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Citric Acid

PubChem CID
311
Structure
Citric Acid_small.png
Citric Acid_3D_Structure.png
Citric Acid__Crystal_Structure.png
Molecular Formula
  • C6H8O7
  • CH2COOH-C(OH)COOH-CH2COOH
Synonyms
  • citric acid
  • 77-92-9
  • Citric acid, anhydrous
  • 2-hydroxypropane-1,2,3-tricarboxylic acid
  • Anhydrous citric acid
Molecular Weight
192.12 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2004-09-16
  • Modify:
    2025-01-18
Description
Citric acid appears as colorless, odorless crystals with an acid taste. Denser than water. (USCG, 1999)
U.S. Coast Guard. 1999. Chemical Hazard Response Information System (CHRIS) - Hazardous Chemical Data. Commandant Instruction 16465.12C. Washington, D.C.: U.S. Government Printing Office.
Citric acid is a tricarboxylic acid that is propane-1,2,3-tricarboxylic acid bearing a hydroxy substituent at position 2. It is an important metabolite in the pathway of all aerobic organisms. It has a role as a food acidity regulator, a chelator, an antimicrobial agent and a fundamental metabolite. It is a conjugate acid of a citrate(1-) and a citrate anion.
A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium-chelating ability. Citric acid is one of the active ingredients in Phexxi, a non-hormonal contraceptive agent that was approved by the FDA on May 2020. It is also used in combination with magnesium oxide to form magnesium citrate, an osmotic laxative.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Citric Acid.png

1.2 3D Conformer

1.3 Crystal Structures

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

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

2-hydroxypropane-1,2,3-tricarboxylic acid
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C6H8O7/c7-3(8)1-6(13,5(11)12)2-4(9)10/h13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

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

2.1.4 SMILES

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

2.2 Molecular Formula

C6H8O7
Computed by PubChem 2.2 (PubChem release 2021.10.14)

C6H8O7

CH2COOH-C(OH)COOH-CH2COOH

2.3 Other Identifiers

2.3.1 CAS

77-92-9

2.3.3 Deprecated CAS

1192555-95-5, 12262-73-6, 136108-93-5, 2023788-69-2, 245654-34-6, 43136-35-2, 623158-96-3, 856568-15-5, 878903-72-1, 890704-54-8, 896506-46-0, 906507-37-7
1192555-95-5, 136108-93-5, 2023788-69-2, 245654-34-6, 43136-35-2, 623158-96-3, 856568-15-5, 878903-72-1, 890704-54-8, 896506-46-0, 906507-37-7

2.3.4 European Community (EC) Number

201-069-1

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 FEMA Number

2.3.11 HMDB ID

2.3.12 ICSC Number

2.3.13 JECFA Number

218

2.3.14 KEGG ID

2.3.15 Metabolomics Workbench ID

2.3.16 NCI Thesaurus Code

2.3.17 Nikkaji Number

2.3.18 NSC Number

2.3.19 PharmGKB ID

2.3.20 Pharos Ligand ID

2.3.21 RXCUI

2.3.22 Wikidata

2.3.23 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Anhydrous Citric Acid
  • Citrate
  • Citric Acid
  • Citric Acid Monohydrate
  • Citric Acid, Anhydrous
  • Uralyt U

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
192.12 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
-1.7
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
7
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
5
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
192.02700259 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
192.02700259 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
132 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
13
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
227
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

Citric acid appears as colorless, odorless crystals with an acid taste. Denser than water. (USCG, 1999)
U.S. Coast Guard. 1999. Chemical Hazard Response Information System (CHRIS) - Hazardous Chemical Data. Commandant Instruction 16465.12C. Washington, D.C.: U.S. Government Printing Office.
NKRA; Pellets or Large Crystals; Pellets or Large Crystals, Liquid; Dry Powder, Pellets or Large Crystals; Dry Powder, Liquid; Dry Powder; Liquid; Liquid, Other Solid; Other Solid
Citric acid is a white or colourless, odourless, crystalline solid, having a strongly acid taste. The monohydrate effloresces in dry air
Colorless and odorless crystals , it has an acid taste; [CAMEO] Deliquescent; [CHEMINFO]
Solid
COLOURLESS CRYSTALS.
White or colourless, odourless, crystalline solid. Monohydrate effloresces in dry air

3.2.2 Color / Form

Crystals; monoclinic holohedra; crystallizes from hot concentrated aqueous solution
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 416
Colorless, translucent crystals or powder
Haynes, W.M. (ed.) CRC Handbook of Chemistry and Physics. 91st ed. Boca Raton, FL: CRC Press Inc., 2010-2011, p. 305
Rhombic crystals from water with 1 mol of water of crystallization
Haynes, W.M. (ed.) CRC Handbook of Chemistry and Physics. 91st ed. Boca Raton, FL: CRC Press Inc., 2010-2011, p. 3-120

3.2.3 Odor

Odorless
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 305

3.2.4 Taste

Strongly acidic taste
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 305
Pleasant, sweet, tart taste
Lopez-Garcia R; Citric Acid. Kirk-Othmer Encyclopedia of Chemical Technology. (1999-2013). New York, NY: John Wiley & Sons. Online Posting Date: 19 Apr 2002

3.2.5 Boiling Point

Decomposes (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Decomposes
Haynes, W.M. (ed.) CRC Handbook of Chemistry and Physics. 91st ed. Boca Raton, FL: CRC Press Inc., 2010-2011, p. 3-120

3.2.6 Melting Point

307 °F (anhydrous) (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
153 °C
PhysProp
153 °C
Haynes, W.M. (ed.) CRC Handbook of Chemistry and Physics. 91st ed. Boca Raton, FL: CRC Press Inc., 2010-2011, p. 3-120

3.2.7 Flash Point

100 °C

3.2.8 Solubility

greater than or equal to 100 mg/mL at 72 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
592000 mg/L (at 20 °C)
MERCK INDEX (1989)
Very soluble in water; freely soluble in ethanol; soluble in ether
In water, 3.83X10+5 mg/L at 25 °C
Yalkowsky, S.H., He, Yan, Jain, P. Handbook of Aqueous Solubility Data Second Edition. CRC Press, Boca Raton, FL 2010, p. 275
Solubility in water: 54.0% w/w at 10 °C; 59.2% at 20 °C; 64.3% at 30 °C; 68.6% at 40 °C; 70.9% at 50 °C; 73.5% at 60 °C; 76.2% at 70 °C; 78.8% at 80 °C; 81.4% at 90 °C; 84.0% at 100 °C
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 416
Very soluble in ethanol; soluble in ether, ethyl acetate; insoluble in benzene, chloroform
Haynes, W.M. (ed.) CRC Handbook of Chemistry and Physics. 91st ed. Boca Raton, FL: CRC Press Inc., 2010-2011, p. 3-120
592.0 mg/mL
Solubility in water, g/100ml at 20 °C: 59
Very soluble in water, slightly soluble in ether
Freely soluble (in ethanol)

3.2.9 Density

1.54 at 68 °F (USCG, 1999) - Denser than water; will sink
U.S. Coast Guard. 1999. Chemical Hazard Response Information System (CHRIS) - Hazardous Chemical Data. Commandant Instruction 16465.12C. Washington, D.C.: U.S. Government Printing Office.
1.665 g/cu cm at 20 °C
Lide, D.R. CRC Handbook of Chemistry and Physics 86TH Edition 2005-2006. CRC Press, Taylor & Francis, Boca Raton, FL 2005, p. 3-120
BULK DENSITY: 56.2 LB/CU FT; HEAT OF SOLN: -3.9 KCAL/MOLE; BUFFERING INDEX: 2.46; STD FREE ENERGY OF ANION FORMATION: -278.8 KCAL FOR AQ SOLN @ 25 °C
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 244
Density: 1.542 g/cu cm /Citric acid monohydrate/
Haynes, W.M. (ed.) CRC Handbook of Chemistry and Physics. 91st ed. Boca Raton, FL: CRC Press Inc., 2010-2011, p. 3-120
White, odorless crystals, granules or powder; cool, saline taste. Stable in air, becomes anhydrous at 150 °C. Density: 1.814. Soluble in 3 parts water, 0.6 parts boiling water. Insoluble in alcohol. The aqueous solution is slightly alkaline to litmus. pH about 8 /Sodium citrate dihydrate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 416

3.2.10 LogP

-1.64
AVDEEF,A (1997)
log Kow = -1.64
Avdeef A; Seminar on Ionization and Lipophilicity. Log P values measured by pION Inc., Brookline, MA (A. Avdeef and C. Berger) (1997)
-1.64
AVDEEF,A (1997)
-1.7

3.2.11 LogS

0.51
ADME Research, USCD

3.2.12 Autoignition Temperature

1850 °F (USCG, 1999)
U.S. Coast Guard. 1999. Chemical Hazard Response Information System (CHRIS) - Hazardous Chemical Data. Commandant Instruction 16465.12C. Washington, D.C.: U.S. Government Printing Office.
1850 °F (POWDER)
U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.

3.2.13 Decomposition

When heated to decomposition it emits acrid smoke and fumes.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 955
Behavior in fire: melts and decomposes. The reaction is not hazardous.
U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.
Decomposes at 175 °C
International Program on Chemical Safety/Commission of the European Union; International Chemical Safety Card on Citric Acid (March 26, 1998). Available from, as of September 13, 2013: https://www.inchem.org/pages/icsc.html
175 °C

3.2.14 Viscosity

2.549 cP 30% aqueous solution at 20 °C
Haynes, W.M. (ed.) CRC Handbook of Chemistry and Physics. 91st ed. Boca Raton, FL: CRC Press Inc., 2010-2011, p. 8-55

3.2.15 Corrosivity

WILL CORRODE COPPER, ZINC, ALUMINUM AND THEIR ALLOYS
U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.

3.2.16 Heat of Combustion

-474.5 KCAL/MOLE
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 244

3.2.17 Refractive Index

INDEX OF REFRACTION: 1.493, 1.498, 1.509 @ 20 °C /CITRIC ACID HYDRATE/
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 244
Index of refraction (30% solution): 1.3744 at 20 °C/D
Haynes, W.M. (ed.) CRC Handbook of Chemistry and Physics. 91st ed. Boca Raton, FL: CRC Press Inc., 2010-2011, p. 8-55

3.2.18 Dissociation Constants

pKa
2.79
SERJEANT,EP & DEMPSEY,B (1979)
pKa = 2.79
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., p. 989

3.2.19 Collision Cross Section

142.4 Ų [M+Na]+ [CCS Type: DT; Method: single field calibrated with Agilent tune mix (Agilent)]
138 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine]

127.1 Ų [M-H]- [CCS Type: DT; Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

143.1 Ų [M+Na]+ [CCS Type: DT; Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

146.11 Ų [M+Na]+ [CCS Type: DT; Method: stepped-field]

148.9 Ų [M+H]+ [CCS Type: DT; Method: stepped-field]

129.49 Ų [M-H]- [CCS Type: DT; Method: stepped-field]

146.1 Ų [M+Na]+

129 Ų [M-H]-

127.4 Ų [M-H]-

143 Ų [M+Na]+

S50 | CCSCOMPEND | The Unified Collision Cross Section (CCS) Compendium | DOI:10.5281/zenodo.2658162

3.2.20 Other Experimental Properties

Heat of formation = -1543.8 kJ/mol at 25 °C
Haynes, W.M. (ed.) CRC Handbook of Chemistry and Physics. 91st ed. Boca Raton, FL: CRC Press Inc., 2010-2011, p. 3-120
HEAT OF COMBUSTION: -471.4 KCAL/MOLE /CITRIC ACID MONOHYDRATE/
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 244
Hydrated form is efflorescent in dry air /Citric acid hydrate/
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 305
Powder. Loses all H2O at 150 °C. Soluble in 170 parts water; freely soluble in dilute HCl or HNO3; practically insoluble in alcohol /Citric acid, barium salt heptahydrate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 416
Orthorhombic crystals from cold aqueous solutions; pleasant, sour taste; density = 1.542; melting point at about 100 °C; loses water of crystallization in dry air or when heated at about 40 to 50 °C; slightly deliquescent in moist air; softens at 75 °C; pH of 0.1 N solution = 2.2; densities of aqueous solution (15 °C/15 °C): 10% = 1.0392, 20% = 1.0805, 30% = 1.1244, 40% = 1.1709, 50% = 1.2204, 60% = 1.2738. Solubility in g/100 g saturated solution: ether 2.17; chloroform 0.007; amyl alcohol 15.43; amyl acetate 5.98; ethyl acetate 5.28. Solubility at 19 °C in g/100 g solvent: methanol 197; propanol 62.8. /Citric acid monohydrate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 416
Bitter, oily liquid. Density: 1.137 at 20 °C. BP: 294 °C at 60 mm Hg; 127 °C at 1.0 mm Hg. Viscosity at 25 °C: 35.2 cP. Index of refraction: 1.4455 at 20 °C/D. Solubility: water approximately 6.9%; peanut oil 0.8%. Miscible with alcohol, ether /Cirtic acid, ethyl ester/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 416
White powder, saline taste. One gram of sesquihydrate dissolves in slightly less than 2 mL water. pH of a 3% w/v solution in water: 4.9 to 5.3 /Citric acid, disodium salt/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 416

3.3 Chemical Classes

Other Classes -> Organic Acids

3.3.1 Drugs

Pharmaceuticals
S10 | SWISSPHARMA | Pharmaceutical List with Consumption Data | DOI:10.5281/zenodo.2623484
Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
3.3.1.1 Human Drugs
Breastfeeding; Lactation; Appetite Depressants; Gastrointestinal Agents; Anti-Obesity Agents;
Human drug -> Active ingredient (CITRIC ACID)
3.3.1.2 Animal Drugs
Active Ingredients (Citric Acid) -> FDA Greenbook
Pharmaceuticals -> UK Veterinary Medicines Directorate List
S104 | UKVETMED | UK Veterinary Medicines Directorate's List | DOI:10.5281/zenodo.7802119

