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Ferulic acid

PubChem CID
445858
Structure
Ferulic acid_small.png
Ferulic acid_3D_Structure.png
Ferulic acid__Crystal_Structure.png
Molecular Formula
Synonyms
  • ferulic acid
  • trans-Ferulic Acid
  • 1135-24-6
  • 537-98-4
  • 4-Hydroxy-3-methoxycinnamic acid
Molecular Weight
194.18 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2004-09-16
  • Modify:
    2025-01-18
Description
Ferulic acid is a ferulic acid consisting of trans-cinnamic acid bearing methoxy and hydroxy substituents at positions 3 and 4 respectively on the phenyl ring. It has a role as an antioxidant, a MALDI matrix material, a plant metabolite, an anti-inflammatory agent, an apoptosis inhibitor and a cardioprotective agent. It is a conjugate acid of a ferulate.
Ferulic acid has been reported in Salvia rosmarinus, Camellia reticulata, and other organisms with data available.
Ferulic acid is a metabolite found in or produced by Saccharomyces cerevisiae.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Ferulic acid.png

1.2 3D Conformer

1.3 Crystal Structures

1 of 3
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CCDC Number
Associated Article
Crystal Structure Data
Crystal Structure Depiction
Crystal Structure Depiction

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoic acid
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C10H10O4/c1-14-9-6-7(2-4-8(9)11)3-5-10(12)13/h2-6,11H,1H3,(H,12,13)/b5-3+
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

KSEBMYQBYZTDHS-HWKANZROSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

COC1=C(C=CC(=C1)/C=C/C(=O)O)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C10H10O4
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

1135-24-6
97274-61-8
171876-65-6

2.3.3 Deprecated CAS

1356408-74-6

2.3.4 European Community (EC) Number

2.3.5 UNII

2.3.6 ChEBI ID

2.3.7 ChEMBL ID

2.3.8 DrugBank ID

2.3.9 DSSTox Substance ID

2.3.10 HMDB ID

2.3.11 KEGG ID

2.3.12 Metabolomics Workbench ID

2.3.13 Nikkaji Number

2.3.14 NSC Number

2.3.15 Pharos Ligand ID

2.3.16 RXCUI

2.3.17 Wikidata

2.3.18 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid
  • 4-hydroxy-3-methoxycinnamic acid
  • 8,8'-diferulic acid
  • cis-ferulic acid
  • ferulic acid
  • ferulic acid, (E)-isomer
  • ferulic acid, (Z)-isomer
  • ferulic acid, monosodium salt
  • sodium ferulate
  • trans-ferulic acid

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
194.18 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
1.5
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
194.05790880 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
194.05790880 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
66.8 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
14
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
224
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

cis-Form is a yellow liquid; trans-Form is a solid; [Merck Index] trans-Isomer: Tan powder; [Alfa Aesar MSDS]
Tan powder; [Alfa Aesar MSDS]
Solid

3.2.2 Melting Point

168 - 171 °C

3.2.3 Vapor Pressure

0.00000269 [mmHg]

3.2.4 LogP

log Kow = 1.51
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 69
1.51
HANSCH,C ET AL. (1995)

3.2.5 Dissociation Constants

pKa = 4.58
Serjeant EP, Dempsey B; Ionisation constants of organic acids in aqueous solution. IUPAC Chem Data Ser No.23. NY,NY: Pergamon pp. 989 (1979)

3.2.6 Collision Cross Section

134.13 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

130.77 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Ross et al. JASMS 2022; 33; 1061-1072. DOI:10.1021/jasms.2c00111
139.8 Ų [M-H]- [CCS Type: DT; Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]
128.8 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]
140.1 Ų [M-H]-
S50 | CCSCOMPEND | The Unified Collision Cross Section (CCS) Compendium | DOI:10.5281/zenodo.2658162

3.2.7 Kovats Retention Index

1 of 2
Semi-standard non-polar
1897.1
2 of 2
Standard non-polar
1881
Semi-standard non-polar
1867 , 1911 , 1875

3.2.8 Other Experimental Properties

Yellow oil. UV max (alcohol): 316 nm /cis-Form/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 692
Orthorhombic needles from water, mp 174 °C. UV max (alcohol): 236, 322 nm. Soluble in hot water, alcohol, ethyl acetate. Moderately soluble in ether. Sparingly soluble in petroleum ether, benzene. Forms a sodium salt. /trans-Form/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 692

3.3 Chemical Classes

Other Classes -> Organic Acids

3.3.1 Drugs

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

3.3.2 Cosmetics

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

4 Spectral Information

4.1 1D NMR Spectra

1D NMR Spectra

4.1.1 1H NMR Spectra

1 of 5
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Spectra ID
Instrument Type
Varian
Frequency
600 MHz
Solvent
Water
pH
7.00
Shifts [ppm]:Intensity
6.90:16.53, 6.39:18.66, 7.11:7.77, 7.12:7.92, 7.10:9.02, 7.30:14.62, 6.36:17.76, 7.22:16.68, 7.33:13.77, 3.89:100.00, 7.22:15.56, 7.10:9.23, 6.92:18.55
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Spectra ID
Instrument Type
JEOL
Frequency
400 MHz
Solvent
DMSO-d6
Shifts [ppm]:Intensity
6.81:205.00, 6.83:217.00, 7.50:172.00, 6.38:202.00, 7.12:88.00, 7.31:170.00, 7.09:95.00, 3.84:1000.00, 6.42:221.00, 7.10:100.00, 12.16:25.00, 7.12:85.00, 9.57:77.00, 7.30:174.00, 7.54:159.00
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4.1.2 13C NMR Spectra

1 of 4
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Spectra ID
Instrument Type
Varian
Frequency
25.16 MHz
Solvent
DMSO-d6
Shifts [ppm]:Intensity
144.38:321.00, 115.54:518.00, 122.70:333.00, 111.09:315.00, 147.81:893.00, 125.68:863.00, 148.98:946.00, 55.59:619.00, 167.86:1000.00, 115.44:452.00
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Spectra ID
Instrument Type
Bruker
Solvent
DMSO
Shifts [ppm]:Intensity
168.04:49.07, 55.71:36.09, 122.88:42.12, 147.94:35.92, 144.55:37.68, 115.65:40.05, 149.10:31.84, 111.14:36.56, 115.53:41.92, 125.80:44.75
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4.2 2D NMR Spectra

4.2.1 1H-13C NMR Spectra

2D NMR Spectra Type
1H-13C HSQC
Spectra ID
Instrument Type
Bruker
Frequency
600 MHz
Solvent
Water
pH
7.00
Shifts [ppm] (F2:F1):Intensity
6.92:118.43:0.36, 7.32:143.74:0.28, 3.89:58.72:1.00, 7.12:124.86:0.54, 7.25:113.77:0.70
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4.3 Mass Spectrometry

4.3.1 GC-MS

1 of 16
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Spectra ID
Instrument Type
GC-MS
Top 5 Peaks

338.0 1

249.0 0.84

308.0 0.75

323.0 0.75

293.0 0.59

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2 of 16
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Spectra ID
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

194.0 99.99

179.0 18.80

150.0 18.80

133.0 15.60

135.0 11.60

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Notes
instrument=HITACHI M-52

4.3.2 MS-MS

1 of 8
View All
Spectra ID
Instrument Type
Quattro_QQQ
Ionization Mode
Positive
Top 5 Peaks

