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Ascorbic Acid

PubChem CID
54670067
Structure
Ascorbic Acid_small.png
Ascorbic Acid_3D_Structure.png
Ascorbic Acid__Crystal_Structure.png
Molecular Formula
Synonyms
  • l-ascorbic acid
  • ascorbic acid
  • vitamin C
  • 50-81-7
  • L-ascorbate
Molecular Weight
176.12 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2011-12-26
  • Modify:
    2025-01-18
Description
L-ascorbic acid is a white to very pale yellow crystalline powder with a pleasant sharp acidic taste. Almost odorless. (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.
L-ascorbic acid is the L-enantiomer of ascorbic acid and conjugate acid of L-ascorbate. It has a role as a coenzyme, a flour treatment agent, a food antioxidant, a plant metabolite, a cofactor, a skin lightening agent, a geroprotector and a food colour retention agent. It is an ascorbic acid and a vitamin C. It is a conjugate acid of a L-ascorbate. It is an enantiomer of a D-ascorbic acid.
A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant.
See also: Sodium Ascorbate (active moiety of); Ascorbic acid calcium salt (is active moiety of); D-ascorbic acid (narrower) ... View More ...

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Ascorbic 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

(2R)-2-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxy-2H-furan-5-one
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C6H8O6/c7-1-2(8)5-3(9)4(10)6(11)12-5/h2,5,7-10H,1H2/t2-,5+/m0/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

CIWBSHSKHKDKBQ-JLAZNSOCSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C([C@@H]([C@@H]1C(=C(C(=O)O1)O)O)O)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C6H8O6
Computed by PubChem 2.2 (PubChem release 2021.10.14)
C6H8O6

2.3 Other Identifiers

2.3.1 CAS

50-81-7
6730-29-6
53262-66-1
24808-52-4
62624-30-0

2.3.3 Deprecated CAS

1018124-03-2, 1129294-89-8, 129940-97-2, 1428525-25-0, 14536-17-5, 154170-90-8, 1703051-92-6, 259133-78-3, 30208-61-8, 50976-75-5, 56172-55-5, 56533-05-2, 57304-74-2, 57606-40-3, 623158-95-2, 882690-91-7, 884381-69-5, 885512-24-3, 88845-26-5, 896436-13-8, 89924-69-6
1018124-03-2, 1129294-89-8, 129940-97-2, 1428525-25-0, 14536-17-5, 154170-90-8, 1703051-92-6, 2252244-20-3, 259133-78-3, 2635329-14-3, 30208-61-8, 50976-75-5, 56172-55-5, 56533-05-2, 57304-74-2, 57606-40-3, 623158-95-2, 882690-91-7, 884381-69-5, 885512-24-3, 88845-26-5, 896436-13-8, 89924-69-6
1018124-03-2, 129940-97-2, 1428525-25-0, 14536-17-5, 154170-90-8, 1703051-92-6, 259133-78-3, 30208-61-8, 50976-75-5, 56172-55-5, 56533-05-2, 57304-74-2, 57606-40-3, 882690-91-7, 884381-69-5, 885512-24-3, 88845-26-5, 89924-69-6

2.3.4 European Community (EC) Number

200-066-2

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 KEGG ID

2.3.14 Metabolomics Workbench ID

2.3.15 NCI Thesaurus Code

2.3.16 Nikkaji Number

2.3.17 Pharos Ligand ID

2.3.18 RXCUI

2.3.19 Wikidata

2.3.20 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Acid, Ascorbic
  • Acid, L-Ascorbic
  • Ascorbate, Ferrous
  • Ascorbate, Magnesium
  • Ascorbate, Sodium
  • Ascorbic Acid
  • Ascorbic Acid, Monosodium Salt
  • di-L-Ascorbate, Magnesium
  • Ferrous Ascorbate
  • Hybrin
  • L Ascorbic Acid
  • L-Ascorbic Acid
  • Magnesium Ascorbate
  • Magnesium Ascorbicum
  • Magnesium di L Ascorbate
  • Magnesium di-L-Ascorbate
  • Magnorbin
  • Sodium Ascorbate
  • Vitamin C

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
176.12 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
-1.6
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
6
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
176.03208797 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
176.03208797 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
107 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
12
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
232
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
2
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

L-ascorbic acid is a white to very pale yellow crystalline powder with a pleasant sharp acidic taste. Almost odorless. (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.
Dry Powder; Liquid
White to pale yellow, odourless crystalline powder
White solid; [Merck Index] White to yellow odorless solid; [ICSC] Powder; [Sigma-Aldrich MSDS]
Solid
ODOURLESS WHITE-TO-SLIGHTLY-YELLOW CRYSTALS OR POWDER.

3.2.2 Color / Form

Crystals (usually plates, sometimes needles, monoclinic system)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 136
White crystals (plates or needles)
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 103
White to slightly yellow crystals or powder ... gradually darkens on exposure to light
FCC; Food chemicals codex. Committee on Food Chemicals Codex, Food and Nutrition Board, Institute of Medicine. 5th. Washington, DC: National Academy Press p. 36 (2003)

3.2.3 Odor

Odorless
Chase et al; Remington's Pharmaceutical Sciences 14th ed. Mack Publ Co. Easton, PA p. 1036 (1970)

3.2.4 Taste

Pleasant, sharp, acidic taste
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 136

3.2.5 Melting Point

374 to 378 °F (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.
191 dec °C
PhysProp
Between 189 °C and 193 °C with decomposition
190-192 °C (some decomposition)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 136
Melting point = 465.15 deg K, decomposes.
Daubert, T.E., R.P. Danner. Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, D.C.: Taylor and Francis, 1989.
191 °C
PhysProp

3.2.6 Solubility

greater than or equal to 100 mg/mL at 73 °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.
400000 mg/L (at 40 °C)
MERCK INDEX (1996)
Insoluble in ether, chloroform, benzene, petroleum ether, oils, fats, fat solvents
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 136
1 g dissolves in about 3 ml of water.
Chase et al; Remington's Pharmaceutical Sciences 14th ed. Mack Publ Co. Easton, PA p. 1036 (1970)
The solubility in g/mL is 0.33 in water, 0.033 in 95 wt% ethanol, 0.02 in absolute ethanol, 0.01 in glycerol USP, 0.05 in propylene glycol.
Kuellmer V; Kirk-Othmer Encyclopedia of Chemical Technology. (2001). New York, NY: John Wiley & Sons; Ascorbic Acid. Online Posting Date: Apr 16, 2001.
Solubility in water: 80% at 100 °C, 40% at 45 °C
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 136
400 mg/mL at 40 °C
MERCK INDEX (1996)
Solubility in water, g/100ml at 20 °C: 33 (freely soluble)

3.2.7 Density

1.65 (NTP, 1992) - Denser than water; will sink
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
1.65 g/cu cm at 25 °C
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-28
Density (at 25 °C): 1.65 g/cm³

3.2.8 LogP

-1.85
AVDEEF,A (1997)
log Kow = -1.85
Avdeef A; Seminar on Ionization and Lipophilicity. Log P values measured by pION Inc., Brookline, MA (1997)
-1.85
AVDEEF,A (1997)
-2.15

3.2.9 Stability / Shelf Life

Stable to air when dry; impure preparation and in many natural products vitamin oxidizes on exposure to air and light. Aqueous solutions are rapidly oxidized by air, accelerated by alkalies, iron, copper
The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 111

3.2.10 Optical Rotation

[α]D/20 between + 20,5° and + 21,5° (10 % w/v aqueous solution)
Specific optical rotation (c = 1 in water): +20.5 to +21.5 deg at 25 °C/D; (c = 1 in methanol): +48 deg at 23 °C/D
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 136
Specific optical rotation: +24 deg at 20 °C/D (in water, 1%)
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V1: 318

3.2.11 Autoignition Temperature

1220 °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.
380 °C
Organization for Economic Cooperation and Development; Screening Information Data Set for L-Ascorbic acid CAS 50-81-7. Available from, as of January 13, 2009: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html

3.2.12 Decomposition

When heated to decomposition it emits acrid smoke and irritating fumes.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 310
190-192 °C

3.2.13 Heat of Vaporization

The heat of vaporization is 1.487X10+8 J/kmol at 465.15 deg K.
Daubert, T.E., R.P. Danner. Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, D.C.: Taylor and Francis, 1989.

3.2.14 pH

Between 2,4 and 2,8 (2 % aqueous solution)
pH = 3 (5 mg/mL); pH = 2 (50 mg/mL)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 136

3.2.15 Surface Tension

4.039X10-2 N/m
Daubert, T.E., R.P. Danner. Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, D.C.: Taylor and Francis, 1989.

3.2.16 Dissociation Constants

pKa
4.7 (at 10 °C)
KORTUM,G ET AL (1961)
pK1 = 4.17; pK2 = 11.57
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 136
pKa = 4.70 at 10 °C
Kortum G et al; Dissociation Constants of Organic Acids in Aqueous Solution. International Union of Pure and Applied Chemistry. London: Butterworth (1961)

3.2.17 Collision Cross Section

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

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

138.6 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated with Agilent tune mix (Agilent)]

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

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

141.6 Ų [M+Na]+

127.9 Ų [M-H]-

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

3.2.18 Other Experimental Properties

log Kow = -2.15 at 23 °C; log Kow = -2.00 at 37 °C
Rose RC; Biochim Biophys Acta 924: 254-256 (1987)
log Kow = -1.64
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 22
Strong reducing agent. Stable to air when dry; aqueous solutions are rapidly oxidized by air.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 136
Dihydrate, triclinic crystals; specific optical rotation: +95.6 deg at 20 °C/D (c= 2.4). Freely soluble in water. Practically insoluble in methanol, ethanol. /Ascorbic acid, calcium salt/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 136
For more Other Experimental Properties (Complete) data for L-Ascorbic Acid (9 total), please visit the HSDB record page.