3.3.2 Cosmetics

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

3.3.3 Food Additives

ANTIMICROBIAL AGENT, ANTIOXIDANT, ENZYME, FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT, LEAVENING AGENT, PH CONTROL AGENT, SEQUESTRANT, SOLVENT OR VEHICLE, SURFACE-ACTIVE AGENT -> FDA Substance added to food

3.3.4 Fragrances

Fragrance Ingredient (Citric acid) -> IFRA transparency List

4 Spectral Information

4.1 1D NMR Spectra

1 of 2
1D NMR Spectra
1H NMR: 7552 (Sadtler Research Laboratories Spectral Collection)
2 of 2
1D NMR Spectra

4.1.1 1H NMR Spectra

1 of 7
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Spectra ID
Instrument Type
Varian
Frequency
500 MHz
Solvent
Water
pH
7.00
Shifts [ppm]:Intensity
2.54:100.00, 2.67:63.28, 2.51:57.85, 2.64:92.38
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Spectra ID
Instrument Type
JEOL
Frequency
400 MHz
Solvent
DMSO-d6
Shifts [ppm]:Intensity
2.64:559.00, 2.75:1000.00, 2.68:994.00, 2.78:570.00
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4.1.2 13C NMR Spectra

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Spectra ID
Instrument Type
Bruker
Frequency
125 MHz
Solvent
Water
pH
7.00
Shifts [ppm]:Intensity
181.86:46.74, 184.52:17.65, 48.45:70.96, 77.91:26.50, 0.00:4.01
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Spectra ID
Frequency
400 MHz
Solvent
H2O
Shifts [ppm]
77.91, 48.45, 181.86, 184.52
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4.2 2D NMR Spectra

4.2.1 1H-1H NMR Spectra

2D NMR Spectra Type
1H-1H TOCSY
Spectra ID
Shifts [ppm] (F2:F1)
2.65:2.50, 2.52:2.67, 2.52:2.63, 2.65:2.54
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4.2.2 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
2.66:48.71:1.00, 2.52:48.71:0.20
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4.3 Mass Spectrometry

4.3.1 GC-MS

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Spectra ID
Instrument Type
GC-MS
Top 5 Peaks

273.0 1

274.0 0.25

211.0 0.24

347.0 0.23

133.0 0.21

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Spectra ID
Instrument Type
GC-EI-TOF
Ionization Mode
positive
Top 5 Peaks

147.0 100

273.0 51.85

133.0 18.12

149.0 18.02

148.0 16.92

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Notes
instrument=Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies

4.3.2 MS-MS

1 of 8
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Spectra ID
Instrument Type
Quattro_QQQ
Ionization Mode
Negative
Top 5 Peaks

110.997 100

190.922 48.34

87.067 26.82

85.086 20.36

128.984 6.83

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Notes
delivery=Flow_Injectionanalyzer=Triple_Quad
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Spectra ID
Instrument Type
Quattro_QQQ
Ionization Mode
Negative
Top 5 Peaks

87.059 100

110.958 51.72

85.078 45.40

67.159 43.10

43.355 41.95

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Notes
delivery=Flow_Injectionanalyzer=Triple_Quad

4.3.3 LC-MS

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Authors
Kevin S. Jewell; Björn Ehlig; Arne Wick
Instrument
TripleTOF 5600 SCIEX
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
NEGATIVE
Ionization
ESI
Collision Energy
130
Fragmentation Mode
CID
Column Name
Zorbax Eclipse Plus C18 2.1 mm x 150 mm, 3.5 um, Agilent
Retention Time
2.078 min
Precursor m/z
191.0197
Precursor Adduct
[M-H]-
Top 5 Peaks
41.0034 999
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License
dl-de/by-2-0
2 of 46
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Authors
Kevin S. Jewell; Björn Ehlig; Arne Wick
Instrument
TripleTOF 5600 SCIEX
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
NEGATIVE
Ionization
ESI
Collision Energy
100
Fragmentation Mode
CID
Column Name
Zorbax Eclipse Plus C18 2.1 mm x 150 mm, 3.5 um, Agilent
Retention Time
2.078 min
Precursor m/z
191.0197
Precursor Adduct
[M-H]-
Top 5 Peaks

41.0032 999

57.0341 111

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dl-de/by-2-0

4.3.4 Other MS

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Other MS
MASS: 8394 (NIST/EPA/MSDC Mass Spectral Database 1990 version)
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MoNA ID
MS Category
Experimental
MS Type
Other
MS Level
MS2
Precursor Type
[M-H]-
Precursor m/z
191.11
Instrument
TQD, Waters
Instrument Type
Flow-injection QqQ/MS
Ionization
ESI
Ionization Mode
negative
Collision Energy
10
Top 5 Peaks

191 100

190 10.63

111 6.77

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4.4 IR Spectra

IR Spectra
IR: 5104 (Coblentz Society Spectral Collection)

4.4.1 FTIR Spectra

1 of 2
Instrument Name
Bruker Tensor 27 FT-IR
Technique
KBr1
Source of Spectrum
Bio-Rad Laboratories, Inc.
Source of Sample
Alfa Aesar, Thermo Fisher Scientific
Catalog Number
36664
Lot Number
D3181403
Copyright
Copyright © 2016-2024 John Wiley & Sons, Inc. All Rights Reserved.
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Instrument Name
Bruker IFS 85
Technique
KBr-Pellet
Copyright
Copyright © 1989, 1990-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.4.2 ATR-IR Spectra

1 of 2
Instrument Name
Bruker Tensor 27 FT-IR
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Bio-Rad Laboratories, Inc.
Source of Sample
TCI Chemicals India Pvt. Ltd.
Catalog Number
36664
Lot Number
D3181403
Copyright
Copyright © 2016-2024 John Wiley & Sons, Inc. All Rights Reserved.
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Source of Sample
Sigma-Aldrich
Catalog Number
240621
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.5 Raman Spectra

1 of 2
Instrument Name
Bruker MultiRAM Stand Alone FT-Raman Spectrometer
Technique
FT-Raman
Source of Spectrum
Bio-Rad Laboratories, Inc.
Source of Sample
Alfa Aesar, Thermo Fisher Scientific
Catalog Number
36664
Lot Number
D3181403
Copyright
Copyright © 2016-2024 John Wiley & Sons, Inc. All Rights Reserved.
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Instrument Name
Bruker MultiRAM Stand Alone FT-Raman Spectrometer
Source of Spectrum
Zenodo
Copyright
Copyright © 2023-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.6 Other Spectra

SADTLER REFERENCE NUMBER: 765 (IR, PRISM)
Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-251

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

7.2 Drug Classes

Breastfeeding; Lactation; Appetite Depressants; Gastrointestinal Agents; Anti-Obesity Agents;

7.3 FDA Approved Drugs

7.4 FDA Orange Book

7.5 FDA National Drug Code Directory

7.6 FDA Green Book

7.7 Drug Labels

Drug and label
Active ingredient and drug
Homeopathic product and label

7.8 Clinical Trials

7.8.1 ClinicalTrials.gov

7.8.2 EU Clinical Trials Register

7.9 Therapeutic Uses

Mesh Heading: Anticoagulants, chelating Agents
National Library of Medicine, SIS; ChemIDplus Record for Citric acid (77-92-9). Available from, as of April 17, 2006: https://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp
/EXPL THER/ Regional citrate anticoagulation (RCA) is an effective form of anticoagulation for continuous renal replacement therapy (CRRT) in patients with contraindications to heparin. Its use has been very limited, possibly because of the need for special infusion solutions and difficult monitoring of the metabolic effects./The objective of this study was/ to investigate the safety and the feasibility of an RCA method for continuous veno-venous hemofiltration (CVVH) using commercially available replacement fluid. We evaluated 11 patients at high risk of bleeding, requiring CVVH. RCA was performed using commercially available replacement fluid solutions to maintain adequate acid-base balance. We adjusted the rate of citrate infusion to achieve a post-filter ionized calcium concentration [iCa] <0.4 mmol/L when blood flow was <250 mL/min, or <0.6 mmol/L when blood flow was >250 mL/min. When needed, we infused calcium gluconate to maintain systemic plasma [iCa] within the normal range. Twenty-nine filters ran for a total of 965.5 hr. Average filter life was 33.6+/-20.5 hr. Asymptomatic hypocalcemia was detected in 6.9% of all samples. No [iCa] values <0.9 mmol/L were observed. Hypercalcemia (1.39+/-0.05 mmol/L) occurred in 2.5% of all samples. /The authors/ observed hypernatremia (threshold 153 mmol/L) and alkalosis (threshold 7.51) in only 9.3% and 9.4% respectively of all samples, mostly concomitantly. No patient showed any signs of citrate toxicity. /They/ developed a protocol for RCA during CVVH using commercially available replacement fluid that proved safe, flexible and applicable in an Intensive Care Unit (ICU) setting.
Cubattoli L et al; Int J Artif Organs. 30 (3): 244-52 (2007)
It has ... been used to dissolve urinary bladder calculi, & as mild astringent.
Troy, D.B. (Ed); Remmington The Science and Practice of Pharmacy. 21 st Edition. Lippincott Williams & Williams, Philadelphia, PA 2005, p. 1085
Citrate ... of ... value in alleviation of chronic metabolic acidosis ... from chronic renal insufficiency or syndrome of renal tubular acidosis ... usually prescribed in form of sodium citrate and citric acid soln, USP ...
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 806
Potassium citrate, up to 10 g daily, has been used as a potassium supplement; the potassium and sodium salts have been used, in similar dosages, as mild diuretics in humans.
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 5:768

7.10 Drug Warnings

A study of abdominal pain and severity of other side effects attributed to Picolax, a combination of citric acid, magnesium oxide and sodium picosulfate, was conducted among 267 patients, 55 of whom had inflammatory bowel disease, all of whom were given a full single dose of Picolax as preparation for radiology or endoscopy. The frequency of increased abdominal pain and severe side effects after Picolax administration was similar in the patients with inflammatory bowel disease and the patients with other colonic disorders. None of the patients with iron deficiency in whom investigations had yielded negative results reported severe side effects; this was significantly different from the proportion reporting severe side effects among the patients with inflammatory bowel disease, the irritable bowel syndrome and diverticular disease. The increase in the mean number of stools/24 hr after Picolax was lower in the patients with inflammatory bowel disease than in the other diagnostic groups. On review 2-4 wk after examination none of the patients with inflammatory bowel disease reported deterioration in their symptoms.
McDonagh AJ et al; Br Med J 299: 776-7 (1989)
Following the occurrence of aluminum encephalopathy in four patients with chronic renal failure, 34 azotemic patients seen during the same year and five volunteers who took varying combinations of aluminum hydroxide and an alkalinizing citrate (Shohl's) solution were studied. It was found that the four encephalopathic cases were older than the 34 azotemic patients (68 years + or - 14 standard deviation, versus 50 + or - 13, p< 0.05), had a higher mean serum aluminum value (727 ug/l + or - 320 versus 92 + or - 73, p< 0.005), had taken more aluminum hydroxide (5 g/day + or - 0.9 versus 1.6 + or - 1.8, p< 0.01), and more Shohl's solution (64 ml/day + or - 19 versus 20 + or - 29, p< 0.01). In all 38 patients the serum aluminum values correlated directly with age (p=0.01), aluminum hydroxide (p=0.001) and concomitant citrate intake (p=0.004). In the five healthy volunteers the 24 hr urinary aluminum excretion increased from a baseline of 22 ug + or - 19 standard deviation to 167 + or - 109 (p=0.05) during aluminum hydroxide intake, rising to 580 + or - 267 (p=0.01) during the simultaneous intake of citrate and aluminum hydroxide. Corresponding serum aluminum values were 11 ug/l + or - 2 standard deviation, 44 + or - 34 (p= 0.1), and 98 + or - 58 (p<0.05). Thus citrate seems to enhance aluminum absorption and may cause encephalopathy in patients with chronic renal failure, especially the elderly.
Bakir AA et al; Clin Nephrol 31 (1): 40-4 (1989)

7.11 Biomarker Information

8 Food Additives and Ingredients

8.1 Food Additive Classes

JECFA Functional Classes
FLAVOURING_AGENT;
Flavoring Agents

8.2 Food Additive Definition

EU Food Additive Definition
Citric acid is produced from lemon or pineapple juice, by fermentation of carbohydrate solutions or other suitable media usingCandidaspp. or non-toxicogenic strains ofAspergillus niger

8.3 FDA Substances Added to Food

Substance
Used for (Technical Effect)
ANTIMICROBIAL AGENT, ANTIOXIDANT, ENZYME, FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT, LEAVENING AGENT, PH CONTROL AGENT, SEQUESTRANT, SOLVENT OR VEHICLE, SURFACE-ACTIVE AGENT
FEMA Number
2306
GRAS Number
3, 25
JECFA Flavor Number
218

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

Chemical Name
CITRIC ACID
Evaluation Year
2014
ADI
NOT LIMITED
Comments
Considered for specifications only.

9 Pharmacology and Biochemistry

9.1 MeSH Pharmacological Classification

Anticoagulants
Agents that prevent BLOOD CLOTTING. (See all compounds classified as Anticoagulants.)
Calcium Chelating Agents
Substances that bind to and sequester CALCIUM ions. (See all compounds classified as Calcium Chelating Agents.)