176.0 100

177.0 36.42

144.0 29.35

152.0 14.89

194.0 11.58

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Notes
delivery=Flow_Injectionanalyzer=Triple_Quad
2 of 8
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Spectra ID
Instrument Type
Quattro_QQQ
Ionization Mode
Positive
Top 5 Peaks

116.0 100

88.0 99.01

89.0 55.53

117.0 41.20

144.0 31.42

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Notes
delivery=Flow_Injectionanalyzer=Triple_Quad

4.3.3 LC-MS

1 of 6
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MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M-H]-
Precursor m/z
193.0505
Instrument
Agilent 6530 Q-TOF
Instrument Type
LC-ESI-QTOF
Ionization Mode
negative
Collision Energy
40 V
Retention Time
1.784
Top 5 Peaks

133.0289 100

114.1446 40.40

160.8440 34.62

105.0313 28.43

118.9376 26.27

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2 of 6
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MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M-H]-
Precursor m/z
193.0505
Instrument
Agilent 6530 Q-TOF
Instrument Type
LC-ESI-QTOF
Ionization Mode
negative
Collision Energy
20 V
Retention Time
1.784
Top 5 Peaks

134.0377 100

160.8415 32.73

133.0282 8.94

106.0396 4.04

178.0198 3.85

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4.3.4 Other MS

1 of 3
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MoNA ID
MS Category
Experimental
MS Type
Other
MS Level
MS2
Precursor Type
[M+H]+
Precursor m/z
195.19
Instrument
TQD, Waters
Instrument Type
Flow-injection QqQ/MS
Ionization
ESI
Ionization Mode
positive
Collision Energy
10
Top 5 Peaks

195 100

177 72.35

194 8.67

176 8.25

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2 of 3
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MoNA ID
MS Category
Experimental
MS Type
Other
MS Level
MS2
Precursor Type
[M+H]+
Precursor m/z
195.19
Instrument
TQD, Waters
Instrument Type
Flow-injection QqQ/MS
Ionization
ESI
Ionization Mode
positive
Collision Energy
20
Top 5 Peaks

177 100

145 36.66

176 19.08

194 7.68

195 6.53

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4.4 UV Spectra

4.4.1 UV-VIS Spectra

Copyright
Copyright © 2008-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.5 IR Spectra

4.5.1 FTIR Spectra

1 of 2
Technique
KBr WAFER
Source of Sample
Greenwood Chemical Company
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Technique
KBr WAFER
Source of Sample
Institute of Paper Chemistry, Appleton, Wisconsin
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.5.2 ATR-IR Spectra

1 of 2
Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Indofine Chemical Company, Inc.
Catalog Number
F-001
Lot Number
703020
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Source of Sample
Aldrich
Catalog Number
128708
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.6 Raman Spectra

1 of 2
Instrument Name
Bio-Rad FTS 175C with Raman accessory
Technique
FT-Raman
Source of Sample
Greenwood Chemical Company
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Indofine Chemical Company, Inc.
Catalog Number
F-001
Lot Number
0703020
Copyright
Copyright © 2014-2024 John Wiley & Sons, Inc. All Rights Reserved.
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6 Chemical Vendors

7 Drug and Medication Information

7.1 FDA National Drug Code Directory

7.2 Drug Labels

Active ingredient and drug

7.3 Clinical Trials

7.3.1 NIPH Clinical Trials Search of Japan

7.4 Therapeutic Uses

Ferulic acid (FA) is an effective scavenger of free radicals and it has been approved in certain countries as food additive to prevent lipid peroxidation.
Srinivasan M et al; J Clin Biochem Nutr 40 (2): 92-100 (2007)
Sodium ferulate (SF) or 3-methoxy-4-hydroxy-cinamate sodium is an active principle from Angelica sinensis, Cimicifuga heracleifolia, Lignsticum chuangxiong, and other plants. It has been used in traditional Chinese medicine and is approved by State Drugs Administration of China as a drug for treatment of cardiovascular and cerebrovascular diseases. SF has antithrombotic, platelet aggregation inhibitory and antioxidant activities in animals and humans. For several decades SF has been widely used in China to treat cardiovascular and cerebrovascular diseases and to prevent thrombosis... /Sodium ferulate/
Wang BH, Ou-Yang JP; Cardiovasc Drug Rev 23 (2): 161-72 (2005)
/EXPL THER/ Ligusticum Chuanxiong and its effective components were studied in the treatment of ischemic stroke, a common emergent disease in China. Some injections of the medicines, including Ligusticum, Ligustrazine, Ligustylid and ferulic acid, were tested clinically and experimentally. The results showed that the effects of the drugs were the same as or even better than those of the controls, such as papaverine, dextran and aspirin-persantin. They could improve brain microcirculation through inhibiting thrombus formation and platelet aggregation as well as blood viscosity.
Chen KJ, Chen K; Chin Med J (Engl). 105 (10): 870-3 (1992)
/EXPL THER/ Although more definitive research is necessary, several natural therapies show promise in treating hot flashes without the risks associated with conventional therapies. Soy and other phytoestrogens, black cohosh, evening primrose oil, vitamin E, the bioflavonoid hesperidin with vitamin C, ferulic acid, acupuncture treatment, and regular aerobic exercise have been shown effective in treating hot flashes in menopausal women.
Philip HA; Altern Med Rev 8 (3): 284-302 (2003)
For more Therapeutic Uses (Complete) data for FERULIC ACID (6 total), please visit the HSDB record page.

7.5 Biomarker Information

8 Food Additives and Ingredients

8.1 Food Additive Classes

Flavoring Agents

8.2 Associated Foods

9 Pharmacology and Biochemistry

9.1 MeSH Pharmacological Classification

Cholagogues and Choleretics
Gastrointestinal agents that stimulate the flow of bile into the duodenum (cholagogues) or stimulate the production of bile by the liver (choleretic). (See all compounds classified as Cholagogues and Choleretics.)
Free Radical Scavengers
Substances that eliminate free radicals. Among other effects, they protect PANCREATIC ISLETS against damage by CYTOKINES and prevent myocardial and pulmonary REPERFUSION INJURY. (See all compounds classified as Free Radical Scavengers.)
Anticoagulants
Agents that prevent BLOOD CLOTTING. (See all compounds classified as Anticoagulants.)
Anti-Inflammatory Agents, Non-Steroidal
Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)
Antihypertensive Agents
Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)
Indicators and Reagents
Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant and Hackh's Chemical Dictionary, 5th ed, p301, p499) (See all compounds classified as Indicators and Reagents.)

