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Isoeugenol

PubChem CID
853433
Structure
Isoeugenol_small.png
Isoeugenol_3D_Structure.png
Molecular Formula
Synonyms
  • Isoeugenol
  • 97-54-1
  • (E)-Isoeugenol
  • trans-Isoeugenol
  • 2-Methoxy-4-propenylphenol
Molecular Weight
164.20 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2004-09-16
  • Modify:
    2025-01-11
Description
Isoeugenol is a pale yellow oily liquid with a spice-clove odor. Freezes at 14 °F. Density 1.08 g / cm3. Occurs in ylang-ylang oil and other essential oils.
Isoeugenol is a phenylpropanoid that is an isomer of eugenol in which the allyl substituent is replaced by a prop-1-enyl group. It has a role as an allergen and a sensitiser. It is a phenylpropanoid and an alkenylbenzene. It is functionally related to a guaiacol.
Isoeugenol is a commonly used fragrance added to many commercially available products, and occurs naturally in the essential oils of plants such as ylang-ylang. It is also a significant dermatologic sensitizer and allergen, and as a result has been restricted to 200 p.p.m. since 1998 according to guidelines issued by the fragrance industry. Allergic reactivity to Isoeugenol may be identified with a patch test.
See also: cis-Isoeugenol (annotation moved to).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Isoeugenol.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

2-methoxy-4-[(E)-prop-1-enyl]phenol
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C10H12O2/c1-3-4-8-5-6-9(11)10(7-8)12-2/h3-7,11H,1-2H3/b4-3+
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

BJIOGJUNALELMI-ONEGZZNKSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C/C=C/C1=CC(=C(C=C1)O)OC
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C10H12O2
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

97-54-1
5932-68-3

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DrugBank ID

2.3.8 DSSTox Substance ID

2.3.9 FEMA Number

2.3.10 HMDB ID

2.3.11 JECFA Number

1260

2.3.12 KEGG ID

2.3.13 Metabolomics Workbench ID

2.3.14 Nikkaji Number

2.3.15 NSC Number

2.3.16 RXCUI

2.3.17 Wikidata

2.3.18 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 2-methoxy-4-propenylphenol
  • isoeugenol
  • isoeugenol, (E)-isomer
  • isoeugenol, (Z)-isomer
  • isoeugenol, sodium salt

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
164.20 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
2.6
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
164.083729621 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
164.083729621 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
29.5 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
12
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
154
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
1
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Isoeugenol is a pale yellow oily liquid with a spice-clove odor. Freezes at 14 °F. Density 1.08 g / cm3. Occurs in ylang-ylang oil and other essential oils.
Liquid
97-54-1: Pale yellow oily liquid with a spice-clove odor; [CAMEO] Clear light yellow-green viscous liquid; [MSDSonline] 5912-86-7: Liquid; [Merck Index] 5932-68-3: Solid; [Merck Index]
Pale yellow, viscous liquid; floral, carnation-like aroma

3.2.2 Color / Form

Oily liquid; easily becomes somewhat yellow
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 895

3.2.3 Odor

Spice-clove odor
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 710

3.2.4 Boiling Point

511 °F at 760 mmHg (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
266 °C
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 895
125.00 to 126.00 °C. @ 14.00 mm Hg
The Good Scents Company Information System

3.2.5 Melting Point

14 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
-10 °C
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 895

3.2.6 Flash Point

235 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
235 °F
>212 °F(>100 °C)(closed cup)
National Fire Protection Association; Fire Protection Guide to Hazardous Materials. 14TH Edition, Quincy, MA 2010, p. 325-76

3.2.7 Solubility

Slightly soluble (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
In water, 810 mg/L at 25 °C
HERA; HERA Risk Assessment of Isoeugenol (Draft). Human and Environmental Risk Assessment on ingredients of Household Cleaning Products. Isoeugenol (CAS 97-54-1). Available from, as of June 23, 2012: https://www.heraproject.com/
Miscible with alcohol and ether
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 895
Soluble in alcohol, ether and other organic solvents
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 710
Soluble in most fixed oils
soluble (in ethanol)

3.2.8 Density

1.08 at 77 °F (NTP, 1992) - Denser than water; will sink
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
1.080 g/cu cm at 25 °C
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 895
1.079-1.085

3.2.9 Vapor Pressure

0.02 mmHg at 77 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
0.02 [mmHg]
0.0135 mm Hg at 25 /extrapolated/
NIST; NIST Chemistry WebBook. Phenol, 2-methoxy-4-(1-propenyl)- (97-54-1). NIST Standard Reference Database No. 69, June 2005 Release. Washington, DC: US Sec Commerce. Available from, as of June 25, 2012: https://webbook.nist.gov

3.2.10 LogP

log Kow = 3.04
Griffin S et al; J Chromatog 864: 221-228 (1999)
3.04
GRIFFIN,S ET AL. (1999)

3.2.11 Decomposition

When heated to decomposition it emits acrid smoke and fumes.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2135

3.2.12 Viscosity

7.476 centipoise at 20 °C
Razdan TK et al; Parfume Kosmet 66: 444-449 (1985)

3.2.13 Heat of Vaporization

14681.396 cal/g mole at normal boiling point
Razdan TK et al; Parfume Kosmet 66: 444-449 (1985)

3.2.14 Surface Tension

30.813 dynes/cm
Razdan TK et al; Parfume Kosmet 66: 444-449 (1985)

3.2.15 Refractive Index

Index of refraction = 1.5739 at 19 °C
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. V4: 4072
1.572-1.577

3.2.16 Dissociation Constants

pKa = 9.88 at 25 °C
Serjeant, E.P., Dempsey B.; Ionisation Constants of Organic Acids in Aqueous Solution. International Union of Pure and Applied Chemistry (IUPAC). IUPAC Chemical Data Series No. 23, 1979. New York, New York: Pergamon Press, Inc.

3.2.17 Kovats Retention Index

1 of 2
Standard non-polar
1429 , 1436.4 , 1420 , 1409 , 1411 , 1418.9
Semi-standard non-polar
1447 , 1473 , 1473 , 1449 , 1447 , 1458.4 , 1465 , 1453 , 1455 , 1459 , 1458 , 1451 , 1453 , 1457 , 1451 , 1449 , 1463 , 1474 , 1447 , 1444 , 1474 , 1410.4 , 1430 , 1454.2
Standard polar
2352 , 2347 , 2309 , 2394 , 2314 , 2383 , 2372 , 2339 , 2344.4 , 2355 , 2368 , 2373
2 of 2
Standard non-polar
1439 , 1410 , 1427 , 1415 , 1430 , 1403 , 1422 , 1420 , 1393 , 1435 , 1424.2 , 1429 , 1438
Semi-standard non-polar
1436.3 , 1403 , 1447 , 1459.4 , 1414.8 , 1448 , 1397 , 1428 , 1452 , 1465 , 1466 , 1468 , 1468 , 1471 , 1474 , 1452 , 1402 , 1408 , 1404 , 1436 , 1396 , 1451 , 1457 , 1404 , 1405 , 1469.2 , 1460 , 1451 , 1451 , 1449.9 , 1456 , 1454 , 1438 , 1448.5 , 1460 , 1399.8 , 1442.9
Standard polar
2350 , 2336 , 2319 , 2356 , 2271 , 2330 , 2268 , 2322 , 2316 , 2332 , 2266 , 2279 , 2271 , 2313.7 , 2326 , 2352 , 2338 , 2269 , 2330 , 2299 , 2308 , 2304 , 2269 , 2343.9