9.2 FDA Pharmacological Classification

1 of 2
FDA UNII
XF417D3PSL
Active Moiety
ANHYDROUS CITRIC ACID
Pharmacological Classes
Mechanisms of Action [MoA] - Acidifying Activity
Pharmacological Classes
Established Pharmacologic Class [EPC] - Calculi Dissolution Agent
Pharmacological Classes
Established Pharmacologic Class [EPC] - Anti-coagulant
Pharmacological Classes
Physiologic Effects [PE] - Decreased Coagulation Factor Activity
Pharmacological Classes
Mechanisms of Action [MoA] - Calcium Chelating Activity
FDA Pharmacology Summary
Anhydrous citric acid is a Calculi Dissolution Agent and Anti-coagulant. The mechanism of action of anhydrous citric acid is as an Acidifying Activity and Calcium Chelating Activity. The physiologic effect of anhydrous citric acid is by means of Decreased Coagulation Factor Activity.
2 of 2
Non-Proprietary Name
ANHYDROUS CITRIC ACID
Pharmacological Classes
Calcium Chelating Activity [MoA]; Decreased Coagulation Factor Activity [PE]; Anti-coagulant [EPC]; Calculi Dissolution Agent [EPC]; Acidifying Activity [MoA]

9.3 ATC Code

A - Alimentary tract and metabolism

A09 - Digestives, incl. enzymes

A09A - Digestives, incl. enzymes

A09AB - Acid preparations

A09AB04 - Citric acid

9.4 Bionecessity

Extremely widespread in nature; also identified in the flowers of Hibiscus subdariffa, cocoa and kiwifruit.
Burdock, G.A. (ed.). Fenaroli's Handbook of Flavor Ingredients. 6th ed.Boca Raton, FL 2010, p. 312
Citric acid and its salts are naturally occurring constituents and common metabolites in plants and animal tissues. Citric acid is an intermediary compound in the Krebs cycle linking oxidative metabolism of carbohydrate, protein and fat. The concentration of naturally occurring citrate is relatively higher in fruits, particularly citrus fruits and juices than vegetables and animal tissues.
Burdock, G.A. (ed.). Fenaroli's Handbook of Flavor Ingredients. 6th ed.Boca Raton, FL 2010, p. 311

9.5 Absorption, Distribution and Excretion

/A portion/ of the circulating (mainly metabolic but also ingested) citric acid is excreted in urine, with 24-hour urine reference values between 1.5 and 3.68 mmol, corresponding to 0.29-0.71 g citric acid excreted per person per day.
United Nations Environment Programme: OECD; Screening Information Data Sheets on Citric Acid (77-92-9) (January 1997). Available from, as of May 9, 2006: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html

9.6 Metabolism / Metabolites

Citric acid is a normal metabolite and an intermediate in cellular oxidative metabolism ... The acid is formed in the mitochondrion after condensation of acetate with oxaloacetate. The six-carbon acid is then successively degraded to a series of four-carbon acids, effectively accomplishing oxidation of acetate in the cell.
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 5:767
In human (as well as in animal and plant) physiology, citric acid is a very common intermediate in one of the central biochemical cycles, the Krebs or tricarboxylic acid cycle, which takes place in every cell. It completes the breakdown of pyruvate formed from glucose through glycolysis, thereby liberating carbon dioxide and a further four hydrogen atoms which are picked up by electron transport molecules. Thus, in man approximately 2 kg of citric acid are formed and metabolised every day. This physiological pathway is very well developed and capable of processing very high amounts of citric acid as long as it occurs in low concentrations.
United Nations Environment Programme: OECD; Screening Information Data Sheets on Citric Acid (77-92-9) (January 2001). Available from, as of May 9, 2006: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html
Citric acid in reaction with enzyme citratase /citrate lyase/ yields oxaloacetic acid & acetic acid.
Fenaroli's Handbook of Flavor Ingredients. Volume 2. Edited, translated, and revised by T.E. Furia and N. Bellanca. 2nd ed. Cleveland: The Chemical Rubber Co., 1975., p. 785

9.7 Mechanism of Action

... The NK(2), and to a lesser extent the NK(1), receptors have been shown to be involved with citric acid-induced bronchoconstriction in the guinea pig, which is in part mediated by endogenously released bradykinin. Tachykinins and bradykinin could also modulate citric acid-induced bronchoconstriction. ... Bronchoconstriction induced by citric acid inhalation in the guinea pig, mainly caused by the tachykinin NK(2) receptor, is counteracted by bronchoprotective NO after activation of bradykinin B(2) and tachykinin NK(1) receptors in airway epithelium.
Ricciardolo FL; Am J Med 111 (Suppl 8A): 18S-24S (2001)
... A concentration of 47.6 mmol/L of citric acid (pH 2.3) in water led to total cell death within three minutes of incubation /with gingival fibroblasts (GF)/. Media containing 23.8 mmol/L and 47.6 mmol/L of citric acid exerted strong cytotoxicity (47 to 90 per cent of cell death) and inhibited protein synthesis (IC50 = 0.28 per cent) of GF within three hours of incubation. Incubation of cells in a medium containing 11.9 mmol/L of citric acid also suppressed the attachment and spreading of fibroblasts on culture plates and Type I collagen, with 58 per cent and 22 per cent of inhibition, respectively. Culture medium supplemented with 11.9, 23.8 and 47.6 mmol/L of citric acid also led to extracellular acidosis by decreasing the pH value from 7.5 to 6.3, 5.2 and 3.8, respectively.
Lan WC et al; Aust Dent J 44 (2): 123-30 (1999)
Inhalation of citric acid (CA) causes airway constriction and coughing. To investigate the role of mast cells in CA-induced airway constriction and cough, three experiments using guinea pigs were carried out. In the first experiment, /the authors/ used compound 48/80 to deplete mast cells, cromolyn sodium to stabilize mast cells, MK-886 to inhibit synthesis of leukotrienes, pyrilamine to antagonize histamine H1 receptor, methysergide to antagonize serotonin receptor, and indomethacin to inhibit cyclooxygenase. In the second experiment, compound 48/80-pretreated animals were divided into 2 parts; the first one was used to test the role of exogenous leukotriene (LT) C4, while the second one to test the role of exogenous histamine. Decreases in respiratory compliance (Crs) and forced expiratory volume in 0.1 sec (FEV0.1) were used as indicators for airway constriction in anesthetized guinea pigs. CA-induced cough was recorded for 12 min using a barometric body plethysmograph in conscious animals. In the third experiment, the activation of mast cells upon CA inhalation was investigated by determining lung tissue or arterial plasma histamine concentration in animals. Exposure to CA induced marked airway constriction and increase in cough number. Compound 48/80, cromolyn sodium, MK-886 and pyrilamine, but not indomethacin or methysergide, significantly attenuated CA-induced airway constriction and cough. Injection of LTC4 or histamine caused a significant increase in CA-induced airway constriction and cough in compound 48/80-pretreated animals. In addition, CA inhalation caused significant increase in lung tissue and plasma histamine concentrations, which were blocked by compound 48/80 pretreatment. These results suggest that mast cells play an important role in CA aerosol inhalation-induced airway constriction and cough via perhaps mediators including LTs and histamine.
Lai YL et al; Chin J Physiol. 52 (5 Suppl): 332-8 (2009)

9.8 Human Metabolite Information

9.8.1 Tissue Locations

  • All Tissues
  • Placenta
  • Prostate

9.8.2 Cellular Locations

  • Cytoplasm
  • Extracellular
  • Mitochondria

9.8.3 Metabolite Pathways

9.9 Biochemical Reactions

9.10 Transformations

10 Use and Manufacturing

10.1 Uses

Cosmetic Ingredient Review Link
CIR ingredient: Citric 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
Sources/Uses
A Compound from citrus fruits that is an intermediate in the tricarboxylic acid (Krebs) cycle. It is used as an acidifying agent in foods, beverages, and pharmaceuticals. Citrate chelates calcium ions and prevents blood clotting. It is also used as an anticoagulant for stored whole blood and red cells and also for blood specimens. (Dorland, 28th ed) [ChemIDplus]
For citric acid (USEPA/OPP Pesticide Code: 21801) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./
National Pesticide Information Retrieval System's Database on Citric Acid (77-92-9). Available from, as of August 27, 2013: https://npirspublic.ceris.purdue.edu/ppis/
Active ingredient in products registered for residential and commercial use as disinfectants, sanitizers and fungicides ... products are used to kill odor-causing bacteria, mildew, pathogenic fungi, certain bacteria and some viruses. Citric acid products are used in bathrooms and in/on dairy and food processing equipment.
USEPA/OPPTS; R.E.D Facts. Citric Acid (77-92-9). Reregistration Eligibility Decisions (REDs) Database. EPA-738-F-92-017. June 1992. Available from, as of Sept 5, 2013: https://www.epa.gov/pesticides/reregistration/status.htm
Acidulant in beverages, confectionary, effervescent salts, in pharmaceutical syrups, elixirs, in effervescent powders and tablets, to adjust pH of foods and as a synergistic antioxidant in processing cheese. Used in beverages, jellies, jams, preserves and candy to provide tartness. In the manufacture of alkyd resins; in esterified form as plasticizer, foam inhibitor. In the manufacture of citric acid salts. As a sequestering agent to remove trace metals. As mordant to brighten colors; in special inks; in electroplating; in analytical chemistry for determining citrate-soluble P2O5; as reagent for albumin, mucin, glucose, bile pigments.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 416
Anticoagulent, generally in solution with glucose, to prevent clotting of blood intended for transfusion
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 416
For more Uses (Complete) data for CITRIC ACID (19 total), please visit the HSDB record page.

Use (kg; approx.) in Germany (2009): >100000

Consumption (g per capita; approx.) in Germany (2009): 1.22

Calculated removal (%): 92.1

10.1.1 Use Classification

EPA Safer Chemical Functional Use Classes -> Antimicrobial Actives;Chelating Agents;Processing Aids and Additives
Safer Chemical Classes -> Green circle Green circle - The chemical has been verified to be of low concern
Food additives
Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients
Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients
Fragrance Ingredients
FLAVOURING_AGENT; -> JECFA Functional Classes
Flavoring Agents -> JECFA Flavorings Index
Cosmetics -> Buffering; Chelating
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

10.1.2 Industry Uses

  • Other (specify)
  • Lubricants and lubricant additives
  • Opacifer
  • Laboratory chemicals
  • Defoamer
  • Surface modifier
  • Solvents (which become part of product formulation or mixture)
  • Oxidizing/reducing agents
  • Corrosion inhibitors and anti-scaling agents
  • Not Known or Reasonably Ascertainable
  • Adhesives and sealant chemicals
  • Aerating and deaerating agents
  • Process regulators
  • Filler
  • Processing aids not otherwise specified
  • Flocculating agent
  • Other
  • Surface active agents
  • pH regulating agent
  • Agricultural chemicals (non-pesticidal)
  • Paint additives and coating additives not described by other categories
  • Surfactant (surface active agent)
  • Plating agents and surface treating agents
  • Processing aids, not otherwise listed

10.1.3 Consumer Uses

  • Not Known or Reasonably Ascertainable
  • Chelating agent
  • Solvents (for cleaning or degreasing)
  • Lubricants and lubricant additives
  • Pigment
  • pH regulating agent
  • Cleaning agent
  • Processing aids, not otherwise listed
  • Softener and conditioner
  • Agricultural chemicals (non-pesticidal)
  • Surfactant (surface active agent)
  • Preservative
  • Binder
  • Process regulators
  • Processing aids not otherwise specified
  • Hardener
  • Other

10.1.4 Household Products

Household & Commercial/Institutional Products

Information on 2599 consumer products that contain Citric acid in the following categories is provided:

• Auto Products

• Commercial / Institutional

• Home Maintenance

• Inside the Home

• Landscaping/Yard

• Personal Care

• Pesticides

• Pet Care

10.2 Methods of Manufacturing

In surface fermentation, Aspergillus niger is grown on a liquid substrate in pans stacked vertically in a chamber. The chamber and pans are sterilized either before or after introduction of the substrate. ... The substrate for the fermentation is a carbohydrate, usually molasses or a sugar, such as raw beet, refined beet, or cane sugars, or a syrup. ... Certain inorganic nutrients, such as ammonium nitrate, potassium phosphate, magnesium sulfate, zinc sulfate, and potassium ferrocyanide, are added. The pH is adjusted to between 3 and 7, depending on the carbohydrate source. Sterilization may be batchwise or continuous; the latter uses less energy and is usually faster. After sterilization, the temperature is adjusted as required. The surface of the sterile substrate in the pans is inoculated with A. niger spores, which germinate and cover the surface of the liquid with a mat of mold. After two to three days the surface is completely covered and citric acid production begins, continuing at almost a constant rate until 80-90% of the sugar is consumed. Fermentation then continues more slowly for an additional six to ten days. The theoretical yield from 100 kg of sucrose is 123 kg of citric acid monohydrate or 112 kg of anhydrous acid. However, the A. niger uses some sugar for growth and respiration, and the actual yield varies between 57 and 77% of theoretical, depending on such factors as substrate purity, the particular strain of organism, and the control of fermentation.
Verhoff FH; Citric Acid. Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2013). NY, NY: John Wiley & Sons. Online Posting Date: October 15, 2011
Submerged fermentation ... takes place in large fermentation tanks. This method is used more frequently because labor costs are lower with large tanks than with small pans; equipment costs are also lower. The fermentation vessel can be short and wide or tall and narrow, and equipped with mixing devices, such as top-entering or side-entering agitators of the turbine or propeller type. Agitation can be increased by use of a draft tube, a recirculation loop, or a nozzle through which air and recirculated substrate is pumped. Spargers located at the bottom of the vessel or under the stirrer supply air, which may be enriched with oxygen. Oxygen is usually recovered from the exhaust gas. The air is supplied by a compressor and passes through a sterile filter; if necessary, the air is cooled. Because the process is exothermic, the vessel must be equipped with heat-exchange surfaces, which can be the outside walls or internal coils. Ports are provided for introducing substrate, inoculum, and steam or other sterilizing agents; sampling and exhaust ports are also provided. The substrate is prepared in a separate tank and its pH adjusted; the micronutrients may be added to this tank or directly to the fermentor. The substrate is sterilized by a batchwise or, more commonly, by a continuous operation. The fermentor is sterilized, charged with substrate, and inoculated. Fermentation requires 3-14 days. After it is completed, the air supply is stopped to prevent the microorganisms from consuming the citric acid.
Verhoff FH; Citric Acid. Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2013). NY, NY: John Wiley & Sons. Online Posting Date: October 15, 2011
The microbial production of citric acid on a commercial scale was begun in 1923 utilizing certain strains of Aspergillus niger to produce citric acid on the surface of a sucrose and salt solution. This tray fermentation technique is still used today, although it is being replaced by a submerged process known as deep tank fermentation. In the deep tank submerged process, Aspergillus niger mold spores are grown under controlled aseptic conditions on a test-tube slant and transferred to a seed tank or inoculum which is added to a fermentor along with pasteurized syrup. The pH is adjusted and nutrients added. Sterile air is sparged into the fermentor while the sugar is converted to citric acid. The complete fermentation cycle can take as long as 15 days. ... Citric acid fermentation broth is generally separated from the biomass using filtration or centrifugation. The citric acid is usually purified using either a lime-sulfuric acid method or a liquid extraction process.
Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V6: 362 (1993)
Mold fermentation of beet or sugar cane molasses, or dextrose (corn sugar)
SRI
For more Methods of Manufacturing (Complete) data for CITRIC ACID (7 total), please visit the HSDB record page.