3.3 SpringerMaterials Properties

3.4 Chemical Classes

Biological Agents -> Vitamins and Derivatives

3.4.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
3.4.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Vitamins
Human drug -> Active ingredient (ASCORBIC ACID)
Human drug -> Prescription
Vitamins and minerals
3.4.1.2 Animal Drugs
Pharmaceuticals -> UK Veterinary Medicines Directorate List
S104 | UKVETMED | UK Veterinary Medicines Directorate's List | DOI:10.5281/zenodo.7802119

3.4.2 Cosmetics

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

3.4.3 Endocrine Disruptors

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

3.4.4 Food Additives

NUTRIENT SUPPLEMENT -> FDA Substance added to food
ANTIMICROBIAL AGENT, ANTIOXIDANT, COLOR OR COLORING ADJUNCT, DOUGH STRENGTHENER, FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT, NUTRIENT SUPPLEMENT, PH CONTROL AGENT, SEQUESTRANT, STABILIZER OR THICKENER -> FDA Substance added to food

3.4.5 Fragrances

Fragrance Ingredient (Ascorbic acid) -> IFRA transparency List

3.4.6 Pesticides

Agrochemicals -> Pesticide active substances
Active substance -> EU Pesticides database: Not approved

4 Spectral Information

4.1 1D NMR Spectra

1D NMR Spectra
1H NMR: 464 (Varian Associates NMR Spectra Catalogue) /Ascorbic acid (DL)/
1D NMR Spectra
MAX ABSORPTION (WATER): 244 NM (LOG E= 3.98); SADTLER REF NUMBER: 13217 (IR, PRISM); 470 (IR, GRATING); 3455 (UV); 3126 (NMR)
1D NMR Spectra
1H NMR: 3126 (Sadtler Research Laboratories spectral collection)

4.1.1 1H NMR Spectra

1 of 2
Instrument Name
Varian A-60
Source of Sample
The Matheson Company, Inc., East Rutherford, New Jersey
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
255564
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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4.1.2 13C NMR Spectra

1 of 3
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13C NMR Spectra
13C NMR: 171 (Johnson and Jankowski, Carbon-13 NMR Spectra, Jphn Wiley & Sons, New York)
13C NMR Spectra
13C NMR: 171 (Johnson and Jankowski, Carbon-13 NMR Spectra, Jphn Wiley & Sons, New York)
13C NMR Spectra
13C NMR: 171 (Johnson and Jankowski, Carbon-13 NMR Spectra, John Wiley & Sons, New York)
2 of 3
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Source of Sample
Tokyo Kasei Kogyo Company, Ltd., Tokyo, Japan
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 11
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Spectra ID
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

177.0 99.99

116.0 17.04

43.0 10.57

85.0 9.73

141.0 9.46

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Notes
instrument=HITACHI M-80
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Spectra ID
Instrument Type
GC-EI-TOF
Ionization Mode
positive
Top 5 Peaks

147.0 100

117.0 48.85

332.0 28.43

133.0 22.62

205.0 17.32

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

4.2.2 MS-MS

1 of 6
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Spectra ID
Instrument Type
NA
Ionization Mode
positive
Top 5 Peaks

95.0128 42.32

85.0284 15.04

141.0182 10.92

129.0182 6.10

57.0338 5.27

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Notes
adduct_type [M+H]+ original_collision_energy NA CannabisDB spectra from MoNa 2020 June Orbitrap GNPS
2 of 6
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Spectra ID
Instrument Type
LC-ESI-QTOF
Ionization Mode
positive
Top 5 Peaks

177.0671 31.97

121.0628 13.67

103.0542 8.07

149.0596 6.08

91.0591 6.08

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Notes
adduct_type [M+H]+ original_collision_energy 35 eV CannabisDB spectra from MoNa 2020 June SCIEX TripleTOF 6600 Fiehn HILIC Library

4.2.3 LC-MS

1 of 3
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MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M+NH4]+
Precursor m/z
194.0659027099609
Instrument
Thermo Q Exactive HF
Instrument Type
ESI-QFT
Ionization Mode
positive
Collision Energy
65HCD
Top 5 Peaks

153.959221 100

57.935032 47.34

61.010819 42.08

70.957871 35.99

137.927875 26.51

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MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M+NH4]+
Precursor m/z
194.0659027099609
Instrument
Thermo Q Exactive HF
Instrument Type
ESI-QFT
Ionization Mode
positive
Collision Energy
45HCD
Top 5 Peaks

153.959184 100

61.010825 77.92

148.971730 43.23

152.951389 38.63

151.969969 22.23

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4.2.4 Other MS

1 of 2
Other MS
MASS: 107119 (NIST/EPA/MSDC Mass Spectral Database, 1990 version) /Ascorbic acid (D)/
Other MS
MASS: 25046 (NIST/EPA/MSDC Mass Spectral Database, 1990 version)
2 of 2
MS Category
Experimental
MS Type
Other
MS Level
MS2
Precursor Type
[M-H]-
Precursor m/z
175.024
Instrument
Orbitrap
Ionization Mode
negative
Top 5 Peaks

87.009476 100

175.032471 49.85

59.012596 48.29

71.013306 44.49

115.007126 43.03

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4.3 UV Spectra

UV max absorption at pH 2: 245 nm (epsilon 1% 1 cm, 695); at pH 6.4: 265 nm (epsilon 1% 1cm, 940)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 136
UV: 3455 (Sadtler Research Laboratories spectral collection)
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V1: 318

4.4 IR Spectra

IR Spectra
IR: 470 (Sadtler Research Laboratories IR grating collection)

4.4.1 FTIR Spectra

1 of 2
Technique
KBr WAFER
Source of Sample
The Matheson Company, Inc., East Rutherford, New Jersey
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Technique
KBr WAFER
Source of Sample
Atlas Pharmaceutical Laboratories, Inc.
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4.2 ATR-IR Spectra

1 of 2
Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II) ground
Source of Spectrum
Forensic Spectral Research
Source of Sample
Supelco, Sigma-Aldrich Inc.
Catalog Number
47863
Lot Number
LB60380
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Sigma-Aldrich Company Llc
Catalog Number
<a href=https://www.sigmaaldrich.com/US/en/product/sial/A92902>A92902</a>
Lot Number
05723BE
Copyright
Copyright © 2014-2024 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
Source of Sample
Spectrochem Pvt. Ltd., India
Catalog Number
10131
Copyright
Copyright © 2014-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Sigma-Aldrich Company LLC
Catalog Number
<a href=https://www.sigmaaldrich.com/US/en/product/sial/A92902>A92902</a>
Lot Number
05723BE
Copyright
Copyright © 2015-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.6 Other Spectra

Intense mass spectral peaks: 85 m/z, 116 m/z, 176 m/z
Pfleger, K., H. Maurer and A. Weber. Mass Spectral and GC Data of Drugs, Poisons and their Metabolites. Parts I and II. Mass Spectra Indexes. Weinheim, Federal Republic of Germany. 1985., p. 250

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Used to treat vitamin C deficiency, scurvy, delayed wound and bone healing, urine acidification, and in general as an antioxidant. It has also been suggested to be an effective antiviral agent.
Used in preventing and treating iron-deficiency anemia.

7.2 Drug Classes

Breast Feeding; Lactation; Milk, Human; Vitamins

7.3 WHO Essential Medicines

Drug
Drug Classes
Vitamins and minerals
Formulation
Oral - Solid: 50 mg
Indication
Scurvy

7.4 FDA Approved Drugs

7.5 FDA Orange Book

7.6 FDA National Drug Code Directory

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

7.8.3 NIPH Clinical Trials Search of Japan

7.9 Therapeutic Uses

Antioxidants; Free Radical Scavengers
National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)
Prophylaxis and treatment of scurvy
Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980., p. 1579
Ascorbic acid 100 to 200 mg daily may be given with desferrioxamine in the treatment of patients with thalassemia, to improve the chelating action of desferrioxamine, thereby increasing the excretion of iron.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.1985.
In iron deficiency states ascorbic acid may increase gastrointestinal iron absorption and ascorbic acid or ascorbate salts are therefore included in some oral iron preparations.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.1985.
For more Therapeutic Uses (Complete) data for L-Ascorbic Acid (30 total), please visit the HSDB record page.

7.10 Drug Warnings

Large doses are reported to cause diarrhea and other gastrointestinal disturbances. It has also been stated that large doses may result in hyperoxaluria and the formation of renal calcium oxalate calculi, and ascorbic acid should therefore be given with care to patients with hyperoxaluria. Tolerance may be induced with prolonged use of large doses, resulting in symptoms of deficiency when intake is reduced to normal. Prolonged or excessive use of chewable vitamin C preparations may cause erosion of tooth enamel.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.1984.
Large doses of ascorbic acid have resulted in hemolysis in patients with G6PD deficiency.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.1984.
Vitamin C intakes of 250 mg/day or higher have been associated with false-negative results for detecting stool and gastric occult blood. Therefore, high dose vitamin C supplements should be discontinued at least two weeks before physical exams to avoid interference with blood and urine tests.
Otten JJ, Hellwig JP, Meyers LD, eds; Dietary Reference Intakes: The Essential Guide to Nutrient Requirements, Washington, DC: The National Academies Press, 2006, p.208
Supplemental vitamin C may reduce the effectiveness of cancer chemotherapy, and its effectiveness in reducing risk from cancer and related death is unclear.
PDR Network, LLC. PDR for Nonprescription Drugs, Dietary Supplements, and Herbs. 31st Ed. PDR Network, LLC, Montvale, NJ. 2010 p. 603
For more Drug Warnings (Complete) data for L-Ascorbic Acid (25 total), please visit the HSDB record page.

7.11 Reported Fatal Dose

1(?) = Practically non-toxic: probable oral lethal dose (human) above 15 g/kg, more than 1 qt for 70 kg person (150 lb). Human poisonings are unknown and even reliable estimates of lethal dose in animals are rare.
Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-266

7.12 Biomarker Information

8 Food Additives and Ingredients

8.1 Food Additive Classes

JECFA Functional Classes
Food Additives -> ANTIOXIDANT;

8.2 FDA Substances Added to Food

1 of 2
Used for (Technical Effect)
NUTRIENT SUPPLEMENT
2 of 2
Used for (Technical Effect)
ANTIMICROBIAL AGENT, ANTIOXIDANT, COLOR OR COLORING ADJUNCT, DOUGH STRENGTHENER, FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT, NUTRIENT SUPPLEMENT, PH CONTROL AGENT, SEQUESTRANT, STABILIZER OR THICKENER
FEMA Number
2109
GRAS Number
3

8.3 Associated Foods

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

Chemical Name
ASCORBIC ACID
Evaluation Year
1981
ADI
NOT SPECIFIED
Comments
Group ADI for ascorbic acid and its sodium, potassium and calcium salts

9 Agrochemical Information

9.1 Agrochemical Category

Pesticide active substances

9.2 EU Pesticides Data

Active Substance
l-ascorbic acid
Status
Not approved [Reg. (EC) No 1107/2009]
Date
Approval: 01/07/2014 Expiration: 30/06/2024
Legislation
Dossier complete 05/751/EC, Reg (EU) 2018/155, Reg. (EU) 2020/2007, Reg. (EU) 2022/489, Reg. (EU) No 149/2014

10 Pharmacology and Biochemistry

10.1 Pharmacodynamics

Ascorbic Acid (vitamin C) is a water-soluble vitamin indicated for the prevention and treatment of scurvy, as ascorbic acid deficiency results in scurvy. Collagenous structures are primarily affected, and lesions develop in bones and blood vessels. Administration of ascorbic acid completely reverses the symptoms of ascorbic acid deficiency.
The major activity of supplemental iron is in the prevention and treatment of iron deficiency anemia. Iron has putative immune-enhancing, anticarcinogenic and cognition-enhancing activities.