3.2.18 Other Experimental Properties

log Kow = 2.11 (measured, pH not specified)
HERA; HERA Risk Assessment of Isoeugenol (Draft). Human and Environmental Risk Assessment on ingredients of Household Cleaning Products. Isoeugenol (CAS 97-54-1). Available from, as of June 23, 2012: https://www.heraproject.com/

3.3 SpringerMaterials Properties

3.4 Chemical Classes

Other Uses -> Food Additives

3.4.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749

3.4.2 Cosmetics

Masking
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

3.4.3 Food Additives

FLAVORING AGENT OR ADJUVANT -> FDA Substance added to food

3.4.4 Fragrances

Fragrance Ingredient (Isoeugenol) -> IFRA transparency List

4 Spectral Information

4.1 1D NMR Spectra

4.1.1 1H NMR Spectra

1 of 3
View All
Spectra ID
Instrument Type
JEOL
Frequency
90 MHz
Solvent
CDCl3
Shifts [ppm]:Intensity
6.82:716.00, 5.71:282.00, 6.86:62.00, 1.80:296.00, 6.23:131.00, 3.81:1000.00, 6.00:30.00, 6.20:43.00, 1.79:192.00, 5.96:25.00, 1.87:205.00, 6.41:34.00, 5.90:35.00, 1.86:302.00, 6.14:107.00, 6.24:100.00, 6.40:31.00, 6.07:99.00, 1.83:47.00
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2 of 3
View All
Instrument Name
BRUKER AC-300
Source of Sample
NIST, Gaithersburg, Maryland Wiley Organics
Copyright
Copyright © 1991-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.1.2 13C NMR Spectra

1 of 3
View All
Spectra ID
Instrument Type
JEOL
Frequency
22.53 MHz
Solvent
CDCl3
Shifts [ppm]:Intensity
108.13:867.00, 119.29:872.00, 144.82:557.00, 146.68:534.00, 114.52:869.00, 18.25:805.00, 123.24:864.00, 130.69:534.00, 130.84:924.00, 55.73:1000.00
Thumbnail
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2 of 3
View All
Source of Sample
Fritzsche Brothers, Inc., New York, New York
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 17
View All
Spectra ID
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

164.0 99.99

77.0 22.10

55.0 21

103.0 17.60

131.0 16.70

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Notes
instrument=HITACHI RMU-6M
2 of 17
View All
Spectra ID
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

164.0 99.99

149.0 36.50

55.0 27.50

103.0 26.50

77.0 25.50

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Notes
instrument=HITACHI RMS-4

4.2.2 MS-MS

1 of 6
View All
Spectra ID
Instrument Type
n/a
Ionization Mode
positive
Top 5 Peaks

137.0592 43.86

133.0643 39.73

105.0693 12.36

150.067 2.14

109.0643 1.18

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Notes
adduct_type [M+H]+ original_collision_energy 35 % nominal CannabisDB spectra from NIST14 2020 June Thermo Finnigan Elite Orbitrap
2 of 6
View All
Spectra ID
Instrument Type
n/a
Ionization Mode
positive
Top 5 Peaks

105.0 95.47

115.1 1.88

55.0 1.69

79.1 0.96

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Notes
adduct_type [133.0]+ original_collision_energy 35 % nominal CannabisDB spectra from NIST14 2020 June Thermo Finnigan Elite Orbitrap

4.2.3 LC-MS

1 of 3
View All
MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M-H]-
Precursor m/z
163.0764536
Instrument
Agilent qTOF 6545
Instrument Type
LC-ESI-QTOF
Ionization Mode
negative
Collision Energy
40 eV
Top 5 Peaks

41.00111 100

91.05956 75.80

77.03506 53.80

119.04641 48.70

91.07661 11

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2 of 3
View All
MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M-H]-
Precursor m/z
163.0764536
Instrument
Thermo Q Exactive HF
Instrument Type
LC-ESI-QFT
Ionization Mode
negative
Collision Energy
HCD (NCE 20-30-40%)
Top 5 Peaks

148.05298 100

163.07651 5.90

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4.2.4 Other MS

Other MS
MASS: 77576 (NIST/EPA/MSDC Mass Spectral Database, 1990 Version)

4.3 IR Spectra

4.3.1 FTIR Spectra

1 of 2
Technique
CAPILLARY CELL: NEAT
Source of Sample
Fluka Chemie AG, Buchs, Switzerland
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Technique
Between salts
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
W246808
Lot Number
00319ME
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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4.3.2 ATR-IR Spectra

Source of Sample
Aldrich
Catalog Number
I17206
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.3.3 Near IR Spectra

1 of 2
Instrument Name
BRUKER IFS 88
Technique
NIR
Source of Spectrum
Prof. Buback, University of Goettingen, Germany
Copyright
Copyright © 1989, 1990-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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2 of 2
Instrument Name
BRUKER IFS 88
Technique
NIR
Source of Spectrum
Prof. Buback, University of Goettingen, Germany
Copyright
Copyright © 1989, 1990-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.3.4 Vapor Phase IR Spectra

1 of 2
Instrument Name
DIGILAB FTS-14
Technique
Vapor Phase
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
Thumbnail
2 of 2
Technique
Vapor Phase
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Aldrich
Catalog Number
I17206
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4 Raman Spectra

Catalog Number
I17206
Copyright
Copyright © 2017-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2017-2024 John Wiley & Sons, Inc. All Rights Reserved.
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6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

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.

7.2 Drug Labels

Active ingredient and drug

8 Food Additives and Ingredients

8.1 Food Additive Classes

Flavoring Agents
JECFA Functional Classes
Flavouring Agent -> FLAVOURING_AGENT;

8.2 FEMA Flavor Profile

Flower, Fragrant

8.3 FDA Substances Added to Food

Substance
Used for (Technical Effect)
FLAVORING AGENT OR ADJUVANT
Document Number (21 eCFR)
FEMA Number
2468
GRAS Number
3
JECFA Flavor Number
1260

8.4 Associated Foods

8.5 Evaluations of the Joint FAO / WHO Expert Committee on Food Additives - JECFA

1 of 4
Chemical Name
2-METHOXY-4-(1-PROPENYL)PHENOL
Evaluation Year
2003
ADI
No safety concern at current levels of intake when used as a flavouring agent
Tox Monograph
2 of 4
Chemical Name
ISOEUGENOL
Evaluation Year
2003
ADI
No safety concern at current levels of intake when used as a flavouring agent
Tox Monograph
3 of 4
Chemical Name
4-PROPENYLGUAIACOL
Evaluation Year
2003
ADI
No safety concern at current levels of intake when used as a flavouring agent
Tox Monograph
4 of 4
Chemical Name
4-HYDROXY-3-METHOXY-1-PROPENYLBENZENE
Evaluation Year
2003
ADI
No safety concern at current levels of intake when used as a flavouring agent
Tox Monograph