10.3 Formulations / Preparations

... Anticoagulant citrate dextrose solution, anticoagulant citrate phosphate dextrose solution, citric acid syrup, & effervescent salts.
Troy, D.B. (Ed); Remmington The Science and Practice of Pharmacy. 21 st Edition. Lippincott Williams & Williams, Philadelphia, PA 2005, p. 1085
Grades of purity: USP; reagent; monohydrate grade.
U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.
Grades: Both hydrous and anhydrous, technical, Chemically Pure, United States Pharmacopeia, Food Chemical Codex.
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 305
Citric acid for pharmaceutical use: not <99.5% anhydrous citric acid; not >5% water; not >0.05% ash; not >0.001% heavy metals; not > 0.0003% As. Hydrous citric acid may contain up to 8.8% water
Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. V6: 160 (1979)
For more Formulations/Preparations (Complete) data for CITRIC ACID (43 total), please visit the HSDB record page.

10.4 Consumption Patterns

In foods & beverages as an acidulant, pH regulator, flavor enhancer, preservative, & antioxidant synergist; 16% in pharmaceutical preparations principally in effervescent antacid powders & tablets; 11% in metal cleaning & finishing, & as a chemical intermediate for esters & salts for detergents & plasticizers. )
SRI Consulting, 2010 Directory of Chemical Producers. Menlo Park, CA. 2010

10.5 U.S. Production

Aggregated Product Volume

2019: 100,000,000 - <250,000,000 lb

2018: 250,000,000 - <500,000,000 lb

2017: 250,000,000 - <500,000,000 lb

2016: 250,000,000 - <500,000,000 lb

(1990) Worldwide citric acid production: Western Europe 41.0%; North America 28.0%; Far East, Australia, and New Zealand 11.0%; South and Central America 9.0%; Remainder of the world 11.0%. /From table/
Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V6 367 (1993)
... 1990 worldwide production estimated at approximately 550,000 metric tons.
Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V6 366 (1993)
(1991) 3.86X10+8 lb
SRI. 1992 Directory of Chemical Producers-United States of America. Menlo Park, CA: SRI International, 1992., p. 538
1,2,3-Propanetricarboxylic acid, 2-hydroxy- is listed as a High Production Volume (HPV) chemical (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).
EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program. 1,2,3-Propanetricarboxylic acid, 2-hydroxy- (77-92-9). Available from, as of August 22, 2013: https://www.epa.gov/hpv/pubs/general/opptsrch.htm
For more U.S. Production (Complete) data for CITRIC ACID (9 total), please visit the HSDB record page.

10.6 U.S. Imports

(1972) 1.46X10+8 GRAMS
SRI
(1975) 3.4X10+8 GRAMS
SRI
(1985) 1.96X10+10 g
BUREAU OF THE CENSUS. U.S. IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS 1985 p.1-577

10.7 U.S. Exports

(1972) 4.94X10+9 GRAMS
SRI
(1975) 4.2X10+9 GRAMS
SRI
(1985) 6.71X10+9 g
BUREAU OF THE CENSUS. U.S. EXPORTS, SCHEDULE E, 1985 p.2-78

10.8 General Manufacturing Information

Industry Processing Sectors
  • Other (requires additional information)
  • Pesticide, Fertilizer, and Other Agricultural Chemical Manufacturing
  • All Other Basic Inorganic Chemical Manufacturing
  • Paint and Coating Manufacturing
  • Agriculture, Forestry, Fishing and Hunting
  • Textiles, apparel, and leather manufacturing
  • Wholesale and Retail Trade
  • Food, beverage, and tobacco product manufacturing
  • Soap, Cleaning Compound, and Toilet Preparation Manufacturing
  • Plastics Material and Resin Manufacturing
  • Not Known or Reasonably Ascertainable
  • All Other Chemical Product and Preparation Manufacturing
  • Oil and Gas Drilling, Extraction, and Support activities
  • Primary Metal Manufacturing
  • Construction
  • Fabricated Metal Product Manufacturing
  • Utilities
  • Paper Manufacturing
EPA TSCA Commercial Activity Status
EPA registered the first citric acid-containing products in the early 1970's.
USEPA/Office of Prevention, Pesticides and Toxic Substance; Reregistration Eligibility Decision Document - Citric Acid p.3 (June 1992). Available from, as of August 30, 2013: https://www.epa.gov/pesticides/reregistration/status.htm
... Dilute aqueous solutions are subject to molding (fermentation), oxalic acid being one of the fermentation products.
Troy, D.B. (Ed); Remmington The Science and Practice of Pharmacy. 21 st Edition. Lippincott Williams & Williams, Philadelphia, PA 2005, p. 1085
To increase effectiveness of antioxidants in lard, shortening, & unsmoked dry sausage; at 0.01% alone or with antioxidants in lard or shortening; 0.001% in ... Sausage with 0.003% BHA.
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 823
The chemical synthesis of citric acid was reported in 1880. Since then, many different synthetic routes have been investigated, reported, and patented. However, none of these have proven to be commercially feasible.
Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V6 364 (1993)
For more General Manufacturing Information (Complete) data for CITRIC ACID (6 total), please visit the HSDB record page.

11 Identification

11.1 Analytic Laboratory Methods

Enzymic, GLC, and HPLC methods for determining sugars and organic acids in strawberries are compared.
REYES FG R ET AL; J ASSOC OFF ANAL CHEM 65 (1): 126 (1982)
Method: AOAC 986.13; Procedure: liquid chromatographic method; Analyte: citric acid; Matrix: cranberry juice cocktail and apple juice; Detection Limit: not provided.
Horwitz W, ed.; Official Methods of Analysis of AOAC International 17th ed. (2003). CD-ROM, AOAC International, Gaithersburg, MD
Method: AOAC 985.11; Procedure: enzymatic method; Analyte: citric acid; Matrix: wine; Detection Limit: not provided.
Horwitz W, ed.; Official Methods of Analysis of AOAC International 17th ed. (2003). CD-ROM, AOAC International, Gaithersburg, MD
Method: AOAC 976.15; Procedure: colorimetric method; Analyte: citric acid; Matrix: cheese; Detection Limit: not provided.
Horwitz W, ed.; Official Methods of Analysis of AOAC International 17th ed. (2003). CD-ROM, AOAC International, Gaithersburg, MD
For more Analytic Laboratory Methods (Complete) data for CITRIC ACID (10 total), please visit the HSDB record page.

12 Safety and Hazards

12.1 Hazards Identification

12.1.1 GHS Classification

1 of 4
View All
Note
Pictograms displayed are for 91.7% (3984 of 4343) of reports that indicate hazard statements. This chemical does not meet GHS hazard criteria for 8.3% (359 of 4343) of reports.
Pictogram(s)
Irritant
Signal
Warning
GHS Hazard Statements

H319 (84.6%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (21.7%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

Precautionary Statement Codes

P261, P264+P265, P271, P280, P304+P340, P305+P351+P338, P319, P337+P317, 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 4343 reports by companies from 51 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 359 of 4343 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 50 notifications provided by 3984 of 4343 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

Eye Irrit. 2 (84.6%)

STOT SE 3 (21.7%)

Eye irritation - category 2A

Skin irritation - category 2

Specific target organ toxicity (single exposure) - category 3

12.1.3 EPA Safer Chemical

Chemical: Citric acid, anhydrous

Green circle Green circle - The chemical has been verified to be of low concern based on experimental and modeled data.

12.1.4 Health Hazards

Inhalation of dust irritates nose and throat. Contact with eyes causes irritation. (USCG, 1999)
U.S. Coast Guard. 1999. Chemical Hazard Response Information System (CHRIS) - Hazardous Chemical Data. Commandant Instruction 16465.12C. Washington, D.C.: U.S. Government Printing Office.

12.1.5 Fire Hazards

Behavior in Fire: Melts and decomposes. The reaction is not hazardous. (USCG, 1999)
U.S. Coast Guard. 1999. Chemical Hazard Response Information System (CHRIS) - Hazardous Chemical Data. Commandant Instruction 16465.12C. Washington, D.C.: U.S. Government Printing Office.
Combustible. Finely dispersed particles form explosive mixtures in air.

12.1.6 Hazards Summary

An irritant to the throat and eyes; [CAMEO] Concentrated solutions can cause severe eye damage and blindness; Animals fed 1.2% citric acid for 90 weeks showed no adverse effects except erosion of tooth enamel. [CHEMINFO]

12.1.7 Fire Potential

Combustible liquid
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 955

12.1.8 Skin, Eye, and Respiratory Irritations

Skin irritation: not irritating.
IUCLID Dataset for Citric Acid (CAS RN 77-92-9). Available from, as of August 28, 2013: https://esis.jrc.ec.europa.eu/doc/IUCLID/data_sheets/77929.pdf
A severe eye and moderate skin irritant.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 955
Inhalation of dust irritates nose and throat. Contact with eyes causes irritation.
U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.

12.2 Safety and Hazard Properties

12.2.1 Flammable Limits

0.28-2.29 KG/CU M (DUST)
U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.

12.2.2 Lower Explosive Limit (LEL)

0.28 kg/m3 (dust) (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.2.3 Upper Explosive Limit (UEL)

2.29 kg/m3 (dust) (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.2.4 Physical Dangers

Dust explosion possible if in powder or granular form, mixed with air.

12.2.5 Explosive Limits and Potential

Dust explosion possible if in powder or granular form, mixed with air.
International Program on Chemical Safety/Commission of the European Union; International Chemical Safety Card on Citric Acid (March 26, 1998). Available from, as of September 13, 2013: https://www.inchem.org/pages/icsc.html
Explosive limits, vol% in air: 0.28-2.29
International Program on Chemical Safety/Commission of the European Union; International Chemical Safety Card on Citric Acid (March 26, 1998). Available from, as of September 13, 2013: https://www.inchem.org/pages/icsc.html
During vacuum evaporation of an aqueous mixture of unspecified mixed metal nitrates and citric acid, the amorphous solid exploded when nearly dry. This was attributed to oxidation of the organic residue by the nitrates present, possibly catalyzed by one of the oxides expected to be produced. /Metal nitrates/
Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 1672
Explosive limits , vol% in air: 0.28-2.29

12.3 First Aid Measures

Inhalation First Aid
Fresh air, rest. Refer for medical attention.
Skin First Aid
Rinse skin with plenty of water or shower. Refer for medical attention .
Eye First Aid
First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.
Ingestion First Aid
Rinse mouth. Refer for medical attention .

12.3.1 First Aid

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. If symptoms (such as redness or irritation) develop, immediately transport the victim to a hospital.

SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.

INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

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

12.4 Fire Fighting

Fire Extinguishing Agents: Water, foam, dry chemical, carbon dioxide (USCG, 1999)
U.S. Coast Guard. 1999. Chemical Hazard Response Information System (CHRIS) - Hazardous Chemical Data. Commandant Instruction 16465.12C. Washington, D.C.: U.S. Government Printing Office.
Use water spray, powder, foam, carbon dioxide.

12.4.1 Fire Fighting Procedures

Extinguish with/ water, foam, dry chem, carbon dioxide.
U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.

12.5 Accidental Release Measures

12.5.1 Spillage Disposal

Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Wash away remainder with plenty of water.

12.5.2 Cleanup Methods

Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Wash away remainder with plenty of water.
International Program on Chemical Safety/Commission of the European Union; International Chemical Safety Card on Citric Acid (March 26, 1998). Available from, as of September 13, 2013: https://www.inchem.org/pages/icsc.html

12.5.3 Disposal Methods

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.
Inject at base of incinerator equipped with afterburner. Flammable solvent may be added.
Sax, N.I. Dangerous Properties of Industrial Materials Reports. New York: Van Nostrand Rheinhold, 1987., p. 9:4 (1989)

12.5.4 Preventive Measures

Do not eat, drink, or smoke during work.
International Program on Chemical Safety/Commission of the European Union; International Chemical Safety Card on Citric Acid (March 26, 1998). Available from, as of September 13, 2013: https://www.inchem.org/pages/icsc.html
Closed system, ventilation, explosion-proof electrical equipment and lighting. Prevent deposition of dust.
International Program on Chemical Safety/Commission of the European Union; International Chemical Safety Card on Citric Acid (March 26, 1998). Available from, as of September 13, 2013: https://www.inchem.org/pages/icsc.html
SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.
SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

12.6 Handling and Storage

12.6.1 Nonfire Spill Response

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

STORAGE PRECAUTIONS: You should store this chemical under refrigerated temperatures, and protect it from moisture. (NTP, 1992)

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

12.6.2 Safe Storage

Separated from strong oxidants, strong bases, metal nitrates and metals. Dry.