9.2 Absorption, Distribution and Excretion

The study described here has investigated the bioavailability of ferulic acid in humans, from tomato consumption, through the monitoring of the pharmacokinetics of excretion in relation to intake. The results show that the peak time for maximal urinary excretion is approximately 7 hr and the recovery of ferulic acid in the urine, on the basis of total free ferulic acid and feruloyl glucuronide excreted, is 11-25% of that ingested.
Bourne LC, Rice Evans C; Biochem Biophys Res Commun 253 (2): 222-7 (1999)
The ... study investigated the urinary excretion of free and conjugated ferulic acid, present in quantitatively detectable amounts in French maritime pine (Pinus maritima) bark extract (PBE), after oral PBE administration to human subjects. Eleven healthy adult subjects (4 women and 7men) consumed either a single dose (200 mg PBE) or two doses of PBE (100 and 200 mg, respectively) within a 48-hr interval. Two days before the oral administration of PBE and during the urine sample collection period volunteers adhered to a diet low in polyphenols. Aliquots of all urine production were collected over 24 hr. Free and conjugated ferulic acid was assessed in urine by HPLC using diode array detection. A close association between the dietary intake of PBE and the urinary excretion of ferulic acid was detected. Moreover, the results indicate that a considerable proportion of ferulic acid is excreted as glucuronide or sulfate after PBE consumption, varying over the range 2 to 20% between individuals. The kinetics of excretion associated with the administration of 100 mg PBE was quite similar to that obtained after 200 mg PBE. A biphasic trend was evident in a number of subjects. All subjects studied here displayed a significant, although variable level of excretion of ferulic acid after supplementation with PBE, Thus, the data provide evidence that at least a part of the phenolic components of PBE are absorbed, metabolized, and eliminated by humans.
Virgili F et al; Free Radic Biol Med 28 (8): 1249-56 (2000) :
The hydroxycinnamates, intermediates in the phenylpropanoid synthetic pathway, are effective in enhancing the resistance of low-density lipoprotein (LDL) to oxidation in the order caffeic acid greater than ferulic acid greater than p-coumaric acid. It is unclear whether the mode of action of ferulic acid as an antioxidant is based on its activities in the aqueous or the lipophilic phase. Partitioning of 14C-labelled ferulic acid into plasma and its components, LDL and the albumin-rich fractions, has been studied under conditions of maximum aqueous solubility. The majority of ferulic acid associates with the albumin-rich fraction of the plasma, although a proportion is also found to partition between the LDL and aqueous phases; however, ferulic acid does not associate with the lipid portion of the LDL particle, suggesting that it exerts its antioxidant properties from the aqueous phase. This is of particular interest since the results demonstrate that ferulic acid is a more effective antioxidant against LDL oxidation than the hydrophilic antioxidant ascorbic acid.
Castelluccio C et al; Biochem J 316 (Pt 2)691-4 (1996):
The major constituents of artichoke extracts are hydroxycinnamic acids such as chlorogenic acid, dicaffeoylquinic acids caffeic acid and ferulic acid, and flavonoids such as luteolin and apigenin glycosides. ...Several studies have shown the effect on animal models of artichoke extracts ... . . Results showed a plasma maximum concentration of 6.4 (SD 1.8) ng/mL for chlorogenic acid after 1 hr and its disappearance within 2 hr (P< 0.05). Peak plasma concentrations of 19.5 (SD 6.9) ng/ml for total caffeic acid were reached within 1 h, while ferulic acid plasma concentrations showed a biphasic profile with 6.4 (SD1.5) ng/mL and 8.4 (SD4.6) ng/mL within 1 hr and after 8 hr respectively. ...A significant increase of dihydrocaffeic acid and dihydroferulic acid total levels after 8 hr (P<0.05) /was observed/. No circulating plasma levels of luteolin and apigenin were present.
Azzini E et al; Br J Nutr 97 (5): 963-9 (2007):

9.3 Metabolism / Metabolites

The bioavailability of ferulic acid (FA; 3-methoxy-4-hydroxycinnamic acid) and its metabolites was investigated in rat plasma and urine after an oral short-term ingestion of 5.15 mg/kg of FA. Free FA, glucuronoconjugates, and sulfoconjugates were quickly detected in plasma with a peak of concentration found 30 min after ingestion. Sulfoconjugates were the main derivates ( approximately 50%). In urine, the cumulative excretion of total metabolites reached a plateau 1.5 h after ingestion, and approximately 40% were excreted by this way. Free FA recovered in urine represented only 4.9 +/-1.5% of the native FA consumed by rats. Glucuronoconjugates and sulfoconjugates represented 0.5 +/- 0.3 and 32.7 +/- 7.3%, respectively. These results suggested that a part of FA incorporated in the diet was quickly absorbed and largely metabolized in sulfoconjugates before excretion in urine.
Rondini F et al; J Agric Food Chem 50 (10): 3037-41(2002):
Ferulic acid (FA) is a phytochemical commonly found in fruits and vegetables such as tomatoes, sweet corn and rice bran. It arises from metabolism of phenylalanine and tyrosine by Shikimate pathway in plants.
Srinivasan M et al; J Clin Biochem Nutr 40 (2): 92-100 (2007)
Ferulic Acid has known human metabolites that include (2S,3S,4S,5R)-6-[4-[(E)-2-carboxyethenyl]-2-methoxyphenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid.
S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560

9.4 Human Metabolite Information

9.4.1 Tissue Locations

  • Epidermis
  • Fibroblasts

9.4.2 Cellular Locations

Cytoplasm

9.5 Biochemical Reactions

9.6 Transformations

10 Use and Manufacturing

10.1 Uses

Sources/Uses
Found in small amounts in many plants; Used as a food preservative; [Merck Index]
Merck Index - O'Neil MJ, Heckelman PE, Dobbelaar PH, Roman KJ (eds). The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th Ed. Cambridge, UK: The Royal Society of Chemistry, 2013.
Sources/Uses
Widely distributed in plants; [Alfa Aesar MSDS]
Food preservative
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 692
/Ferulic acid was one of several compounds identified in/ ... a survey of 624 commercially available supplements targeted towards bodybuilding athletes...
Grunewald KK, Bailey RS; Sports Med 15 (2): 90-103 (1993) .
Synthetic Polymer MALDI Matrix Compounds

10.1.1 Use Classification

Food additives -> Flavoring Agents
Cosmetics -> Antimicrobial
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

10.2 Methods of Manufacturing

Prepared by the interaction of vanillin, malonic acid and piperidine in pyridine for 3 weeks, then precipitating with HCl
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 692
Ferulic acid is easily prepared in large quantities from rice bran pitch, a blackish brown waste oil with high viscosity, discharged in the process of the rice bran oil production.
Taniguchi H et al; Anticancer Res 19 (5A): 3757-61(1999)

10.3 General Manufacturing Information

EPA TSCA Commercial Activity Status
2-Propenoic acid, 3-(4-hydroxy-3-methoxyphenyl)-, (2E)-: ACTIVE
EPA TSCA Regulatory Flag
PMN - indicates a commenced PMN (Pre-Manufacture Notices) substance.
EPA TSCA Commercial Activity Status
2-Propenoic acid, 3-(4-hydroxy-3-methoxyphenyl)-: ACTIVE
Ferulic acid is an extremely abundant, preformed phenolic aromatic chemical found widely in nature. Ferulic acid is viewed as a commodity scale, renewable chemical feedstock for biocatalytic conversion to other useful aromatic chemicals. Most attention is focused on bioconversions of ferulic acid itself. Topics covered include cinnamoyl side-chain cleavage; nonoxidative decarboxylation; mechanistic details of styrene formation; purification and characterization of ferulic acid decarboxylase; conversion of ferulic acid to vanillin; O-demethylation; and reduction reactions.
Rosazza JP et al; J Ind Microbiol 15 (6): 457-71 (1995)

11 Identification

11.1 Analytic Laboratory Methods

A high-performance liquid chromatographic method was developed for selective determination of ferulic acid in 7 min in the extracts from wheat flour and ground whole wheat at typical levels of 50 and 500 micrograms/g, respectively. Recovery of 99.9% was obtained when ferulic acid was extracted into dilute sulfuric acid, followed by enzymatic treatment of the extract with an alpha-amylase preparation. The chromatographic system included a 100-mm column packed with Hypersil 5 micron reversed-phase ODS operating isocratically with 12% methanol-citrate buffer (pH 5.4) mixture. The selectivity and sensitivity of both ultraviolet diode array and fluorescence detectors was investigated. The optimum wavelengths selected were 320 nm and 312 nm/418 nm respectively. Relative standard deviations of the analytical procedure were 2.43% and 5.10% for whole wheat and flour samples, respectively.
Pussayanawin V, Wetzel DL; J-Chromatogr 391 (1): 243-55 (1987):