10.2 MeSH Pharmacological Classification

Antioxidants
Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues. (See all compounds classified as Antioxidants.)
Vitamins
Organic substances that are required in small amounts for maintenance and growth, but which cannot be manufactured by the human body. (See all compounds classified as Vitamins.)

10.3 FDA Pharmacological Classification

1 of 3
FDA UNII
PQ6CK8PD0R
Active Moiety
ASCORBIC ACID
Pharmacological Classes
Established Pharmacologic Class [EPC] - Vitamin C
Pharmacological Classes
Chemical Structure [CS] - Ascorbic Acid
FDA Pharmacology Summary
Ascorbic acid is a Vitamin C.
2 of 3
Non-Proprietary Name
ASCORBIC ACID
Pharmacological Classes
Vitamin C [EPC]; Ascorbic Acid [CS]
3 of 3
Non-Proprietary Name
L-ASCORBIC ACID
Pharmacological Classes
Ascorbic Acid [CS]; Vitamin C [EPC]

10.4 ATC Code

S - Sensory organs

S01 - Ophthalmologicals

S01X - Other ophthalmologicals

S01XA - Other ophthalmologicals

S01XA15 - Ascorbic acid

B - Blood and blood forming organs

B03 - Antianemic preparations

B03A - Iron preparations

B03AA - Iron bivalent, oral preparations

B03AA10 - Ferrous ascorbate

G - Genito urinary system and sex hormones

G01 - Gynecological antiinfectives and antiseptics

G01A - Antiinfectives and antiseptics, excl. combinations with corticosteroids

G01AD - Organic acids

G01AD03 - Ascorbic acid

A - Alimentary tract and metabolism

A11 - Vitamins

A11G - Ascorbic acid (vitamin c), incl. combinations

A11GA - Ascorbic acid (vitamin c), plain

A11GA01 - Ascorbic acid (vit C)

A11GA01

10.5 Bionecessity

Vitamin C (ascorbic acid) is a water-soluble nutrient that acts as an antioxidant by virtue of its high reducing power. It has a number of functions: as a scavenger of free radicals; as a cofactor for several enzymes involved in the biosynthesis of carnitine, collagen, neurotransmitters, and in vitro processes; and as a reducing agent. Evidence for in vivo antioxidant functions of ascorbate include the scavenging of reactive oxidants in activated leukocytes, lung, and gastric mucosa, and diminished lipid peroxidation as measured by urinary isoprostane excretion.
Otten JJ, Hellwig JP, Meyers LD, eds; Dietary Reference Intakes: The Essential Guide to Nutrient Requirements, Washington, DC: The National Academies Press, 2006, p.203
The biological functions of ascorbic acid are based on its ability to provide reducing equivalents for a variety of biochemical reactions. Because of its reducing power, the vitamin can reduce most physiologically relevant reactive oxygen species. As such, the vitamin functions primarily as a cofactor for reactions requiring a reduced iron or copper metalloenzyme and as a protective antioxidant that operates in the aqueous phase both intra- and extracellularly. Both the one- and the two-electron oxidation products of the vitamin are readily regenerated in vivo - chemically and enzymatically - by glutathione, nicotinamide adenine dinucleotide (NADH), and nicotinamide adenine dinucleotide phosphate (NADPH) dependent reductases.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press, Washington, D.C., pg. 96, 2000. Available from, as of March 4, 2010: https://www.nap.edu/catalog/9810.html

The adult requirements for vitamin C are based on estimates of body pool or tissue vitamin C levels that are deemed adequate to provide antioxidant protection. Smokers have an increased requirement. The adverse effects upon which the Tolerable Upper Intake Level (UL) is based are osmotic diarrhea and gastrointestinal disturbances. DRI values are listed by life stage group in the table.

Table: Dietary Reference Intakes (DRIs) for Vitamin C by Life Stage Group, mg/day

Life Stage Group
0-6 mo
Adequate Intake
40
Tolerable Upper Intake Level
Not determined
7-12 mo
Adequate Intake
50
Tolerable Upper Intake Level
Not determined
1-3 yr
Estimated Average Requirement
13 (male &amp; female)
Recommended Dietary Allowance
15 (male &amp; female)
Tolerable Upper Intake Level
400
4-8 yr
Estimated Average Requirement
22 (male &amp; female)
Recommended Dietary Allowance
25 (male &amp; female)
Tolerable Upper Intake Level
650
9-13 yr
Estimated Average Requirement
39 (male &amp; female)
Recommended Dietary Allowance
45 (male &amp; female)
Tolerable Upper Intake Level
1200
14-18 yr
Estimated Average Requirement
63 (male) 56 (female)
Recommended Dietary Allowance
75 (male) 65 (female)
Tolerable Upper Intake Level
1800
19-30 yr
Estimated Average Requirement
75 (male) 60 (female)
Recommended Dietary Allowance
90 (male) 75 (female)
Tolerable Upper Intake Level
2000
31-50 yr
Estimated Average Requirement
75 (male) 60 (female)
Recommended Dietary Allowance
90 (male) 75 (female)
Tolerable Upper Intake Level
2000
51-70 yr
Estimated Average Requirement
75 (male) 60 (female)
Recommended Dietary Allowance
90 (male) 75 (female)
Tolerable Upper Intake Level
2000
> 70 yr
Estimated Average Requirement
75 (male ) 60 (female)
Tolerable Upper Intake Level
2000
Pregnancy
< or = 18 yr
Estimated Average Requirement
66
Recommended Dietary Allowance
80
Tolerable Upper Intake Level
1800
19-50 yr
Estimated Average Requirement
70
Recommended Dietary Allowance
85
Tolerable Upper Intake Level
2000
Lactation
< or = 18 yr
Estimated Average Requirement
96
Recommended Dietary Allowance
115
Tolerable Upper Intake Level
1800
19-50 yr
Estimated Average Requirement
100
Recommended Dietary Allowance
120
Tolerable Upper Intake Level
2000

Otten JJ, Hellwig JP, Meyers LD, eds; Dietary Reference Intakes: The Essential Guide to Nutrient Requirements, Washington, DC: The National Academies Press, 2006, p.202-3
The classic disease of severe vitamin C deficiency is scurvy, which is characterized by the symptoms related to connective tissue defects. Scurvy usually occurs at a plasma concentration of < 11 umol/L (0.2 mg/dL). The signs and symptoms of scurvy include the following: follicular hyperkeratosis; petechiae /(tiny, perfectly round, purplish hemorrhagic spots on the skin)/; ecchymoses /(hemorrhagic spots on the skin or mucous membranes)/; coiled hairs; inflamed and bleeding gums; perifollicular hemorrhages; joint effusions; arthralgia; impaired wound healing. Other signs and symptoms include dyspnea, edema, Sjogren's syndrome (dry eyes and mouth), weakness, fatigue, and depression. In experimental subjects who were made vitamin C deficient but not frankly scorbutic, gingival inflammation and fatigue were among the most sensitive markers of deficiency.
Otten JJ, Hellwig JP, Meyers LD, eds; Dietary Reference Intakes: The Essential Guide to Nutrient Requirements, Washington, DC: The National Academies Press, 2006, pp. 207-8
For more Bionecessity (Complete) data for L-Ascorbic Acid (57 total), please visit the HSDB record page.

10.6 Absorption, Distribution and Excretion

Absorption
70% to 90%
Absorption
The efficiency of absorption depends on the salt form, the amount administered, the dosing regimen and the size of iron stores. Subjects with normal iron stores absorb 10% to 35% of an iron dose. Those who are iron deficient may absorb up to 95% of an iron dose.
Ascorbic acid is readily absorbed from the gastrointestinal tract and is widely distributed in the body tissues. Plasma concentrations of ascorbic acid rise as the dose ingested is increased until a plateau is reached with doses of about 90 to 150 mg daily. Body stores of ascorbic acid in health are about 1.5 g although more may be stored at intakes above 200 mg daily. The concentration is higher in leucocytes and platelets than in erythrocytes and plasma. In deficiency states the concentration in leucocytes declines later and at a slower rate, and has been considered to be a better criterion for the evaluation of deficiency than the concentration in plasma.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.1984.
Ascorbic acid is reversibly oxidized to dehydroascorbic acid; some is metabolized to ascorbate-2-sulfate, which is inactive, and oxalic acid which are excreted in the urine. Ascorbic acid in excess of the body's needs is also rapidly eliminated unchanged in the urine; this generally occurs with intakes exceeding 100 mg daily.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.1984.
Ascorbic acid crosses the placenta and is distributed into breast milk. It is removed by hemodialysis.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.1984.
The renal threshold for ascorbic acid is approx 14 ug/mL, but this level varies among individuals. When the body is saturated with ascorbic acid and blood concentrations exceed the threshold, unchanged ascorbic acid is excreted in the urine. When tissue saturation and blood concentrations of ascorbic acid are low, administration of the vitamin results in little or no urinary excretion of ascorbic acid. Inactive metabolites of ascorbic acid such as ascorbic acid-2-sulfate and oxalic acid are excreted in the urine ... Ascorbic acid is also excreted in the bile but there is no evidence for enterohepatic circulation ...
IPCS; Poisons Information Monograph 046: Ascorbic acid (2006). Available from, as of March 9, 2010: https://www.inchem.org/pages/pims.html
For more Absorption, Distribution and Excretion (Complete) data for L-Ascorbic Acid (29 total), please visit the HSDB record page.