12.6.3 Storage Conditions

Crystalline citric acid, anhydrous, can be stored in dry form without difficulty, although conditions of high humidity and elevated temperatures should be avoided to prevent caking. Storage should be in tight containers to prevent exposure to moist air. Several granulations are commercially available with the larger particle sizes having less tendency toward caking.
Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V6 364 (1993)
Temperature: ambient; Venting: open.
U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.
Containers: 230 lb Barrels, bags, kegs, boxes, cartons, fiber drums, bottles.
Sax, N.I. Dangerous Properties of Industrial Materials Reports. New York: Van Nostrand Rheinhold, 1987., p. 9:4 (1989)
Separated from strong oxidants, strong bases, metal nitrates and metals. Dry.
International Program on Chemical Safety/Commission of the European Union; International Chemical Safety Card on Citric Acid (March 26, 1998). Available from, as of September 13, 2013: https://www.inchem.org/pages/icsc.html

12.7 Exposure Control and Personal Protection

Maximum Allowable Concentration (MAK)
2.0 [mg/m3], inhalable fraction[German Research Foundation (DFG)]

12.7.1 Occupational Exposure Limits (OEL)

MAK (Maximale Arbeitsplatz Konzentration)
(inhalable fraction): 2 mg/m

12.7.2 Inhalation Risk

Evaporation at 20 °C is negligible; a nuisance-causing concentration of airborne particles can, however, be reached quickly when dispersed.

12.7.3 Effects of Short Term Exposure

The substance is irritating to the eyes, skin and respiratory tract.

12.7.4 Effects of Long Term Exposure

The substance may have effects on the teeth. This may result in erosion.

12.7.5 Allowable Tolerances

Unless specifically excluded, residues resulting from the use of the following substance as either an inert or an active ingredient in a pesticide chemical formulation, including antimicrobial pesticide chemicals, is exempted from the requirement of a tolerance under FFDCA section 408, if such use is in accordance with good agricultural or manufacturing practices. Citric acid is included on this list.
40 CFR 180.950 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of August 21, 2013: https://www.ecfr.gov/cgi-bin/ECFR?page=browse

12.7.6 Personal Protective Equipment (PPE)

Dust mask; goggles or face shield; protective gloves (USCG, 1999)
U.S. Coast Guard. 1999. Chemical Hazard Response Information System (CHRIS) - Hazardous Chemical Data. Commandant Instruction 16465.12C. Washington, D.C.: U.S. Government Printing Office.
Use ventilation (not if powder).
International Program on Chemical Safety/Commission of the European Union; International Chemical Safety Card on Citric Acid (March 26, 1998). Available from, as of September 13, 2013: https://www.inchem.org/pages/icsc.html
Dust mask; goggles or face shield; protective gloves
U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.

12.7.7 Preventions

Fire Prevention
NO open flames. Closed system, dust explosion-proof electrical equipment and lighting. Prevent deposition of dust.
Exposure Prevention
PREVENT DISPERSION OF DUST!
Inhalation Prevention
Use ventilation (not if powder).
Skin Prevention
Protective gloves.
Eye Prevention
Wear safety goggles.
Ingestion Prevention
Do not eat, drink, or smoke during work.

12.8 Stability and Reactivity

12.8.1 Air and Water Reactions

The pure material is moisture sensitive (undergoes slow hydrolysis) Water soluble.

12.8.2 Reactive Group

Acids, Carboxylic

Alcohols and Polyols

12.8.3 Reactivity Profile

CITRIC ACID reacts with oxidizing agents, bases, reducing agents and metal nitrates (NTP, 1992). Reactions with metal nitrates are potentially explosive. Heating to the point of decomposition causes emission of acrid smoke and fumes [Lewis].
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.8.4 Hazardous Reactivities and Incompatibilities

Potentially explosive reaction with metal nitrates.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 955
Reacts with oxidants and bases. Attacks metals.
International Program on Chemical Safety/Commission of the European Union; International Chemical Safety Card on Citric Acid (March 26, 1998). Available from, as of September 13, 2013: https://www.inchem.org/pages/icsc.html

12.9 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: 1,2,3-Propanetricarboxylic acid, 2-hydroxy-
REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
Citric acid: Does not have an individual approval but may be used under an appropriate group standard

12.9.1 FIFRA Requirements

Unless specifically excluded, residues resulting from the use of the following substance as either an inert or an active ingredient in a pesticide chemical formulation, including antimicrobial pesticide chemicals, is exempted from the requirement of a tolerance under FFDCA section 408, if such use is in accordance with good agricultural or manufacturing practices. Citric acid is included on this list.
40 CFR 180.950 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of August 21, 2013: https://www.ecfr.gov/cgi-bin/ECFR?page=browse
Section 4(g)(2)(A) of FIFRA requires the Agency to determine, after consideration of relevant data concerning an active ingredient whether products containing the active ingredient are eligible for reregistration. For products containing citric acid as an active ingredient the Agency has waived all generic data requirements except for those basic product identity and chemistry. These data were submitted and reviewed. In addition to these data, the Agency has considered the factors ... regarding citric acid's natural occurrence, common use as a food item, and the lack of reported adverse effects information. The Agency has completed its consideration of these data and other factors and has determined this information is sufficient to support reregistration of products containing citric acid as an active ingredient.
USEPA/Office of Prevention, Pesticides and Toxic Substance; Reregistration Eligibility Decision Document - Citric Acid p.6 (June 1992). Available from, as of August 30, 2013: https://www.epa.gov/pesticides/reregistration/status.htm
As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer saftey standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. Citric acid is found on List D. Case No: 021801; Pesticide type: fungicide/ antimicobial; Case Status: RED Approved 08/92 - OPP has made a decision that some/all uses of the pesticide are eligible for reregistration, as reflected in a Reregistration Eligibility Decision (RED) Document.; Active ingredient (AI): Citric acid; AI Status: RED Completed - OPP has completed a Reregistration Eligibility Decision (RED) document for the case/AI.
United States Environmental Protection Agency/ Prevention, Pesticides and Toxic Substances; Status of Pesticides in Registration, Reregistration, and Special Review. (1998) EPA 738-R-98-002, p. 302

12.9.2 FDA Requirements

Substance added directly to human food affirmed as generally recognized as safe (GRAS).
21 CFR 184.1033 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of August 22, 2013: https://www.ecfr.gov
Citric acid used as a general purpose food additive in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice.
21 CFR 582.1033 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of August 22, 2013: https://www.ecfr.gov
Citric acid used as a sequestrant in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice.
21 CFR 582.6033 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of August 22, 2013: https://www.ecfr.gov
Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: citric acid is included in weight control drug products.
21 CFR 310.545(a) (20) (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of August 22, 2013: https://www.ecfr.gov

12.10 Other Safety Information

Chemical Assessment

IMAP assessments - Citric acid: Human health tier II assessment

IMAP assessments - 1,2,3-Propanetricarboxylic acid, 2-hydroxy-: Environment tier I assessment

12.10.1 Special Reports

Leung HW, Paustenbach DJ; Organic Acids and Bases: Review of Toxicological Studies; Am J Ind Med 18 (6): 717-35 (1990).
USEPA/Office of Prevention, Pesticides and Toxic Substance; Reregistration Eligibility Decision Document - Citric Acid (June 1992). The RED summarizes the risk assessment conclusions and outlines any risk reduction measures necessary for the pesticide to continue to be registered in the U.S.[Available from, as of August 30, 2013: http://www.epa.gov/pesticides/reregistration/status.htm]

13 Toxicity

13.1 Toxicological Information

13.1.1 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

No data are available on cellulose and citric acid use during breastfeeding. However, the drug is not absorbed from the gastrointestinal tract, so it cannot enter the breastmilk. Cellulose and citric acid is acceptable to use during breastfeeding.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

13.1.2 Exposure Routes

The substance can be absorbed into the body by inhalation and by ingestion.

13.1.3 Symptoms

Inhalation Exposure
Cough. Shortness of breath. Sore throat.
Skin Exposure
Redness.
Eye Exposure
Redness. Pain.
Ingestion Exposure
Abdominal pain. Sore throat.

13.1.4 Adverse Effects

Dermatotoxin - Skin burns.

13.1.5 Acute Effects

13.1.6 Interactions

... Citric acid aerosol inhalation caused decreases in dynamic respiratory compliance and forced expiratory volume in 0.1 s (FEV0.1). This airway constriction was significantly attenuated by MK-886, mepyramine, cromolyn sodium, and compound 48/80, but not by either methysergide or indomethacin. Both LTC4 and histamine infusion significantly increased the magnitude of citric acid-induced airway constriction in compound 48/80-pretreated guinea pigs. Citric acid inhalation caused significant increase in histamine level in the bronchoalveolar lavage sample, which was significantly suppressed by compound 48/80.
Lin CH, Lai YL; Toxicol Appl Pharmacol 206 (3): 343-50 (2005)
The relative efficacy of citric, malic, malonic, oxalic and succinic acids, and deferoxamine mesylate on the toxicity, distribution and excretion in mice exposed to aluminum were compared. Chelating agents were administered ip at a dose equal to one-fourth of their respective LD50. To determine the effect of the various chelators on the toxicity of aluminum, various doses of aluminum nitrate (938-3188 mg/kg) were administered ip, followed by one of the chelators. Survival was recorded at the end of 14 days. ... Malic acid and deferoxamine mesylate were the most effective in increasing the urinary excretion of aluminum. Citric acid was the most effective in increasing the fecal excretion of aluminum. Malonic, oxalic and succinic acids had no overall beneficial effects. Citric acid would appear to be the most effective agent of those tested in the prevention of acute aluminium intoxication.
Domingo JL et al; Hum Toxicol 7 (3): 259-62 (1988)
... When aluminum hydroxide and citric acid (133 mg Al/kg and 62 mg/kg, respectively) were simultaneously given orally to mice, fetal skeletal development defects resulted.
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 2:373
The primary purpose of this study was to determine the relative usefulness of various measures to monitor body aluminum burden in weanling rats fed various amounts of aluminum (0.39 umol aluminum/g diet for 29 days, approximately 40 umol aluminum/g diet with or without citrate for 29 days and approximately 100 umol aluminum/g diet with citrate for 12 or 29 days) or injected ip with graded doses of aluminum (0.01, 4.6, 11.8, 23.5 or 94 umol aluminum). Twenty four hours prior to sacrifice, all rats were injected ip with either desferrioxamine (75 mg) or buffer. All seven indices of aluminum exposure monitored (eg: tibia, liver, kidney and serum aluminum concn; changes in serum aluminum concn in response to desferrioxamine; urinary aluminum excretion with and without desferrioxamine treatment) were highly (p< 0.001) correlated to parenteral aluminum exposure. Ingestion of citrate had small but significant effects on aluminum retention. /Citrate/
Greger JL, Powers CF; Toxicol 76 (2): 119-32 (1992)
For more Interactions (Complete) data for CITRIC ACID (7 total), please visit the HSDB record page.

13.1.7 Antidote and Emergency Treatment

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Organic acids and related compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 176
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist respirations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . 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. Activated charcoal is not effective ... . Do not attempt to neutralize because of exothermic reaction. Cover skin burns with dry, sterile dressings after decontamination ... . /Organic acids and related compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 176-7
/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. Early intubation, at the first sign of upper airway obstruction, may be necessary. 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 (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Organic acids and related compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 177

13.1.8 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ While presumably aqueous solutions (2% in one case, not stated in the other) may produce pain or "sting", patch testing of 60 eczema patients with 2.5% citric acid in petrolatum did not produce any irritant or allergic reactions; thus, the reaction appears to reflect mainly the acid effect of the substance...
United Nations Environment Programme: OECD; Screening Information Data Sheets on Citric Acid (77-92-9) (January 2001). Available from, as of May 9, 2006: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html
/HUMAN EXPOSURE STUDIES/ Repeated exposure of up to 15 g/d of potassium and sodium citrate as medications did not cause any reported marked side effects, but minor gastrointestinal disturbances (diarrhea, indigestion, nausea, "burning") were experienced by 22 out of 81 patients taking potassium citrate in water and 7 out of 75 taking solid potassium citrate (doses not stated in both groups) for the treatment of renal calculi. /Potassium and Sodium Citrates/
United Nations Environment Programme: OECD; Screening Information Data Sheets on Citric Acid (77-92-9) (January 2001). Available from, as of May 9, 2006: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html
/SIGNS AND SYMPTOMS/ Injection of large volumes of citrated blood during transfusion may lead to hypocalcemia and changes in blood composition with concomitant nausea, muscle weakness, breathing difficulties and even cardiac arrest.
United Nations Environment Programme: OECD; Screening Information Data Sheets on Citric Acid (77-92-9) (January 2001). Available from, as of May 9, 2006: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html
/SIGNS AND SYMPTOMS/ ... Within a concentration range of 0.625-320.0 mg/ml, inhaled citric acid caused cough in all subjects. Geometric mean (range) cough threshold was 13 (2.5-160) in normal subjects, 14 (5-40) in patients with mild, and 32 (20-40) mg/mL in patients with moderate to severe asthma, 40 (20-80) in current smokers, and 119 (80-160) in occasional smokers.
Schmidt D et al; Eur J Med Res 2 (9): 384-8 (1997)
For more Human Toxicity Excerpts (Complete) data for CITRIC ACID (14 total), please visit the HSDB record page.