12 Safety and Hazards

12.1 Hazards Identification

12.1.1 GHS Classification

1 of 3
View All
Note
Pictograms displayed are for 97.4% (304 of 312) of reports that indicate hazard statements. This chemical does not meet GHS hazard criteria for 2.6% (8 of 312) of reports.
Pictogram(s)
Irritant
Signal
Warning
GHS Hazard Statements

H315 (97.4%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (97.4%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (97.4%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

Precautionary Statement Codes

P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+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 312 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 8 of 312 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 6 notifications provided by 304 of 312 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

Skin Irrit. 2 (97.4%)

Eye Irrit. 2 (97.4%)

STOT SE 3 (97.4%)

Skin Irrit. 2 (99%)

Eye Irrit. 2A (99%)

STOT SE 3 (98.1%)

12.1.3 Hazards Summary

Causes changes in motor activity, ataxia, and rigidity (including catalepsy) in intraperitoneal lethal-dose studies of mice (LD50 > 350 mg/kg); [RTECS] May cause irritation; [Alfa Aesar MSDS] See Cinnamic acid. See See Sinapinic acid.
A skin and strong eye irritant; [Alfa Aesar MSDS] See Ferulic acid.

12.2 Accidental Release Measures

12.2.1 Disposal Methods

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

12.3 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: 2-Propenoic acid, 3-(4-hydroxy-3-methoxyphenyl)-
REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
2-Propenoic acid, 3-(4-hydroxy-3-methoxyphenyl)-: Does not have an individual approval but may be used under an appropriate group standard

13 Toxicity

13.1 Toxicological Information

13.1.1 Adverse Effects

Neurotoxin - Other CNS neurotoxin

13.1.2 Acute Effects

13.1.3 Interactions

The effects of topically applied curcumin, chlorogenic acid, caffeic acid, and ferulic acid on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced epidermal ornithine decarboxylase activity, epidermal DNA synthesis, and the promotion of skin tumors were evaluated in female CD-1 mice. Topical application of 0.5, 1, 3, or 10 umol of curcumin inhibited by 31, 46, 84, or 98%, respectively, the induction of epidermal ornithine decarboxylase activity by 5 nmol of TPA. In an additional study, the topical application of 10 umol of curcumin, chlorogenic acid, caffeic acid, or ferulic acid inhibited by 91, 25, 42, or 46%, respectively, the induction of ornithine decarboxylase activity by 5 nmol of TPA. The topical application of 10 umol of curcumin together with 2 or 5 nmol of TPA inhibited the TPA-dependent stimulation of the incorporation of [3H]-thymidine into epidermal DNA by 49 or 29%, respectively, whereas lower doses of curcumin had little or no effect. Chlorogenic acid, caffeic acid, and ferulic acid were less effective than curcumin as inhibitors of the TPA-dependent stimulation of DNA synthesis. Topical application of 1, 3, or 10 mumol of curcumin together with 5 nmol of TPA twice weekly for 20 weeks to mice previously initiated with 7,12-dimethylbenz[a]anthracene inhibited the number of TPA-induced tumors per mouse by 39, 77, or 98%, respectively. Similar treatment of mice with 10 mumol of chlorogenic acid, caffeic acid, or ferulic acid together with 5 nmol of TPA inhibited the number of TPA-induced tumors per mouse by 60, 28, or 35%, respectively, and higher doses of the phenolic acids caused a more pronounced inhibition of tumor promotion. The possibility that curcumin could inhibit the action of arachidonic acid was evaluated by studying the effect of curcumin on arachidonic acid-induced edema of mouse ears. The topical application of 3 or 10 umol of curcumin 30 min before the application of 1 umol of arachidonic acid inhibited arachidonic acid-induced edema by 33 or 80%, respectively.
Huang MT et al; Cancer-Res 48 (21): 5941-6 (1988):
... A series of in vivo experiments/were/ carried out to evaluate the ability of caffeic and ferulic acids to reduce, in healthy human volunteers, UVB-induced skin erythema, monitored by means of reflectance spectrophotometry. Caffeic and ferulic acids, dissolved in saturated aqueous solution pH 7.2, proved to afford a significant protection to the skin against UVB-induced erythema...
Saija A et al; Int J Pharm 199 (1): 39-47 (2000)
A variety of synthetic and dietary polyphenols protect mammalian and bacterial cells from cytotoxicity induced by hydroperoxides, especially hydrogen peroxide (H2O2). Cytotoxicity of H2O2 on Chinese hamster V79 cells was assessed with a colony formation assay. Cytotoxicity and mutagenicity of H2O2 on Salmonella TA104 were assessed with the Ames test. SOS response induced by H2O2 was investigated in the SOS chromotest with Escherichia coli PQ37. The polyphenol-bearing o-dihydroxy (catechol) structure, i.e., nordihydroguaiaretic acid, caffeic acid ester, gallic acid ester, quercetin, and catechin, were effective for suppression of H2O2-induced cytotoxicity in these assay systems. In contrast, neither ferulic acid ester-bearing o-methoxyphenol structure nor alpha-tocopherol were effective, indicating that o-dihydroxy or its equivalent structure in flavonoids is essential for the protection. There are many reports describing that polyphenols act as prooxidants in the presence of metal ions. /These/ results suggest, however, that they act as antioxidants in the cells, when no metal ions are added to the medium.
Nakayama T; Cancer Res 54 (7 Suppl):1991s-1993s (1994)
This review describes the modes of mice radiation injuries induced by soft X-irradiation under various conditions and the protective effects of several kinds of substances on these injuries. The models of radiation injuries in this study were bone marrow death after lethal irradiation, skin damage induced by irradiation with long length soft X-ray and leukocytopenia in the peripheral blood after sublethal irradiation. Two bioassay methods were established for the survival effect on the lethal irradiation and protective potency on the skin damage induced by soft X-irradiation. The protective potencies of various sulfur compounds, related compounds of ferulic acid, nucleic acid constitutional compounds, crude drugs and Chinese traditional medicines were determined and then many effective drugs were recognized. Effective components in the methanol extracts of Cnidii Rhizoma and Aloe arborescens recognized as radioprotectable were fractionated. As a result of these studies, it was observed that the active principles in Cnidii Rhizoma were identified as ferulic acid and adenosine. The scavenger action of active oxygens, a protective effect on the damages of deoxyribonucleic acid and superoxide dismutase by in vitro soft X-irradiation were evaluated as radiation protective mechanisms.
Shinoda M; Yakugaku Zasshi;115 (1): 24-41 (1995)
For more Interactions (Complete) data for FERULIC ACID (8 total), please visit the HSDB record page.

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 if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the 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. /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/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 needed. 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 ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/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 ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160-1

13.1.5 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ The aim of this study is to investigate the effects of ferulic acid (FA) on human sperm motility, viability, lipid peroxidation, and cyclic nucleotides in fertile and asthenozoospermic infertile individuals in vitro. The sperm samples were obtained from 10 fertile volunteers and 10 asthenozoospermic infertile patients. Washed spermatozoa were incubated at 37 degrees C in Ham's F-10 medium with 0, 0.1, 0.2, 0.4, 0.8, or 1.6 mM of FA. Samples were analyzed for viability, determined by eosin-Y dye exclusion method at 0, 1, 2, 3, 5, and 6 hr of incubation; motility, determined by the trans-membrane migration method within 2 hr of incubation; LPO, determined by thiobarbituric acid (TBA) method at 3 hr of incubation and the intracellular cAMP and cGMP, determined, respectively, by 3H-cAMP and 125I-cGMP radioimmunoassay at 3 hr of incubation. The results showed: in both fertile and infertile spermatozoa, the viability, trans-membrane migration ratio (TMMR) and the levels of intracellular cAMP and cGMP in FA-treated spermatozoa were significantly higher than those of spermatozoa in control groups, while TBA-reactive substances contents in treated spermatozoa were significantly lower than those in control spermatozoa. The effects of FA on these processes were concentration dependent. These data suggested that FA is beneficial to sperm viability and motility in both fertile and infertile individuals, and that reduction of lipid peroxidative damage to sperm membranes and increase of intracellular cAMP and cGMP may be involved in these benefits.
Zheng R, Zhang H; Free Radic Biol Med 22 (4): 581-6 (1997):
/GENOTOXICITY/ In the present study, the effects of extracts and polyphenol-rich fractions as well as monomer polyphenols identified in them, from both red and white grapes, on mitomycin C (MMC) induced sister chromatid exchanges (SCEs) in human peripheral blood lymphocytes were investigated. The grape extracts and two of the three polyphenol-rich fractions promoted MMC-induced SCEs at concentrations from 75 to 300 ug/mL. However, none of the extracts or fractions alone induced SCEs. Thus, these results suggest caution especially with regard to the use of grape extracts as dietary supplements. On the other hand, the fact that these extracts were not genotoxic alone may indicate a selective activity against genetically damaged cells. This is the first study regarding the clastogenic effects of grape extracts in human cells. Moreover, from the tested polyphenols, caffeic acid, gallic acid, and rutin hydrate enhanced MMC-induced clastogenicity, whereas ferulic acid, protocatechuic acid, (+)-catechin, (-)-epicatechin, and trans-resveratrol had no effect at concentrations between 5 and 100 uM. The differences in the chemical structures of the tested polyphenols may account for their differential effects on MMC clastogenicity.
Stagos-D et al; J Agric Food Chem 55 (13): 5246-52 (2007):
/ALTERNATIVE and IN VITRO TESTS/ ... The effects of more physiological concentrations (0.1 um) of various individual polyphenols on gene expression were ... investigated in cultured human umbilical vein endothelial cells (HUVEC) using both microarray and quantitative RT-PCR methodologies. Treatment of HUVEC with ferulic acid, quercetin or resveratrol (0.1 um) resulted in changes to gene expression that for the three treatments amounted to significant (>2-fold) down-regulation of the expression of 363 genes and significant (>2-fold) up-regulation of 233 genes of the 10,000 genes present on the microarray. The majority of these genes were affected by resveratrol. Quantitative RT-PCR studies indicated that resveratrol (0.1 um) significantly increased the expression of the gene encoding endothelial NO synthase (eNOS), which synthesizes the vasodilator molecule NO, and both resveratrol and quercetin decreased expression of the potent vasoconstrictor, endothelin-1 (ET-1), while ferulic acid had no effect...
Nicholson SK et al;: Proc Nutr Soc 67 (1): 42-7 (2008)
/ALTERNATIVE and IN VITRO TESTS/ The possible effects of naturally occurring plant phenolics, caffeic acid (CA), chlorogenic acid (CGA) and ferulic acid (FA) on arylamine N-acetyltransferase (NAT) activities on human gastrointestinal microflora, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Citrobacter koseri and Pseudomonas aeruginosa, were examined. The bacterial NAT activities were determined by HPLC measuring the acetylation of 2-aminofluorene (2-AF). Among all examined bacteria, P. aeruginosa exerted the highest NAT activity while C. koseri possessed the lowest NAT activity. CA, CGA and FA could suppress the bacterial NAT activities dose-dependently both in the intact cell and cytosolic fraction analysis. According to the analysis of kinetic parameters in E. coli and P. aeruginosa, CA, CGA and FA were shown to be potent noncompetitive inhibitors of bacterial NAT activities. For the time course experiment, 4 mM of CA and FA could inhibit bacterial NAT activities for at least 4 hour but 4 mM of CGA could only significantly suppress NAT activity in E. coli for the same reaction time. These results strongly demonstrated that CA, CGA and FA inhibited NAT activities in human gastrointestinal bacteria.
Lo HH,: Chung JG; Anticancer-Res 19 (1A): 133-9 (1999)

13.1.6 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The modifying effects of dietary administration of the plant phenolic antioxidants caffeic acid (CA), ellagic acid (EA), chlorogenic acid (CGA) and ferulic acid (FA) during the initiation phase on 4-nitroquinoline-1-oxide (4-NQO)-induced tongue carcinogenesis and on the number and area of silver-stained nucleolar organizer region proteins (AgNORs), a new cell proliferation marker, of the tongue squamous epithelium were investigated in male F344 rats. Rats were fed the diet containing 500 ppm CA, 400 ppm EA, 250 ppm CGA or 500 ppm FA for 7 weeks. One week after the commencement of the diets, 4-NQO (20 p.p.m.) was administered in the drinking water for 5 weeks. Feeding of four phenolic compounds significantly reduced the incidences of tongue neoplasms (squamous cell papilloma and carcinoma) and preneoplastic lesions (hyperplasia and dysplasia) by 32 weeks, and rats fed CA or EA had no tongue neoplasms. The number and area of AgNORs per nucleus were decreased significantly by dietary treatment with these four phenolics. Thus, CA, EA, CGA and FA inhibited the tongue carcinogenesis induced by 4-NQO when they were administered concurrently with the carcinogen. These results might suggest possible application of these natural substances for cancer chemoprevention in tongue in addition to other tissues (skin, lung, liver and esophagus).
Tanaka T et al; Carcinogenesis 14 (7): 1321-5 (1993):
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Effects of ... on -induced oral carcinogenesis were examined in 4 groups of male rats. The incidences of tongue carcinomas and preneoplastic lesions (severe dysplasia) in rats of the group given ferulic acid (FA) in the diet at a dose of 500 ppm after exposure to 4-nitroquinoline-1-oxide (4NQO) for 5 weeks in drinking water at a dose of 20 ppm, was significantly lower on termination of the experiment (32 weeks) in the group with the carcinogen alone (P less than 0.005 and P less than 0.001 respectively). The results suggest chemopreventive activity for this phenolic compound on oral cancer.
Mori H et al; Anticancer Res 19 (5A): 3775-8 (1999):
/ALTERNATIVE and IN VITRO TESTS/ The modifying effects of dietary administration of the plant phenolic antioxidants caffeic acid (CA), ellagic acid (EA), chlorogenic acid (CGA) and ferulic acid (FA) during the initiation phase on 4-nitroquinoline-1-oxide (4-NQO)-induced tongue carcinogenesis and on the number and area of silver-stained nucleolar organizer region proteins (AgNORs), a new cell proliferation marker, of the tongue squamous epithelium were investigated in male F344 rats. Rats were fed the diet containing 500 ppm CA, 400 ppm EA, 250 ppm CGA or 500 ppm FA for 7 weeks. One week after the commencement of the diets, 4-NQO (20 p.p.m.) was administered in the drinking water for 5 weeks. Feeding of four phenolic compounds significantly reduced the incidences of tongue neoplasms (squamous cell papilloma and carcinoma) and preneoplastic lesions (hyperplasia and dysplasia) by 32 weeks, and rats fed CA or EA had no tongue neoplasms. The number and area of AgNORs per nucleus were decreased significantly by dietary treatment with these four phenolics. Thus, CA, EA, CGA and FA inhibited the tongue carcinogenesis induced by 4-NQO when they were administered concurrently with the carcinogen. These results might suggest possible application of these natural substances for cancer chemoprevention in tongue in addition to other tissues (skin, lung, liver and esophagus).
Tanaka T et al; Carcinogenesis 14 (7): 1321-5 (1993):
/ALTERNATIVE and IN VITRO TESTS/ The ... study describes the protective effect of ferulic acid (FA), a naturally occurring nutritional compound on nicotine-induced DNA damage and cellular changes in cultured rat peripheral blood lymphocytes in comparison with N-acetylcysteine (NAC), a well-known antioxidant. One-hour exposure of lymphocytes to nicotine at the doses of 0.125, 0.25, 0.5, 1, 2, 3 and 4 mM induced a statistically significant dose-dependent increase in the levels of thiobarbituric acid reactive substances (TBARS), a lipid peroxidative marker and decrease in the levels of reduced glutathione (GSH), an important endogenous antioxidant. The lowest concentration eliciting significant damage was 1 mM nicotine and maximum damage was observed with 3 mM concentration. Hence, the test concentration was fixed at 3 mM nicotine. ... 5 different doses of FA (10, 50, 100, 150 and 300 uM) and NAC (0.25, 0.5, 1, 2 and 4 mM) /were used/ to test their protective effects. In all the groups, FA and NAC showed a dose-dependent inhibitory effect. Maximum protection was observed at the dose of 150 microM FA and 1mM NAC. So, 150 microM FA and 1mM NAC were used for further studies. There was a significant increase in the levels of lipid peroxidative index (TBARS and hydroperoxides (HP)), severity of DNA damage (evaluated by comet assay) in nicotine-treated group, which were significantly decreased in FA and NAC-treated groups. Nicotine treatment significantly decreased the endogenous antioxidant status viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), GSH, vitamin A, E and C. Co-administration of FA and NAC to nicotine-treated lymphocytes showed a significant increase in the antioxidant status. The protective effect of FA was merely equal to that of NAC effect. FA and NAC treatment alone did not produce any toxicity to the normal lymphocytes at their effective doses. On the whole, there is overwhelming evidence that FA has the ability to modulate DNA damage and a variety of cellular changes that occur during nicotine-induced toxicity in rat peripheral blood lymphocytes.
Sudheer -AR et al; Toxicol In Vitro 21 (4): 576-85 (2007):
For more Non-Human Toxicity Excerpts (Complete) data for FERULIC ACID (7 total), please visit the HSDB record page.

13.2 Ecological Information

13.2.1 Environmental Fate / Exposure Summary

Ferulic acid is widely found in soil humus, as a result of the natural breakdown of lignin from wood/plant materials. Ferulic acid has been found in atmospheric particulate matter, the source of which is wood combustion. If released to air, an estimated vapor pressure of 2.7X10-6 mm Hg at 25 °C indicates ferulic acid will exist in both the vapor and particulate phases in the atmosphere. Vapor-phase ferulic acid 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 8 hours. Particulate-phase ferulic acid will be removed from the atmosphere by wet or dry deposition. Ferulic acid contains a chromophore that absorbs at wavelengths >290 nm and therefore may be susceptible to direct photolysis by sunlight. If released to soil, ferulic acid is expected to have high mobility based upon an estimated Koc of 57. The pKa of ferulic acid is 4.58, indicating that this compound will almost entirely exist in anion form. Anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil surfaces is not expected to be an important fate process because ferulic acid exists as an anion and anions do not volatilize. Ferulic acid is not expected to volatize from dry soil surfaces based upon an estimated vapor pressure of 2.7X10-6 mm Hg. Ferulic acid undergoes 60-77% aerobic biodegradation in soil under neutral or acidic conditions over 28 days. Under alkaline conditions, ferulic acid undergoes 13% aerobic biodegradation over 28 days. If released into water, ferulic acid is not expected to adsorb to suspended solids and sediment based upon the estimated Koc of 57. Ferulic acid undergoes 86-98% anaerobic biodegradation in water over 9-24 days. A pKa of 4.58 indicates ferulic acid will exist almost entirely exist in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. An estimated BCF of 3.2 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Occupational exposure to ferulic acid may occur through inhalation and dermal contact with this compound at workplaces where ferulic acid is produced or used. Monitoring data indicate that the general population may have limited exposure to ferulic acid via inhalation of particulates in ambient air, ingestion of surface water, and dermal contact with soil. (SRC)

13.2.2 Natural Pollution Sources

Ferulic acid is found in soil humus, and is derived from the breakdown of lignin from wood/plant materials(1). Ferulic acid has been found in atmospheric particulate matter, the source of which is wood combustion(2).
(1) Martin JP, Haider K; Soil Sci Soc Am J 40: 377-80 (1976)
(2) Nolte CG et al; Environ Sci Technol 35: 1912-1919 (2001)

13.2.3 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 57(SRC), determined from a log Kow of 1.51(2) and a regression-derived equation(3), indicates that ferulic acid is expected to have high mobility in soil(SRC). The pKa of ferulic acid is 4.58(4), indicating that this compound will almost entirely exist in the anion form. In the environment, anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization of ferulic acid from moist soil surfaces is not expected to be an important fate process(SRC) given the anionic nature of ferulic acid in the environment. Ferulic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.7X10-6 mm Hg(SRC), determined from a fragment constant method(6). Under neutral and acidic conditions in soil, ferulic acid is expected to undergo rapid aerobic biodegradation(7)(8). Under alkaline conditions in soil, ferulic acid is not expected to undergo rapid aerobic biodegradation(8).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. Ed., Washington, DC: Amer Chem Soc p. 99 (1995)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9 (1990)
(4) Serjeant EP, Dempsey B; Ionisation Constants of Organic Acids in Aqueous Solution. IUPAC Chem Data Ser No.23. NY,NY: Pergamon p. 989 (1979)
(5) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(6) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(7) Martin JP, Haider K; Soil Sci Soc Am J 40: 377-80 (1976)
(8) Martin JP, Haider K; Soil Sci Soc Am J 43: 917-20 (1979)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 57(SRC), determined from a log Kow of 1.51(2) and a regression-derived equation(3), indicates that ferulic acid is not expected to adsorb to suspended solids and sediment(SRC). A pKa of 4.58(4) indicates ferulic acid will exist almost entirely in the anion form at pH values of 5 to 9, and therefore volatilization from water surfaces/moist soil is not expected to be an important fate process(5). According to a classification scheme(6), an estimated BCF of 3.2(SRC), from its log Kow of 1.51(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Ferulic acid is expected to biodegrade rapidly in water under anaerobic conditions(8).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 99 (1995)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9, 15-1 to 15-29 (1990)
(4) Serjeant EP, Dempsey B; Ionisation Constants of Organic Acids in Aqueous Solution. IUPAC Chem Data Ser No.23. NY,NY: Pergamon p. 989 (1979)
(5) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds, Boca Raton, FL: Lewis Publ (2000)
(6) Franke C et al; Chemosphere 29: 1501-14 (1994)
(7) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
(8) Healy JB JR, Young LY; Appl Environ Microbiol 38: 84-9 (1979)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ferulic acid, which has a an estimated vapor pressure of 2.7X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases. Vapor-phase ferulic acid 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 8 hours(SRC), calculated from its rate constant of 4.8X10-11 cu cm/molecule-sec at 25 °C(SRC), derived using a structure estimation method(3). Particulate-phase ferulic acid may be removed from the air by wet or dry deposition(SRC). Ferulic acid contains a chromophore that absorbs light at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(4) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990

13.2.4 Environmental Biodegradation

AEROBIC: Ferulic acid, present at 100 ppm in Greenfield (California) sandy loam with a pH of 7, underwent 60-72% decomposition via 14-CO2 evolution in 28 days(1). In a similar study, ferulic acid, present at 100 ppm in Chino (California) loam with a pH of 5.6, underwent 77% decomposition via 14-CO2 evolution after 28 days(2); in San Jacinto (California) sandy loam with a pH of 8, 100 ppm ferulic acid underwent 13% decomposition by 14-CO2 evolution over 28 days(2). This lower level of decomposition was thought to be due to polymerization of ferulic acid to humic acid type compounds(2). Therefore, under neutral and acidic conditions in soil, ferulic acid is expected to biodegrade rapidly; under alkaline conditions in soil, biodegradation of ferulic acid is not expected to be rapid.
(1) Martin JP, Haider K; Soil Sci Soc Am J 40: 377-80 (1976)
(2) Martin JP, Haider K; Soil Sci Soc Am J 43: 917-20 (1979)
ANAEROBIC: Ferulic acid, present at 300 ppm in water, reached 86% of its theoretical degradation by conversion to CO2 in 24 days, employing a mixed inoculum obtained from sludge(1). Ferulic acid, present at 300 ppm in water, reached 98% of its theoretical degradation by CO2 production in 9 days, employing a mixed inoculum obtained from sludge(2), in which the medium had been acclimated with ferulic acid for 540 days. Degradation products detected were p-hydroxycinnamic acid, cinnamic acid, and phenylpropionic acid(2). Therefore, ferulic acid is expected to biodegrade rapidly in water under anaerobic conditions.
(1) Healy JB JR, Young LY; Appl Environ Microbiol 38: 84-9 (1979)
(2) Grbic-Galic D; Appl Environ Microbiol 46: 1442-6 (1983)

13.2.5 Environmental Abiotic Degradation

The rate constant for the vapor-phase reaction of ferulic acid with photochemically-produced hydroxyl radicals has been estimated as 4.8X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 8 hours at an atmospheric concentration of 5.0X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of ferulic acid with ozone has been estimated as 1.1X10-17 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 1 day at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(1). The measured rate constant for the reaction of hydroxyl radicals in aqueous solutions of ferulic acid at neutral pH is 1.0X10+10 L/mol-sec(2); this corresponds to an aquatic half-life of about 80 days at an aquatic concentration of 1X10-17 moles hydroxyl radicals per liter(3). Ferulic acid is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(4). Ferulic acid contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC).
(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(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, 8-12 (1990)

13.2.6 Environmental Bioconcentration

An estimated BCF of 3.2 was calculated in fish for ferulic acid, using a measured log Kow of 1.51 (1) and a regression-derived equation (2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organism is low(SRC), provided the compound is not metabolized by the organism(SRC).
(1) Hansch et al; Exploring QSAR: Hydrophobic, Electronic and Steric Constants. Washington, DC: Amer Chem Soc pp.99 (1995)
(2) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

13.2.7 Soil Adsorption / Mobility

The Koc of ferulic acid is estimated as 57(SRC), using a log Kow of 1.51(1)(SRC) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that ferulic acid is expected to have high mobility in soil. The pKa of ferulic acid is 4.58(4), indicating that this compound will almost entirely exist in the anion form in the environment. Anions generally do not adsorb more strongly to soils containing organic carbon and clay, in comparison with their neutral counterparts(5).
(1) Hansch et al; Exploring QSAR: Hydrophobic, Electronic and Steric Constants. Washington, DC: Amer Chem Soc pp.99 (1995)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9 (1990)
(3) Swann RL et al; Res Rev 85: 17-28 (1983)
(4) Serjeant EP, Dempsey B; Ionisation Constants of Organic Acids in Aqueous Solution. IUPAC Chem Data Ser No.23. NY,NY: Pergamon pp. 989 (1979)
(5) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)

13.2.8 Volatilization from Water / Soil

Ferulic acid, with a pKa of 4.58(1), will almost entirely exist in the anion form in the environment at pH values of 5 to 9, and therefore ferulic acid is expected to be essentially nonvolatile from water surfaces and moist soil(2). Ferulic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.7X10-6 mm Hg(SRC), determined from a fragment constant method(3).
(1) Serjeant EP, Dempsey B; Ionisation Constants of Organic Acids in Aqueous Solution. IUPAC Chem Data Ser No.23. NY,NY: Pergamon pp. 989 (1979)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)
(3) Lyman WJ; p.31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)

13.2.9 Environmental Water Concentrations

SURFACE WATER: Ferulic acid was detected in two of three surface water samples collected from the Tama River and the Sumida River, Tokyo(Japan) between September 11, 1973 and December 6, 1973 at concentrations ranging from 10-90 ng/L(1). The most likely source of ferulic acid was from the degradation of lignin derived from wood/plant materials.
(1) Matsumoto G et al; Water Res 11: 693-698 (1977)

13.2.10 Sediment / Soil Concentrations

SEDIMEMT: Ferulic acid was detected in four out of four sediment samples collected from the Tama River (Japan), Yatsuse River (Japan), Lake Haruma (Japan) and Komgari Reservoir (Japan) on unknown dates at concentrations ranging from 6.5-22 ug/g dry sediment, with an average of 13 ug/g dry sediment(1); the source was likely from the detritus of vascular plants(1).
(1) Matsumoto G, Hanya T; J Chromatogr 193: 89-94 (1980)
SOIL: Ferulic acid was detected in one soil sample collected in Tokyo (Japan) between February 1976 and January 1978 at the concentration of 11 ug/g dry soil(1).
(1) Matsumoto G, Hanya T; J Chromatogr 193: 89-94 (1980)

13.2.11 Atmospheric Concentrations

URBAN/SUBURBAN: Ferulic acid was detected in five out of eight atmospheric fallout samples collected in Tokyo (Japan) between February 1976 and January 1978 at concentrations ranging from 0.06 and 0.74 ug/sq m-day, with an average of 0.43 ug/sq m-day(1). Ferulic acid was detected in two out of two atmospheric particulate samples collected in Bakersfield (California) and Fresno (California) between December 5, 1995 and January 6, 1996 and at concentrations ranging from 0.3 ng/cu m, with an average of 0.45 ng/cu m(2).
(1) Matsumoto G, Hanya T; Atmos Environ 14: 1409-1419 (1980)
(2) Nolte CG et al; Environ Sci Technol 35: 1912-1919 (2001)
RURAL/REMOTE: Ferulic acid was not detected in one atmospheric particulate sample collected in the Kern Wildlife Refuge (Delano, California) between December 5, 1995 and January 6, 1996(1).
(1) Nolte CG et al; Environ Sci Technol 35: 1912-1919 (2001)

13.2.12 Probable Routes of Human Exposure

Occupational exposure to ferulic acid may occur through inhalation and dermal contact with this compound at workplaces where ferulic acid is produced or used. Monitoring data indicate that the general population may have limited exposure to ferulic acid via inhalation of particulates in ambient air, ingestion of surface water, and dermal contact with soil. (SRC)

14 Associated Disorders and Diseases

Disease
Colorectal cancer
References

PubMed: 7482520, 19006102, 23940645, 24424155, 20156336, 19678709, 22148915, 25105552, 21773981, 25037050, 27015276, 27107423, 27275383, 28587349

Silke Matysik, Caroline Ivanne Le Roy, Gerhard Liebisch, Sandrine Paule Claus. Metabolomics of fecal samples: A practical consideration. Trends in Food Science & Technology. Vol. 57, Part B, Nov. 2016, p.244-255: http://www.sciencedirect.com/science/article/pii/S0924224416301984

Disease
Eosinophilic esophagitis
References
Mordechai, Hien, and David S. Wishart

15 Literature

15.1 Consolidated References

15.2 NLM Curated PubMed Citations

15.3 Springer Nature References

15.4 Thieme References

15.5 Wiley References

15.6 Chemical Co-Occurrences in Literature

15.7 Chemical-Gene Co-Occurrences in Literature

15.8 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

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

17.2 Chemical-Target Interactions

17.3 Drug-Drug Interactions

17.4 Drug-Food Interactions

Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.