10.7 Metabolism / Metabolites

Hepatic. Ascorbic acid is reversibly oxidised (by removal of the hydrogen from the enediol group of ascorbic acid) to dehydroascorbic acid. The two forms found in body fluids are physiologically active. Some ascorbic acid is metabolized to inactive compounds including ascorbic acid-2-sulfate and oxalic acid.
Ascorbic acid-2-sulfate has ... been identified as metabolite of Vitamin C in human urine.
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1548
Ascorbate is oxidized to CO2 in rats and guinea pigs, but considerably less conversion can be detected in man. One route of metabolism of the vitamin in man involves its conversion to oxalate and eventual excretion in the urine; dehydroascorbate is presumably an intermediate.
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1548
... Young male guinea pigs /were fed/ diets containing either 2 g/kg (18 control animals) or 86 g/kg (29 treatment animals) of ascorbic acid for 275 days. The average weight gain was significantly higher in the control group. Eight control and eight treatment animals, chosen to maintain comparable weights between the groups, were then given a totally deficient ascorbic acid diet 24 hr before a metabolic study was initiated. In the metabolic study, (14)C-labeled L-ascorbic acid (628 g) was then injected intraperitoneally into both treatment and control guinea pigs to study the catabolism and excretion of the ascorbic acid. Catabolism of the labeled ascorbic acid to respiratory (14)CO2 was increased in treatment guinea pigs. The control and treatment animals were then divided into two groups. One group received 3 mg/kg ascorbic acid (chronic deficiency) for 68 days. The other received a diet devoid of ascorbic acid (acute deficiency) for 44 days. Four control and three treatment animals from the chronic deficiency group and three control and four treatment animals from the acute deficiency group were given a totally deficient ascorbic acid diet 24 hr before a second metabolic study was initiated. (14)C-labeled L-ascorbic acid (628 g) was injected intraperitoneally as above. Treatment animals in the chronic deficiency and the acute deficiency groups had increased catabolism of the labeled ascorbic acid to respiratory (14)CO2 compared to control animals in the chronic and acute deficiency groups. The amount of radioactivity recovered in the urine and feces was similar for both groups except for an increased urinary excretion of the label in treated animals exposed to the totally deficient diet. The treatment animals maintained higher tissue stores of ascorbic acid than the control animals. However, this difference was significant only in the testes. When subjected to a totally deficient diet the treatment animals were depleted of ascorbic acid at a faster rate than the control animals. The accelerated catabolism was not reversible by subnormal intakes of the vitamin ...
Cosmetic Ingredient Review Expert Panel; Int J Toxicol 24 (Suppl 2): 51-111 (2005).
... Hartley guinea pigs approximately 30 days pregnant /were divided/ into a control group receiving 25 mg ascorbic acid and a treated group receiving 300 mg/kg/day ascorbic acid daily. All animals were fed a 0.05% ascorbic acid diet. The groups were maintained for 10 days on their respective diets. Pups (both sexes) were randomly chosen on either day 5 or day 10 for the metabolic study. L-l-(14)C-Ascorbic Acid (10 uCi/mM) was injected intraperitoneally into the pups and they were placed in a metabolic chamber for five hours to collect expired (14)CO2. From day 11 all pups were caged individually and weaned to a diet containing only traces of ascorbic acid. Every third day the animals were examined for physical signs of scurvy. Once signs appeared, the animals were examined daily until death. Necropsies were performed on all animals. Pups from the treated group demonstrated a marked increase in (14)CO2 excretion following the intraperitoneal injection. Signs of scurvy appeared 4 days earlier in the treated group and mortality of the treated pups occurred approximately one week earlier. When excretion of labeled CO2 in both groups was correlated with the day of onset of scurvy signs, a linear correlation was found between the two parameters, suggesting that the earlier appearance of signs of scurvy on the experimental pups is secondary to an increased rate of ascorbic acid catabolism ...
Cosmetic Ingredient Review Expert Panel; Int J Toxicol 24 (Suppl 2): 51-111 (2005).
For more Metabolism/Metabolites (Complete) data for L-Ascorbic Acid (10 total), please visit the HSDB record page.
Ascorbic acid has known human metabolites that include Ascorbic acid-2-sulfate.
S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560

10.8 Biological Half-Life

16 days (3.4 hours in people who have excess levels of vitamin C)
The plasma half-life is reported to be 16 days in humans. This is different in people who have excess levels of vitamin C where the half-life is 3.4 hours
IPCS; Poisons Information Monograph 046: Ascorbic acid (2006). Available from, as of March 9, 2010: https://www.inchem.org/pages/pims.html
Vitamin C has a 96 hr half-life in guinea pigs.
Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 651
Due to homeostatic regulation, the biological half-life of ascorbate varies widely from 8 to 40 days and is inversely related to the ascorbate body pool.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press, Washington, D.C., pg. 100, 2000. Available from, as of March 4, 2010: https://www.nap.edu/catalog/9810.html

10.9 Mechanism of Action

In humans, an exogenous source of ascorbic acid is required for collagen formation and tissue repair by acting as a cofactor in the posttranslational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins. Ascorbic acid is reversibly oxidized to dehydroascorbic acid in the body. These two forms of the vitamin are believed to be important in oxidation-reduction reactions. The vitamin is involved in tyrosine metabolism, conversion of folic acid to folinic acid, carbohydrate metabolism, synthesis of lipids and proteins, iron metabolism, resistance to infections, and cellular respiration.
Iron is necessary for the production of hemoglobin. Iron-deficiency can lead to decreased production of hemoglobin and a microcytic, hypochromic anemia.
Ascorbic Acid reducing potential and conversion to AFR (ascorbate free radical) are key to its biological activity, including its free radical scavenging and its relationship to the oxidation of transition metals such as iron and copper at enzyme active sites and in food.
Cosmetic Ingredient Review Expert Panel; Int J Toxicol 24 (Suppl 2): 51-111 (2005).
Vitamin C is known to be an electron donor for eight human enzymes. Three participate in collagen hydroxylation; two in carnitine biosynthesis; and three in hormone and amino acid biosynthesis. The three enzymes that participate in hormone and amino acid biosynthesis are dopamine-beta-hydroxylase, necessary for the biosynthesis of the catecholamines norepinephrine and epinephrine; peptidyl-glycine monooxygenase, necessary for amidation of peptide hormones; and 4-hydroxyphenylpyruvatedioxygenase, involved in tyrosine metabolism. Ascorbate's action with these enzymes involves either monooxygenase or dioxygenase activities.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press, Washington, D.C., pg. 96-97, 2000. Available from, as of March 4, 2010: https://www.nap.edu/catalog/9810.html
As a cofactor for hydroxylase and oxygenase metalloenzymes, ascorbic acid is believed to work by reducing the active metal site, resulting in reactivation of the metal-enzyme complex, or by acting as a co-substrate involved in the reduction of molecular oxygen. The best known of these reactions is the posttranslational hydroxylation of peptide-bound proline and lysine residues during formation of mature collagen. In these reactions, ascorbate is believed to reactivate the enzymes by reducing the metal sites of prolyl (iron) and lysyl (copper) hydroxylases.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press, Washington, D.C., pg. 97-98, 2000. Available from, as of March 4, 2010: https://www.nap.edu/catalog/9810.html
Evidence also suggests that ascorbate plays a role in or influences collagen gene expression, cellular procollagen secretion, and the biosynthesis of other connective tissue components besides collagen, including elastin, fibronectin, proteoglycans, bone matrix, and elastin-associated fibrillin. The primary physical symptoms of ascorbic acid's clinical deficiency disease, scurvy, which involves deterioration of elastic tissue, illustrate the important role of ascorbate in connective tissue synthesis.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press, Washington, D.C., pg. 98, 2000. Available from, as of March 4, 2010: https://www.nap.edu/catalog/9810.html
For more Mechanism of Action (Complete) data for L-Ascorbic Acid (11 total), please visit the HSDB record page.

10.10 Human Metabolite Information

10.10.1 Tissue Locations

  • Adipose Tissue
  • Adrenal Cortex
  • Adrenal Medulla
  • Bladder
  • Brain
  • Epidermis
  • Erythrocyte
  • Eye Lens
  • Fibroblasts
  • Heart
  • Intestine
  • Leukocyte
  • Liver
  • Lung
  • Neuron
  • Ovary
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Spleen
  • Testis

10.10.2 Cellular Locations

  • Cytoplasm
  • Extracellular

10.10.3 Metabolite Pathways

10.11 Biochemical Reactions

10.12 Transformations

11 Use and Manufacturing

11.1 Uses

Cosmetic Ingredient Review Link
CIR ingredient: L-Ascorbic 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
An antioxidant essential in the human diet; Used as an antioxidant for foods and therapeutic vitamin; [Merck Index] Used as an antioxidant and pH adjustor in cosmetics (over 75% in hair dyes and colors), for abscission of citrus fruit in harvesting, as a reducing agent in analytical chemistry, skin protectant, and UV sunscreen; [HSDB] Used in chemical synthesis; [IUCLID] Used as flavoring agent, antimicrobial agent, antioxidant, dough strengthener, nutritional supplement, pH control agent, sequestrant, and stabilizer or thickener for foods; [FDA] Permitted for use as an inert ingredient in non-food pesticide products; [EPA]
Merck Index - O'Neil MJ, Heckelman PE, Dobbelaar PH, Roman KJ (eds). The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th Ed. Cambridge, UK: The Royal Society of Chemistry, 2013.
Dietary supplement
Burdock, G.A. (ed.). Fenaroli's Handbook of Flavor Ingredients. 4th ed.Boca Raton, FL 2002, p. 113
As antimicrobial and antioxidant in foodstuffs
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 136
Nutrition, color fixing, flavoring and preservative in meats and other foods, oxidant in bread dough, abscission of citrus fruit in harvesting, reducing agent in analytical chemistry
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 103
The iron, calcium, and sodium salts are available for biochemical research.
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 103
For more Uses (Complete) data for L-Ascorbic Acid (12 total), please visit the HSDB record page.

11.1.1 Use Classification

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

11.1.2 Industry Uses

  • Plating agents and surface treating agents
  • Not Known or Reasonably Ascertainable

11.1.3 Consumer Uses

Not Known or Reasonably Ascertainable

11.1.4 Household Products

Household & Commercial/Institutional Products

Information on 252 consumer products that contain Ascorbic acid in the following categories is provided:

• Personal Care

• Pet Care

11.2 Methods of Manufacturing

The classical Reichstein - Grussner synthesis starts with reduction of D-glucose to D-sorbitol by hydrogenation over a nickel catalyst. The microbiological oxidation of D-sorbitol to L-sorbose is carried out with Acetobacter xylinum. On treatment of L-sorbose with acetone at low temperature in the presence of sulfuric acid, 2,3:4,6-di-O-isopropylidene-alpha-L-sorbofuranose is formed. The di-O-isopropylidenyl protection of the hydroxyl-groups at C-2, C-3 and C-4, C-6 allows high-yield oxidation to di-O-isopropylidene-2-ketogulonic acid, without over-oxidation or other side reactions. The oxidation is carried out with potassium permanganate in alkaline solution. Treatment of /di-O-isopropylidene-2-ketogulonic acid/ with hot water affords 2-keto-L-gulonic acid, which is converted to L-ascorbic acid by heating in water at 100 °C (20% yield) or by esterification and treatment with sodium methoxide in methanol followed by acidification with hydrogen chloride, yielding ca. 70% of /L-ascorbic acid /. The overall yield of ascorbic acid from D-glucose is 15-18%.
Eggersdorfer M et al; Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (2008). New York, NY: John Wiley & Sons; Vitamins. Online Posting Date: June 15, 2000