13.1.9 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ Coughing is reported for guinea pigs exposed for 30 minutes to atmospheric citric acid concentrations of 81 mg/cu m (aerosolised 6% solution). Coughing was also produced in guinea pigs exposed to 75 mg citric acid/mL as an aerosol for 3 minutes. ...Coughing was also caused by instillation of 1 mL of an approx. 5.2% solution to the lower trachea in lambs, but not by instillation to the mid-trachea or laryngeal area.
United Nations Environment Programme: OECD; Screening Information Data Sheets on Citric Acid (77-92-9) (January 2001). Available from, as of May 9, 2006: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html
/LABORATORY ANIMALS: Acute Exposure/ The application of a 50% citric acid solution to the tongue of dogs for 5 minutes resulted in severe ulceration and tissue damage.
United Nations Environment Programme: OECD; Screening Information Data Sheets on Citric Acid (77-92-9) (January 2001). Available from, as of May 9, 2006: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html
/LABORATORY ANIMALS: Acute Exposure/ ... Acute administration of citric-acid /to mice and rats by oral, subcutaneous, and intraperitoneal administration/ resulted in ataxia, other motor changes, and death caused by respiratory or cardiac failure. Median lethal dose values for citric-acid were similar to those for commercial citric-acid. ... Subacute administration resulted in normal behavior and no significant hematological changes. Increased protein was seen in the urine and a decrease was seen in plasma protein, albumin, and cholesterol. Histopathology revealed no specific deleterious effects of citric-acid on the organs and tissues studied.
Yokotani H et al; J Takeda Res Laboratories 30 (1): 25-31 (1971)
/LABORATORY ANIMALS: Acute Exposure/ ... Citric acid and malic acid caused 71% and 43% fall in Mean Arterial Blood Pressure (MABP) of rats at the doses of 15 mg/kg and 30 mg/kg respectively while pyridine hydrochloride produced 34% rise in the MABP of rats at the dose of 30 mg/kg. LD50 and LD100 of citric acid in mice have been determined as 545 mg/kg and 1000 mg/kg, respectively.
Saleem R et al; Arch Pharm Res 27 (10): 1037-42 (2004)
For more Non-Human Toxicity Excerpts (Complete) data for CITRIC ACID (19 total), please visit the HSDB record page.

13.1.10 Non-Human Toxicity Values

LD50 Rat oral 3000 mg/kg; 12000 mg/kg; 11700 mg/kg /observed in separate experiments/
IUCLID Dataset for Citric Acid (CAS RN 77-92-9). Available from, as of August 28, 2013: https://esis.jrc.ec.europa.eu/doc/IUCLID/data_sheets/77929.pdf
LD50 Rat oral 6730 mg/kg
Milne, G.W.A. Veterinary Drugs: Synonyms and Properties. Ashgate Publishing Limited, Aldershot, Hampshire, England 2002., p. 155
LD50 Mouse iv 42 mg/kg /From table/
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 5:751
LD50 Mouse oral 5040 mg/kg /From table/
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 5:751
For more Non-Human Toxicity Values (Complete) data for CITRIC ACID (10 total), please visit the HSDB record page.

13.2 Ecological Information

13.2.1 Ecotoxicity Values

LC50; Species: Carcinus maenas (Green or European shore crab); Conditions: renewal; Concentration: 160 mg/L for 48 hr /formulated product/
Portmann JE, Wilson KW; Shellfish Information Leaflet No.22 (2nd ed) Ministry of Agric Fish Food:12 (1971) Available from, as of April 20, 2006

13.2.2 Ecotoxicity Excerpts

/OTHER TERRESTRIAL SPECIES/ The entomopathogenic fungus, Beauveria bassiana, produced citric acids in liquid cultures containing grasshopper (Melanoplus sanguinipes) cuticle as the sole nutrient source. Citric acids solubilized cuticular proteins as well as commercial preparations of elastin and collagen. Melanoplus sanguinipes treated with Beauveria bassiana showed a LT50 of 7.33 days, while Melanoplus sanguinipes treated with citric acid showed a LT50 of 7.25 and 13.28 days, respectively. Melanoplus sanguinipes treated with citric acid followed by a Beauveria bassiana conidia treatment showed a LT50 of 3.88 days. Analysis of the bioassay data revealed that the relationship between citric acid together with Beauveria bassiana conidia in grasshopper mortality was markedly synergistic. It is suggested that acid metabolites produced by Beauveria bassiana may play a role in cuticle solubilization and subsequent hyphal penetration.
Bidochka MJ, Khachatourians GG; J Invertebr Pathol 58 (1): 106-17 (1991)

13.2.3 Environmental Fate / Exposure Summary

Citric acid's production and use as an acidulant in beverages, confectionery, effervescent salts, in pharmaceutical syrups, elixirs; in processing cheese, in chemical manufacture, a foam inhibitor, a sequestering agent, a mordant, in electroplating, in special inks, an anticoagulant, and in water-conditioning agent and detergent builder may result in its release to the environment through various waste streams. Citric acid is widely distributed in plants and in animal tissues and fluids. If released to air, a vapor pressure of 1.66X10-8 mm Hg at 25 °C indicates citric acid will exist solely in the particulate phase in the atmosphere. Particulate-phase citric acid will be removed from the atmosphere by wet and dry deposition. Citric acid absorbs light at wavelengths up to 260 nm and, therefore, is not expected to be susceptible to direct photolysis since sunlight consists of wavelengths above 290 nm. If released to soil, citric acid is expected to have very high mobility based upon an estimated Koc of 10. The pKa of citric acid is 2.79, indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Citric acid is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Citric acid reached 53% of its theoretical BOD in 5 days using a sludge inoculum, suggesting that biodegradation may be an important environmental fate process in soil. If released into water, citric acid is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Theoretical biodegradation values of 66.4% and 67.3% after 5 days using freshwater and seawater inoculums, respectively, indicate that biodegradation is an important environmental fate process in water. The pKa indicates citric acid will exist almost entirely 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 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 (pH 5 to 9). Occupational exposure to citric acid may occur through dermal contact with this compound at workplaces where citric acid is produced or used. Monitoring data indicate that the general population may be exposed to citric acid via ingestion of food and dermal contact with consumer products containing citric acid. (SRC)

13.2.4 Natural Pollution Sources

Citric acid is widely distributed in plants and in animal tissues and fluids(1). It is extremely widespread in plants and has been identified in flowers of Hibiscus subdariffa(3).
(1) O'Neil MJ, ed; The Merck Index. 15th ed. Cambridge, UK: The Royal Society of Chemistry. p. 416 (2013)
(2) USDA; Dr. Duke's Phytochemical and Ethnobotanical Databases. Plants with a chosen chemical. Citric Acid. Washington, DC: US Dept Agric, Agric Res Service. Available from, as of Sept 5, 2013: https://www.ars-grin.gov/duke/
(3) Furia TE, Bellanca N, eds; Fenaroli's Handbook of Flavor Ingredients. Volume 2. 2nd ed. Cleveland, OH: The Chemical Rubber Co. p. 78 (1975)
In nature, the citric acid cycle (Krebs cycle, TCA cycle, tricarboxylic acid cycle) is a series of enzymatic reactions occurring in living cells of aerobic organisms, the net result of which is the conversion of pyruvic acid, formed by anaerobic metabolism of carbohydrates, into carbon dioxide and water. The metabolic intermediates are degraded by a combination of decarboxylation and dehydrogenation. It is the major terminal pathway of oxidation in animal, bacterial, and plant cells. Recent research indicates that the TCA cycle may have predated life on earth and may have provided the pathway for formation of amino acids(1).
(1) Lewis RJ Sr; Hawley's Condensed Chemical Dictionary. 15th ed. New York, NY: John Wiley & Sons, Inc. p. 305 (2007)

13.2.5 Artificial Pollution Sources

Citric acid's production and use as an acidulant in beverages, confectionery, effervescent salts, in pharmaceutical syrups, elixirs, to adjust the pH of foods and as synergistic antioxidant, in processing cheese, in chemical manufacture, a foam inhibitor, a sequestering agent, a mordant, in electroplating, in special inks, an anticoagulant, and in water-conditioning agents and detergent builders(1,2) may result in its release to the environment through various waste streams(SRC).
(1) O'Neil MJ, ed; The Merck Index. 15th ed. Cambridge, UK: The Royal Society of Chemistry. p. 416 (2013)
(2) Lewis RJ Sr; Hawley's Condensed Chemical Dictionary. 15th ed. New York, NY: John Wiley & Sons, Inc. p. 305 (2007)

13.2.6 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that citric acid is expected to have very high mobility in soil(SRC). The pKa of citric acid is 2.79(3), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Citric acid is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 1.66X10-8 mm Hg at 25 °C(5). Citric acid reached 53% of its theoretical BOD in 5 days using a sludge inoculum(6), suggesting that biodegradation may be an important environmental fate process in soil(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Sept 6, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Serjeant EP, Dempsey B; Ionisation constants of organic acids in aqueous solution. IUPAC Chem Data Ser No.23. New York, NY: Pergamon pp. 989 (1979)
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(5) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Supplement 1. New York, NY: Hemisphere Pub Corp (1991)
(6) Heukelekian H, Rand MC; J Water Pollut Contr Assoc 27: 1040-53 (1955)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that citric acid is not expected to adsorb to suspended solids and sediment(SRC). A pKa of 2.79(3) indicates citric acid will exist almost entirely 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(SRC). According to a classification scheme(4), an estimated BCF of 3(SRC), from its log Kow of -1.64(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Theoretical biodegradation values of 66.4% and 67.3% after 5 days using freshwater and seawater inoculums, respectively(6), indicate that biodegradation is an important environmental fate process in water(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Sept 6, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Serjeant EP, Dempsey B; Ionisation constants of organic acids in aqueous solution. IUPAC Chem Data Ser No.23. New York, NY: Pergamon pp. 989 (1979)
(4) Franke C et al; Chemosphere 29: 1501-14 (1994)
(5) Avdeef A; Seminar on Ionization and Lipophilicity. Log P values measured by pION Inc., Brookline, MA (A. Avdeef and C. Berger) (1997)
(6) Takemoto S et al; Suishitsu Odaku Kenkyu 4: 80-90 (1981)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), citric acid, which has an estimated vapor pressure of 1.7X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase. Particulate-phase citric acid may be removed from the air by wet and dry deposition(SRC). Citric acid absorbs light at wavelengths up to 260 nm(3) and, therefore, is not expected to be susceptible to direct photolysis since sunlight consists of wavelengths above 290 nm(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Sept 6, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) NIST; NIST Chemistry WebBook. Citric acid (77-92-9). NIST Standard Reference Database No. 69, June 2005 Release. Washington, DC: US Sec Commerce. Available from, as of Sept 6, 2013: https://webbook.nist.gov

13.2.7 Environmental Biodegradation

AEROBIC: The biodegradability of citric acid was determined in six different tests and results found it to be well degraded in all tests(1). Citric acid achieved 93% DOC removal in a coupled units test (sludge inoculum), 85% DOC removal after 1 day in a Zahn-Wellens test (sludge inoculum), 100% DOC removal in an AFNOR test (42 days, germs inoculum simulating polluted river water), 100% DOC removal in a Sturm test (42 days, sewage treatment plant effluent), 100% DOC removal in an OECD screening test (19 days, effluent simulating surface water), and 90% BODT in a closed bottle test (30 days, effluent simulating surface water)(1). Citric acid reached 53% of its theoretical BOD in 5 days using a sludge inoculum(2). Citric acid, present at 500 mg/L, reached 46% of its theoretical oxygen demand in 12 hours using a phenol acclimated activated sludge inoculum(3).Citric acid, present at 500 mg/L, reached 98.4% of its theoretical BOD in 22 to 24 hours using an activated sludge inoculum at 2,228 mg/L(4). Citric acid (1% w/v) displayed BOD values of 6,410 and 6,040 mg/L using a defined microbial mixture and sewage inoculums, respectively(5). Citric acid, present at 10 mg/L, reached 66.4% and 67.3% of its theoretical BOD after 5 days using freshwater and seawater inoculums, respectively(6).
(1) Gerike P, Fischer WK; Ecotox Environ Safety 3: 159-73 (1979)
(2) Heukelekian H, Rand MC; J Water Pollut Contr Assoc 27: 1040-53 (1955)
(3) McKinney RE et al; Sew Indust Wastes 28: 547-57 (1956)
(4) Placak OR, Ruchhoft CC; Sewage Works J 19: 423-40 (1947)
(5) Sharma A et al; Bull Environ Contam Toxicol 57: 34-40 (1996)
(6) Takemoto S et al; Suishitsu Odaku Kenkyu 4: 80-90 (1981)
ANAEROBIC: Citric acid, present at 800 mg/L, exhibited a degradation rate of 77.2 (12.7 mg/g-VSS/day with a lag phase of 3 days in 39 days under sulfate reducing conditions, indicating that the compound is biodegradable under anaerobic conditions (1).
(1) Hollingsworth J et al; Chemosphere 59: 1219-1228 (2005)]
PURE CULTURE: In NASA wastewater inoculated with batch microbial cultures, citric acid (5 mg/mL) was degraded more than 50% after 15 days by Achromobacter sp.(1).
(1) Nwankwoala AU et al; Biodegradation 10: 105-12 (1999)

13.2.8 Environmental Abiotic Degradation

A citric acid aqueous solution (pH 1), with a hydroxy radical concentration of 1X10-17 mol/L, had a reaction rate constant of 3.0X10+7 L/mol-sec at room temperature(1). This corresponds to a calculated half-life of 73 years(1). Citric acid is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Citric acid absorbs light at wavelengths up to 260 nm(3) and, therefore, is not expected to be susceptible to direct photolysis since sunlight consists of wavelengths above 290 nm(SRC).
(1) Anbar M, Neta P; Int J of Appl Radiation and Isotopes 18:493-523 (1967)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5 (1990)
(3) NIST; NIST Chemistry WebBook. Citric acid (77-92-9). NIST Standard Reference Database No. 69, June 2005 Release. Washington, DC: US Sec Commerce. Available from, as of Sept 6, 2013: https://webbook.nist.gov

13.2.9 Environmental Bioconcentration

An estimated BCF of 3 was calculated for citric acid(SRC), using a log Kow of -1.64(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) Avdeef A; Seminar on Ionization and Lipophilicity. Log P values measured by pION Inc., Brookline, MA (A. Avdeef and C. Berger) (1997)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Sept 6, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm/
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

13.2.10 Soil Adsorption / Mobility

Using a structure estimation method based on molecular connectivity indices(1), the Koc of citric acid can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that citric acid is expected to have very high mobility in soil. The pKa of citric acid is 2.79(3), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). A 2 uM solution of citric acid in Gulfstream seawater showed equilibrium absorption values of 79% and 94% onto 0.01 and 0.25 g of hydroxyapatite, respectively(5).
(1) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Sept 6, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(2) Swann RL et al; Res Rev 85: 17-28 (1983)
(3) Serjeant EP, Dempsey B; Ionisation constants of organic acids in aqueous solution. IUPAC Chem Data Ser No.23. New York, NY: Pergamon pp. 989 (1979)
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(5) Gordon AS, Millero FJ; Microb Ecol 11: 289-98 (1985)

13.2.11 Volatilization from Water / Soil

A pKa of 2.79(1) indicates citric acid will exist almost entirely 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(SRC). Citric acid is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure of 1.66X10-8 mm Hg at 25 °C(2).
(1) Serjeant EP, Dempsey B; Ionisation constants of organic acids in aqueous solution. IUPAC Chem Data Ser No.23. New York, NY: Pergamon pp. 989 (1979)
(2) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Supplement 1. New York, NY: Hemisphere Pub Corp (1991)

13.2.12 Food Survey Values

Plants containing citric acid, concentrations reported(1).

