Isoeugenol

164.2

164.20

1909602

202-590-7

28FSR1NAY4

209522|6769

DTXSID7022413|DTXSID50872350

Oily liquid; easily becomes somewhat yellow

2909500000

29.5

2.6

Clear yellow Viscous Liquid

1.0869 g/cm³ @ Temp: 20 °C

-10 °C

266 °C

>230 °F

1.578

soluble in alcohol, ether and other organic solvents

0-6°C

<0.01 mm Hg ( 20 °C)

>1 (vs air)

LD50 orally in rats: 1560 mg/kg (Jenner)

Spice-clove odor

Henry's Law constant = 3.6X10-6 atm-cu m/mol at 25 °C (est)

pKa = 9.88 at 25 °C

log Kow = 2.11 (measured, pH not specified)|Hydroxyl radical reaction rate constant = 8.9X10-11 cu cm/molecule-sec at 25 °C (est)

Slightly water soluble (NTP, 1992).

Hydrocarbons, Aliphatic Unsaturated

14681.396 cal/g mole at normal boiling point

Crticial temperature: 718.774 deg K; critical pressure: 30.142 atm

NONH for all modes of transport

2

22-36/37/38-43

26-36-36/37-24/25

SL7875000

Xn

Stable. Incompatible with strong oxidizing agents.

P261-P280-P305 + P351 + P338

H302-H315-H317-H319-H335

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.

Isoeugenol 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.

This chemical is combustible. (NTP, 1992)

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P272, P280, P301+P312, P302+P352, P305+P351+P338, P312, P321, P322, P330, P332+P313, P333+P313, P337+P313, P362, P363, and P501|Aggregated GHS information provided by 1873 companies from 22 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302+H312+H332 (36.3%): Harmful if swallowed, in contact with skin or if inhaled [Warning Acute toxicity, oral; acute toxicity, dermal; acute toxicity, inhalation]|P261, P264, P270, P271, P272, P280, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P312, P321, P322, P330, P332+P313, P333+P313, P337+P313, P362, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 146 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P272, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P322, P330, P332+P313, P333+P313, P337+P313, P362, P363, P403+P233, P405, and P501|P260, P261, P264, P270, P272, P280, P301+P312, P302+P352, P305+P351+P338, P309+P311, P312, P314, P321, P322, P330, P332+P313, P333+P313, P337+P313, P362, P363, P405, and P501

This compound is not very flammable but any fire involving this compound may produce dangerous vapors. You should evacuate the area. All firefighters should wear full-body protective clothing and use self-contained breathing apparatuses. You should extinguish any fires involving this chemical with a dry chemical, carbon dioxide, foam, or halon extinguisher. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: If you spill this chemical, 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 alcohol followed by washing with a strong 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. STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

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)

| 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.

Two condensate effluents generated at a Canadian mill involved with bleached softwood pulp production contained isoeugenol concentrations of 10 ng/mL and 121 ng/mL(1). Isoeugenol was detected in 6 effluents collected from 13 paper and pulp in Quebec Canada in 1990 at a concentration of 0 (detection limit not specified) to 28643 ug/L(2). The emission rate of isoeugenol in wood smoke from the combustion of oak, eucalyptus and pine wood was reported as 1.0, 0.5 and 17 ug/g respectively(3). The emission rate of isoeugenol in wood smoke from the combustion of pine wood logs, oak wood logs and synthetic logs was reported as 8.04 mg/kg, 0.16 mg/kg and not detected respectively(4).

The emission rate of isoeugenol in wood smoke from the combustion of oak, eucalyptus and pine wood was reported as 1.0, 0.5 and 17 ug/g respectively(1). The emission rate of isoeugenol in wood smoke from the combustion of pine wood logs, oak wood logs and synthetic logs was reported as 8.04 mg/kg, 0.16 mg/kg and not detected respectively(2).

