; static, 15 +/-1 °C, mean hardness 95 mg/L CaCO3, average fish loading density was 0.4 (0.3-0.5) g/L, within a bioassay test volume of 20 L.

LC50 Pimephales promelas (Fathead minnow) 24 mg/L/1, 24, 48, 72, 96 hr; static /formulated product/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 340(SRC), determined from a log Kow of 2.49(2) and a regression-derived equation(3), indicates that eugenol is expected to have moderate mobility in soil(SRC). Volatilization of eugenol from moist soil surfaces is expected to occur(SRC) given a an estimated Henry's Law constant of 1.92X10-6 atm-cu m/mole(SRC), estimated from its vapor pressure, 0.0221 mm Hg at 25 °C(4), and water solubility, 2460 mg/L(5). A theoretical model of soil volatilization predicts that 4-33% of eugenol applied to a soil surface will volatilize during the first 10 days(6); the fastest volatilization rates occur with lowest soil organic content and moisture content(6). Isoeugenol, which is structurally similar to eugenol, was found to be readily biodegradable using a Manometric Respirometry Test in which isoeugenol reached 79% biodegradation after 28 days(7); by analogy, eugenol may also be readily biodegradable(SRC). Eugenol absorbs uv light at wavelengths >290 nm(8), and therefore may be susceptible to direct photolysis on soil surfaces exposed to sunlight(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 340(SRC), determined from a log Kow of 2.49(2) and a regression-derived equation(3), indicates that eugenol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected to occur slowly(4) based upon an estimated Henry's Law constant of 1.92X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 0.0221 mm Hg at 25 °C(5), and water solubility, 2460 mg/L(6). Using this Henry's Law constant and an estimation method(4), volatilization half-lives for a model river and model lake are 25 and 183 days, respectively(SRC). According to a classification scheme(7), an estimated BCF of 20(SRC), from its log Kow and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Eugenol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(4). Eugenol absorbs UV light at wavelengths >290 nm(8), and therefore may be susceptible to direct photolysis by sunlight in water(SRC). Isoeugenol, which is structurally similar to eugenol, was found to be readily biodegradable using a Manometric Respirometry Test (OECD Guideline 301F) in which isoeugenol reached 79% biodegradation after 28 days(9); by analogy, eugenol may also be readily biodegradable(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), eugenol, which has a vapor pressure of 0.0221 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase eugenol 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 5.9 hours(SRC), calculated from its rate constant of 6.5X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Vapor-phase eugenol is also degraded in the atmosphere by reaction with ozone(SRC); the half-life for this reaction in air is estimated to be 23 hours(SRC), calculated from its rate constant of 1.2X10-17 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Eugenol absorbs UV light at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). Irradiation of eugenol in methanol solution yields 4-cyclopropyl-2-methoxyphenol as the main photodegradation product(5); sunlight degrades the main constituents of essential oils(5).

Eugenol was identified as a volatile aroma component from frankfurters and sausages(1,2). Eugenol was identified as a volatile component from the edible Korean Chamchwi plant(3). A red wine with an initial eugenol concentration of 15 mg/L had the eugenol concentration increase to 23.6 to 80.95 mg/L after aging in Spanish, French and American oak barrels(4).

REPORTED USED IN NON-ALCOHOLIC BEVERAGES 1.4 PPM; ICE CREAM, ICES, ETC 3.1 PPM; CANDY 32 PPM; BAKED GOODS 33 PPM; GELATINS & PUDDINGS 0.60 PPM; CHEWING GUM 500 PPM; CONDIMENTS 9.6-100 PPM; MEATS 40-2000 PPM.

The Flavor and Extract Manufacturers' Association of the United States (1978) has reported the occurrence of eugenol, without specific concentrations, in the following food sources: cocoa, Japanese ginger oil, loganberries, mace essential oil, sweet marjoram dried mushrooms, nutmeg, yellow passion fruit, black pepper, peppermint, pimento berry oil and tomatoes.

Eugenol was detected in the skin and pulp of Queen Anne's pocket melon (Cucumis melo var dudaim (L.) Naudin) at respective concentrations of 2302.4 mg/kg and 225.1 mg/kg(1).

Eugenol concentrations in various plants(1).[Table#823]

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from, as of June 21, 2012: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=97-53-0]

Eugenol was qualitatively detected in the wastewater effluent from one of ten publicly-owned treatment works in Illinois in 1980(1). A eugenol concentration of 0.18 ug/L was detected in the secondary effluent from a rapid infiltration site in Fort Polk, LA in 1980(2). A eugenol concentration of 0.025 mg/L was detected in the effluent from a kraft paper mill in GA(3). Eugenol was detected in 8 effluents collected from 13 paper and pulp in Quebec, Canada in1990 at a concentration of 0 (detection limit not specified) to 18743 ug/L(2).