11.3 Impurities

Oxalic acid < 0.2%
Organization for Economic Cooperation and Development; Screening Information Data Set for L-Ascorbic acid CAS 50-81-7. Available from, as of January 13, 2009: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html
Heavy metals (as Pb): < 10 mg/kg
Burdock, G.A. (ed.). Fenaroli's Handbook of Flavor Ingredients. 6th ed.Boca Raton, FL 2010, p. 121

11.4 Formulations / Preparations

Ascorbic Acid (various manufacturers) Injection: 500 mg/mL, In 50 mL vials. Ascor L 500 (McGuff) Injection: 500 mg/mL, 0.025% EDTA. Preservative-free. In 50 mL.
Novak, K.M. (ed.). Drug Facts and Comparisons2008 Edition. Wolters Kluwer Health. St. Louis, Missouri 2008., p. 27
Ascorbic Acid (as Ascorbic Acid or Sodium Ascorbate): Bulk: Powder. Oral: Capsules, extended-release 250 mg 500 mg. Lozenges 60 mg, Solution 25 mg/drop, 100 mg//mL, 500 mg/5 mL. Tablets: 100 mg, 250 mg, 500 mg, 1 g. Tablets, chewable ; 100 mg, 250 mg, 500 mg, 1 g. Tablets, extended-release: 500 mg, 1 g. 1.5 g. (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name.)
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009)
Ascorbic acid and sodium ascorbate are also commercially available in combination with other vitamins, minerals, amino acids, analgesic-antipyretics, anticholinergics, antihistamines, anti-inflammatory agents, cerebral stimulants, cough suppressants, enzymes, expectorants, hormones, infant formulas, keratolytic agents, laxatives, protein supplements, sedatives, and sympathomimetics. For iv infusion, ascorbic acid or sodium ascorbate is also commercially available in combination with other vitamins in caloric and electrolyte solutions.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009)
Grades: USP; FCC[Lewis RJ Sr; Hawley's Condensed Chemical Dictionary 15th ed Wiley (2007)
CD-ROM]

11.5 Consumption Patterns

CHEMICAL PROFILE: Ascorbic Acid. US End-use Pattern for Ascorbic Acid in 1986.

Table: US End-use pattern for ascorbic acid in 1986.

End-use
Pharmaceutical preparations
Percent
65
End-use
Food and beverages
Percent
30
End-use
Exports
Percent
5

Anonymous; Chemical Marketing Reporter 231 (2): 46 (1987); 12 January 1987

CHEMICAL PROFILE: Ascorbic acid. US End-use Pattern for Ascorbic Acid in 1989.

Table: US End-use pattern for ascorbic acid in 1989

End-use
Pharmaceutical preparations
Percent
55
End-use
Food and beverages
Percent
35
End-use
Animal feed
Percent
10

Anonymous; Chemical Marketing Reporter 237 (9): 42 (1990); 26 February 1990

CHEMICAL PROFILE: Ascorbic acid. US End-use Pattern for Ascorbic Acid in 1992.

Table: US End-use pattern for ascorbic acid in 1992

End-use
Pharmaceutical preparations
Percent
55
End-use
Food and beverages
Percent
35
End-use
Animal feed
Percent
10

Anonymous; Chemical Marketing Reporter 243 (7): 45 (1993); 15 February 1993

CHEMICAL PROFILE: Ascorbic acid. US End-use Pattern for Ascorbic Acid in 1995.

Table: US End-use pattern for ascorbic acid in 1995

End-use
Pharmaceutical preparations
Percent
55
End-use
Food and beverages
Percent
35
End-use
Animal feed
Percent
10

Anonymous; Chemical Marketing Reporter 249 (1): 37 (1996); 1 January 1996
For more Consumption Patterns (Complete) data for L-Ascorbic Acid (12 total), please visit the HSDB record page.

11.6 U.S. Production

Aggregated Product Volume

2019: 570,387 lb

2018: 1,170,267 lb

2017: 900,936 lb

2016: 689,182 lb

(1972) 7.08 X 10+9 g
SRI
In 1979, ca 10,000 metric tons/yr of L-ascorbic acid was produced.
Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. V24 26
(1992) Europe > 20,000 tons per year; World approx 46,000 tons per year
Organization for Economic Cooperation and Development; Screening Information Data Set for L-Ascorbic acid CAS 50-81-7. Available from, as of January 13, 2009: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html
CHEMICAL PROFILE: Ascorbic acid. US Production Capacity: 1986: 32 million pounds/year.
Anonymous; Chemical Marketing Reporter 231 (2): 46 (1987); 12 January 1987
For more U.S. Production (Complete) data for L-Ascorbic Acid (11 total), please visit the HSDB record page.

11.7 U.S. Imports

(1972) 2.5 X 10+9 g
SRI
(1975) 2.13X10+9 g (including salts)
SRI
CHEMICAL PROFILE: Ascorbic acid. US Imports: 1989: about 13 million pounds.
Anonymous; Chemical Marketing Reporter 237 (9): 42 (1990); 26 February 1990
CHEMICAL PROFILE: Ascorbic acid. US Imports: 1992: roughly 8-12 million pounds.
Anonymous; Chemical Marketing Reporter 243 (7): 45 (1993); 15 February 1993
For more U.S. Imports (Complete) data for L-Ascorbic Acid (6 total), please visit the HSDB record page.

11.8 U.S. Exports

(1972) 2.27 X 10+8 g
SRI
(1975) 7.76 X 10+7 g
SRI
CHEMICAL PROFILE: Ascorbic acid. US Exports: 1989: 1-4 million pounds.
Anonymous; Chemical Marketing Reporter 237 (9): 42 (1990); 26 February 1990
CHEMICAL PROFILE: Ascorbic acid. US Exports: 1992: 1-4 million pounds.
Anonymous; Chemical Marketing Reporter 243 (7): 45 (1993); 15 February 1993
For more U.S. Exports (Complete) data for L-Ascorbic Acid (6 total), please visit the HSDB record page.

11.9 General Manufacturing Information

Industry Processing Sectors
  • Not Known or Reasonably Ascertainable
  • Miscellaneous Manufacturing
EPA TSCA Commercial Activity Status
L-Ascorbic acid: ACTIVE
The most significant characteristic of l-ascorbic acid is its oxidation to dehydro-l-ascorbic acid, with which it forms a reversible redox system. This reducing property, together with its nutritional qualities and low toxicity, is the main reason for the numerous applications of vitamin C in the food and pharmaceutical industries.
Eggersdorfer M et al; Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (2008). New York, NY: John Wiley & Sons; Vitamins. Online Posting Date: June 15, 2000
1 unit (USP or International) is the Vitamin C activity of 0.05 mg of the USP ascorbic acid reference standard.
Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 130
... Because of ascorbic acid's sensitivity to oxidation ... its stability in foods has received more attention than that of other vitamins ... Ascorbic acid oxidase is present in a variety of plant foods and may be responsible for significant losses if not inactivated during tissue maceration.
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 101
Stability ... in potato products has been of interest since they are a significant dietary source in many countries. Reduced ascorbic acid decreased 50% in potatoes stored three months - from 25 to 13 mg/100 g. Additional degradation occurs during cooking and washing - from 13 to 6 mg/100 g.
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 101
For more General Manufacturing Information (Complete) data for L-Ascorbic Acid (10 total), please visit the HSDB record page.

12 Identification

12.1 Analytic Laboratory Methods

AOAC Method 967.21. Vitamin C (Ascorbic Acid) in Vitamin Preparations and Juices. 2,4-Dichloroindophenol Titrimetric Method. Ascorbic acid reduces oxidation-reduction indicator dye, 2,4-dichloroindophenol, to colorless solution. At end point, excess unreduced dye is rose pink in acid solution. Vitamin is extracted and titration is performed in presence of HPO3-HOAc or HPO3-HOAc-H2SO4 solution to maintain proper acidity for reaction and to avoid autoxidation of ascorbic acid at high pH.
Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC: Association of Analytical Chemists, 1990, p. 1059
AOAC Method 967.22. Vitamin C (Ascorbic Acid) in Vitamin Preparations. Microfluorometric Method. Ascorbic acid is oxidized to dehydroascorbic acid in presence of Norit. Oxidized form is reacted with 0-phenylenediamine to produce fluorophor having activation max. at ca 350 nm and fluorescence max. at ca 430 nm. Fluorescence intensity is proportional to concentration.
Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC: Association of Analytical Chemists, 1990, p. 1059
AOAC Method 984.26. Vitamin C (Total) in Food. Semiautomated Fluorometric Method.
Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC: Association of Analytical Chemists, 1990, p. 1060
AOAC Method 985.33. Vitamin C (Reduced Ascorbic Acid) in Ready- to-Feed Milk-Based Infant Formula. 2,6-Dichloroindophenol Titrimetric Method. Ascorbic acid is estimated by titration with colored oxidation-reduction indicator, 2,6-dichlororindophenol. EDTA is added as chelating agent to remove Fe and Cu interferences.
Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC: Association of Analytical Chemists, 1990, p. 1108
For more Analytic Laboratory Methods (Complete) data for L-Ascorbic Acid (8 total), please visit the HSDB record page.

13 Safety and Hazards

13.1 Hazards Identification

13.1.1 GHS Classification

1 of 2
View All
Note
This chemical does not meet GHS hazard criteria for 97.2% (553 of 569) of all reports. Pictograms displayed are for 2.8% (16 of 569) of reports that indicate hazard statements.
GHS Hazard Statements

Not Classified

Reported as not meeting GHS hazard criteria by 553 of 569 companies (only 2.8% companies provided GHS information). For more detailed information, please visit ECHA C&L website.

ECHA C&L Notifications Summary

Aggregated GHS information provided per 569 reports by companies from 8 notifications to the ECHA C&L Inventory.

Reported as not meeting GHS hazard criteria per 553 of 569 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 5 notifications provided by 16 of 569 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.

13.1.2 Hazard Classes and Categories

Not Classified

13.1.3 EPA Safer Chemical

Chemical: Ascorbic acid

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

13.1.4 Health Hazards

SYMPTOMS: Symptoms of exposure to this compound may include irritation of the skin, eyes and respiratory tract. Ingestion of large amounts may cause gastrointestinal distress and diarrhea. Exposure may also cause the formation of renal calcium oxalate calculi. There have been cases of allergic reaction with eczema, urticaria and asthma. The mucolytic effect of this compound might render the cervical mucus less permeable to spermatozoa.

ACUTE/CHRONIC HAZARDS: This compound may cause irritation of the skin, eyes and respiratory tract. When heated to decomposition it emits acrid smoke and irritating fumes. (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.

13.1.5 Fire Hazards

Flash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Combustible under specific conditions. Gives off irritating or toxic fumes (or gases) in a fire. Finely dispersed particles form explosive mixtures in air.