Table: Reported Concentrations

Species
Hibiscus sabdariffa
Common name(s)
Indian Sorrel, Jamaica Sorrel
Part
fruit
Concn (ppm)
170,000
Species
Citrus mitis
Common name(s)
Calamansi
Part
fruit; fruit juice
Concn (ppm)
28,100-281,000; 36,00-55,200
Species
Ananas comosus
Common name(s)
Pineapple
Part
fruit
Concn (ppm)
86,000
Species
Euphorbia tirucalli
Common name(s)
Aveloz
Part
plant
Concn (ppm)
74,000
Species
Citrus limon
Common name(s)
Lemon
Part
fruit
Concn (ppm)
59,500
Species
Solanum nigrum
Common name(s)
Black Nightshade
Part
leaf
Concn (ppm)
50,000
Species
Solanum sessilflorum
Common name(s)
Cocona
Part
fruit
Concn (ppm)
8,000-80,000
Species
Ribes nigrum
Common name(s)
Black Currant
Part
fruit
Concn (ppm)
35,000
Species
Passiflora edulis
Common name(s)
Maracuya, Passionfruit
Part
fruit
Concn (ppm)
20,000-45,600
Species
Physalis peruviana
Common name(s)
Cape Gooseberry, Ground Cherry
Part
fruit
Concn (ppm)
22,000
Species
Citrus paradisi
Common name(s)
Grapefruit
Part
fruit
Concn (ppm)
21,000
Species
Ribes rubrum
Common name(s)
Red Currant, White Currant
Part
fruit
Concn (ppm)
20,200
Species
Rosa canina
Common name(s)
Dog Rose, Dogbrier, Rose
Part
fruit
Concn (ppm)
15,000
Species
Garcinia mangostana
Common name(s)
Mangosteen
Part
fruit
Concn (ppm)
4,300-27,815
Species
Glycine max
Common name(s)
Soybean
Part
seed
Concn (ppm)
13,000
Species
Punica granatum
Common name(s)
Pomegranate
Part
fruit juice
Concn (ppm)
12,300
Species
Citrus reticulata
Common name(s)
Manderin, Tangerine
Part
fruit
Concn (ppm)
12,200
Species
Zizyphus jujuba
Common name(s)
Ta-Tsao
Part
fruit
Concn (ppm)
12,000
Species
Physalis ixocarpa
Common name(s)
Tomatillo
Part
fruit
Concn (ppm)
11,960
Species
Citrus sinensis
Common name(s)
Orange
Part
fruit
Concn (ppm)
9,800
Species
Ribes uva-crispa
Common name(s)
Goosberry
Part
fruit
Concn (ppm)
8,800
Species
Fagopyrum esculentum
Common name(s)
Buckwheat
Part
leaf
Concn (ppm)
8,200
Species
Fragaris spp
Common name(s)
Strawberry
Part
fruit
Concn (ppm)
8,000
Species
Theobroma cacao
Common name(s)
Cacao
Part
seed
Concn (ppm)
7,500
Species
Averrhoa carambola
Common name(s)
Star Fruit
Part
fruit
Concn (ppm)
0-13,200
Species
Portulaca oleracea
Common name(s)
Purslane, Verdolaga
Part
plant
Concn (ppm)
5,100
Species
Opuntia ficus-indica
Common name(s)
Indian Fig, Prickly Pear
Part
fruit
Concn (ppm)
4,560
Species
Ficus carica
Common name(s)
Fig
Part
fruit
Concn (ppm)
4,400
Species
Mammea americana
Common name(s)
Mamey
Part
fruit
Concn (ppm)
0-6,000
Species
Panax quinquefolius
Common name(s)
Ginseng
Part
plant
Concn (ppm)
3,000
Species
Solanum tuberosum
Common name(s)
Potato
Part
tuber
Concn (ppm)
2,000
Species
Helianthus annuus
Common name(s)
Sunflower
Part
seed
Concn (ppm)
1,900
Species
Citrus aurantiifolia
Common name(s)
Lime
Part
fruit
Concn (ppm)
800
Species
Datura stramonium
Common name(s)
Jimsonweed
Part
plant
Concn (ppm)
750
Species
Lactuca sativa
Common name(s)
Lettuce
Part
leaf
Concn (ppm)
500

(1) USDA; Dr. Duke's Phytochemical and Ethnobotanical Databases. Plants with a chosen chemical. Citric Acid. Washington, DC: US Dept Agric, Agric Res Service. Available from, as of Sept 5, 2013: https://www.ars-grin.gov/duke/

Plants containing citric acid, concentrations not reported(1).

Table: Detected, Not Quantified

Species
Aconitum nappellus
Common name(s)
Bear's-Foot, Blue Rocket, Monkshood
Part
plant
Species
Adonis vernalis
Common name(s)
Spring Adonis
Part
plant
Species
Aesculus hipposactanum
Common name(s)
Horse CHestnut
Part
bark
Species
Allium cepa
Common name(s)
Onion, Shallot
Part
bulb
Species
Allium schoenoprasum
Common name(s)
Chives
Part
leaf
Species
Alocasia macrorrhiza
Common name(s)
Giant Taro
Part
plant
Species
Anabasis aphylla
Common name(s)
Anabasis
Part
plant
Species
Annona muricata
Common name(s)
Soursop
Part
plant
Species
Annona squamosa
Common name(s)
Sugar-apple, Sweetsop
Part
plant
Species
Apium graveolens
Common name(s)
Celery
Part
pt
Species
Arctostaphylos uva-ursi
Common name(s)
Bearberry
Part
leaf
Species
Avena sativa
Common name(s)
Oats
Part
petiole
Species
Berberis vulgaris
Common name(s)
Barberry
Part
plant
Species
Beta vulgaris
Common name(s)
Sugar Beet
Part
root
Species
Brassica oleracea var botrytis
Common name(s)
Cauliflower
Part
flower; plant
Species
Brassica oleracea var capitata
Common name(s)
Cabbage
Part
leaf
Species
Brassica oleracea var gemmifera
Common name(s)
Brussel-Sprouts
Part
leaf
Species
Brassica oleracea var gongylodes
Common name(s)
Kohlrabi
Part
stem
Species
Brassica oleracea var sabellica
Common name(s)
Curly Kale
Part
leaf
Species
Capparis spinosa
Common name(s)
Caper
Part
plant
Species
Capsella bursa-pastoris
Common name(s)
Shepards Purse
Part
plant
Species
Capsicum annum
Common name(s)
Bell Pepper
Part
fruit
Species
Capsicum frutescens
Common name(s)
Cayenne
Part
fruit
Species
Carica papaya
Common name(s)
Papaya
Part
fruit
Species
Catalpa ovata
Common name(s)
Kissage
Part
fruit
Species
Cephaelis ipecacuanha
Common name(s)
Ipecac, Raicilla
Part
plant
Species
Chaenomeles lagenaria
Common name(s)
Chinese Quince
Part
fruit
Species
Chelidonium majus
Common name(s)
Celandine
Part
plant
Species
Citrus aurantium
Common name(s)
Bitter Orange
Part
fruit; plant
Species
Cocos nucifera
Common name(s)
Coconut
Part
seed
Species
Coffea arabica
Common name(s)
Coffee
Part
seed
Species
Convallaria majalis
Common name(s)
Lily-Of-The-Valley
Part
plant
Species
Crataegus laevigata
Common name(s)
English Hawthorn
Part
fruit
Species
Cryptostegia grandifolia
Common name(s)
Rubber Vine
Part
latex exudate
Species
Cucumis melo
Common name(s)
Canteloupe
Part
leaf
Species
Daucus carota
Common name(s)
Carrot
Part
root
Species
Digitalis purpurea
Common name(s)
Purple Foxglove
Part
leaf
Species
Eriobotrya japonica
Common name(s)
Loquat
Part
leaf
Species
Euonymus atropurpureus
Common name(s)
Burning Bush, Wahoo
Part
plant
Species
Filipendula ulmaria
Common name(s)
Meadowsweet, Queen of the Meadow
Part
flower
Species
Foeniculum vulgare
Common name(s)
Fennel
Part
fruit
Species
Galium odoratum
Common name(s)
Waldmeister, Woodruff
Part
plant
Species
Ginkgo biloba
Common name(s)
Ginkgo
Part
seed
Species
Hippophae rhamnoides
Common name(s)
Sallow Thorn
Part
fruit
Species
Juglans regia
Common name(s)
English Walnut
Part
fruit
Species
Kalanchoe pinnata
Common name(s)
Air Plant
Part
leaf
Species
Lactuca scariola
Common name(s)
Prickly Lettuce
Part
latex exudate
Species
Lactuca virosa
Common name(s)
Bitter Lettuce
Part
plant
Species
Ledum palustre
Common name(s)
Marsh Tea, Wild Rosemary
Part
plant
Species
Leonurus cardiaca
Common name(s)
Motherwort
Part
plant
Species
Lupinus alba
Common name(s)
White Lupine
Part
seed
Species
Lycopersicon esculentum
Common name(s)
Tomato
Part
fruit
Species
Malus domestica
Common name(s)
Apple
Part
plant
Species
Mangifera indica
Common name(s)
Mango
Part
fruit
Species
Medicago sativa
Common name(s)
Alfalfa, Lucerne
Part
plant
Species
Morus alba
Common name(s)
White Mulberry
Part
plant
Species
Musa x paradisiaca
Common name(s)
Banana
Part
fruit
Species
Myrtus communis
Common name(s)
Myrtle
Part
fruit
Species
Nicotiana tabacum
Common name(s)
Tobacco
Part
leaf
Species
Panax ginseng
Common name(s)
Ginseng
Part
root
Species
Papaver somniferum
Common name(s)
Opium Poppy
Part
latex exudate
Species
Pairs quandrifolia
Common name(s)
Herb Paris
Part
plant
Species
Piscidia piscipula
Common name(s)
Jamaica Dogwood
Part
plant
Species
Pisum sativum
Common name(s)
Pea
Part
seed
Species
Plantago major
Common name(s)
Common Plantain
Part
plant
Species
Polypodium vulgare
Common name(s)
Common Polypody, Sweet Fern
Part
root
Species
Prunus armeniaca
Common name(s)
Apricot
Part
fruit
Species
Prunus cerasus
Common name(s)
Sour Cherry
Part
fruit
Species
Prunus domestica
Common name(s)
Plum
Part
fruit
Species
Prunus persica
Common name(s)
Peach
Part
fruit
Species
Psidium guajava
Common name(s)
Guava
Part
fruit
Species
Pyrus communis
Common name(s)
Pear
Part
fruit
Species
Quisqualis indica
Common name(s)
Rangoon Creeper
Part
fruit
Species
Rheum rhabarbarum
Common name(s)
Rhubarb
Part
pt
Species
Rhododendron ferrugineum
Common name(s)
Rusty-Leaved Alpenrose
Part
leaf
Species
Rosa Laevigata
Common name(s)
Cherokee Rose
Part
fruit
Species
Rosa spp
Common name(s)
Rose Hips
Part
fruit
Species
Rubus chiingii
Common name(s)
Chinese Raspberry
Part
fruit
Species
Schisandra chinensis
Common name(s)
Chinese Magnolia Vine
Part
plant
Species
Sclerocarya caffra
Common name(s)
Marula
Part
fruit
Species
Sophora pachycarpa
Common name(s)
Siberian Pachycarpa
Part
plant
Species
Sorbus aucubaria
Common name(s)
Rowan Berry
Part
fruit
Species
Tamarindus indica
Common name(s)
Indian Tamarind
Part
fruit
Species
Vaccinium myrtillus
Common name(s)
Billberry
Part
leaf
Species
Vacciniium vitis-idaea
Common name(s)
Cowberry, Lingonbery
Part
fruit
Species
Vanilla planifolia
Common name(s)
Vanilla
Part
fruit
Species
Viburnum opulus
Common name(s)
Crampbark, Snowballbush
Part
bark
Species
Vibernum prunifolium
Common name(s)
Black Haw
Part
root bark
Species
Vicia faba
Common name(s)
Broadbean, Faba Bean
Part
fruit
Species
Vitis vinifera
Common name(s)
European Grape, Grapevine
Part
fruit; leaf