LD50 Rat oral 1560 mg/kg|LD50 Guinea pig oral 1410 mg/kg

Groups of 10 male and 10 female rats were exposed to isoeugenol in corn oil by gavage at doses of 0, 37.5, 75, 150, 300, or 600 mg/kg, 5 days per week for 14 weeks. All rats survived to the end of the study except one 600 mg/kg male and one 37.5 mg/kg female that were killed in dosing accidents. Mean body weights of all exposed groups of males were significantly less than that of the vehicle control group; however, only the decrease for the 600 mg/kg group exceeded 10% and was considered related to isoeugenol exposure. Liver weights were significantly increased in 300 and 600 mg/kg females. The incidences of minimal atrophy of the olfactory epithelium of the nose were significantly increased in 150 mg/kg or greater males and in 300 or 600 mg/kg females. The incidence of atrophy of olfactory nerve bundles was significantly increased in 600 mg/kg females. Minimal to mild periportal hepatocellular cytoplasmic alteration occurred in all 300 or 600 mg/kg females.|Groups of 10 male and 10 female mice were exposed to isoeugenol in corn oil by gavage at doses of 0, 37.5, 75, 150, 300, or 600 mg/kg, 5 days per week for 14 weeks. All mice survived to the end of the study. The mean body weight of 600 mg/kg males was significantly less (12%) than that of the vehicle controls. Liver weights of 300 and 600 mg/kg males were significantly greater than those of the vehicle controls. Minimal to moderate atrophy of olfactory epithelial tissue and nerve bundles was observed in 600 mg/kg males and females.|Groups of 50 male and 50 female /F344/N/ rats were exposed to isoeugenol in corn oil by gavage at doses of 0, 75, 150, or 300 mg/kg, 5 days per week for 105 weeks. Survival rates of exposed male and female rats were similar to those of vehicle controls. Mean body weights of 300 mg/kg male rats were 9% greater than the vehicle controls at the end of the study. The general lack of toxicity and nonneoplastic lesions indicates that rats might have been able to tolerate higher doses. Two male rats in the 300 mg/kg group had rare benign or malignant thymomas, while two other males in this group had rare mammary gland carcinomas. Low incidences of minimal atrophy and minimal to mild respiratory metaplasia of the olfactory epithelium were increased in 150 mg/kg males and 300 mg/kg males and females. Similar incidences of minimal to mild olfactory epithelial degeneration in 300 mg/kg males were also increased. Incidences of keratoacanthoma of the skin were decreased in 150 and 300 mg/kg males. ... Under the conditions of these 2-year gavage studies, there was equivocal evidence of carcinogenic activity of isoeugenol in male F344/N rats based on increased incidences of rarely occurring thymoma and mammary gland carcinoma. There was no evidence of carcinogenic activity of isoeugenol in female F344/N rats administered 75, 150, or 300 mg/kg. ... Exposure to isoeugenol resulted in nonneoplastic lesions of the nose in male and female rats ... .|Groups of 50 male and 50 female /B6C3F1/ mice were exposed to isoeugenol in corn oil by gavage at doses of 0, 75, 150, or 300 mg/kg, 5 days per week for 104 (females) or 105 (males) weeks. Survival of 300 mg/kg males was significantly decreased compared to the vehicle controls. Mean body weights of 300 mg/kg male and female groups were less than those of vehicle controls at the end of the study, 10% and 15% less, respectively. In all groups of exposed males, the incidences of hepatocellular adenoma, hepatocellular carcinoma, and hepatocellular adenoma or carcinoma (combined) were significantly greater than those in the vehicle control group; incidences of multiple hepatocellular adenoma were also significantly increased. Incidences of clear cell focus were significantly increased in 75 and 150 mg/kg male mice. There was a significant positive trend in the incidences of histiocytic sarcoma in females, and this neoplasm occurred in multiple tissues. Incidences of respiratory metaplasia in olfactory epithelium in all exposed groups and of atrophy and hyaline droplet accumulation in all exposed groups except 75 mg/kg females were significantly greater than those in corresponding vehicle control groups. Incidences of minimal to marked hyperplasia of Bowman's gland were increased significantly in all exposed groups. Incidences of minimal to mild necrosis of renal papilla and mild to moderate necrosis of renal tubules were increased significantly in 300 mg/kg females. Incidences of forestomach squamous hyperplasia, inflammation, and ulceration (males only) increased with exposure and were significant in the 300 mg/kg groups. The incidence of glandular stomach ulcers was low but significantly increased in the 300 mg/kg groups. ... Under the conditions of this 2-year gavage studies, ... there was clear evidence of carcinogenic activity of isoeugenol in male B6C3F1 mice based on increased incidences of hepatocellular adenoma, hepatocellular carcinoma, and hepatocellular adenoma or carcinoma (combined). There was equivocal evidence of carcinogenic activity of iso-eugenol in female B6C3F1 mice based on increased incidences of histiocytic sarcoma. Exposure to isoeugenol resulted in nonneoplastic lesions of the ... nose, forestomach, and glandular stomach in male and female mice; and of the kidney in female mice.|Isoeugenol was not mutagenic in two independent assays in bacteria (S. typhimurium and E. coli) conducted with and without exogenous metabolic activation (S9 liver enzymes). Neither did it induce chromosomal aberrations in cultured Chinese hamster ovary cells, with or without S9 activation. Frequencies of micronucleated erythrocytes were not increased in peripheral blood of Isoeugenol, male mice exposed to isoeugenol by gavage for 3 months; however, an increasing trend and a threefold increase in the 600 mg/kg group indicate a positive result for this test in female mice.