9 Pharmacology and Biochemistry

9.1 Absorption, Distribution and Excretion

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.
Badger DA et al; Food Chem Toxicol 40 (12): 1757-65 (2002)

9.2 Metabolism / Metabolites

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.
Badger DA et al; Food Chem Toxicol 40 (12): 1757-65 (2002)
Trans-isoeugenol has known human metabolites that include trans-Isoeugenol-O-glucuronide.
S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560

9.3 Biological Half-Life

Following iv administration (15.6 mg/kg, 100 uCi/kg) /of/ isoeugenol ... the half life was 12 min ... .
Badger DA et al; Food Chem Toxicol 40 (12): 1757-65 (2002)

9.4 Mechanism of Action

/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.
Galbiati V et al; Arch Toxicol 86 (2): 239-48 (2012)
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.
Park KR et al; Int Immunopharmacol 7 (9): 1251-8 (2007)
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 ... .
Kalmes M, Blomeke B; J Toxicol Environ Health A 75 (8-10): 478-91 (2012)
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.
Li W et al; Biomed Res 27 (2): 69-74 (2006)
For more Mechanism of Action (Complete) data for Isoeugenol (8 total), please visit the HSDB record page.

9.5 Human Metabolite Information

9.5.1 Cellular Locations

Membrane

9.6 Biochemical Reactions

9.7 Transformations

10 Use and Manufacturing

10.1 Uses

EPA CPDat Chemical and Product Categories
The Chemical and Products Database, a resource for exposure-relevant data on chemicals in consumer products, Scientific Data, volume 5, Article number: 180125 (2018), DOI:10.1038/sdata.2018.125
Sources/Uses
Occurs in ylang-ylang oil and other essential oils; [CAMEO] Used in perfumes, vanillin, and flavoring agents; [Hawley] Approved by the FDA as a food flavor; Used in cosmetics, medications, and dental materials; Occurs naturally in the oils of clove, ylang-ylang, tuberose, and jonquil; [Marks, p. 175]
Hawley - Lewis RJ. _Hawley's Condensed Chemical Dictionary, _15th Ed. New York: John Wiley & Sons, 2007.
Marks - Marks JG, DeLeo VA. Contact and Occupational Dermatology, 2nd Ed. St. Louis: Mosby, 1997., p. 175
Manufacture of vanillin.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 895
Used as a fragrance in household laundry and cleaning products including, most notably, laundry powders (maximum concentration: 60 ppm), laundry liquids (maximum concentration: 70 ppm), dish-washing liquids (maximum concentration: less than 10 ppm), hard surface cleaning products (maximum concentration: 40 ppm) and toilet cleaning products (maximum concentration: less than 10 ppm)
HERA; HERA Risk Assessment of Isoeugenol (Draft). Human and Environmental Risk Assessment on ingredients of Household Cleaning Products. Isoeugenol (CAS 97-54-1). Available from, as of June 23, 2012: https://www.heraproject.com/

Reported Uses:

Table: Reported uses (ppm): (FEMA, 1994)

Food Category
Alcoholic beverages
Usual
0.21
Max.
0.35
Food Category
Baked goods
Usual
10.88
Max.
14.38
Food Category
Chewing gum
Usual
0.14
Max.
0.17
Food Category
Condiment, relish
Usual
0.00
Max.
0.04
Food Category
Frozen dairy
Usual
4.25
Max.
6.63
Food Category
Gelatins, puddings
Usual
4.56
Max.
6.42
Food Category
Hard candy
Usual
3.60
Max.
3.60
Food Category
Meat products
Usual
4.34
Max.
4.34
Food Category
Nonalcoholic beverages
Usual
3.27
Max.
5.61
Food Category
Soft candy
Usual
6.22
Max.
9.62

Burdock, G.A. (ed.). Fenaroli's Handbook of Flavor Ingredients. 6th ed.Boca Raton, FL 2010, p. 1003
Isoeugenol is used in perfumery in a large number of blossom compositions, mostly for clove and carnation types, but also in oriental perfumes. ... Small amounts are employed in aromas and in reconstituted essential oils.
Fahlbusch K-G et al; Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2012). NY, NY: John Wiley & Sons; Flavors and Fragrances. Online Posting Date: January 15, 2003
AQUI-S is a fish anesthetic/sedative that is approved for use in a number of countries throughout the world and has the potential for use in the United States. The active ingredient in AQUI-S is isoeugenol.
Meinertz JR et al; J AOAC Int 91 (4): 884-91 (2008)

10.1.1 Use Classification

Food additives -> Flavoring Agents
Fragrance Ingredients
Flavouring Agent -> FLAVOURING_AGENT; -> JECFA Functional Classes
Flavoring Agents -> JECFA Flavorings Index
Cosmetics -> Masking
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

10.1.2 Industry Uses

  • Fragrance
  • Flavoring and nutrient

10.1.3 Consumer Uses

Fragrance

10.1.4 Household Products

Household & Commercial/Institutional Products

Information on 89 consumer products that contain Isoeugenol in the following categories is provided:

• Auto Products

• Commercial / Institutional

• Inside the Home

• Personal Care

10.2 Methods of Manufacturing

From eugenol by isomerization with caustic potash.
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 710
The sodium or potassium salt of eugenol is isomerized to isoeugenol by heating. Isomerization can also be carried out catalytically in the presence of ruthenium or rhodium compounds.
Fahlbusch K-G et al; Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2012). NY, NY: John Wiley & Sons; Flavors and Fragrances. Online Posting Date: January 15, 2003
Guaiacol is esterified with propionic acid, and the resulting guaiacyl propionate rearranges in the presence of aluminum chloride to give 4-hydroxy-3-methoxypropiophenone. Reduction of the ketone to the corresponding secondary alcohol and dehydration finally yield isoeugenol.
Fahlbusch K-G et al; Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2012). NY, NY: John Wiley & Sons; Flavors and Fragrances. Online Posting Date: January 15, 2003

10.3 IFRA Fragrance Standards

IFRA Substance
Isoeugenol
Synonyms
1-Hydroxy-2-methoxy-4-propen-1-ylbenzene; 4-Hydroxy-3-methoxy-1-propen-1-ylbenzene; 4-Hydroxy-3-methoxy-1-propenylbenzene; iso-Eugenol; 3-Methoxy-4-hydroxy-1-propen-1-ylbenzene; 2-Methoxy-4-propenylphenol; 2-Methoxy-4-(1-propenyl)phenol; Phenol, 2-methoxy-4-(1-propenyl)-; 4-Propenylguaiacol
Amendment
49
IFRA Standard type
Restriction: This material should be used only in the limited quantity as stated in the Standard
Intrinsic property driving the risk management measure
DERMAL SENSITIZATION AND SYSTEMIC TOXICITY
Flavor use consideration
Due to the possible ingestion of small amounts of fragrance ingredients from their use in products in Categories 1 and 6, materials must not only comply with IFRA Standards but must also be recognized as safe as a flavoring ingredient as defined by the IOFI Code of Practice (www.iofi.org). For more details see chapter 1 of the Guidance for the use of IFRA Standards.