13.1.6 Hazards Summary

A strong reducing agent; A skin, eye, and respiratory tract irritant; [ICSC] Excessive doses (chronic ingestion or intravenous) can cause acute renal failure or nephropathy secondary to a metabolite, oxalic acid. Chronic ingestion of more than 4 g/day can produce nephropathy. [Olson, p. 445-6] No evidence of carcinogenicity in mice or rats; [NTP] May cause irritation; [Sigma-Aldrich MSDS]
Olson - Olson KR (ed). Poisoning & Drug Overdose, 7th Ed. New York: Lange Medical Books/McGraw-Hill, 2018., p. 445-6

13.2 Safety and Hazard Properties

13.2.1 Critical Temperature & Pressure

Critical temperature = 783 deg K; critical pressure = 5.29X10+6 Pa.
Daubert, T.E., R.P. Danner. Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, D.C.: Taylor and Francis, 1989.

13.2.2 Physical Dangers

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

13.2.3 Explosive Limits and Potential

Dust forms explosible mixtures in air with moderate explosion severity.
Organization for Economic Cooperation and Development; Screening Information Data Set for L-Ascorbic acid CAS 50-81-7. Available from, as of January 13, 2009: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html

13.3 First Aid Measures

Inhalation First Aid
Fresh air, rest.
Eye First Aid
Rinse with plenty of water (remove contact lenses if easily possible).
Ingestion First Aid
Rinse mouth.

13.3.1 First Aid

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

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

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

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

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

13.4 Fire Fighting

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (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.
Use water spray, powder, carbon dioxide.

13.5 Accidental Release Measures

13.5.1 Spillage Disposal

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

13.5.2 Disposal Methods

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.
SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

13.6 Handling and Storage

13.6.1 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 protect this chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store under refrigerated temperatures. (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.

13.6.2 Safe Storage

Separated from strong oxidants and strong bases.

13.6.3 Storage Conditions

Solutions of ascorbic acid are rapidly oxidized in air and in alkaline media; the drug should be protected from air and light.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009)

13.7 Exposure Control and Personal Protection

13.7.1 Inhalation Risk

No indication can be given about the rate at which a harmful concentration of this substance in the air is reached on evaporation at 20 °C.

13.7.2 Acceptable Daily Intakes

JECFA: ADI: Not specified (intake from food does not represent a hazard to health)
Burdock, G.A. (ed.). Fenaroli's Handbook of Flavor Ingredients. 6th ed.Boca Raton, FL 2010, p. 121

13.7.3 Allowable Tolerances

Unless specifically excluded, residues resulting from the use of the following substances as either an inert or an active ingredient in a pesticide chemical formulation, including antimicrobial pesticide chemicals, are exempted from the requirement of a tolerance under FFDCA section 408, if such use is in accordance with good agricultural or manufacturing practices. Ascorbic 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 March 19, 2010: https://www.ecfr.gov

13.7.4 Personal Protective Equipment (PPE)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

13.7.5 Preventions

Fire Prevention
NO open flames. PREVENT DISPERSION OF DUST.
Inhalation Prevention
Use ventilation.
Eye Prevention
Wear safety spectacles.

13.8 Stability and Reactivity

13.8.1 Air and Water Reactions

May be sensitive to prolonged exposure to air and light. Sensitive to moisture. Soluble in water. Aqueous solutions are oxidized by air in a reaction that is accelerated by alkalis, iron and copper. The rate depends on the pH and on oxygen concentration. Also subject to degradation under anaerobic conditions.

13.8.2 Reactive Group

Alcohols and Polyols

Esters, Sulfate Esters, Phosphate Esters, Thiophosphate Esters, and Borate Esters

Hydrocarbons, Aliphatic Unsaturated

Acids, Weak

13.8.3 Reactivity Alerts

Strong Reducing Agent

13.8.4 Reactivity Profile

L-ASCORBIC ACID is a lactone. Reacts as a relatively strong reducing agent and decolorizes many dyes. Forms stable metal salts. Incompatible with oxidizers, dyes, alkalis, iron and copper. Also incompatible with ferric salts and salts of heavy metals, particularly copper, zinc and manganese (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.

13.9 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: L-Ascorbic acid
Status Regulation (EC)
Dossier complete 05/751/EC, Reg (EU) 2018/155, Reg. (EU) 2020/2007, Reg. (EU) 2022/489, Reg. (EU) No 149/2014
REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
Ascorbic acid: Does not have an individual approval but may be used under an appropriate group standard
New Zealand EPA Inventory of Chemical Status
Ascorbic acid: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

13.9.1 FIFRA Requirements

Unless specifically excluded, residues resulting from the use of the following substances as either an inert or an active ingredient in a pesticide chemical formulation, including antimicrobial pesticide chemicals, are exempted from the requirement of a tolerance under FFDCA section 408, if such use is in accordance with good agricultural or manufacturing practices. Ascorbic 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 March 19, 2010: https://www.ecfr.gov

13.9.2 FDA Requirements

Ascorbic acid used as a chemical preservative in food for human consumption is generally recognized as safe when used in accordance with good manufacturing practice.
21 CFR 182.3013 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 19, 2010: https://www.ecfr.gov
Ascorbic acid used as a nutrient in food for human consumption is generally recognized as safe when used in accordance with good manufacturing practice.
21 CFR 182.8013 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 19, 2010: 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: ascorbic 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 March 19, 2010: https://www.ecfr.gov
Ascorbic acid used as a chemical preservative in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice.
21 CFR 582.3013 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 19, 2010: https://www.ecfr.gov
Ascorbic acid used as a nutrient and/or dietary supplement in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice.
21 CFR 582.5013 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 19, 2010: https://www.ecfr.gov

13.10 Other Safety Information

Chemical Assessment

IMAP assessments - L-Ascorbic acid: Environment tier I assessment

IMAP assessments - L-Ascorbic acid: Human health tier I assessment

13.10.1 Special Reports

European Commission, ESIS; IUCLID Dataset, Ascorbic acid (50-81-7) (2000 CD-ROM edition) contains information on use, toxicology, and environmental effects of this chemical as supplied to the European Union by industry.[Available from, as of January 12, 2009: http://esis.jrc.ec.europa.eu/]
Organization for Economic Cooperation and Development; Screening Information Data Set for L-Ascorbic acid (CAS No. 50-81-7). This OECD Initial Assessment of HPV Chemicals is part of a series of OECD SIDS documents published by UNEP Chemicals to facilitate the access to information needed for health and environmental risk assessments of chemicals.[Available from, as of January 13, 2009: http://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html]
IPCS; Poisons Information Monograph: Ascorbic Acid (PIM 046) (1996). Poisons Information Monographs (PIM) are a global database with evaluated information on substances commonly involved in cases of poisoning.[Available from, as of May 16, 2008: http://www.inchem.org/pages/pims.html]
DHHS/NTP; Carcinogenesis Bioassay of L-Ascorbic Acid (Vitamin C) (CAS No. 50-81-7) in F344/N Rats and B6C3F1 Mice (Feed Study) Technical Report Series No. 247 (1983) NIH Publication No. 83-2503[Available from, as of March 5, 2010: http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr247.pdf]
For more Special Reports (Complete) data for L-Ascorbic Acid (6 total), please visit the HSDB record page.

14 Toxicity

14.1 Toxicological Information

14.1.1 Toxicity Summary

IDENTIFICATION: Origin of the substance: Ascorbic acid is of both natural and synthetic origin. Natural origin: ascorbic acid is found in fresh fruit and vegetables. Citrus fruits are a particularly good source of ascorbic acid and also hip berries, acerola and fresh tea leaves. Ascorbic acid exists as colorless, or white or almost white crystals. It is odorless or almost odorless. It has a pleasant, sharp acidic taste. It is freely soluble in water and sparingly soluble in ethanol. It is practically insoluble in ether and chloroform. HUMAN EXPOSURE: Main risks and target organs: The main target organs for toxicity are found in the gastrointestinal, renal and hematological systems. Summary of clinical effects: In individuals with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, hemolytic anemia may develop after administration of ascorbic acid. In individuals predisposed to renal stones, chronic administration of high doses may lead to renal calculi formation. In some cases, acute renal failure may be observed under both conditions. Indications: Prevention and treatment of scurvy. It has been used as a urinary acidifier and in correcting tyrosinemia in premature infants on high-protein diets. The drug may be useful to treat idiopathic methemoglobinemia. Contraindications: Ascorbic acid is contraindicated in patients with hyperoxaluria and G-6-PD deficiency. Routes of entry: Oral: Ascorbic acid is usually administered orally in extended-release capsule form, tablets, lozenges, chewable tablets, solutions and extended-release tablets and capsules Absorption by route of exposure: Ascorbic acid is readily absorbed after oral administration but the proportion does decrease with the dose. GI absorption of ascorbic acid may be reduced in patients with diarrhea or GI diseases. Distribution by route of exposure: Normal plasma concentrations of ascorbic acid are about 10 to 20 ug/mL. Total body stores of ascorbic acid have been estimated to be about 1.5 g with about a 30 to 45 mg daily turnover. Plasma concentrations of ascorbic acid rise as the dose ingested is increased until a plateau is reached with doses of about 90 to 150 mg daily. Ascorbic acid becomes widely distributed in body tissues with large concentrations found in the liver, leukocytes, platelets, glandular tissues, and the lens of the eye. In the plasma about 25% of the ascorbic acid is bound to proteins. Ascorbic acid crosses the placenta; cord blood concentration are generally 2 to 4 times the concentration in maternal blood. Ascorbic acid is distributed into milk. In nursing mothers on a normal diet the milk contains 40 to 70 ug/mL of the vitamin. Biological half-life by route of exposure: The plasma half-life is reported to be 16 days in humans. This is different in people who have excess levels of vitamin C where the half-life is 3.4 hours. Metabolism: Ascorbic acid is reversibly oxidized to dehydroascorbic acid in the body. This reaction, which proceeds by removal of the hydrogen from the enediol group of ascorbic acid, is part of the hydrogen transfer system. The two forms found in body fluids are physiologically active. Some ascorbic acid is metabolized to inactive compounds including ascorbic acid-2-sulfate and oxalic acid. Elimination by route of exposure: The renal threshold for ascorbic acid is approximately 14 ug/mL, but this level varies among individuals. When the body is saturated with ascorbic acid and blood concentrations exceed the threshold, unchanged ascorbic acid is excreted in the urine. When tissue saturation and blood concentrations of ascorbic acid are low, administration of the vitamin results in little or no urinary excretion of ascorbic acid. Inactive metabolites of ascorbic acid such as ascorbic acid-2-sulfate and oxalic acid are excreted in the urine. Ascorbic acid is also excreted in the bile but there is no evidence for enterohepatic circulation. Pharmacology and toxicology: Mode of action: Toxicodynamics: Hyperoxaluria may result after administration of ascorbic acid. Ascorbic acid may cause acidification of the urine, occasionally leading to precipitation of urate, cystine, or oxalate stones, or other drugs in the urinary tract. Urinary calcium may increase, and urinary sodium may decrease. Ascorbic acid reportedly may affect glycogenolysis and may be diabetogenic but this is controversial. Pharmacodynamics: In humans, an exogenous source of ascorbic acid is required for collagen formation and tissue repair. Vitamin C is a co-factor in many biological processes including the conversion of dopamine to noradrenaline, in the hydroxylation steps in the synthesis of adrenal steroid hormones, in tyrosine metabolism, in the conversion of folic acid to folinic acid, in carbohydrate metabolism, in the synthesis of lipids and proteins, in iron metabolism, in resistance to infection, and in cellular respiration. Vitamin C may act as a free oxygen radical scavenger. Toxicity: Human data: Adults: Diarrhea may occur after oral dosage of large amounts of ascorbic acid. Interactions: Concurrent administration of more than 200 mg of ascorbic acid per 300 mg of elemental iron increases absorption of iron from the GI tract. Increased urinary excretion of ascorbic acid and decreased excretion of aspirin occur when the drugs are administered concurrently. Ascorbic acid increases the apparent half-life of paracetamol. Interference with anticoagulant therapy has been reported. Carcinogenicity: It has been reported that there is no evidence of carcinogenicity. Some studies suggest that vitamin C may amplify the carcinogenic effect of other agents. L-ascorbic acid increases the oral carcinoma size induced by dimethylbenz(a)anthracene. Also, butylated hydroxyanisole induced forestomach carcinogenesis in rats. Teratogenicity: There is no evidence of teratogenicity. Mutagenicity: Ascorbic acid is reported to increase the rate of mutagenesis in cultured cells but this only occurs in cultures with elevated levels of Cu(2+) or Fe(2+). This effect may be due to the ascorbate induced generation of oxygen-derived free radicals. However, there is no evidence of ascorbate induced mutagenesis in vivo.
International Programme on Chemical Safety; Poisons Information Monograph: Ascorbic Acid (PIM 046) (1996) Available from, as of May 16, 2008: https://www.inchem.org/pages/pims.html