The eugenol concentration in the fine particle emissions from the fireplace combustion of six species of wood grown in the northeastern US ranged from0.059 to 0.254 mg/g organic content emitted(1). The eugenol concentration in the fine particle emissions from the fireplace combustion of six species of wood grown in the southern US ranged from 0.044 to 0.161 mg/g organic content emitted(2). The emission rate of eugenol in wood smoke from the combustion of pine wood logs, oak wood logs and synthetic logs was reported as 1.44 mg/kg, not detected and not detected respectively(3). The eugenol concentration in the particle emissions from the open-burning of six biomass fuels ranged from 0.0012-0021 percent of particle mass(4); the eugenol concentration in the gas-phase emissions from the open-burning of six biomass fuels ranged from 10.11-37.32 mg/kg(4). Eugenol concentrations in emissions from the combustion of wood (pine, oak, eucalyptus) was 10.8-57.2 mg/kg burned wood in the gas-phase and 0.381 mg/kg in the particle phase(5). Eugenol concentrations of 0.01-0.09 ug/mg were detected in the PM2.5 particulates from the combustion of wheat and Kentucky bluegrass(6).

The Koc of eugenol is estimated as 340(SRC), using a log Kow of 2.49(1) and a regression-derived equation(2). According to a classification scheme(3), these estimated Koc values suggest that eugenol is expected to have moderate to lowmobility in soil.

Eugenol is the main component of several essential oils; clove leaf oil and cinnamon leaf oil may contain >90% and eugenol occurs in small amounts in many other essential oils(1) such as pimento, bay, sassafras, massoy bark oils as well as oil of camphor and chamchwi plants(2). Clove leaf oil from Madagascar has eugenol content in the range of 82-92%; in Indonesia, the eugenol content is somewhat lower, 78-86%(3). Eugenol has been identified as a component of particulate and gas-phase emissions from the combustion of wood, wheat and grass(4-9).

Eugenol is obtained from many natural sources including clove, cinnamon leaf, pimento, bay, sassafras, massoy bark oils as well as oil of camphor and chamchwi plants(1).

... PRESENT IN OIL OF CAMPHOR, JAVA CITRONELLA, CALIFORNIA LAUREL & ACACIA FLOWERS. ... REMARKABLE AMT ... IN OCIMUM SANCTUM (70%) AND OCIMUM GRATISSIMUM (60%). EUGENOL IS ... FOUND IN OIL FROM VIOLET FLOWERS (21%). IN SOME PLANTS PROBABLY OCCURS AS GLUCOSIDE.

EUGENOL ... OCCURS IN PIMENTO OIL (80%), & BAY OIL (60%).

For more Natural Pollution Sources (Complete) data for EUGENOL (6 total), please visit the HSDB record page.

Substance added directly to human food affirmed as generally recognized as safe (GRAS).

Synthetic flavoring substances and adjuvants /for animal drugs, feeds, and related products/ that are generally recognized as safe for their intended use, within the meaning of section 409 of the Act. Eugenol is included on this list.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: Eugenol is included in external analgesic drug products and skin protectant drug products.

Zinc oxide-eugenol is a device composed of zinc oxide-eugenol intended to serve as a temporary tooth filling or as a base cement to affix a temporary tooth filling, to affix dental devices such as crowns or bridges, or to be applied to a tooth to protect the tooth pulp.

Exemptions for pesticides of a character not requiring FIFRA regulation. The pesticides or classes of pesticides listed in this section have been determined to be of a character not requiring regulation under FIFRA, and are therefore exempt from all provisions of FIFRA when intended for use, and used, only in the manner specified. Eugenol is included on this list.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer saftey standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. Eugenol is found on List D. Case No: 4038; Pesticide type: insecticide; Case Status: Pesticides in the case have been exempted from regulation under FIFRA Section 25 (b).; Active ingredient (AI): eugenol; AI Status: OPP has completed a Reregistration Eligibility Decision (RED) for the case/AI.

The exact mechanism of action of eugenol is unknown. However, eugenol has been shown to interrupt action potentials, which may be involved in its anti-pain activity. Research has also shown eugenol to have anti-inflammatory, neuroprotective, antipyretic, antioxidant, antifungal and analgesic properties.

... Thymocyte suspension was irradiated by gamma-rays, and the malondialdehyde (MDA) formation was measured with the thiobarbituric acid reactive species (TBARS) method. The results showed an increase in MDA in irradiated (2 Gy) thymocytes, which was inhibited in samples treated with increasing concentrations of eugenol (10-200 uM) prior to irradiation. The concentration of eugenol required to inhibit half of the MDA formation (IC(50)) in irradiated thymocytes was 100 uM. A dose-dependent increase in the generation of ROS was observed in irradiated thymocytes (0.5-200 cGy) as measured by 2,7-dichlorodihydro fluorescein diacetate (DCH-FDA), which was inhibited by eugenol administered before irradiation.