Isoeugenol occurs in ylang-ylang and other essential oils(1). Isoeugenol was detected in the skin and pulp of Queen Anne's pocket melon (Cucumis melo var dudaim L. Naudin)(2). Isoeugenol was identified as an odorant component of ginger oil(3). Isoeugenol was identified as an emission component in wood smoke from the combustion of wood(4,5).

Isoeugenol's production and use as a fragrance in household laundry and cleaning products(1) and perfumes(2), as a flavoring agent and in the manufacture of vanillin(3) may result in its release to the environment through various waste streams(SRC). Its application as a fish anesthetic/sedative(4) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 680(SRC), determined from a structure estimation method(2), indicates that isoeugenol is expected to have low mobility in soil(SRC). Volatilization of isoeugenol from moist soil surfaces is expected to occur(SRC) given an estimated Henry's Law constant of 3.6X10-6 atm-cu m/mole(SRC), based upon its vapor pressure, 0.0135 mm Hg at 25 °C(3), and water solubility, 810 mg/L(4). Isoeugenol is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3). Isoeugenol was found to be readily biodegradable using a Manometric Respirometry Test in which isoeugenol reached 79% biodegradation after 28 days(4); the biodegradation started on day 2 and reached 79% at the end of the 10-day window period(4).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 680(SRC), determined from a structure estimation method(2), indicates that isoeugenol 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 3.6X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 0.0135 mm Hg at 25 °C(4), and water solubility, 810(5). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 13 and 100 days, respectively(SRC). According to a classification scheme(6), an estimated BCF of 47(SRC), from its log Kow and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Isoeugenol is degraded in natural water by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in water is estimated to be 20.6 days(SRC), calculated from its rate constant of 3.9X10+10 L/mol-sec(7). Isoeugenol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), isoeugenol, which has an extrapolated vapor pressure of 0.0135 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase isoeugenol 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 4.3 hours(SRC), calculated from its rate constant of 8.9X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Vapor-phase isoeugenol is also degraded in the atmosphere by reaction with ozone(SRC); the half-life for this reaction in air is estimated to be 3 hours(SRC), calculated from its rate constant of 1X10-16 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3).

The rate constant for the vapor-phase reaction of isoeugenol with photochemically-produced hydroxyl radicals has been estimated as 8.9X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 4.3 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of isoeugenol with ozone has been estimated as 1X10-16 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 3 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(1). The rate constant for the reaction of hydroxyl radicals in aqueous solutions is 3.9X10+10 L/mol-sec(2); this corresponds to an aquatic half-life of 20.6 days at an aquatic concentration of 1X10-17 hydroxyl radicals per liter(3). Isoeugenol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(4).

An estimated BCF of 47 was calculated in fish for isoeugenol(SRC), using a log Kow of 3.04(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).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of isoeugenol can be estimated to be 680(SRC). According to a classification scheme(2), this estimated Koc value suggests that isoeugenol is expected to have low mobility in soil.

The Henry's Law constant for isoeugenol is estimated as 3.6X10-6 atm-cu m/mole(SRC) derived from its extrapolated vapor pressure, 0.0135 mm Hg at 25 °C(1), and water solubility, 810 mg/L at 25 °C(2). This Henry's Law constant indicates that isoeugenol is expected to volatilize from water surfaces(3). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(3) is estimated as 13 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(3) is estimated as 100 days(SRC). Isoeugenol's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Isoeugenol is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 35,171 workers (24,980 of these were female) were potentially exposed to isoeugenol in the US(1). Occupational exposure to isoeugenol may occur through inhalation and dermal contact with this compound at workplaces where isoeugenol is produced or used(2). The general population is exposed to isoeugenol from consumer uses of laundry detergents, fabric conditioners, hard surface cleaners, toilet cleaners, cleaning sprays and dish-washing products containing isoeugenol(2); dermal contact is the primary route of exposure(2), but inhalation can also occur(SRC).

Isoeugenol is approved by the FDA for use within allergenic epicutaneous patch tests which are indicated for use as an aid in the diagnosis of allergic contact dermatitis (ACD) in persons 6 years of age and older.