10.3.1 Restriction Limits in the Finished Product (%)

Category 1 (%)
0.019 [Products applied to the lips]
Category 2 (%)
0.0057 [Products applied to the axillae]
Category 3 (%)
0.12 [Products applied to the face/body using fingertips]
Category 4 (%)
0.11 [Products related to fine fragrances]
Category 5A (%)
0.027 [Products applied to the body using the hands (palms), primarily leave-on (Body lotion)]
Category 5B (%)
0.027 [Products applied to the face using the hands (palms), primarily leave-on (Face moisturizer)]
Category 5C (%)
0.027 [Products applied to the hands using the hands (palms), primarily leave-on (Hand cream)]
Category 5D (%)
0.009 [Products applied to babies using the hands (palms), primarily leave-on (Baby cream, oil, talc)]
Category 6 (%)
0.063 [Products with oral and lip exposure]
Category 7A (%)
0.22 [Rinse-off products applied to the hair with some hand contact]
Category 7B (%)
0.22 [Leave-on products applied to the hair with some hand contact]
Category 8 (%)
0.009 [Products with significant anogenital exposure (tampon)]
Category 9 (%)
0.21 [Products with body and hand exposure, primarily rinse off]
Category 10A (%)
0.21 [Household care products with mostly hand contact (excluding aerosol/spray products)]
Category 10B (%)
0.75 [Household care products with mostly hand contact (household aerosol/spray products)]
Category 11A (%)
0.009 [Products with intended skin contact but minimal transfer of fragrance to skin from inert substrate without UV exposure]
Category 11B (%)
0.009 [Products with intended skin contact but minimal transfer of fragrance to skin from inert substrate with potential UV exposure]
Category 12 (%)
No Restriction [Other air care products not intended for direct skin contact, minimal or insignificant transfer to skin]

10.4 Formulations / Preparations

Perfumer's grade, FCC.
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 710

10.5 U.S. Production

Aggregated Product Volume

2019: <1,000,000 lb

2018: <1,000,000 lb

2017: <1,000,000 lb

2016: <1,000,000 lb

Production volumes for non-confidential chemicals reported under the Inventory Update Rule.
Year
1986
Production Range (pounds)
10 thousand - 500 thousand
Year
1990
Production Range (pounds)
10 thousand - 500 thousand
Year
1994
Production Range (pounds)
10 thousand - 500 thousand
Year
1998
Production Range (pounds)
10 thousand - 500 thousand
Year
2002
Production Range (pounds)
No Reports
US EPA; Non-confidential Production Volume Information Submitted by Companies for Chemicals Under the 1986-2002 Inventory Update Rule (IUR). Phenol, 2-methoxy-4-(1-propenyl)- (97-54-1). Available from, as of June 12, 2012: https://www.epa.gov/oppt/iur/tools/data/2002-vol.html

10.6 General Manufacturing Information

Industry Processing Sectors
  • All Other Chemical Product and Preparation Manufacturing
  • Food, beverage, and tobacco product manufacturing
  • All Other Basic Organic Chemical Manufacturing
EPA TSCA Commercial Activity Status
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.
Fahlbusch K-G et al; Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2012). NY, NY: John Wiley & Sons; Flavors and Fragrances. Online Posting Date: January 15, 2003

11 Identification

11.1 Clinical Laboratory Methods

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.
Meinertz JR et al; J AOAC Int 91 (4): 884-91 (2008)

12 Safety and Hazards

12.1 Hazards Identification

12.1.1 GHS Classification

1 of 7
View All
Note
Pictograms displayed are for > 99.9% (1972 of 1973) of reports that indicate hazard statements. This chemical does not meet GHS hazard criteria for < 0.1% (1 of 1973) of reports.
Pictogram(s)
Irritant
Signal
Warning
GHS Hazard Statements

H302 (99.5%): Harmful if swallowed [Warning Acute toxicity, oral]

H312 (96.5%): Harmful in contact with skin [Warning Acute toxicity, dermal]

H315 (99.5%): Causes skin irritation [Warning Skin corrosion/irritation]

H317 (99.7%): May cause an allergic skin reaction [Warning Sensitization, Skin]

H319 (99%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (10%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

Precautionary Statement Codes

P261, P264, P264+P265, P270, P271, P272, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P319, P321, P330, P332+P317, P333+P317, P337+P317, P362+P364, P403+P233, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 1973 reports by companies from 33 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 1 of 1973 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 32 notifications provided by 1972 of 1973 reports by companies with hazard statement code(s).

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

12.1.2 Hazard Classes and Categories

Acute Tox. 4 (99.5%)

Acute Tox. 4 (96.5%)

Skin Irrit. 2 (99.5%)

Skin Sens. 1A (99.7%)

Eye Irrit. 2 (99%)

STOT SE 3 (10%)

Acute Tox. 4 (98.6%)

Acute Tox. 4 (98.6%)

Skin Irrit. 2 (87.9%)

Skin Sens. 1A (100%)

Eye Irrit. 2 (98.6%)

Acute Tox. 4 (65.7%)

STOT SE 3 (65.7%)

12.1.3 NFPA Hazard Classification

NFPA 704 Diamond
2-2-0
NFPA Health Rating
2 - Materials that, under emergency conditions, can cause temporary incapacitation or residual injury.
NFPA Fire Rating
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.
NFPA Instability Rating
0 - Materials that in themselves are normally stable, even under fire conditions.

12.1.4 Fire Hazards

This chemical is combustible. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.1.5 Hazards Summary

An irritant; Possible sensitizer; [MSDSonline] Isoeugenol is a fragrance allergen that causes allergic contact dermatitis. [Marks, p. 168, 172] Danger of skin sensitization; [MAK] Common allergen in cosmetics and perfumes; [Kanerva, p. 1805] See Eugenol.
Marks - Marks JG, DeLeo VA. Contact and Occupational Dermatology, 2nd Ed. St. Louis: Mosby, 1997., p. 168, 172
Kanerva - Rustemeyer L, Elsner P, John SM, Maibach HI (eds). Kanerva's Occupational Dermatology, 2nd Ed. Berlin: Springer-Verlag, 2012., p. 1805

12.2 Safety and Hazard Properties

12.2.1 Critical Temperature & Pressure

Crticial temperature: 718.774 deg K; critical pressure: 30.142 atm
Razdan TK et al; Parfume Kosmet 66: 444-449 (1985)

12.3 First Aid Measures

12.3.1 First Aid

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)

National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.4 Fire Fighting

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)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.5 Accidental Release Measures

12.5.1 Disposal Methods

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.