(1) USDA; Dr. Duke's Phytochemical and Ethnobotanical Databases. Plants with a chosen chemical. Citric Acid. Washington, DC: US Dept Agric, Agric Res Service. Available from, as of Sept 5, 2013: https://www.ars-grin.gov/duke/
Citric acid was detected as a flavoring constituent of farine collected from St. Lucia in the Caribbean(1). Citric acid was detected in 6 edible mushroom species sampled in Portugal in 2003. Concentrations were reported as follows (mg/kg and in combination with ketoglutaric acid): Amanita caesarea 452.07; Boletus edulis 432.89-785.45; Gyroporus castaneus 1282.85; Lactarius deliciosus 92.97-6112-72; Suillus collintus 362.73-2903.02; and Xerocomus chrysenteron 377.97(2).
(1) Dougan J et al; J Sci Food Agric 34:874-84 (1983)
(2) Valentao P et al; J Agric Food Chem 53: 3626-3630 (2005)
MID, TO INCR EFFECTIVENESS OF ANTIOXIDANTS IN LARD, SHORTENING, & UNSMOKED DRY SAUSAGE; @ 0.01% ALONE OR WITH ANTIOXIDANTS IN LARD OR SHORTENING; 0.001% IN ... SAUSAGE WITH 0.003% BHA.
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 823

13.2.13 Other Environmental Concentrations

In a study to determine the characteristics of urban organic aerosols (PM2.5) from Nanjing, China, citric acid concentrations were reported as follows (ng/cu m): summer - daytime range: 2.50-5.69 and nighttime range: 0.00-6.09; winter - daytime range 1.36-4.06 and nighttime range 0.00-3.05. In the summer, foliage emissions were the most prevalent source of organic aerosols, contributing over 33% to total compound mass(1).
(1) Wang G, Kawamura K; Environ Sci Technol 39: 7430-7438 (2005)

13.2.14 Probable Routes of Human Exposure

NIOSH (NOES Survey 1981-1983) has statistically estimated that 1,691,218 workers (1,083,005 of these are female) are potentially exposed to citric acid in the US(1). NIOSH (NOES Survey 1981-1983) has statistically estimated that 130 workers (108 of these are female) are potentially exposed to citric acid powder in the US(1). Occupational exposure to citric acid may occur through dermal contact with this compound at workplaces where citric acid is produced or used(SRC). Monitoring data indicate that the general population may be exposed to citric acid via ingestion of food and dermal contact with consumer products containing citric acid(SRC).
(1) NIOSH; NOES. National Occupational Exposure Survey conducted from 1981-1983. Estimated numbers of employees potentially exposed to specific agents by 2-digit standard industrial classification (SIC). Available from, as of Sept 6, 2013: https://www.cdc.gov/noes/

13.2.15 Body Burden

Citric acid was found to be excreted by humans through urine at a rate of 3-17 mg/kg body weight/day and through sweat at 0.2 mg/100 mL(1).
(1) Verschueren K; Handbook of Environmental Data on Organic Chemicals, Vol 1-2, 4th ed. John Wiley and Sons; New York, NY (2001)

14 Associated Disorders and Diseases

Disease
Hyperoxalemia
References
PubMed: 15353324
Disease
Pancreatic cancer
References
Disease
Early preeclampsia
References
PubMed: 22494326
Disease
Pregnancy
References

PubMed: 3252730, 663967, 12833386, 2994907, 17704099, 12698507, 17061063, 16925883, 22420377, 18059417, 22494326, 23159745, 23313728, 23535240, 24704061

The Merck Manual, 17th ed. Mark H. Beers, MD, Robert Berkow, MD, eds. Whitehouse Station, NJ: Merck Research Labs, 1999.

Disease
Late-onset preeclampsia
References
PubMed: 23159745
Disease
2-Ketoglutarate dehydrogenase complex deficiency
References

PubMed: 1640293, 7075624, 8295396

MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)

Disease
Irritable bowel syndrome
References
Disease
Frontotemporal dementia
References
PubMed: 23857558
Disease
Lewy body disease
References
PubMed: 23857558
Disease
Paraquat poisoning
References
PubMed: 9625050
Disease
Lung Cancer
References
Disease
Rhabdomyolysis
References
PubMed: 12089184
Disease
Diabetes mellitus type 1
References

PubMed: 12067838, 22279428, 16452910

Lorena Ivona ŞTEFAN, Alina NICOLESCU, Simona POPA, Maria MOŢA, Eugenia KOVACS and Calin DELEANU. 1H-NMR URINE METABOLIC PROFILING IN TYPE 1 DIABETES MELLITUS. Rev. Roum. Chim., 2010, 55(11-12), 1033-1037

Disease
Argininosuccinic aciduria
References

PubMed: 5075233, 19551947, 12408190

MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)

Disease
Propionic acidemia
References

PubMed: 19809936, 19551947, 2226555, 28853722

MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)

Disease
Tyrosinemia I
References

PubMed: 19551947, 25443793, 12872835, 22455637

MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)

Physician's Guide to the Laboratory Diagnosis of Metabolic Diseases. 2nd ed. Berlin, Germany, Springer, 2003

Disease
Phenylketonuria
References

PubMed: 7333014, 2091926, 12101068, 17574536, 6790852, 466810, 2116554, 19551947, 25964343, 15168722, 4837567

MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)

Disease
Maple syrup urine disease
References

PubMed: 12101068, 10508118, 10472531, 19551947, 11978597, 10234605, 6422161, 23430924, 18088602

MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de)

Peritoneal dialysis in maple-syrup-urine disease: Studies on branched-chain amino and keto acids. Eur J Pediatr (1980) 134: 57. https://doi.org/10.1007/BF00442404

Disease
Eosinophilic esophagitis
References
Mordechai, Hien, and David S. Wishart
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
Primary hypomagnesemia
References
Disease
Amish lethal microcephaly
References
PubMed: 12376931
Disease
Deafness, Onychodystrophy, Osteodystrophy, Mental Retardation, and Seizures Syndrome
References
PubMed: 17994565

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 Nature Journal References

15.7 Chemical Co-Occurrences in Literature

15.8 Chemical-Gene Co-Occurrences in Literature

15.9 Chemical-Disease Co-Occurrences in Literature

16 Patents

16.1 Depositor-Supplied Patent Identifiers

16.2 WIPO PATENTSCOPE

16.3 FDA Orange Book Patents

16.4 Chemical Co-Occurrences in Patents

16.5 Chemical-Disease Co-Occurrences in Patents

16.6 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 Pathways

18 Biological Test Results

18.1 BioAssay Results

19 Taxonomy

WormJam Metabolites Local CSV for MetFrag | DOI:10.5281/zenodo.3403364
WormJam: A consensus C. elegans Metabolic Reconstruction and Metabolomics Community and Workshop Series, Worm, 6:2, e1373939, DOI:10.1080/21624054.2017.1373939
Zebrafish Pathway Metabolite MetFrag Local CSV (Beta) | DOI:10.5281/zenodo.3457553
The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

20 Classification

20.1 MeSH Tree

20.2 NCI Thesaurus Tree

20.3 ChEBI Ontology

20.4 KEGG: Metabolite

20.5 KEGG: ATC

20.6 KEGG: JP15

20.7 KEGG: Risk Category of Japanese OTC Drugs

20.8 WHO ATC Classification System

20.9 FDA Pharm Classes

20.10 EPA Safer Choice

20.11 ChemIDplus

20.12 CAMEO Chemicals

20.13 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

20.14 ChEMBL Target Tree

20.15 UN GHS Classification

20.16 EPA CPDat Classification

20.17 NORMAN Suspect List Exchange Classification

20.18 CCSBase Classification

20.19 EPA DSSTox Classification

20.20 Consumer Product Information Database Classification

20.21 EPA TSCA and CDR Classification

20.22 LOTUS Tree

20.23 EPA Substance Registry Services Tree

20.24 MolGenie Organic Chemistry Ontology

21 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
    1,2,3-Propanetricarboxylic acid, 2-hydroxy-
    https://services.industrialchemicals.gov.au/search-assessments/
    1,2,3-Propanetricarboxylic acid, 2-hydroxy-
    https://services.industrialchemicals.gov.au/search-inventory/
  2. CAMEO Chemicals
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    https://cameochemicals.noaa.gov/help/reference/terms_and_conditions.htm?d_f=false
    CAMEO Chemical Reactivity Classification
    https://cameochemicals.noaa.gov/browse/react
  3. CAS Common Chemistry
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    https://creativecommons.org/licenses/by-nc/4.0/
  4. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  5. DrugBank
    LICENSE
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    https://www.drugbank.ca/legal/terms_of_use
  6. DTP/NCI
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  7. EPA Chemical Data Reporting (CDR)
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    1,2,3-Propanetricarboxylic acid, 2-hydroxy-
    https://www.epa.gov/chemical-data-reporting
  8. EPA Chemicals under the TSCA
    1,2,3-Propanetricarboxylic acid, 2-hydroxy-
    https://www.epa.gov/chemicals-under-tsca
    EPA TSCA Classification
    https://www.epa.gov/tsca-inventory
  9. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  10. European Chemicals Agency (ECHA)
    LICENSE
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    https://echa.europa.eu/web/guest/legal-notice
  11. FDA Global Substance Registration System (GSRS)
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  12. Hazardous Substances Data Bank (HSDB)
  13. Human Metabolome Database (HMDB)
    LICENSE
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    http://www.hmdb.ca/citing
  14. ILO-WHO International Chemical Safety Cards (ICSCs)
  15. International Fragrance Association (IFRA)
    LICENSE
    (c) The International Fragrance Association, 2007-2021. All rights reserved.
    https://ifrafragrance.org/links/copyright
  16. New Zealand Environmental Protection Authority (EPA)
    LICENSE
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    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  17. BindingDB
    LICENSE
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    https://www.bindingdb.org/rwd/bind/info.jsp
  18. 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.
    http://ctdbase.org/about/legal.jsp
  19. 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
  20. IUPHAR/BPS Guide to PHARMACOLOGY
    LICENSE
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    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  21. Therapeutic Target Database (TTD)
  22. EU Food Improvement Agents
  23. Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
    LICENSE
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  24. Joint FAO/WHO Expert Committee on Food Additives (JECFA)
    LICENSE
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    https://www.who.int/about/policies/publishing/copyright
  25. ChEBI
  26. E. coli Metabolome Database (ECMDB)
    LICENSE
    ECMDB is offered to the public as a freely available resource.
    https://ecmdb.ca/citations
  27. FDA Pharm Classes
    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
  28. LOTUS - the natural products occurrence database
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    https://lotus.nprod.net/
  29. NCI Thesaurus (NCIt)
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  30. Open Targets
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  31. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  32. 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/
    CITRIC ACID
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  33. 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
  34. 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
  35. Consumer Product Information Database (CPID)
    LICENSE
    Copyright (c) 2024 DeLima Associates. All rights reserved. Unless otherwise indicated, all materials from CPID are copyrighted by DeLima Associates. 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://www.whatsinproducts.com/contents/view/1/6
    Consumer Products Category Classification
    https://www.whatsinproducts.com/
  36. Cosmetic Ingredient Review (CIR)
  37. EPA Chemical and Products Database (CPDat)
  38. 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/
  39. The Cambridge Structural Database
  40. DailyMed
  41. IUPAC Digitized pKa Dataset
    1,2,3-Propanetricarboxylio acid, 2-hydroxy-
    https://github.com/IUPAC/Dissociation-Constants
  42. Drugs and Lactation Database (LactMed)
  43. Drugs@FDA
    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
  44. ECI Group, LCSB, University of Luxembourg
    LICENSE
    Data: CC-BY 4.0; Code: Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    citric acid
  45. Natural Product Activity and Species Source (NPASS)
  46. EPA Safer Choice
    EPA Safer Chemical Ingredients Classification
    https://www.epa.gov/saferchoice
  47. FDA Approved Animal Drug Products (Green Book)
    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
  48. FDA Orange Book
    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
  49. EU Clinical Trials Register
  50. Hazardous Chemical Information System (HCIS), Safe Work Australia
  51. Regulation (EC) No 1272/2008 of the European Parliament and of the Council
    LICENSE
    The copyright for the editorial content of this source, the summaries of EU legislation and the consolidated texts, which is owned by the EU, is licensed under the Creative Commons Attribution 4.0 International licence.
    https://eur-lex.europa.eu/content/legal-notice/legal-notice.html
  52. 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
  53. FDA Substances Added to Food
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  54. Flavor and Extract Manufacturers Association (FEMA)
  55. NMRShiftDB
  56. 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
  57. MassBank Europe
  58. 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
  59. SpectraBase
    3-CARBOXY-3-HYDROXYPENTANEDIOIC ACID
    https://spectrabase.com/spectrum/1BishNflhG2
    1,2,3-Propanetricarboxylic acid, 2-hydroxy-
    https://spectrabase.com/spectrum/7sY9VeRpJJ3
    1,2,3-Propanetricarboxylic acid, 2-hydroxy-
    https://spectrabase.com/spectrum/Jy4uytepdkZ
  60. Japan Chemical Substance Dictionary (Nikkaji)
  61. 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
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Drugs listed in the Japanese Pharmacopoeia
    http://www.genome.jp/kegg-bin/get_htext?br08311.keg
    Risk category of Japanese OTC drugs
    http://www.genome.jp/kegg-bin/get_htext?br08312.keg
  62. MarkerDB
    LICENSE
    This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
    https://markerdb.ca/
  63. Metabolomics Workbench
  64. Nature Chemical Biology
  65. 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
  66. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  67. Pharos
    LICENSE
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    https://pharos.nih.gov/about
  68. Protein Data Bank in Europe (PDBe)
  69. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
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    https://www.rcsb.org/pages/policies
  70. Springer Nature
  71. Thieme Chemistry
    LICENSE
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    https://creativecommons.org/licenses/by-nc-nd/4.0/
  72. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
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    https://www.whocc.no/copyright_disclaimer/
  73. Wikidata
  74. Wikipedia
  75. Wiley
  76. Medical Subject Headings (MeSH)
    LICENSE
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    https://www.nlm.nih.gov/copyright.html
  77. PubChem
  78. GHS Classification (UNECE)
  79. EPA Substance Registry Services
  80. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  81. PATENTSCOPE (WIPO)
  82. NCBI
CONTENTS