Following a single oral dose of (14)C-isoeugenol (156 mg/kg, 50 uCi/kg), greater than 85% of the administered dose was excreted in the urine predominantly as sulfate or glucuronide metabolites by 72 hr. Approximately 10% was recovered in the feces, and less than 0.1% was recovered as CO(2) or expired organics. No parent isoeugenol was detected in the blood at any of the time points analyzed. Following iv administration (15.6 mg/kg, 100 uCi/kg), isoeugenol disappeared rapidly from the blood. The half life was 12 min and the Cl(s) was 1.9 L/min/kg. Excretion characteristics were similar to those of oral administration. The total amount of radioactivity remaining in selected tissues by 72 hr was less than 0.25% of the dose following either oral or intravenous administration. Results of these studies show that isoeugenol is rapidly metabolized and is excreted predominantly in the urine as phase II conjugates of the parent compound.

Following a single oral dose of (14)C-isoeugenol (156 mg/kg, 50 uCi/kg), greater than 85% of the administered dose was excreted in the urine predominantly as sulfate or glucuronide metabolites by 72 hr. Approximately 10% was recovered in the feces, and less than 0.1% was recovered as CO(2) or expired organics. No parent isoeugenol was detected in the blood at any of the time points analyzed. Following iv administration (15.6 mg/kg, 100 uCi/kg), isoeugenol disappeared rapidly from the blood. The half life was 12 min and the Cl(s) was 1.9 L/min/kg. Excretion characteristics were similar to those of oral administration. The total amount of radioactivity remaining in selected tissues by 72 hr was less than 0.25% of the dose following either oral or intravenous administration. Results of these studies show that isoeugenol is rapidly metabolized and is excreted predominantly in the urine as phase II conjugates of the parent compound.|Trans-isoeugenol has known human metabolites that include trans-Isoeugenol-O-glucuronide.

Following iv administration (15.6 mg/kg, 100 uCi/kg) /of/ isoeugenol ... the half life was 12 min ... .