14.1.2 Drug Induced Liver Injury

Compound
vitamin c
DILI Annotation
No-DILI-Concern
Label Section
No match
References

M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007

M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

14.1.3 Carcinogen Classification

NTP Technical Report
TR-247: Carcinogenesis Bioassay of L-Ascorbic Acid (Vitamin C) (CASRN 50-81-7) in F344/N Rats and B6C3F1 Mice (Feed Study) (1983 )
Peer Review Date
Conclusion for Male Rat
No Evidence No Evidence
Conclusion for Female Rat
No Evidence No Evidence
Conclusion for Male Mice
No Evidence No Evidence
Conclusion for Female Mice
No Evidence No Evidence
Summary
Under the conditions of this bioassay, L-ascorbic acid was not carcinogenic for male and female F344/N rats or male and female B6C3F1 mice.

14.1.4 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Vitamin C is a normal component of human milk and is a key milk antioxidant. The recommended vitamin C intake in lactating women is 120 mg daily, and for infants aged 6 months or less is 40 mg daily. High daily doses up to 1000 mg increase milk levels, but not enough to cause a health concern for the breastfed infant and is not a reason to discontinue breastfeeding. Nursing mothers may need to supplement their diet to achieve the recommended intake or to correct a known deficiency. Maternal doses of vitamin C in prenatal vitamins at or near the recommended intake do not alter milk levels.

Freezing (-20 degrees C) freshly expressed mature milk from hospitalized mothers of term and preterm infants does not change milk vitamin C levels for at least 3 months of freezer storage. After 6 to 12 months of freezing (-20 degrees C), vitamin C levels can decrease by 15 to 30%. Storage at -80 degrees C preserves vitamin C levels for up to 8 months, with 15% loss by 12 months.

◉ Effects in Breastfed Infants

Sixty healthy lactating women between 1 and 6 months postpartum exclusively breastfeeding their infants were given vitamin C 500 mg plus vitamin E 100 IU once daily for 30 days, or no supplementation. Infants of supplemented mothers had increased biochemical markers of antioxidant activity in their urine. Clinical outcomes were not reported.

Eighteen preterm infants, seven of whom were less than 32 weeks gestational age, who were fed pooled, Holder-pasteurized donor milk beginning during the first three days of life had their average blood plasma ascorbic acid concentrations decrease from 15.5 mg/L at birth to 5.4 mg/L by 1 week of age, and to 4.1 mg/L by 3 weeks of age. The authors described the 1- and 3-week levels as subtherapeutic (<6 mg/L) and indicative of inadequate intake, potentially jeopardizing postnatal growth potential. Although this study was conducted before advances in the provision of parenteral nutrition and enteral milk fortification for preterm infants, contemporary studies suggest that inadequate vitamin C intake from pooled, pasteurized donor milk may be a potential health problem for preterm infants receiving donor milk.

◉ Effects on Lactation and Breastmilk

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

14.1.5 Exposure Routes

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

14.1.6 Symptoms

Inhalation Exposure
Cough.
Eye Exposure
Redness.

14.1.7 Acute Effects

14.1.8 Interactions

BALB/c male mice (288) were allocated into four groups: group 1 (48 animals), control diet; group 2 (48 animals), control diet and 500 ppm 2-acetylaminofluorene (2-AAF); group 3 (96 animals), control diet and 250 mg/mL of ascorbic acid in water; group 4 (96 animals), control diet, 2-AAF, and ascorbic acid. Food and water consumptions were measured at weekly intervals. The animals were killed at 28 days and necropsied. There were no detectable differences in relative food consumption due to the addition of ascorbic acid or to an interaction of ascorbic acid with 2-AAF. However the presence of ascorbic acid in the water was associated with a significant reduction in relative water consumption. The addition of 2-AAF caused a significant increase in relative water consumption, and a significant interaction of ascorbic acid with 2-AAF was detected. Major histological findings were restricted to the urinary bladder. Vacuolization of the transitional epithelium, simple and nodular urothelial hyperplasia, fibrosis, and chronic inflammation of the lamina propria were found in varying degrees in the urinary bladders of mice receiving 2-AAF alone and in combination with ascorbic acid. The most severe lesions were seen in the mice given the combination of 2-AAF and ascorbic acid. The urinary bladders of mice receiving the control diet and ascorbic acid alone were normal. The chronic inflammation and fibrosis were restricted primarily to the fundus of the urinary bladder. The lamina propria contained an increased amount of collagen, an increase in the vasculature and an infiltration of mononuclear inflammatory cells ...
Cosmetic Ingredient Review Expert Panel; Int J Toxicol 24 (Suppl 2): 51-111 (2005).

Effect of ascorbic acid on metal toxicity.

Table: Effect of Ascorbic Acid on Metal Toxicity

Metal
Copper
Species
Pig
Effects of Ascorbic Acid
Reduced iron deficiency induced by copper
Metal
Rubidium
Species
Rat
Effects of Ascorbic Acid
Ascorbic acid supplementation afforded some protection agains the alterations of certain liver enzymes as well as in regard to the histological changes of either liver and kidney effects caused by Rb
Metal
Lead
Species
Human
Effects of Ascorbic Acid
Ameliorated toxicity
Metal
Lead
Species
Human
Effects of Ascorbic Acid
No effect on toxicity
Metal
Lead
Species
Guinea pig
Effects of Ascorbic Acid
Variable toxicity
Metal
Lead
Species
Rat
Effects of Ascorbic Acid
1% Ascorbic acid prevented growth depression, reduction of food consumption, anemia, and decreased the accumulation of lead in tissues (long-term)
Metal
Selenium
Species
Rat
Effects of Ascorbic Acid
Marginal benefit from toxicity
Metal
Vanadium
Species
Chick
Effects of Ascorbic Acid
Ameliorated toxicity
Metal
Chromate pigments (Na, Ca, Zn, and basic Pb chromates)
Species
Cell culture media
Effects of Ascorbic Acid
Increased production of reactive oxygen species (ROS)
Metal
Chromate
Species
Rat
Effects of Ascorbic Acid
Chromate and ascorbic acid administered concomitantly completely prevented proteinuria by enhancement of extracellular reduction of chromate IV to III
Metal
Aluminum
Species
Rat
Effects of Ascorbic Acid
Aluminum concentrations in the bone, kidney, liver, and spleen were significantly increased, as was the overall cumulative urinary excretion of Al due to the gastric intubation of ascorbic acid

Cosmetic Ingredient Review Expert Panel; Int J Toxicol 24 (Suppl 2): 51-111 (2005).
... Male F344 rats /were injected/ intraperitoneally with 0, 458, or 687 umol/kg 4-aminophenol (PAP). PAP caused selective necrosis to the pars recta of the proximal tubule. Coadministration of ascorbic acid (457 and 687 umol/kg) with PAP protected the rats against the nephrotoxicity, markedly reduced the effect on renal function, and limited the extent of renal tubular necrosis.
Cosmetic Ingredient Review Expert Panel; Int J Toxicol 24 (Suppl 2): 51-111 (2005).
Oxytocin decreases the rate of placental transmission of ascorbic acid.
LaDu, B.N., H.G. Mandel, and E.L. Way. Fundamentals of Drug Metabolism and Disposition. Baltimore: Williams and Wilkins, 1971., p. 96
For more Interactions (Complete) data for L-Ascorbic Acid (41 total), please visit the HSDB record page.