12.6 Handling and Storage

12.6.1 Nonfire Spill Response

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)

National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.7 Exposure Control and Personal Protection

12.7.1 Personal Protective Equipment (PPE)

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)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.8 Stability and Reactivity

12.8.1 Air and Water Reactions

Slightly water soluble (NTP, 1992).
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.8.2 Reactive Group

Hydrocarbons, Aliphatic Unsaturated

Phenols and Cresols

12.9 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: Phenol, 2-methoxy-4-(1-propenyl)-
The Australian Inventory of Industrial Chemicals
Chemical: Phenol, 2-methoxy-4-(1-propenyl)-, (E)-
California Safe Cosmetics Program (CSCP) Reportable Ingredient

Hazard Traits - Carcinogenicity; Fragrance Allergen

Authoritative List - Annex III of the EU Cosmetics Regulation No. 1223/2009 - Fragrance Allergens; IARC Carcinogens - 2B

Report - regardless of intended function of ingredient in the product

REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
Phenol, 2-methoxy-4-(1-propenyl)-: Does not have an individual approval but may be used under an appropriate group standard

12.9.1 FDA Requirements

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.
21 CFR 172.515 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 19, 2012: https://www.ecfr.gov

12.10 Other Safety Information

Chemical Assessment

IMAP assessments - Isoeugenol and its constituent isomers: Human health tier II assessment

IMAP assessments - Phenol, 2-methoxy-4-(1-propenyl)-: Environment tier I assessment

Chemical Assessment
IMAP assessments - Isoeugenol and its constituent isomers: Human health tier II assessment

13 Toxicity

13.1 Toxicological Information

13.1.1 Carcinogen Classification

1 of 3
IARC Carcinogenic Agent
Isoeugenol
IARC Carcinogenic Classes
Group 2B: Possibly carcinogenic to humans
IARC Monographs
Volume 134: (2024) Aspartame, Methyleugenol, and Isoeugenol
2 of 3
Substance
NTP Technical Report
TR-551: NTP Toxicology and Carcinogenesis Studies of Isoeugenol (CASRN 97-54-1) in F344/N Rats and B6C3F1 Mice (Gavage studies) (2010 )
Peer Review Date
Conclusion for Male Rat
Equivocal Evidence Equivocal Evidence
Conclusion for Female Rat
No Evidence No Evidence
Conclusion for Male Mice
Clear Evidence Clear Evidence
Conclusion for Female Mice
Equivocal Evidence Equivocal Evidence
Summary

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. 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 isoeugenol in female B6C3F1 mice based on increased incidences of histiocytic sarcoma.

Exposure to isoeugenol resulted in nonneoplastic lesions of the nose in male and female rats; of the nose, forestomach, and glandular stomach in male and female mice; and of the kidney in female mice.

3 of 3
Carcinogen Classification
No indication of carcinogenicity to humans (not listed by IARC).

13.1.2 Adverse Effects

Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

IARC Carcinogen - Class 3: Chemicals are not classifiable by the International Agency for Research on Cancer.

13.1.3 Acute Effects

13.1.4 Antidote and Emergency Treatment

/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/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 277
/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/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 277
/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/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 277

13.1.5 Human Toxicity Excerpts

/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.
Thompson GR et al; Food Chem Toxicol 21 (6): 735-40 (1983)
/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.
Andersen KE et al; Toxicol Appl Pharmacol 170 (3): 166-71 (2001)
/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.
Bruze M et al; Contact Dermatitis 52 (5): 260-7 (2005)
/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). ...
Turic P et al; Coll Antropol. 2011 Mar;35(1):83-7 (2011)

13.1.6 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ The sensitizing potential of eugenol and isoeugenol was studied in mice and guinea pigs. Eugenol or isoeugenol at concentrations up to 25% was applied to the dorsum of the ears of 6 to 12 week (wk) old female BALB/c-mice. The contact sensitization potential of the compounds was evaluated using the standard murine local lymph node assay (LLNA). The respiratory sensitizing potential of the two chemicals was assessed using the mouse immunoglobulin-E (IgE) test. In this assay, 7 days after the initial treatment, the chemicals were applied to the dorsum of the ears at half the initial concentrations. After another 7 days, the mice were killed. Serum was analyzed for total IgE by an enzyme linked immunosorbent assay. Six to 12 wk old female Dunkin-Hartley guinea pigs were also administered 5, 10, or 25% eugenol or isoeugenol topically. The contact sensitizing potential of the compounds was assessed using the guinea pig maximization test (GPMT). Eugenol and isoeugenol induced positive responses in both the GPMT and the murine LLNA. Isoeugenol produced the stronger responses. Eugenol at 2.5% induced a significant increase in serum total IgE concentration in the mouse IgE test. Higher concentrations did not increase IgE concentrations. The positive response induced by 2.5% eugenol was not considered biologically relevant. Isoeugenol had no significant effect on serum IgE concentrations in the assay. ... The results of the murine LLNA and GPMT confirm that eugenol and isoeugenol are contact sensitizers. Neither compound appears to be a respiratory sensitizer. The definite negative response produced by isoeugenol in the mouse IgE test and the lack of any reports of occupational pulmonary reactions suggest that isoeugenol may be useful as a negative control for developing and validating new tests for identifying respiratory allergens.
Hilton J et al; J Applied Toxicol 16 (5): 459-64 (1996)
/LABORATORY ANIMALS: Acute Exposure/ Allergic contact dermatitis is the serious unwanted effect arising from the use of consumer products such as cosmetics. Isoeugenol is a fragrance chemical with spicy, carnation-like scent, is used in many kinds of cosmetics and is a well-known moderate human sensitizer. It was previously reported that the dimerization of eugenol yielded two types of dimer possessing different sensitization potencies. This study reports the differences in skin sensitization potencies for isoeugenol and two types of dimer, beta-O-4-dilignol and dehydrodiisoeugenol (DIEG), as evaluated by the non-radioisotopic local lymph node assay (non-RI LLNA) and guinea pig maximization test. In the guinea pig maximization test, isoeugenol, beta-O-4-dilignol and DIEG were classified as extreme, weak and moderate sensitizers, respectively. As for the results of non-RI LLNA, the EC3 for isoeugenol, beta-O-4-dilignol and DIEG were calculated as 12.7%, >30% and 9.4%, respectively. The two types of isoeugenol dimer showed different sensitizing activities similar to the case for eugenol dimers. A reduction of sensitization potency achieved by dimerization may lead to developing safer cosmetic ingredients. Isoeugenol dimers are not currently used for fragrance chemicals. However, the dimerization of isoeugenol may yield a promising candidate as a cosmetic ingredient with low sensitization risk. The data may also provide useful information for the structure-activity relationship (SAR) in skin sensitization.
Takeyoshi M et al; J Appl Toxicol 28 (4): 530-4 (2008)
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ 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 ... and 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. ... 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. 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 in male and female rats; of the nose, forestomach, and glandular stomach in male and female mice; and of the kidney in female mice.
DHHS/NTP; NTP Technical Report on Toxicology and Carcinogenesis Studies of Isoeugenol in F344/N Rats and B6C3F1 Mice (Gavage Studies) (CAS No. 97-54-1) p.7 (1983) Technical Rpt Series No. 551 NIH Pub No. 10-5892. Available from, as of July 28, 2012: https://ntp-server.niehs.nih.gov/
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Isoeugenol, used as a perfumery and flavoring agent, was evaluated for developmental toxicity. Timed-pregnant CD((R)) outbred albino Sprague-Dawley rats received isoeugenol (250, 500, or 1000 mg/kg/day) or vehicle (5 mL/kg corn oil) by gavage on gestational days (gd) 6 through 19. Maternal food and water consumption, body weight, and clinical signs were monitored at regular intervals throughout gestation. At termination (gd 20), confirmed-pregnant females (23-25 per group) were evaluated for gestational outcome. All live fetuses were weighed and examined for external malformations, and approximately 50% were evaluated for visceral or skeletal malformations. There were no treatment-related maternal deaths. Clinical signs associated with isoeugenol exposure included dose-related evidence of sedation and aversion to treatment (rooting behavior) in all isoeugenol groups, as well as an increased incidence of piloerection at >/= 500 mg/kg/day. Maternal body weight, weight gain, and gestational weight gain (corrected for gravid uterine weight) were reduced at all doses in a dose-related manner. Gravid uterine weight was significantly decreased at the mid and high doses, whereas maternal relative liver weight was increased at all three dose levels. During treatment (gd 6 to 20), maternal relative food consumption was significantly decreased at the high dose, and maternal relative water consumption was elevated in the mid- and high-dose groups. Prenatal mortality (resorption or late fetal death) was unaffected. At 1000 mg/kg/day, average fetal body weight/litter was decreased by 7% (male) or 9% (female). Incidences of fetal morphological anomalies were statistically equivalent among groups, except for an increase in the incidence of unossified sternebra(e), a skeletal variation, at the high dose. In summary, the maternal toxicity lowest observed adverse effect level (LOAEL) was 250 mg/kg/day based primarily on reduced body weight and gestational weight gain (corrected for gravid uterine weight), and the maternal toxicity no observed adverse effect level (NOAEL) was not determined in this study. The developmental toxicity LOAEL was 1000 mg/kg/day based on intrauterine growth retardation and mildly delayed skeletal ossification. The developmental toxicity NOAEL was 500 mg/kg/day.
George JD et al; Toxicol Sci 60 (1): 112-20 (2001)
For more Non-Human Toxicity Excerpts (Complete) data for Isoeugenol (6 total), please visit the HSDB record page.