/The investigators/ previously demonstrated in the human promyelocytic cell line THP-1 that all allergens tested, with the exception of the prohapten isoeugenol, induced a dose-related release of interleukin-8 (IL-8). .. The present study ... investigated whether this abnormal behavior was regulated by the AU-rich element-binding proteins HuR and tristetraprolin (TTP) or by the downstream molecule suppressor of cytokine signaling (SOCS)-3. The contact allergens isoeugenol, diethylmaleate (DEM), and 2,4-dinitrochlorobenzene (DNCB), and the irritant salicylic acid were used as reference compounds. Chemicals were used at concentrations that induced a 20% decrease in cell viability as assessed by propidium iodide staining, namely 100 ug/mL (0.61 mM) for isoeugenol, 100 ug/mL (0.58 mM) for DEM, 3 ug/mL (14.8 uM) for DNCB, and 250 ug/mL (1.81 mM) for salicylic acid. Time course experiments of IL-8 mRNA expression and assessment of IL-8 mRNA half-life, indicated a decreased IL-8 mRNA stability in isoeugenol-treated cells. We could demonstrate that a combination and regulation of HuR and TTP following exposure to contact allergens resulted in a different modulation of IL-8 mRNA half-life and release. The increased expression of TTP in THP-1 cells treated with isoeugenol results in destabilization of the IL-8 mRNA, which can account for the lack of IL-8 release. In contrast, the strong allergen DNCB failing to up-regulate TTP, while inducing HuR, resulted in longer IL-8 mRNA half-life and protein release. SOCS-3 was induced only in isoeugenol-treated cells; however, its modulation did not rescue the lack of IL-8 release, indicating that it is unlikely to be involved in the lack of IL-8 production. Finally, the destabilization effect of isoeugenol on IL-8 mRNA expression together with SOCS-3 expression resulted in an anti-inflammatory effect, as demonstrated by the ability of isoeugenol to modulate LPS or ionomycin-induced cytokine release.|Isoeugenol and its structural analog eugenol suppressed the lymphoproliferative response to concanavalin A stimulation in B6C3F1 mouse splenocyte cultures. Isoeugenol inhibited phorbol 12-myristate 13-acetate (PMA) plus ionomycin (Io)-induced IL-2 mRNA expression and protein secretion in B6C3F1 mouse splenocytes, and in EL4.IL-2 mouse T-cells, as determined by real-time RT-PCR and ELISA, respectively. To further characterize the inhibitory mechanism of isoeugenol at the transcriptional level, ... the DNA binding activity of the transcription factors for IL-2 using an electrophoretic mobility shift assay /was examined/. Isoeugenol decreased the binding activity of NF-AT and NF-kappaB in PMA/Io-stimulated EL4.IL-2 cells, but no significant effect was observed for AP-1 or Oct binding activity. Western blot analysis showed that isoeugenol also decreased the nuclear translocation of cytoplasmic NF-AT and NF-kappaB. These results suggest that isoeugenol suppresses IL-2 production through a decrease of IL-2 mRNA expression and that the inhibition is mediated, at least in part, through the down-regulation of NF-AT and NF-kappaB.|The phenolic derivatives eugenol and isoeugenol, which are naturally found in essential oils of different spices, are commonly used as fragrances. Recently data demonstrated that growth suppression produced by these substances occurs in keratinocytes and that the effects may be mediated via aryl hydrocarbon receptor (AhR) interactions. In this study the effects of eugenol and isoeugenol were determined on intracellular localization of AhR, AhR target gene expression, AhR-dependent cell cycle regulation, and proliferation in HaCaT cells. Both compounds produced a rapid and marked translocation of AhR into the nucleus, induced the expression of the AhR target genes cytochrome P-450 1A1 (CYP1A1) and AhR repressor (AhRR), and inhibited proliferation of HaCaT cells. Among the G(1) phase cell cycle-related proteins, levels of the retinoblastoma protein (RB), which is known to interact with AhR, and levels of the cyclin dependent kinase (CDK) 6 were reduced by eugenol and isoeugenol, whereas steady-state levels of CDK2 and CDK4 remained unaffected. Protein levels of CDK inhibitor (CKI) p27(KIP1), known to be modulated in an AhR-dependent manner, were increased after treatment with both substances. In conclusion, data show that the antiproliferative properties of eugenol and isoeugenol in HaCaT cells are mediated through AhR ... .|Effects of eugenol compounds on the production of nitric oxide (NO) in RAW264.7 macrophages were analyzed in relation to the anti-inflammatory action of these compounds. Eugenol and isoeugenol inhibited lipopolysaccharide (LPS)-dependent production of NO, which was due to the inhibition of protein synthesis of inducible nitric oxide synthase (iNOS). Isoeugenol showed the most effective inhibitory effect and eugenol was less effective. LPS-dependent expression of cyclooxygenase-2 (COX-2) protein was also inhibited markedly by isoeugenol, and less effectively by eugenol. Anti-inflammatory action of eugenol compounds may be explained by the inhibition of NO production and COX-2 expression, the pro-inflammatory mediators.|For more Mechanism of Action (Complete) data for Isoeugenol (8 total), please visit the HSDB record page.

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. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Phenols and related compounds/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Administer activated charcoal ... . Do not use emetics. Cover skin burns with dry, sterile dressings after decontamination ... . Maintain body temperature. /Phenols and related compounds/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. ... Treat seizures with diazepam or lorazepam. ... Use proparacaine hydrochloride to assist eye irrigation ... . /Phenols and related compounds/

/HUMAN EXPOSURE STUDIES/ The potential of isoeugenol, an important fragrance and flavor ingredient, to induce delayed contact hypersensitivity or to elicit pre-existing sensitization reactions in man was evaluated by analyzing patch-test data from dermatitic and non-dermatitic subjects. Results from a total of 6512 patch tests (involving approximately 5850 subjects) on isoeugenol alone and on various consumer products and fragrance blends containing isoeugenol, were collected from fragrance and formulator companies. Hypersensitivity induced by isoeugenol was concentration dependent. All but two of the reactions occurring in this survey were at exposure concentrations greater than or equal to 0.8% isoeugenol. No induced reactions occurred in the 1004 patch tests reported at isoeugenol concentrations between 0.03 and 0.5%. One induced reaction in 32 patch tests was attributable to isoeugenol at a concentration of 0.02% while another induced reaction in 23 patch tests conducted at the same concentration was resolved to an isoeugenol-eugenol mixture. One elicited reaction at an isoeugenol concentration of 0.04% occurred in the 6512 patch tests reported in this survey. This single elicitation was resolved to an isoeugenol-eugenol mixture, but the specific causative agent was not identified. The results of this survey indicate that isoeugenol has a very low potential for either eliciting pre-existing sensitization reactions ('elicited' reactions) or inducing hypersensitivity ('induced' reactions) in subjects exposed to consumer products containing this ingredient.|/HUMAN EXPOSURE STUDIES/ The elicitation response in allergic contact dermatitis is dose dependent, but the time-concentration relationship for elicitation has not previously been described. In this study 27 isoeugenol-sensitive patients participated in serial dilution patch tests with isoeugenol and a double-blinded Repeated Open Application Test (ROAT) using two concentrations of isoeugenol, 0.2 and 0.05%. Seven controls without isoeugenol allergy were also included. The participants applied 3.72 +/- 1.57 (mean +/- SD) mg/sq cm of coded isoeugenol solutions twice a day to a 3 x 3 sq cm area on the volar aspect of the right and left arm, respectively. For each test site the applications continued until a reaction appeared or for a maximum of 28 days. The minimal criteria for a positive reaction regarded as allergic contact dermatitis was persistent erythema at the ROAT test site. All controls were negative and 16/24 (66.7%) of the included isoeugenol-sensitive subjects showed a positive ROAT to the 0.2% solution within the study period (Fisher's test, p = 0.0024). Ten of the positive patients also reacted to the 0.05% solution. The median number of days until a positive reaction to the 0.2% solution was 7 days and was 15 days for the 0.05% solution. There was a highly significant correlation between the patients' patch test threshold and the number of days until a positive ROAT. In conclusion, the time until an isoeugenol allergic individual reacts in a ROAT depends on the individual sensitivity as well as the exposure concentrations; for low concentrations of the allergen or low degree of sensitivity, the allergic contact dermatitis may develop after several weeks of exposure. Therefore, a negative ROAT after 7 days may be a false negative.|/HUMAN EXPOSURE STUDIES/ Axillary dermatitis is common and overrepresented in people with contact allergy to fragrances. Many people suspect their deodorants to be the incriminating products. In order to investigate the significance of isoeugenol in deodorants for the development of axillary dermatitis when used by people with and without contact allergy to isoeugenol, patch tests with deodorants and ethanol solutions with isoeugenol, as well as repeated open application tests (ROAT) with roll-on deodorants with and without isoeugenol at various concentrations, were performed in 35 dermatitis patients, 10 without and 25 with contact allergy to isoeugenol. A positive ROAT was observed only in patients hypersensitive to isoeugenol (P<0.001) and only in the axilla to which the deodorants containing isoeugenol had been applied (P<0.001). Deodorants containing isoeugenol in the concentration range of 0.0063-0.2% used 2 times daily on healthy skin can thus elicit axillary dermatitis within a few weeks in people with contact allergy to isoeugenol.|/HUMAN EXPOSURE STUDIES/ ... During a five-year period 3,065 patients with contact dermatitis were patch tested using a specific mix of fragrances. 509 (16.6%) patients were allergic to the fragrance mix, while 258 (8.4%) patients exhibited an allergic reaction to Myroxylon pereirae (balsam of Peru). Between those 509 patients, 157 were patch tested with eight individual substances contained in the fragrance mix: cinnamal, cinnamyl alcohol, eugenol, isoeugenol, geraniol, hydroxycitronellal, alpha-amyl cinnamal and Evernia prunastri (oak moss). The most frequent allergens were isoeugenol 57.9% (91/157), eugenol 55.4% (87/157), cinnamyl alcohol 34.4% (54/157) and Evernia prunastri (oak moss) 24.2% (38/157). ...

2-methoxy-4-propenylphenol

Perfumer's grade, FCC.

Phenol, 2-methoxy-4-(1-propen-1-yl)-: ACTIVE|Commercial isoeugenol is a mixture of cis- and trans-isomers, in which the trans-isomer dominates because it is thermodynamically more stable.

A method was developed and evaluated for determining isoeugenol concentrations in fillet tissue using relatively common procedures and equipment. The method produced accurate and precise results with fillet tissue from 10 freshwater fish species. The percentage of isoeugenol recovered from samples fortified with isoeugenol at nominal concentrations of 1, 50, and 100 ug/g for all species was always >80 and <97%. Within-day precision for samples fortified at those same concentrations was < or =10%, and day-to-day precision was < or =4.0%. Method precision with fillet tissue containing biologically incurred isoeugenol was < or =8.1%. There were no or minimal chromatographic interferences in control fillet tissue extracts from 9 of the 10 species. The method detection limits for all but one species ranged from 0.004 to 0.014 microg/g, and the quantitation limits ranged from 0.012 to 0.048 ug/g.

Food additives -> Flavoring Agents|Flavoring Agents -> JECFA Flavorings Index|Cosmetics -> Masking

Flavoring Agents