Respiratory inhibition of isolated rat liver mitochondria by eugenol was dose related and uncoupled oxidative phosphorylation from electron transfer.

Polymorphonuclear leukocytes (PMNL) play an important role in the modulation of inflammatory conditions in humans. PMNL cells recruited at the site of inflammation, release inflammatory mediators such as leukotrienes, proteolytic enzymes and reactive oxygen species. Among these, leukotrienes are implicated in pathophysiology of allergic and inflammatory disorders like asthma, allergic rhinitis, arthritis, inflammatory bowel disease and psoriasis. 5-lipoxygenase (5-LO) is the key enzyme in biosynthetic pathway of leukotrienes. Our earlier studies showed that spice phenolic active principles significantly inhibit 5-LO enzyme in human PMNLs. In this study we have further characterized the inhibitory mechanism of eugenol, the active principle of spice-clove on 5-LO enzyme and also its effect on leukotriene C((4)) (LTC(4)). Substrate dependent enzyme kinetics showed that the inhibitory effect of eugenol on 5-LO was of a non-competitive nature. Further, eugenol was found to significantly inhibit the formation of LTC(4) in calcium ionophore A23187 and arachidonic acid (AA) stimulated PMNL cells. These data clearly suggest that eugenol inhibits 5-LO by non-competitive mechanism and also inhibits formation of LTC(4) in human PMNL cells and thus may have beneficial role in modulating 5-LO pathway in human PMNL cells.

The Ca(2+)-activated Cl(-) channel TMEM16A is involved in epithelial fluid secretion, smooth muscle contraction and neurosensory signaling. We identified a Thai herbal antidiarrheal formulation that inhibited TMEM16A Cl(-) conductance. C18-reversed-phase HPLC fractionation of the herbal formulation revealed >98% of TMEM16A inhibition activity in one out of approximately 20 distinct peaks. The purified, active compound was identified as eugenol (4-allyl-2-methoxyphenol), the major component of clove oil. Eugenol fully inhibited TMEM16A Cl(-) conductance with single-site IC(50)~150 uM. Eugenol inhibition of TMEM16A in interstitial cells of Cajal produced strong inhibition of intestinal contraction in mouse ileal segments. TMEM16A Cl(-) channel inhibition adds to the list of eugenol molecular targets and may account for some of its biological activities.

For more Mechanism of Action (Complete) data for EUGENOL (21 total), please visit the HSDB record page.

Following ip injection of (14)C eugenol into rats, ... the presence of (14)CO2 in expired air indicated the demethylation of eugenol.

The metabolism and toxic effects of eugenol were studied in isolated rat hepatocytes. Incubation of hepatocytes with eugenol resulted in the formation of conjugates with sulfate, glucuronic acid and glutathione. The major metabolite formed was the glucuronic acid conjugate. Covalent binding to cellular protein was observed using (3)H eugenol. Loss of intracellular glutathione and cell death were also observed in these incubations. Concentrations of 1 mM eugenol caused a loss of over 90% of intracellular glutathione and resulted in approximately 85% cell death over a 5 hr incubation period. The loss of the majority of glutathione occurred prior to the onset of cell death (2 hr). The effects of eugenol were concentration dependent. The addition of 1 mM N-acetylcysteine to incubations containing 1 mM eugenol was able to completely prevent glutathione loss and cell death as well as inhibit the covalent binding of eugenol metabolites to protein. Conversely, pretreatment of hepatocytes with diethylmaleate to deplete intracellular glutathione increased the cytotoxic effects of eugenol. These results demonstrate that eugenol is actively metabolized in hepatocytes and suggest that the cytotoxic effects of eugenol are due to the formation of a reactive intermediate, possibly a quinone methide.

Two metabolites of eugenol, 3-piperidyl-1-(3'-methoxy-4'-hydroxyphenyl)-1-propanone and 3-pyrrolidinyl-1-(3'-methoxy-4'-hydroxyphenyl)-1-propanone, have been isolated from rat urine.

Epoxidation of eugenol by rat liver cell cultures has been reported. The dihydrodiol metabolite of eugenol has been isolated from liver homogenates and urine of rats pretreated with eugenol.

For more Metabolism/Metabolites (Complete) data for EUGENOL (9 total), please visit the HSDB record page.

Eugenol has known human metabolites that include Hydroxychavicol and (2S,3S,4S,5R)-3,4,5-Trihydroxy-6-(2-methoxy-4-prop-2-enylphenoxy)oxane-2-carboxylic acid.

3T8H1794QW

EUGENOL

Established Pharmacologic Class [EPC] - Standardized Chemical Allergen

Physiologic Effects [PE] - Increased Histamine Release

Physiologic Effects [PE] - Cell-mediated Immunity

Chemical Structure [CS] - Allergens

Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection.