17.5 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
A metabolome atlas of the aging mouse brain. Nat Commun. 2021 Oct 15;12(1):6021. DOI:10.1038/s41467-021-26310-y. PMID:34654818; PMCID:PMC8519999.
The Metabolome Atlas of the Aging Mouse Brain: https://mouse.atlas.metabolomics.us

20 Classification

20.1 MeSH Tree

20.2 ChEBI Ontology

20.3 KEGG: Phytochemical Compounds

20.4 ChemIDplus

20.5 ChEMBL Target Tree

20.6 UN GHS Classification

20.7 NORMAN Suspect List Exchange Classification

20.8 CCSBase Classification

20.9 EPA DSSTox Classification

20.10 NIST Synthetic Polymer MALDI Recipes Database Classification

20.11 EPA TSCA and CDR Classification

20.12 LOTUS Tree

20.13 EPA Substance Registry Services Tree

20.14 MolGenie Organic Chemistry Ontology

21 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
    2-Propenoic acid, 3-(4-hydroxy-3-methoxyphenyl)-
    https://services.industrialchemicals.gov.au/search-inventory/
  2. CAS Common Chemistry
    LICENSE
    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  3. ChemIDplus
    3-(4-Hydroxy-3-methoxyphenyl)-2-propenoic acid homopolymer
    https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0097274618
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  4. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  5. DTP/NCI
    LICENSE
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    https://www.cancer.gov/policies/copyright-reuse
  6. EPA Chemicals under the TSCA
    2-Propenoic acid, 3-(4-hydroxy-3-methoxyphenyl)-, (2E)-
    https://www.epa.gov/chemicals-under-tsca
    EPA TSCA Classification
    https://www.epa.gov/tsca-inventory
  7. EPA DSSTox
    (2E)-3-(4-Hydroxy-3-methoxyphenyl)-2-propenoic acid
    https://comptox.epa.gov/dashboard/DTXSID70892035
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  8. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
    4-hydroxy-3-methoxycinnamic acid
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  9. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  10. Hazardous Substances Data Bank (HSDB)
  11. Human Metabolome Database (HMDB)
    LICENSE
    HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications.
    http://www.hmdb.ca/citing
  12. New Zealand Environmental Protection Authority (EPA)
    LICENSE
    This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International licence.
    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  13. BindingDB
    LICENSE
    All data curated by BindingDB staff are provided under the Creative Commons Attribution 3.0 License (https://creativecommons.org/licenses/by/3.0/us/).
    https://www.bindingdb.org/rwd/bind/info.jsp
  14. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
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  15. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
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    CCSbase Classification
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    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
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    (2E)-3-(4-Hydroxy-3-methoxyphenyl)-2-propenoic acid
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  20. LOTUS - the natural products occurrence database
    LICENSE
    The code for LOTUS is released under the GNU General Public License v3.0.
    https://lotus.nprod.net/
  21. Yeast Metabolome Database (YMDB)
    LICENSE
    YMDB is offered to the public as a freely available resource.
    http://www.ymdb.ca/downloads
  22. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  23. Crystallography Open Database (COD)
    LICENSE
    All data in the COD and the database itself are dedicated to the public domain and licensed under the CC0 License. Users of the data should acknowledge the original authors of the structural data.
    https://creativecommons.org/publicdomain/zero/1.0/
  24. The Cambridge Structural Database
  25. DailyMed
  26. EU Food Improvement Agents
    4-Hydroxy-3-methoxycinnamic acid (mixture of isomers)
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    LICENSE
    FooDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (FooDB) and the original publication.
    https://foodb.ca/about
  28. Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
    LICENSE
    Copyright (c) 2022 Haz-Map(R). All rights reserved. Unless otherwise indicated, all materials from Haz-Map are copyrighted by Haz-Map(R). No part of these materials, either text or image may be used for any purpose other than for personal use. Therefore, reproduction, modification, storage in a retrieval system or retransmission, in any form or by any means, electronic, mechanical or otherwise, for reasons other than personal use, is strictly prohibited without prior written permission.
    https://haz-map.com/About
  29. NIST Synthetic Polymer MALDI Recipes Database
    LICENSE
    Formerly known as NIST Standard Reference Database 172
    https://www.nist.gov/disclaimer
    ferulic acid (FA)
    https://maldi.nist.gov/
  30. IUPAC Digitized pKa Dataset
    propenoic acid, 3-(4-hydroxy-3-methoxyphenyl)-
    https://github.com/IUPAC/Dissociation-Constants
  31. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
  32. NIST Mass Spectrometry Data Center
    LICENSE
    Data covered by the Standard Reference Data Act of 1968 as amended.
    https://www.nist.gov/srd/public-law
  33. SpectraBase
    2-Propenoic acid, 3-(4-hydroxy-3-methoxyphenyl)-
    https://spectrabase.com/spectrum/Aj4hMKhcukU
    (2E)-3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid
    https://spectrabase.com/spectrum/JpKmr9SxJC9
    4-HYDROXY-3-METHOXYCINNAMIC ACID
    https://spectrabase.com/spectrum/ItdR88LBccq
    4-HYDROXY-3-METHOXYCINNAMIC ACID
    https://spectrabase.com/spectrum/4yPSjGuH7CV
  34. Japan Chemical Substance Dictionary (Nikkaji)
  35. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
  36. KNApSAcK Species-Metabolite Database
  37. Natural Product Activity and Species Source (NPASS)
  38. West Coast Metabolomics Center-UC Davis
    Ferulic acid
  39. MarkerDB
    LICENSE
    This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
    https://markerdb.ca/
  40. Metabolomics Workbench
  41. National Drug Code (NDC) Directory
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  42. NIPH Clinical Trials Search of Japan
  43. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  44. NMRShiftDB
  45. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  46. Protein Data Bank in Europe (PDBe)
  47. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
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    https://www.rcsb.org/pages/policies
  48. Springer Nature
  49. Thieme Chemistry
    LICENSE
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    https://creativecommons.org/licenses/by-nc-nd/4.0/
  50. Wikidata
  51. Wikipedia
  52. Wiley
  53. PubChem
  54. Medical Subject Headings (MeSH)
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    https://www.nlm.nih.gov/copyright.html
    Anti-Inflammatory Agents, Non-Steroidal
    https://www.ncbi.nlm.nih.gov/mesh/68000894
  55. GHS Classification (UNECE)
  56. EPA Substance Registry Services
  57. MolGenie
    MolGenie Organic Chemistry Ontology
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  58. PATENTSCOPE (WIPO)
  59. NCBI
CONTENTS