13.1.7 Non-Human Toxicity Values

LD50 Rat oral 1560 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2134
LD50 Guinea pig oral 1410 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2134

13.1.8 Ongoing Test Status

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=97-54-1]

13.1.9 National Toxicology Program Studies

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.
DHHS/NTP; NTP Technical Report on Toxicology and Carcinogenesis Studies of Isoeugenol in F344/N Rats and B6C3F1 Mice (Gavage Studies) (CAS No. 97-54-1) p.7 (1983) Technical Rpt Series No. 551 NIH Pub No. 10-5892. Available from, as of July 28, 2012: https://ntp-server.niehs.nih.gov/
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.
DHHS/NTP; NTP Technical Report on Toxicology and Carcinogenesis Studies of Isoeugenol in F344/N Rats and B6C3F1 Mice (Gavage Studies) (CAS No. 97-54-1) p.8 (1983) Technical Rpt Series No. 551 NIH Pub No. 10-5892. Available from, as of July 28, 2012: https://ntp-server.niehs.nih.gov/
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 ... .
DHHS/NTP; NTP Technical Report on Toxicology and Carcinogenesis Studies of Isoeugenol in F344/N Rats and B6C3F1 Mice (Gavage Studies) (CAS No. 97-54-1) p.8 (1983) Technical Rpt Series No. 551 NIH Pub No. 10-5892. Available from, as of July 28, 2012: https://ntp-server.niehs.nih.gov/
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.
DHHS/NTP; NTP Technical Report on Toxicology and Carcinogenesis Studies of Isoeugenol in F344/N Rats and B6C3F1 Mice (Gavage Studies) (CAS No. 97-54-1) p.8 (1983) Technical Rpt Series No. 551 NIH Pub No. 10-5892. Available from, as of July 28, 2012: https://ntp-server.niehs.nih.gov/
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.
DHHS/NTP; NTP Technical Report on Toxicology and Carcinogenesis Studies of Isoeugenol in F344/N Rats and B6C3F1 Mice (Gavage Studies) (CAS No. 97-54-1) p.8 (1983) Technical Rpt Series No. 551 NIH Pub No. 10-5892. Available from, as of July 28, 2012: https://ntp-server.niehs.nih.gov/

13.2 Ecological Information

13.2.1 Environmental Fate / Exposure Summary

Isoeugenol's production and use as a fragrance in household laundry and cleaning products and perfumes, as a flavoring agent and in the manufacture of vanillin may result in its release to the environment through various waste streams. Its application as a fish anesthetic/sedative will result in its direct release to the environment. Isoeugenol occurs in essential oils, has been detected in various plants, and has been detected in wood smoke from the combustion of wood. If released to air, an extrapolated vapor pressure of 0.0135 mm Hg at 25 °C indicates isoeugenol will exist solely as a vapor in the atmosphere. Vapor-phase isoeugenol will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 4.3 hours. Vapor-phase isoeugenol will also be degraded in the atmosphere by reaction with ozone; the half-life for this reaction in air is estimated to be 3 hours. If released to soil, isoeugenol is expected to have low mobility based upon an estimated Koc value of 680. Volatilization from moist soil surfaces is expected to occur given an estimated Henry's Law constant of 3.6X10-6 atm-cu m/mole. Isoeugenol was found to be readily biodegradable using a Manometric Respirometry Test in which isoeugenol reached 79% biodegradation after 28 days. If released into water, isoeugenol is expected to adsorb to suspended solids and sediment based upon the estimated Koc value. Volatilization from water surfaces is expected based upon this compound's estimated Henry's Law constant. Estimated volatilization half-lives for a model river and model lake are 13 and 100 days, respectively. Isoeugenol can be degraded in the natural water by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction is estimated to be 20.6 days. An estimated BCF of 47 suggests the potential for bioconcentration in aquatic organisms is moderate. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to isoeugenol may occur through inhalation and dermal contact with this compound at workplaces where isoeugenol is produced or used. 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; dermal contact is the primary route of exposure, but inhalation can also occur. (SRC)

13.2.2 Natural Pollution Sources

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).
(1) O'Neil MJ, ed; The Merck Index. 14th ed., Whitehouse Station, NJ: Merck and Co., Inc., p. 895 (2006)
(2) Aubert C, Pitrat M; J Agric Food Chem 54: 8177-8182 (2006)
(3) Nishimura O; J Agric Food Chem 43: 2941-2945 (1995)
(4) Nolte CG et al; Environ Sci Technol 35: 1912-1919 (2001)
(5) Rogge WF et al; Environ Sci Technol 32: 13-22 (1998)

13.2.3 Artificial Pollution Sources

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).
(1) HERA; HERA Risk Assessment of Isoeugenol (Draft). Human and Environmental Risk Assessment on ingredients of Household Cleaning Products. Isoeugenol (CAS 97-54-1). Available from, as of June 23, 2012: https://www.heraproject.com/
(2) Lewis RJ, Sr; Hawley's Condensed Chemical Dictionary 15th ed. New York, NY: John Wiley & Sons, Inc, p. 710 (2007)
(3) O'Neil MJ. ed; The Merck Index. 14th ed., Whitehouse Station, NJ: Merck and Co., Inc., p. 895 (2006)
(4) Meinertz JR et al; J AOAC Int 9: 884-91 (2008)

13.2.4 Environmental Fate

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).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Jun 22, 2012: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) NIST; NIST Chemistry WebBook. Phenol, 2-methoxy-4-(1-propenyl)- (97-54-1). NIST Standard Reference Database No. 69, June 2005 Release. Washington, DC: US Sec Commerce. Available from, as of Jun 25, 2012: https://webbook.nist.gov
(4) HERA; HERA Risk Assessment of Isoeugenol (Draft). Human and Environmental Risk Assessment on ingredients of Household Cleaning Products. Isoeugenol (CAS 97-54-1). Available from, as of June 23, 2012: https://www.heraproject.com/
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).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Jun 22, 2012: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 15-1 to 15-29 (1990)
(4) NIST; NIST Chemistry WebBook. Phenol, 2-methoxy-4-(1-propenyl)- (97-54-1). NIST Standard Reference Database No. 69, June 2005 Release. Washington, DC: US Sec Commerce. Available from, as of Jun 25, 2012: https://webbook.nist.gov
(5) HERA; HERA Risk Assessment of Isoeugenol (Draft). Human and Environmental Risk Assessment on ingredients of Household Cleaning Products. Isoeugenol (CAS 97-54-1). Available from, as of June 23, 2012: https://www.heraproject.com/
(6) Franke C et al; Chemosphere 29: 1501-14 (1994)
(7) Buxton GV et al; J Phys Chem Ref Data 17: 513-882 (1988)
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).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) NIST; NIST Chemistry WebBook. Phenol, 2-methoxy-4-(1-propenyl)- (97-54-1). NIST Standard Reference Database No. 69, June 2005 Release. Washington, DC: US Sec Commerce. Available from, as of Jun 25, 2012: https://webbook.nist.gov
(3) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Jun 22, 2012: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm

13.2.5 Environmental Biodegradation

AEROBIC: Isoeugenol, at a concentration of 100 mg/L, was found to be readily biodegradable using a Manometric Respirometry Test (OECD Guideline 301F) in which isoeugenol reached 79% biodegradation after 28 days(1); the biodegradation started on day 2 and reached 79% at the end of the 10-day window period(1).
(1) HERA; HERA Risk Assessment of Isoeugenol (Draft). Human and Environmental Risk Assessment on ingredients of Household Cleaning Products. Isoeugenol (CAS 97-54-1). Available from, as of June 23, 2012: https://www.heraproject.com/

13.2.6 Environmental Abiotic Degradation

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).
(1) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Jun 22, 2012: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(2) Buxton GV et al; J Phys Chem Ref Data 17: 513-882 (1988)
(3) Mill T et al; Science 207: 886-887 (1980)
(4) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5 (1990)

13.2.7 Environmental Bioconcentration

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).
(1) Griffin S et al; J Chromatog 864: 221-228 (1999)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Jun 22, 2012: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

13.2.8 Soil Adsorption / Mobility

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.
(1) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Jun 22, 2012: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(2) Swann RL et al; Res Rev 85: 17-28 (1983)

13.2.9 Volatilization from Water / 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).
(1) NIST; NIST Chemistry WebBook. Phenol, 2-methoxy-4-(1-propenyl)- (97-54-1). NIST Standard Reference Database No. 69, June 2005 Release. Washington, DC: US Sec Commerce. Available from, as of Jun 25, 2012: https://webbook.nist.gov
(2) HERA; HERA Risk Assessment of Isoeugenol (Draft). Human and Environmental Risk Assessment on ingredients of Household Cleaning Products. Isoeugenol (CAS 97-54-1). Available from, as of June 23, 2012: https://www.heraproject.com/
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)

13.2.10 Effluent Concentrations

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).
(1) Belknap AM et al; Environ Toxicol Chem 25(9): 2322-2333 (2006)
(2) Lavallee HC et al; Sci Tech Eau 25: 501-510 (1992)
(3) Nolte CG et al; Environ Sci Technol 35: 1912-1919 (2001)
(4) Rogge WF et al; Environ Sci Technol 32: 13-22 (1998)

13.2.11 Plant Concentrations

Isoeugenol was detected in the skin and pulp of Queen Anne's pocket melon (Cucumis melo var dudaim (L.) Naudin) at respective concentrations of 25.4 mg/kg and 2.7 mg/kg(1). Isoeugenol was identified as an odorant component of ginger oil(2).
(1) Aubert C, Pitrat M; J Agric Food Chem 54: 8177-8182 (2006)
(2) Nishimura O; J Agric Food Chem 43: 2941-2945 (1995)
Isoeugenol concentrations in various plants(1).
Genus species
Acorus calamus L.
Plant
Calamus, Flagroot, Myrtle Flag, Sweet Calamus, Sweetflag, Sweetroot
Part
Rhizome
Concn (ppm)
12,510
Genus species
Myristica fragrans
Plant
Mace, Muskatnussbaum (Ger.), Nutmeg, nogal moscado (Sp.), nuez moscada (Sp.)
Part
Seed
Concn (ppm)
320
Genus species
Satureja odora
Plant
Scented Pampa Savory
Part
Shoot
Concn (ppm)
0-525
Genus species
Ocimum basilicum
Plant
Basil, Cuban Basil, Sweet Basil
Part
Plant
Concn (ppm)
95
Genus species
Origanum sipyleum
Plant
Bayircayi, Guveyoto
Part
Shoot
Concn (ppm)
0-20
Genus species
Cinnamomum verum
Plant
Ceylon Cinnamon, Cinnamon
Part
Bark
Concn (ppm)
8
Genus species
Origanum sipyleum L.
Plant
Bayircayi, Guveyoto
Part
Shoot
Concn (ppm)
0-5
(1) USDA; Dr. Duke's Phytochemical and Ethnobotanical Databases. Plants with a chosen chemical. Eugenol. Washington, DC: US Dept Agric, Agric Res Service. Available from, as of Aug 1, 2012: https://www.ars-grin.gov/duke/

13.2.12 Other Environmental Concentrations

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).
(1) Nolte CG et al; Environ Sci Technol 35: 1912-1919 (2001)
(2) Rogge WF et al; Environ Sci Technol 32: 13-22 (1998)

13.2.13 Probable Routes of Human Exposure

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).
(1) NIOSH; NOES. National Occupational Exposure Survey conducted from 1981-1983. Estimated numbers of employees potentially exposed to specific agents by 2-digit standard industrial classification (SIC). Available from, as of June 23, 2012: https://www.cdc.gov/noes/
(2) HERA; HERA Risk Assessment of Isoeugenol (Draft). Human and Environmental Risk Assessment on ingredients of Household Cleaning Products. Isoeugenol (CAS 97-54-1). Available from, as of June 23, 2012: https://www.heraproject.com/

14 Associated Disorders and Diseases

Associated Occupational Diseases with Exposure to the Compound
Contact dermatitis, allergic [Category: Skin Disease]

15 Literature

15.1 Consolidated References

15.2 NLM Curated PubMed Citations

15.3 Springer Nature References

15.4 Thieme References

15.5 Chemical Co-Occurrences in Literature

15.6 Chemical-Gene Co-Occurrences in Literature

15.7 Chemical-Disease Co-Occurrences in Literature

16 Patents

16.1 Depositor-Supplied Patent Identifiers

16.2 WIPO PATENTSCOPE

16.3 Chemical Co-Occurrences in Patents

16.4 Chemical-Disease Co-Occurrences in Patents

16.5 Chemical-Gene Co-Occurrences in Patents

17 Interactions and Pathways

17.1 Protein Bound 3D Structures

17.1.1 Ligands from Protein Bound 3D Structures

1 of 2
View All
PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

17.2 Chemical-Target Interactions

17.3 Pathways

18 Biological Test Results

18.1 BioAssay Results

19 Taxonomy

The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

20 Classification

20.1 MeSH Tree

20.2 ChEBI Ontology

20.3 ChemIDplus

20.4 CAMEO Chemicals

20.5 ChEMBL Target Tree

20.6 UN GHS Classification

20.7 EPA CPDat Classification

20.8 NORMAN Suspect List Exchange Classification

20.9 EPA DSSTox Classification

20.10 International Agency for Research on Cancer (IARC) Classification

20.11 Consumer Product Information Database Classification

20.12 EPA TSCA and CDR Classification

20.13 LOTUS Tree

20.14 MolGenie Organic Chemistry Ontology

21 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
  2. CAMEO Chemicals
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    https://cameochemicals.noaa.gov/help/reference/terms_and_conditions.htm?d_f=false
    CAMEO Chemical Reactivity Classification
    https://cameochemicals.noaa.gov/browse/react
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    Phenol, 2-methoxy-4-(1-propen-1-yl)-
    https://www.epa.gov/chemical-data-reporting
  8. EPA Chemicals under the TSCA
    Phenol, 2-methoxy-4-(1-propen-1-yl)-
    https://www.epa.gov/chemicals-under-tsca
    EPA TSCA Classification
    https://www.epa.gov/tsca-inventory
  9. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  10. European Chemicals Agency (ECHA)
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    https://echa.europa.eu/web/guest/legal-notice
    (E)-2-methoxy-4-(prop-1-enyl)phenol
    https://chem.echa.europa.eu/100.025.162
  11. FDA Global Substance Registration System (GSRS)
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  12. Hazardous Substances Data Bank (HSDB)
  13. Human Metabolome Database (HMDB)
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    http://www.hmdb.ca/citing
  14. International Fragrance Association (IFRA)
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    https://ifrafragrance.org/links/copyright
  15. New Zealand Environmental Protection Authority (EPA)
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    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  16. California Safe Cosmetics Program (CSCP) Product Database
  17. Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
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    https://haz-map.com/About
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    https://haz-map.com/Agents/7845
  18. Joint FAO/WHO Expert Committee on Food Additives (JECFA)
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    https://www.who.int/about/policies/publishing/copyright
  19. ChEBI
  20. LOTUS - the natural products occurrence database
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    https://lotus.nprod.net/
  21. Toxin and Toxin Target Database (T3DB)
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    http://www.t3db.ca/downloads
  22. Yeast Metabolome Database (YMDB)
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    YMDB is offered to the public as a freely available resource.
    http://www.ymdb.ca/downloads
    E-4-Propenyl-2-methoxyphenol
    https://www.ymdb.ca/compounds/YMDB01677
  23. ChEMBL
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    http://www.ebi.ac.uk/Information/termsofuse.html
  24. Comparative Toxicogenomics Database (CTD)
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    http://ctdbase.org/about/legal.jsp
  25. Consumer Product Information Database (CPID)
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    https://www.whatsinproducts.com/contents/view/1/6
    Consumer Products Category Classification
    https://www.whatsinproducts.com/
  26. DailyMed
  27. EPA Chemical and Products Database (CPDat)
  28. EU Food Improvement Agents
  29. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    (E)-Isoeugenol
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  30. Hazardous Chemical Information System (HCIS), Safe Work Australia
  31. NITE-CMC
    Isoeugenol - FY2011 (New/original classication)
    https://www.chem-info.nite.go.jp/chem/english/ghs/11-mhlw-0070e.html
  32. Regulation (EC) No 1272/2008 of the European Parliament and of the Council
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  33. FDA Substances Added to Food
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  34. Flavor and Extract Manufacturers Association (FEMA)
  35. FooDB
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    https://foodb.ca/about
  36. IUPAC Digitized pKa Dataset
    phenol, 2-methoxy-4-(1-propenyl)-
    https://github.com/IUPAC/Dissociation-Constants
  37. MassBank of North America (MoNA)
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    https://mona.fiehnlab.ucdavis.edu/documentation/license
  38. NIST Mass Spectrometry Data Center
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    https://www.nist.gov/srd/public-law
    Phenol, 2-methoxy-4-(1-propenyl)-
    http://www.nist.gov/srd/nist1a.cfm
  39. SpectraBase
    PHENOL, 2-METHOXY-4-(1-PROPENYL)-
    https://spectrabase.com/spectrum/D1TnPKyKi1q
    trans-2-METHOXY-4-PROPENYLPHENOL
    https://spectrabase.com/spectrum/8k7N0tyrPXh
    trans-2-methoxy-4-propenylphenol
    https://spectrabase.com/spectrum/LAcNDpIUHj0
    trans-2-METHOXY-4-PROPENYLPHENOL
    https://spectrabase.com/spectrum/1lY303mnGnY
    2-Methoxy-4-(trans-2-propenyl)-phenol
    https://spectrabase.com/spectrum/2Tbq6oo3Bs1
    trans-2-METHOXY-4-PROPENYLPHENOL
    https://spectrabase.com/spectrum/LrjrB9Kh9dt
    Phenol, 2-methoxy-4-(1-propenyl)-
    https://spectrabase.com/spectrum/EIADOi89B40
    Phenol, 2-methoxy-4-(1-propenyl)-
    https://spectrabase.com/spectrum/yPE6X8Fd48
  40. International Agency for Research on Cancer (IARC)
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    IARC Classification
    https://www.iarc.fr/
  41. NTP Technical Reports
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  43. KEGG
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  44. KNApSAcK Species-Metabolite Database
  45. Natural Product Activity and Species Source (NPASS)
  46. Metabolomics Workbench
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  48. Protein Data Bank in Europe (PDBe)
  49. RCSB Protein Data Bank (RCSB PDB)
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  50. Rhea - Annotated Reactions Database
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  51. Springer Nature
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  58. GHS Classification (UNECE)
  59. MolGenie
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    https://github.com/MolGenie/ontology/
  60. PATENTSCOPE (WIPO)
CONTENTS