Liquids that dissolve other substances (solutes), generally solids, without any change in chemical composition, as, water containing sugar. (Grant &amp; Hackh&apos;s Chemical Dictionary, 5th ed)

Intraperitoneal injection of a single 450 mg/kg dose of (14)C methoxy labelled eugenol resulted in rapid distribution to all organs. Both ether- and water soluble materials were recovered from most tissues and excretions. Only 0.2-1.0% of the dose was eliminated as expired (14)CO2. Over 70% of a lethal dose of eugenol was recovered on death, from the urine of rabbits.

No penetration of mouse skin was demonstrated after dermal application of eugenol.

A fragrance and spice derived from the oil of cloves; used in cosmetics, over-the-counter drugs, toothpastes, and foods; [Marks, p. 172-3] From numerous natural sources and the main active ingredient in cloves; Used in perfumery, flavoring, manufacture of vanillin, medicine (germicide and in over the counter drugs), dentistry (analgesic, root canal disinfectant, and in cements and other materials); Also used as an insect attractant, chemical intermediate, and denaturant for alcohol; Has been used as fungicide in pharmaceuticals and cosmetics, as antiputrescent, and to treat flatulent colic; [HSDB] Active ingredient in consumer insecticides and Japanese beetle baits/traps; [NPIRS]

For eugenol (USEPA/OPP Pesticide Code: 102701) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Insecticide

Perfumes, essential oils, medicine (anaglesic), production of isoeugenol for the manufacture of vanillin, flavoring.

Eugenol is used in perfumery in clove and carnation compositions as well as for oriental and spicy notes. It is a common component of clove and other aroma compositions. In dentistry, it is used as an antiseptic.

For more Uses (Complete) data for EUGENOL (10 total), please visit the HSDB record page.

Rubifacient

In perfumery instead of oil of cloves; manufacture of vanillin.

Insect attractant derived essentially from clove oil.

Clove oil substitute in foods; germicide used in medicine; flavor chemical; intermediate for 4-allylveratrole & isoeugenol (perfume)

For more U.S. Imports (Complete) data for EUGENOL (8 total), please visit the HSDB record page.

2023: 8,500,000 - <10,000,000 lb

(1972) 2.15X10+8 g

(1975) 1.45X10+8 g

(1984) 1.63X10+8 g

Production volumes for non-confidential chemicals reported under the Inventory Update Rule.[Table#824]

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: Phenol, 2-methoxy-4-(2-propen-1-yl)-. Aggregated National Production Volume: < 500,000 lbs.

Eugenol is used primarily as a fragrance and flavoring agent, as an analgesic in dental materials and nonprescription drug products, as an insect attractant, and as a chemical intermediate. Several other applications have been reported, the commercial status of which is unknown. (1985)

Eugenol

Eugenol; 4-Allylcatechol-2-methyl ether; 1-Allyl-4-hydroxy-3-methoxybenzene; 4-Allyl-2-methoxyphenol; Caryophyllic acid; 2-Hydroxy-5-allylanisole; 1-Hydroxy-2-methoxy-4-allylbenzene; 4-Hydroxy-3-methoxy-1-allylbenzene; 1-Hydroxy-2-methoxy-4-propenylbenzene; 2-Methoxy-4-allylphenol; 2-Methoxy-4-(2-propenyl)phenol; Phenol, 2-methoxy-4-(2-propenyl)-; Eugenic acid; Allylguaiacol; 4-Allylguaiacol

IFRA_STD_035.pdf

51

IFRA 51st Amendment - Guidance for the use of IFRA Standards

Restriction: This material should be used only in the limited quantity as stated in the Standard

The oil containing eugenol is treated with a 3% aqueous solution of NaOH; the nonacid components are extracted with ether; the alkaline solution is acidified to isolate the phenols and subsequently is fractionally distilled under reduced pressure; to avoid the formation of emulsions, a pretreatment of the oil with tartaric acid is preferred.

It can be extracted from clove oil with aqueous potassium hydroxide, followed by liberation with an acid, and distillation in a stream of CO2. It can be synthesized by the reaction of allyl chloride with guaiacol.

Since sufficient eugenol can be isolated from cheap essential oils, synthesis is not industrially important. Eugenol is still preferentially isolated from clove leaf and cinnamon leaf oil (e.g., by extraction with sodium hydroxide solution). Nonphenolic materials are then removed by steam distillation. After the alkaline solution is acidified at low temperature, pure eugenol is obtained by distillation.

Technical product contains 95-100% eugenol.

Grades: Technical, USP, FCC.

Cosmetics product ingredient: Phenol, 2-methoxy-4-(2-propenyl)- (EUGENOL)

Information on 424 consumer products that contain Eugenol in the following categories is provided:

Fragrance Ingredients

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavoring Agents -> JECFA Flavorings Index

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes