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Kojic acid

PubChem CID
3840
Structure
Kojic acid_small.png
Kojic acid_3D_Structure.png
Molecular Formula
Synonyms
  • kojic acid
  • 501-30-4
  • 5-Hydroxy-2-(hydroxymethyl)-4H-pyran-4-one
  • 5-Hydroxy-2-(hydroxymethyl)-4-pyrone
  • 4H-PYRAN-4-ONE, 5-HYDROXY-2-(HYDROXYMETHYL)-
Molecular Weight
142.11 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-25
  • Modify:
    2025-01-11
Description
Kojic acid is a pyranone that is 4H-pyran substituted by a hydroxy group at position 5, a hydroxymethyl group at position 2 and an oxo group at position 4. It has been isolated from the fungus Aspergillus oryzae. It has a role as a NF-kappaB inhibitor, an Aspergillus metabolite, a skin lightening agent, an EC 1.10.3.1 (catechol oxidase) inhibitor, an EC 1.10.3.2 (laccase) inhibitor, an EC 1.13.11.24 (quercetin 2,3-dioxygenase) inhibitor, an EC 1.14.18.1 (tyrosinase) inhibitor and an EC 1.4.3.3 (D-amino-acid oxidase) inhibitor. It is an enol, a primary alcohol and a member of 4-pyranones. It derives from a hydride of a 4H-pyran.
Kojic acid has been reported in Phaeosphaeria fuckelii, Aspergillus flavus, and other organisms with data available.
Kojic acid is a synthetic intermediate for production of food additives. Kojic acid has been shown to exhibit anti-neoplastic function (A7859).
A7859: Novotny L, Rauko P, Abdel-Hamid M, Vachalkova A: Kojic acid--a new leading molecule for a preparation of compounds with an anti-neoplastic potential. Neoplasma. 1999;46(2):89-92. PMID:10466431

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Kojic acid.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

5-hydroxy-2-(hydroxymethyl)pyran-4-one
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C6H6O4/c7-2-4-1-5(8)6(9)3-10-4/h1,3,7,9H,2H2
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

BEJNERDRQOWKJM-UHFFFAOYSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

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

2.2 Molecular Formula

C6H6O4
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

2.3.2 Deprecated CAS

123712-78-7

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 HMDB ID

2.3.10 KEGG ID

2.3.11 Metabolomics Workbench ID

2.3.12 Nikkaji Number

2.3.13 NSC Number

2.3.14 RXCUI

2.3.15 Wikidata

2.3.16 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 5-((3-aminopropyl)phosphinooxy)-2-(hydroxymethyl)-4H-pyran-4-one
  • kojic acid
  • kojyl-APPA

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
142.11 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
-0.9
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
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
142.02660867 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
142.02660867 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
10
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
214
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
0
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

Solid

3.2.2 Color / Form

Prismatic needles from acetone, ethanol+ether or methanol+ethyl acetate
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 920
Crystals
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 732
Prisms, needles from acetone
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-292

3.2.3 Melting Point

153.5 °C
PhysProp
153.5 °C
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-292
161 °C

3.2.4 Solubility

Soluble in ethanol, ethyl ether, acetone, DMSO; slightly soluble in benzene
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-292
Soluble in water, acetone; slightly solluble in ether; insoluble in benzene
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 732
Sparingly soluble in pyridine
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 920

3.2.5 LogP

-0.64
KONTOGHIORGHES,GJ (1988)
log Kow = -0.64
Kontoghiorghes GJ; Inorg Chem Acta 151: 101-6 (1988)
-0.64

3.2.6 Dissociation Constants

pKa = 7.66 (approx., 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.

3.2.7 Collision Cross Section

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

3.2.8 Kovats Retention Index

Semi-standard non-polar
1192.1 , 1220.3

3.3 SpringerMaterials Properties

3.4 Chemical Classes

3.4.1 Drugs

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

3.4.2 Cosmetics

Cosmetic ingredients (Kojic Acid) -> CIR (Cosmetic Ingredient Review)
Antioxidant
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

3.4.3 Endocrine Disruptors

Potential endocrine disrupting compound
S109 | PARCEDC | List of 7074 potential endocrine disrupting compounds (EDCs) by PARC T4.2 | DOI:10.5281/zenodo.10944198

4 Spectral Information

4.1 1D NMR Spectra

1 of 2
1D NMR Spectra
1H NMR: 445 (Varian Associates NMR spectra collection)
2 of 2
1D NMR Spectra

4.1.1 1H NMR Spectra

1 of 2
Instrument Name
Varian A-60
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
220469
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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4.1.2 13C NMR Spectra

1 of 2
Source of Sample
Fluka AG, Buchs, Switzerland
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Instrument Name
Varian XL-100
Copyright
Copyright © 2002-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 16
View All
Spectra ID
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

142.0 99.99

69.0 74

29.0 53

39.0 40

113.0 36

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Notes
instrument=HITACHI RMU-6E
2 of 16
View All
Spectra ID
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

142.0 99.99

69.0 72

29.0 52

39.0 40

113.0 34

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Notes
instrument=HITACHI RMU-6E

4.2.2 MS-MS

1 of 3
View All
Spectra ID
Instrument Type
LC-ESI-QTOF
Ionization Mode
negative
Top 5 Peaks

141.0187 100

111.0091 13.98

113.0238 13.44

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Notes
instrument=Agilent 1200 RRLC; Agilent 6520 QTOF
2 of 3
View All
Spectra ID
Instrument Type
Linear Ion Trap
Ionization Mode
negative
Top 5 Peaks

84.889112 5.91

82.863063 4.43

112.892554 2.66

68.887761 1.74

96.865712 1.46

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Notes
instrument=Thermo Finnigan LTQ

4.2.3 LC-MS

1 of 24
View All
Authors
Derek Holzscherer, Justin B. Renaud, Mark W. Sumarah, Agriculture and Agri-Food Canada
Instrument
Q-Exactive Orbitrap Thermo Scientific
Instrument Type
LC-ESI-ITFT
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
10(NCE)
Fragmentation Mode
HCD
Column Name
Agilent RRHD Eclipse 50 x 2 mm, 1.8 uM
Retention Time
1.55
Precursor m/z
143.0333
Precursor Adduct
[M+H]+
Top 5 Peaks

143.0339 999

69.0335 85

97.0284 77

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License
CC BY-SA
2 of 24
View All
Authors
Derek Holzscherer, Justin B. Renaud, Mark W. Sumarah, Agriculture and Agri-Food Canada
Instrument
Q-Exactive Orbitrap Thermo Scientific
Instrument Type
LC-ESI-ITFT
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
20(NCE)
Fragmentation Mode
HCD
Column Name
Agilent RRHD Eclipse 50 x 2 mm, 1.8 uM
Retention Time
1.55
Precursor m/z
143.0333
Precursor Adduct
[M+H]+
Top 5 Peaks

143.0339 999

69.0335 81

97.0284 73

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License
CC BY-SA

4.2.4 Other MS

1 of 5
View All
Other MS
MASS: 3946 (NIST/EPA/MSDC Mass Spectral database, 1990 version); 534 (National Bureau of Standards)
2 of 5
View All
Authors
NAKATA H, DEPT. OF CHEMISTRY, AICHI KYOIKU UNIV.
Instrument
HITACHI RMU-6E
Instrument Type
EI-B
MS Level
MS
Ionization Mode
POSITIVE
Ionization
ENERGY 70 eV
Top 5 Peaks

142 999

69 740

29 530

39 400

113 360

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License
CC BY-NC-SA

4.3 UV Spectra

UV: 17671 (Sadtler Research Laboratories spectral collection)
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V5: 4624

4.3.1 UV-VIS Spectra

1 of 2
Copyright
Copyright © 2008-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Copyright
Copyright © 2008-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4 IR Spectra

IR Spectra
IR: 5765 (Coblentz Society spectral collection)

4.4.1 FTIR Spectra

1 of 2
Technique
KBr WAFER
Source of Sample
Borups Alle Apotek, Copenhagen, Denmark
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
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2 of 2
Technique
Mull
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Aldrich
Catalog Number
220469
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4.2 ATR-IR Spectra

Source of Sample
Aldrich
Catalog Number
220469
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4.3 Vapor Phase IR Spectra

Instrument Name
DIGILAB FTS-14
Technique
Vapor Phase
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.5 Raman Spectra

Catalog Number
220469
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 FDA National Drug Code Directory

7.2 Drug Labels

Drug and label
Active ingredient and drug

7.3 Clinical Trials

7.3.1 ClinicalTrials.gov

7.4 Therapeutic Uses

Depigmenting agent /for skin lightening/
Zhu W, Gao J; J Investig Dermatol Symp Proc 13 (1): 20-4 (2008)
Melasma is a chronic and recurrent disorder. It has been underdiagnosed and undertreated due to lack of effective therapies and the perception that it is merely a cosmetic nuisance. Hydroquinone, corticosteroids, licorice extracts and kojic acid have been used as monotherapy to treat melasma. However, the present standard of care in melasma therapy is combination therapy. To date, the most effective treatment is a triple-combination agent that contains hydroquinone 4%, tretinoin 0.05% and fluocinolone acetonide 0.01%...
Rendon MI; J Drugs Dermatol (5 Suppl):S27-34 (2004)
... Combination regimens, including frequent applications of superficial- and medium-depth chemical peels, appear to be particularly effective and well tolerated in dark-skinned patients with melanosis. Post-inflammatory hyperpigmentation is the result of excess pigment deposition following an inflammatory skin disorder. Topical tretinoin, hydroquinone, azelaic acid, kojic acid, and glycolic acid peels have been employed with variable degrees of success...
Stratigos AJ, Katsambas A; Am J Clin Dermatol 5 (3): 161-8 (2004)
Facial and neck pigmentations are ... common in middle-aged women, and are related to endogenous (hormones) and exogenous factors (such as use of cosmetics and perfumes, and exposure to sun radiation). Melasma (chloasma) is the most common cause of facial pigmentation, but there are many other forms such as Riehl's melanosis, poikiloderma of Civatte, erythrose peribuccale pigmentaire of Brocq, erythromelanosis follicularis of the face and neck, linea fusca, and cosmetic hyperpigmentations. Treatment of melasma and other facial pigmentations has always been challenging and discouraging.... Several hypopigmenting agents have been used with differing results. Topical hydroquinone 2 to 4% alone or in combination with tretinoin 0.05 to 0.1% is an established treatment. Topical azelaic acid 15 to 20% can be as efficacious as hydroquinone, but is less of an irritant. Tretinoin is especially useful in treating hyperpigmentation of photoaged skin. Kojic acid, alone or in combination with glycolic acid or hydroquinone, has shown good results, due to its inhibitory action on tyrosinase. Chemical peels are useful to treat melasma: trichloroacetic acid, Jessner's solution, Unna's paste, alpha-hydroxy acid preparations, kojic acid, and salicyclic acid, alone or in various combinations have shown good results. In contrast, laser therapies have not produced completely satisfactory results, because they can induce hyperpigmentation and recurrences can occur. New laser approaches could be successful at clearing facial hyperpigmentation in the future.
Perez-Bernal A et al; Am J Clin Dermatol 1 (5): 261-8 (2000)
For more Therapeutic Uses (Complete) data for KOJIC ACID (7 total), please visit the HSDB record page.

8 Pharmacology and Biochemistry

8.1 MeSH Pharmacological Classification

Antioxidants
Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues. (See all compounds classified as Antioxidants.)

8.2 Metabolism / Metabolites

The structure of kojic acid indicates a relatively simple route of metabolism much like dietary hexoses.
Burdock GA et al; Regul Toxicol Pharmacol 33 (1): 80-101 (2001)
Kojic acid is absorbed by the gastrointestinal tract, enters the circulation, and is probably metabolized similar to hexoses. (A3073)
A3073: Burdock GA, Soni MG, Carabin IG: Evaluation of health aspects of kojic acid in food. Regul Toxicol Pharmacol. 2001 Feb;33(1):80-101. PMID:11259181

8.3 Mechanism of Action

The mechanism of action of kojic acid is well defined and it has been shown to act as a competitive and reversible inhibitor of animal and plant polyphenol oxidases, xanthine oxidase, and D- and some L-amino acid oxidases.
Burdock GA et al; Regul Toxicol Pharmacol 33 (1): 80-101 (2001)
The activation of NF-kappaB induced by kojic acid, an inhibitor of tyrosinase for biosynthesis of melanin in melanocytes, was investigated in human transfectant HaCaT and SCC-13 cells. These two keratinocyte cell lines transfected with pNF-kappaB-SEAP-NPT plasmid were used to determine the activation of NF-kappaB. Transfectant cells release the secretory alkaline phosphatase (SEAP) as a transcription reporter in response to the NF-kappaB activity and contain the neomycin phosphotransferase (NPT) gene for the dominant selective marker of geneticin resistance. NF-kappaB activation was measured in the SEAP reporter gene assay using a fluorescence detection method. Kojic acid showed the inhibition of cellular NF-kappaB activity in both human keratinocyte transfectants. It could also downregulate the ultraviolet ray (UVR)-induced activation of NF-kappaB expression in transfectant HaCaT cells. Moreover, the inhibitory activity of kojic acid in transfectant HaCaT cells was found to be more potent than known antioxidants, e.g., vitamin C and N-acetyl-L-cysteine. These results indicate that kojic acid is a potential inhibitor of NF-kappaB activation in human keratinocytes, and suggest the hypothesis that NF-kappaB activation may be involved in kojic acid induced anti-melanogenic effect.
Moon KY et al; Arch Pharm Res 24 (4): 307-11 (2001):

8.4 Human Metabolite Information

8.4.1 Cellular Locations

  • Cytoplasm
  • Extracellular

9 Use and Manufacturing

9.1 Uses

Cosmetic Ingredient Review Link
CIR ingredient: Kojic Acid
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
Converted to maltol and ethyl maltol, flavor-enhancing additives. Food additive to inhibit tyrosinase.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 920
Chemical intermediate, metal chelates, ... antifungal and antimicrobial agent
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 732
Mildly antibiotic
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 732
Kojic acid is widely used as a food additive for preventing enzymatic browning, and in cosmetic preparations as a skin-lightening or bleaching agent.
Burdock GA et al; Regul Toxicol Pharmacol 33 (1): 80-101 (2001)
Laboratory reagent used as standard chemical for tyrosinase inhibitor assays.
Okunji C et al; J Chromatogr A 1151 (1-2) 45-50 (2007)
Kojic acid is a chelation agent and mycotoxin produced by several species of Aspergillus, Acetobacter, and Penicillium fungi, especially Aspergillus oryzae, which has the Japanese common name koji. Kojic acid is a by-product in the fermentation process of malting rice, and is used in the manufacturing of numerous foods, including miso, soy sauce, and sake. Kojic acid is a mild inhibitor of the formation of pigment in plant and animal tissues, and is used in food and cosmetics to preserve or change colors of substances, such as in skin-lightening or bleaching formulas. It is also used as a food additive for preventing enzymatic browning and in seafood to preserve pink and red colors. Kojic acid also has antibacterial and antifungal properties and is used in skin diseases like melasma. (L1968, A3073)
A3073: Burdock GA, Soni MG, Carabin IG: Evaluation of health aspects of kojic acid in food. Regul Toxicol Pharmacol. 2001 Feb;33(1):80-101. PMID:11259181
L1968: Wikipedia. Kojic acid. Last Updated 14 May 2010. http://en.wikipedia.org/wiki/Kojic_acid

9.1.1 Use Classification

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

9.2 Methods of Manufacturing

Antibiotic substance produced in an aerobic process by a variety of microorganisms from a wide-range of carbon sources.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 920
Fermentation of starches and sugars by certain molds.
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 732
... Readily obtained from D-glucose either enzymatically by Aspergillus oryzae (growing on steamed rice) or chemically via pyranoid 3,2-enolones.
Lichtenthaler FW; Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (2008). NY, NY: John Wiley & Sons; Carbohydrates. Online Posting Date: Jan 15, 2003.

9.3 General Manufacturing Information

Kojic acid is a fungal metabolite commonly produced by many species of Aspergillus, Acetobacter, and Penicillium. The Aspergillus flavus group has traditionally been used in the production of a number of foods, including miso (soybean paste), shoyu (soy sauce), and sake.... Because kojic acid is often produced during the fermentation of historically used dietary staples, it has a long history of consumption. Various types of compounds, such as glucose, sucrose, acetate, ethanol, arabinose, and xylose, have been used as carbon sources for kojic acid production. Different Aspergillus species are known to produce variable amounts of kojic acid.
Burdock GA et al; Regul Toxicol Pharmacol 33 (1): 80-101 (2001)

10 Safety and Hazards

10.1 Hazards Identification

10.1.1 GHS Classification

Note
This chemical does not meet GHS hazard criteria for 87.3% (69 of 79) of all reports. Pictograms displayed are for 12.7% (10 of 79) of reports that indicate hazard statements.
Pictogram(s)
Health Hazard
Signal
Warning
GHS Hazard Statements
H351 (12.7%): Suspected of causing cancer [Warning Carcinogenicity]
Precautionary Statement Codes

P203, P280, P318, 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 79 reports by companies from 4 notifications to the ECHA C&L Inventory.

Reported as not meeting GHS hazard criteria per 69 of 79 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 2 notifications provided by 10 of 79 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.

10.1.2 Hazard Classes and Categories

Carc. 2 (12.7%)

10.2 Accidental Release Measures

10.2.1 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.

10.3 Regulatory Information

New Zealand EPA Inventory of Chemical Status
4H-Pyran-4-one, 5-hydroxy-2-(hydroxymethyl)-: Does not have an individual approval but may be used under an appropriate group standard

11 Toxicity

11.1 Toxicological Information

11.1.1 Toxicity Summary

Kojic acid acts as a competitive and reversible inhibitor of animal and plant polyphenol oxidases (tyrosinases), xanthine oxidase, and D- and some L-amino acid oxidases. Inhibition of tyrosinases prevents melanosis, while inhibition of the oxidases prevents metabolism of certain amino acids. Kojic acid also reversibly affects thyroid function by inhibiting iodine uptake, leading to decreases in thyroid hormones T3 and T4 and increases in thyroid-stimulating hormone (TSH). Increased TSH from pituitary gland in turn stimulates thyroid hyperplasia. (A3073, A3074)
A3073: Burdock GA, Soni MG, Carabin IG: Evaluation of health aspects of kojic acid in food. Regul Toxicol Pharmacol. 2001 Feb;33(1):80-101. PMID:11259181
A3074: Noh JM, Kwak SY, Seo HS, Seo JH, Kim BG, Lee YS: Kojic acid-amino acid conjugates as tyrosinase inhibitors. Bioorg Med Chem Lett. 2009 Oct 1;19(19):5586-9. doi: 10.1016/j.bmcl.2009.08.041. Epub 2009 Aug 14. PMID:19700313

11.1.2 Carcinogen Classification

1 of 2
IARC Carcinogenic Agent
Kojic acid
IARC Carcinogenic Classes
Group 3: Not classifiable as to its carcinogenicity to humans
IARC Monographs
Volume 79: (2001) Some Thyrotropic Agents
2 of 2
Carcinogen Classification
3, not classifiable as to its carcinogenicity to humans. (L135)

11.1.3 Health Effects

Animals studies have shown that kojic acid increases the occurrence of thyroid cancer and thyroid adenomas, though it is not known whether this is also true in humans. (A3073)
A3073: Burdock GA, Soni MG, Carabin IG: Evaluation of health aspects of kojic acid in food. Regul Toxicol Pharmacol. 2001 Feb;33(1):80-101. PMID:11259181

11.1.4 Exposure Routes

Oral, dermal, inhalation, and parenteral (contaminated drugs). (A3101)
A3101: Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. PMID:11370295

11.1.5 Symptoms

Sensitive individuals may develop contact dermatitis. (A3073)
A3073: Burdock GA, Soni MG, Carabin IG: Evaluation of health aspects of kojic acid in food. Regul Toxicol Pharmacol. 2001 Feb;33(1):80-101. PMID:11259181

11.1.6 Acute Effects

11.1.7 Interactions

Kojic acid (5-hydroxy-2-hydroxymethyl-gamma-pyrone) is a bacterial metabolic product used intensively in the food industry. In the presence of visible light and molecular oxygen it was found to cause breakage of calf thymus DNA. Such degradation was considerably enhanced in the presence of the transition metal ions Fe(III), Fe(II) and Cu(II). The cleavage of DNA in the presence of Fe(III) did not appear to have any preferred site(s) or sequence(s) for strand scission. Kojic acid catalysed the reduction of transition metal which in the case of Cu(II) was found to play an essential role in the degradation of DNA. Kojic acid also reduced oxygen to superoxide and hydroxyl radicals were formed in the presence of metal ions. The involvement of these active oxygen species in the reaction was established by the inhibition of DNA breakage by superoxide dismutase, catalase, iodide, mannitol, formate and sodium azide.
Bhat R,: Hadi SM; Mutagenesis 7 (2): 119-24 (1992) :
... The anti-wrinkling activity of kojic acid /was evaluated/ by using hairless mice exposed to chronic solar-simulating ultraviolet (UV) irradiation as a model animal. At the end of a 20-week irradiation period, topical application of kojic acid before UV irradiation was observed to dramatically prevent: (1) the wrinkling, (2) hyperplasia of the epidermis, (3) fibrosis of the lower dermis, and (4) the increase of extracellular matrix components in the upper dermis. These findings indicate that kojic acid is a typical agent preventing wrinkling of the skin due to chronic photodamage.
Milani H et al; Eur J Pharmacol 411 (1-2): 169-174 (2001):
The individual and combined effects of kojic acid and aflatoxin were studied in male broiler chicks (Peterson x Hubbard). The experiment had a two by two factorial arrangement of treatments with dietary treatments of 0 and 2,500 mg kojic acid/kg feed and 0 and 2.5 mg aflatoxin/kg feed. The broilers were obtained at 1 day of age and housed in electrically heated batteries with feed and water available for ad libitum intake until they reached 3 wk of age. The toxicity of kojic acid was characterized by significant (P less than .05) reductions in body weight, the relative weight of the bursa of Fabricius, serum cholesterol concentration, and serum alkaline phosphatase activity, and by significant (P less than .05) increases in the relative weight of the pancreas, proventriculus, and gizzard, and serum concentrations of uric acid and triglycerides. Aflatoxicosis was characterized by significant (P less than .05) reductions in body weight, serum concentrations of total protein, albumin, cholesterol, and inorganic phosphorus, serum glutamic oxalacetic transaminase activity, and mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. Significant (P less than .05) increases in the relative weight of the liver, kidney, spleen, pancreas, proventriculus, and heart, and the serum pyruvic transaminase activity were also caused by aflatoxin alone. The only significant (P less than .05) interaction between kojic acid and aflatoxin, which can best be described as antagonistic, was seen through an increase in mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. These data indicate that kojic acid is not an aflatoxin synergist at the levels used in the present study.
Giroir LE et al; Poult Sci 70 (6): 1351-6 (1991)

11.1.8 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

11.1.9 Human Toxicity Excerpts

/ALTERNATIVE and IN VITRO TESTS/ To discover safe and effective topical skin-lightening agents ... alkyl esters of the natural product gentisic acid (GA) ... , four putative tyrosinase inhibitors, /were evaluated/ utilizing mammalian melanocyte cell cultures and cell-free extracts. Desirable characteristics include the ability to inhibit melanogenesis in cells (IC50 less than 100 ug/mL) without cytotoxicity, preferably due to tyrosinase inhibition. Of the six esters synthesized, the smaller esters (e.g. methyl and ethyl) were more effective enzyme inhibitors (IC50 approximately 11 and 20 ug/mL, respectively). For comparison, hydroquinone (HQ), a commercial skin "bleaching" agent, was a less effective enzyme inhibitor (IC50 approximately 72 ug/mL), and was highly cytotoxic to melanocytes in vitro at concentrations substantially lower than the IC50 for enzymatic inhibition. Kojic acid was a potent inhibitor of the mammalian enzyme (IC50 approximately 6 ug/mL), but did not reduce pigmentation in cells. Both arbutin and magnesium ascorbyl phosphate were ineffective in the cell-free and cell-based assays... .
Curto EV et al;:Biochem-Pharmacol 57 (6): 663-72 (1999):

11.1.10 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ Acute or subchronic toxicity resulting from an oral dose has not been reported, but convulsions may occur if kojic acid is injected.
Burdock GA et al; Regul Toxicol Pharmacol 33 (1): 80-101 (2001)
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ To clarify the mechanism of tumorigenesis by kojic acid (KA), dose and time dependence of iodine uptake in the thyroid gland and serum thyroid stimulating hormone (TSH) and thyroid hormone levels were investigated in F344 rats fed a diet containing 2% KA. After 4 weeks, thyroid hyperplasia was apparent in males, associated with a decrease in (125)I uptake into the thyroid gland to only 3% of that in controls. The serum triiodothyronine (T(3)) and thyroxine (T(4)) levels dropped to 0.36 ng/ml, 1.7 micrograms/dl from the initial values of 0.61 ng/mL, 4.0 micrograms/dl and TSH increased seven times to 15 ng/mL. In females, the effects on thyroid weight and (125)I uptake were less prominent, although the changes in serum T(3), T(4) and TSH levels were similar to those in males. Time-dependent changes in serum T(3), T(4) and TSH levels correlated with the inhibition of iodine uptake in the thyroid. Inhibition of organic iodine formation was only observed after 3 weeks treatment. On return to the control diet, normal serum T(3), T(4) and TSH levels became evident within 48 rh in both sexes. These data suggest that KA interrupts thyroid function, primarily by inhibiting iodine intake, consequently causing a decrease in serum T(3) and T(4). Increased TSH from the pituitary gland in turn stimulates thyroid hyperplasia, which is reversible on withdrawal of KA.
Fujimoto N et al; Carcinogenesis 20 (8): 1567-7 (1999)
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In order to elucidate the mechanisms of reduction of serum thyroid hormones caused by continuous administration of kojic acid (KA) and its thyroid tumor-promotion effects, male F344 rats were given pulverized basal diet containing 0.008%, 0.03%, 0.125%, 0.5%, or 2% KA for 4 weeks. As an untreated control group, additional rats were given basal diet alone for the same period. The thyroid 125I uptake was significantly decreased in the groups receiving 0.03% or more. In addition, significant reduction of organic formation of iodine and serum T3 and T4 levels were observed in the 2% KA group along with pronounced elevation of serum (TSH). Both absolute and relative thyroid weights were significantly increased in the groups receiving 0.5% of KA or more. Histopathologically, decreased colloid in the thyroid follicles and follicular cell hypertrophy in the thyroid were apparent at high incidences in the groups given 0.03% or more. In addition, thyroid capsular fibrosis was evident in all rats of the 2% KA group. In quantitative morphometrical analysis, the ratio of the area of follicular epithelial cells to the area of colloids was significantly increased in the groups given 0.03% KA or more. The results suggest that KA alteration of thyroid-related hormone levels in the 2% KA group are due to inhibition of iodide uptake and iodine organification in the thyroid, with tumor-promoting effects on development of thyroid proliferative lesions, probably secondary to prolonged serum TSH stimulation resulting from negative feedback through the pituitary-thyroid axis.
Tamura T et al; Toxicol Sci 47 (2): 170-5 (1999):
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In order to examine whether kojic acid (KA) exerts a promoting effect on thyroid carcinogenesis, male F344 rats were initiated with N-bis(2-hydroxypropyl)nitrosamine (BHP; 2800 mg/kg body wt, single sc injection) and, starting 1 week later, received pulverized basal diet containing 2 or 0% KA for 12 weeks. Untreated control rats were given basal diet for 13 weeks. As an additional experiment, two groups without BHP initiation received basal diet or diet containing 2% KA for 20 weeks. The serum triiodothyronine (T3) and thyroxine (T4) levels were significantly decreased (half to one-third of values of the BHP alone group) and serum thyroid-stimulating hormone (TSH) was markedly increased (13-19 times higher than the values of the BHP-alone group) in the BHP + KA group at weeks 4 and 12. Similar changes in serum thyroid-related hormones were observed in the group with 2% KA alone at week 4, but not at week 20. Thyroid weights were significantly increased in the BHP + KA and KA-alone groups. Focal thyroid follicular hyperplasias and adenomas were observed in 4/5 and 3/ 5 rats in the BHP + KA group at week 4, respectively. At weeks 12, these lesions were observed in all rats in the BHP + KA group. Animals of the KA alone group showed marked diffuse hypertrophy of follicular epithelial cells at weeks 4 and 20. No changes in thyroid-related hormone levels or thyroid histopathological lesions were observed in either the BHP alone or the untreated control groups. Measurement of liver T4-uridine diphosphate glucuronosyltransferase (UDP-GT) activity at week 4 revealed no significant intergroup differences. These results suggest that thyroid proliferative lesions were induced by KA administration due to continuous serum TSH stimulation through the negative feedback mechanism of the pituitary-thyroid axis, with decreases of T3 and T4 caused by a mechanism independent of T4-UDP-GT activity.
Mitsumori K et al; Carcinogenesis 20 (1): 173-6 (1999)
For more Non-Human Toxicity Excerpts (Complete) data for KOJIC ACID (12 total), please visit the HSDB record page.

11.2 Ecological Information

11.2.1 Environmental Fate / Exposure Summary

Kojic acid's production and use as a flavoring agent, food additive, chemical intermediate and antimicrobial may result in its release to the environment through various waste streams. It is an antibiotic substance produced in an aerobic process by a variety of microorganisms from a wide-range of carbon sources. If released to air, an estimated vapor pressure of 3.2X10-6 mm Hg at 25 °C indicates kojic acid will exist in both the vapor and particulate phases in the atmosphere. Vapor-phase kojic 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 6 hours. Particulate-phase kojic acid will be removed from the atmosphere by wet or dry deposition. Kojic acid contains chromophores that absorb at wavelengths >290 nm and therefore may be susceptible to direct photolysis by sunlight. If released to soil, kojic acid is expected to have very high mobility based upon an estimated Koc of 11. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 2.4X10-7 atm-cu m/mole. Kojic acid is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Biodegradation data were not available. If released into water, kojic acid is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 3 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 kojic acid may occur through inhalation and dermal contact with this compound at workplaces where kojic acid is produced or used. Use data indicate that the general population may be exposed to kojic acid via ingestion of food. (SRC)

11.2.2 Natural Pollution Sources

Kojic acid is a fungal metabolite commonly produced by many species of Aspergillus, Acetobacter, and Penicillium. ... Different Aspergillus species are known to produce variable amounts of kojic acid.
Burdock GA et al; Regul Toxicol Pharmacol 33 (1): 80-101 (2001)
Kojic acid is an antibiotic substance produced in an aerobic process by a variety of microorganisms from a wide-range of carbon sources(1).
(1) O'Neil MJ, ed; The Merck Index. 15th ed. Whitehouse Station, NJ: Merck and Co., Inc., p. 920 (2006)

11.2.3 Artificial Pollution Sources

Kojic acid's production and use as a flavoring agent, food additive(1), chemical intermediate and antimicrobial(2) may result in its release to the environment through various waste streams(SRC).
(1) O'Neil MJ, ed; The Merck Index. 15th ed. Whitehouse Station, NJ: Merck and Co., Inc., p. 920 (2006)
(2) Lewis RJ, Sr; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY p. 732 (2007)

11.2.4 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 11(SRC), determined from a log Kow of -0.64(2) and a regression-derived equation(3), indicates that kojic acid is expected to have very high mobility in soil(SRC). Volatilization of kojic acid from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.4X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Kojic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.2X10-6 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2008).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Kontoghiorghes GJ; Inorg Chem Acta 151: 101-6 (1988)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9 (1990)
(4) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(5) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 11(SRC), determined from a log Kow of -0.64(2) and a regression-derived equation(3), indicates that kojic acid is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.4X10-7 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2008).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Kontoghiorghes GJ; Inorg Chem Acta 151: 101-6 (1988)
(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) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(5) Franke C et al; Chemosphere 29: 1501-14 (1994)
(6) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), kojic acid, which has an estimated vapor pressure of 3.2X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase kojic 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 6 hours(SRC), calculated from its rate constant of 6.4X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Vapor-phase kojic acid is degraded in the atmosphere by reaction with ozone radicals(SRC); the half-life for this reaction in air is estimated to be 21 hours(SRC), calculated from its rate constant of 1.3X10-17 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase kojic acid may be removed from the air by wet or dry deposition(SRC). Kojic acid contains chromophores that absorb 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)

11.2.5 Environmental Abiotic Degradation

The rate constant for the vapor-phase reaction of kojic acid with photochemically-produced hydroxyl radicals has been estimated as 6.4X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 6 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of kojic acid with ozone has been estimated as 1.3X10-17 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 21 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). Kojic acid is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Kojic acid contains chromophores that absorb at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight(SRC).
(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(2) Atkinson R, Carter WPL; Chem Rev 84: 437-70 (1984)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990)

11.2.6 Environmental Bioconcentration

An estimated BCF of 3 was calculated in fish for kojic acid(SRC), using a log Kow of -0.64(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).
(1) Kontoghiorghes GJ; Inorg Chem Acta 151: 101-6 (1988)
(2) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

11.2.7 Soil Adsorption / Mobility

The Koc of kojic acid is estimated as 11(SRC), using a log Kow of -0.64(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that kojic acid is expected to have very high mobility in soil.
(1) Kontoghiorghes GJ; Inorg Chem Acta 151: 101-6 (1988)
(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)

11.2.8 Volatilization from Water / Soil

The Henry's Law constant for kojic acid is estimated as 2.4X10-7 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that kojic acid is expected to be essentially nonvolatile from moist soil surfaces(2). Kojic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.2X10-6 mm Hg(SRC), determined from a fragment constant method(3).
(1) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(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)

11.2.9 Food Survey Values

Kojic acid is a fungal metabolite commonly produced by many species of Aspergillus, Acetobacter, and Penicillium. The Aspergillus flavus group has traditionally been used in the production of a number of foods, including miso (soybean paste), shoyu (soy sauce), and sake.... Because kojic acid is often produced during the fermentation of historically used dietary staples, it has a long history of consumption.
Burdock GA et al; Regul Toxicol Pharmacol 33 (1): 80-101 (2001)

11.2.10 Probable Routes of Human Exposure

Occupational exposure to kojic acid may occur through inhalation and dermal contact with this compound at workplaces where kojic acid is produced or used. Use data indicate that the general population may be exposed to kojic acid via ingestion of food. (SRC)

12 Associated Disorders and Diseases

13 Literature

13.1 Consolidated References

13.2 NLM Curated PubMed Citations

13.3 Springer Nature References

13.4 Thieme References

13.5 Wiley References

13.6 Nature Journal References

13.7 Chemical Co-Occurrences in Literature

13.8 Chemical-Gene Co-Occurrences in Literature

13.9 Chemical-Disease Co-Occurrences in Literature

14 Patents

14.1 Depositor-Supplied Patent Identifiers

14.2 WIPO PATENTSCOPE

14.3 Chemical Co-Occurrences in Patents

14.4 Chemical-Disease Co-Occurrences in Patents

14.5 Chemical-Gene Co-Occurrences in Patents

15 Interactions and Pathways

15.1 Protein Bound 3D Structures

15.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

15.2 Chemical-Target Interactions

16 Biological Test Results

16.1 BioAssay Results

17 Taxonomy

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

18 Classification

18.1 MeSH Tree

18.2 ChEBI Ontology

18.3 ChemIDplus

18.4 ChEMBL Target Tree

18.5 UN GHS Classification

18.6 EPA CPDat Classification

18.7 NORMAN Suspect List Exchange Classification

18.8 CCSBase Classification

18.9 EPA DSSTox Classification

18.10 International Agency for Research on Cancer (IARC) Classification

18.11 The Natural Products Atlas Classification

18.12 LOTUS Tree

18.13 EPA Substance Registry Services Tree

18.14 MolGenie Organic Chemistry Ontology

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    http://www.ebi.ac.uk/Information/termsofuse.html
  20. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  21. Cosmetic Ingredient Review (CIR)
  22. EPA Chemical and Products Database (CPDat)
  23. 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/
    Kojic acid
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  24. DailyMed
  25. MassBank Europe
  26. 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
  27. NMRShiftDB
  28. 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
    4H-Pyran-4-one, 5-hydroxy-2-(hydroxymethyl)-
    http://www.nist.gov/srd/nist1a.cfm
  29. SpectraBase
    5-HYDROXY-2-HYDROXYMETHYLPYRAN-4-ONE
    https://spectrabase.com/spectrum/DzgqlgiVAWs
    5-HYDROXY-2-(HYDROXYMETHYL)-4H-PYRAN-4-ONE
    https://spectrabase.com/spectrum/JPgqH5tSgp0
    5-Hydroxy-2-hydroxymethyl-4-pyrone
    https://spectrabase.com/spectrum/Ea6ugung9Hz
    5-hydroxy-2-hydroxymethyl-4H-pyran-4-one
    https://spectrabase.com/spectrum/6YarXISwuu7
    5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one
    https://spectrabase.com/spectrum/8uVzkncvOK0
    5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one
    https://spectrabase.com/spectrum/CK6xHm8gPi5
    4H-PYRAN-4-ONE, 5-HYDROXY-2-/HYDROXY- METHYL/-,
    https://spectrabase.com/spectrum/1f34u5HyS8P
  30. International Agency for Research on Cancer (IARC)
    LICENSE
    Materials made available by IARC/WHO enjoy copyright protection under the Berne Convention for the Protection of Literature and Artistic Works, under other international conventions, and under national laws on copyright and neighbouring rights. IARC exercises copyright over its Materials to make sure that they are used in accordance with the Agency's principles. All rights are reserved.
    https://publications.iarc.fr/Terms-Of-Use
    IARC Classification
    https://www.iarc.fr/
  31. Japan Chemical Substance Dictionary (Nikkaji)
  32. 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
  33. KNApSAcK Species-Metabolite Database
  34. Natural Product Activity and Species Source (NPASS)
  35. Metabolomics Workbench
  36. 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
  37. Nature Chemical Biology
  38. 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
  39. Protein Data Bank in Europe (PDBe)
  40. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
    Data files contained in the PDB archive (ftp://ftp.wwpdb.org) are free of all copyright restrictions and made fully and freely available for both non-commercial and commercial use. Users of the data should attribute the original authors of that structural data.
    https://www.rcsb.org/pages/policies
  41. Springer Nature
  42. SpringerMaterials
  43. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  44. Wikidata
  45. Wikipedia
  46. Wiley
  47. PubChem
  48. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
  49. GHS Classification (UNECE)
  50. The Natural Products Atlas
    LICENSE
    The Natural Products Atlas is licensed under a Creative Commons Attribution 4.0 International License.
    https://www.npatlas.org/terms
    The Natural Products Atlas Classification
    https://www.npatlas.org/
  51. EPA Substance Registry Services
  52. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  53. PATENTSCOPE (WIPO)
CONTENTS