14.1.9 Antidote and Emergency Treatment

All sources of vitamin C should be withdrawn and treatment for gastrointestinal symptoms provided, including antiemetics. If significant hemolysis occurs, intravenous hydration to maintain urine output should be administered. Monitoring renal function should be performed, and rarely, transfusion of packed red blood cells is required.
Dart, R.C. (ed). Medical Toxicology. Third Edition, Lippincott Williams & Wilkins. Philadelphia, PA. 2004., p. 1022
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160-1

14.1.10 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ Repeated application of 10% solution ... to eyes of patients ... caused no injury.
Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 120
/HUMAN EXPOSURE STUDIES/ ... Doses of Ascorbic Acid up to 6000 mg /were administered/ to 29 infants, 93 children of preschool and school age, and 20 adults for more than 1400 days. Toxic effects at the higher doses were observed in five adults and four infants and included nausea, vomiting, diarrhea, flushing of the face, headache, fatigue, and disturbed sleep. Skin rashes were also seen in the infants.
Cosmetic Ingredient Review Expert Panel; Int J Toxicol 24 (Suppl 2): 51-111 (2005).
/HUMAN EXPOSURE STUDIES/ ... A study /was conducted/ in which six volunteers were fed, initially, a synthetic liquid diet deficient in Vitamin C but adequate in all other nutrients. Isotopic labeling was accomplished through the administration of L-ascorbic acid-l-(14)C on the 23rd day of deficiency. Repletion, which commenced on the 100th day, was accomplished through the daily administration of controlled amounts of the labeled vitamin. The total ascorbic acid intake during the repletion phase ranged from 6.5 to 66.5 mg. Labeling the body ascorbic acid pool during the depletion phase resulted in no detectable urinary excretion of (14)C-labeled reduced ascorbic acid or dehydroascorbic acid. Urinary excretion of (14)C by all subjects occurred as a first order process during the depletion phase. The first clinical signs of mild scurvy appeared in the subjects when their body ascorbic acid pool had been reduced to approximately 300 mg. Once the body pool of ascorbic acid was repleted to a level of 1.5 g, urinary loss of reduced ascorbic acid occurred. The rate of repletion of ascorbic acid was found to be a zero-order process and proportional to the daily intake of ascorbic acid. The daily intake of 6.5 mg/kg of ascorbic acid was sufficient to alleviate the clinical signs in one of the subjects ...
Cosmetic Ingredient Review Expert Panel; Int J Toxicol 24 (Suppl 2): 51-111 (2005).
/HUMAN EXPOSURE STUDIES/ 1 g/day ascorbic acid /was administered/ for 3 months to 12 men and 12 women. Six of each sex served as controls. Blood samples were drawn before administration and one month and three months after administration. Ascorbic acid did not significantly influence the levels of serum concentrations of cholesterol, plasminogen activator activity, plasminogen, fibrinogen, FR-antigen, partial thromboplastin time, platelet adhesiveness, alpha1-antitrypsin, or alpha2-macroglobulin.
Cosmetic Ingredient Review Expert Panel; Int J Toxicol 24 (Suppl 2): 51-111 (2005).
For more Human Toxicity Excerpts (Complete) data for L-Ascorbic Acid (42 total), please visit the HSDB record page.

14.1.11 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ Skin irritation /test/: Test Substance: L-Ascorbic Acid Technical Grade >99.0%; Test Species/Strain: Rabbit: New Zealand White; Method: OECD Guidelines 404 12 May 1981; Test Results: give maximum scores after 4 hours. When applied to the intact and abraded skin under semi-occlusive conditions for 4 hours the primary irritation score was 0.00. L-Ascorbic Acid (Technical Grade) was found to be non-irritating to the skin.
Organization for Economic Cooperation and Development; Screening Information Data Set for L-Ascorbic acid CAS 50-81-7. Available from, as of January 13, 2009: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html
/LABORATORY ANIMALS: Acute Exposure/ Eye Irritation /Test/: Test Substance: L-Ascorbic Acid Technical Grade >99.0%; Test Species/Strain: Rabbit: New Zealand White; Method: OECD Guidelines 405 February 1987; Test Results: give maximum scores after 72 hours (not rinsed), 0.1 mL of a saturated solution (0.3 g/mL) instilled into the conjunctival sac gave a primary irritation score of 0.33 after 24 hr, a 1:3 dilution of saturated solution in distilled water gave an irritation score of 0.00. L-Ascorbic Acid is classified as non-irritating for the rabbit eye.
Organization for Economic Cooperation and Development; Screening Information Data Set for L-Ascorbic acid CAS 50-81-7. Available from, as of January 13, 2009: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html
/LABORATORY ANIMALS: Acute Exposure/ Ascorbic acid /was injected/ intraperitoneally into thirty male and female albino rats at a dose of 100 mg/kg bw. Blood samples were collected from the tail of each animal at 15 min, at 30 min, and at 60 min post injection. There was a rapid and significant rise in blood glucose after the injection and the hyperglycemic effect peaked at 30 min and declined at 60 min. A significant decrease of plasma cholesterol from a marked lipolytic effect was suggested by the significant rise of plasma glycerol. There was no effect on the BUN /(blood urea nitrogen)/ at 15 and 30 min, but a significant lowering of BUN at 60 min ...
Cosmetic Ingredient Review Expert Panel; Int J Toxicol 24 (Suppl 2): 51-111 (2005).
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Subconjunctival injections of 1 mL of 10% solutionn daily for 10 days in rabbits caused no significant irritation.
Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 120
For more Non-Human Toxicity Excerpts (Complete) data for L-Ascorbic Acid (61 total), please visit the HSDB record page.

14.1.12 Non-Human Toxicity Values

LD50 Rat oral 11,900 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 310
LD50 Rat oral > 5000 mg/kg bw /From table/
Organization for Economic Cooperation and Development; Screening Information Data Set for L-Ascorbic acid CAS 50-81-7. Available from, as of January 13, 2009: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html
LD50 Rat sc 5,000 mg/kg bw /From table/
Organization for Economic Cooperation and Development; Screening Information Data Set for L-Ascorbic acid CAS 50-81-7. Available from, as of January 13, 2009: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html
LD50 Rat iv 1,000 mg/kg bw /From table/
Organization for Economic Cooperation and Development; Screening Information Data Set for L-Ascorbic acid CAS 50-81-7. Available from, as of January 13, 2009: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html
For more Non-Human Toxicity Values (Complete) data for L-Ascorbic Acid (24 total), please visit the HSDB record page.

14.1.13 Ongoing Test Status

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=50-81-7]

14.1.14 National Toxicology Program Studies

A carcinogenesis bioassay of L-ascobic acid (>97% pure) was conducted by administering diets containing 25,000 or 50,000 ppm L-ascorbic acid to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 weeks. Controls consisted of 50 untreated rats and untreated mice of each sex. Fifty-thousand ppm is the highest dose recommended for chronic studies. Survival of dosed and control female rats and of dosed and control female mice were comparable. Survival of high-dose male rats was slightly greater than that of the controls (P=0.087). Survival of high-dose male mice was significantly greater (P=0.009)th an that of the controls. Throughout most of the study, mean body weights of dosed female rats and dosed female mice were lower than those of the controls. Final body weights were comparable among groups, except for the high-dose female rats (< 13%); marginal differences (<8%) were observed for low-dose female rats and for dosed female mice (8%-11%). Food consumption was equivalent among groups. Most observational differences were confined to the female rat. The incidence of low-dose female rats with undifferentiated (mononuclear-cell) leukemias (control, 6/ 50, 12%; low-dose, 17/ 50, 34%; high-dose, 12/50,24%) was significantly higher (P<0.02) than that in controls. These tumors were not considered to be related to administration of L-ascorbic acid because they did not occur in the female high-dose group at incidences significantly greater (P>0.07) than those in the controls, the trend test was not significant (P10.07), and no increases were observed for male rats. Under the conditions of this bioassay, L-ascorbic acid was not carcinogenic for male and female F344/N rats or male and female B6C3F1 mice. /L-Ascorbic acid/
DHHS/NTP; Toxicology & Carcinogenesis Studies of L-Ascorbic Acid in F344/N Rats and B6C3F1 Mice Technical Report Series No. 247 (1983) NIH Publication No. 83-2503

14.1.15 Populations at Special Risk

People with hemochromatosis, glucose-6-phosphate dehydrogenase deficiency, and renal disorders may be particularly susceptible to the adverse effects of excess vitamin C intake and therefore should be cautious about ingesting vitamin C at levels greater than the RDA. Vitamin C may enhance iron absorption and exacerbate iron-induced tissue damage in individuals with hemochromatosis, while those with renal disorders may have increased risk of oxalate kidney stone formation from excess vitamin C intake.
Otten JJ, Hellwig JP, Meyers LD, eds; Dietary Reference Intakes: The Essential Guide to Nutrient Requirements, Washington, DC: The National Academies Press, 2006, p.205
There are reports of hemolysis in patients with G6PD deficiency after large doses of ascorbic acid either intravenously or in soft drinks.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.1984.
Vitamin C may enhance iron absorption and exacerbate iron-induced tissue damage in individuals with hemochromatosis.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press, Washington, D.C., pg. 160, 2000. Available from, as of March 4, 2010: https://www.nap.edu/catalog/9810.html
Individuals with renal disorders may have increased risk of oxalate kidney stone formation from excess vitamin C intake.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press, Washington, D.C., pg. 160, 2000. Available from, as of March 4, 2010: https://www.nap.edu/catalog/9810.html
For more Populations at Special Risk (Complete) data for L-Ascorbic Acid (9 total), please visit the HSDB record page.

14.1.16 Protein Binding

25%

14.2 Ecological Information

14.2.1 Ecotoxicity Values

LC50 Species: /Oncorhynchus mykiss/ (Rainbow trout); Concentration: 1,020 mg/L for 96 hr /Conditions of bioassay not specified in source examined/
Organization for Economic Cooperation and Development; Screening Information Data Set for L-Ascorbic acid CAS 50-81-7. Available from, as of January 13, 2009: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html

14.2.2 Ecotoxicity Excerpts

/AQUATIC SPECIES/ Although no formal long-term toxicity studies have been performed L-Ascorbic Acid is widely used to supplement the diet of fish reared for food production. The tolerance to L-Ascorbic Acid has been reviewed by the Sub-Committee on Vitamin Tolerance of the US Board on Agriculture National Research Council. The following dietary levels are reported to have no adverse effect in developing hatchlings: trout 10 g/kg for 16 weeks, no adverse effect; catfish, approx wt 25 g, 5 g/kg for 150 days, no adverse effect /From table/. These dietary concentrations are approximately 100 times the normal requirements for healthy growth and wound healing in trout and catfish which are respectively 100 mg/kg and 60 mg/kg.
Organization for Economic Cooperation and Development; Screening Information Data Set for L-Ascorbic acid CAS 50-81-7. Available from, as of January 13, 2009: https://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html

14.2.3 Environmental Fate / Exposure Summary

L-Ascorbic acid's production and use as in nutrition, color fixing, flavoring and preservative in meats and other foods, as an oxidant in bread dough, in abscission of citrus fruit in harvesting, as a reducing agent in analytical chemistry, and as an antimicrobial and antioxidant in foodstuffs may result in its release to the environment through various waste streams. L-Ascorbic acid is widely distributed in the plant and animal kingdom. If released to air, an estimated vapor pressure of 9.8X10-11 mm Hg at 25 °C indicates L-ascorbic acid will exist solely in the particulate phase in the atmosphere. Particulate-phase L-ascorbic acid will be removed from the atmosphere by wet or dry deposition. L-Ascorbic acid contains chromophores that absorb at wavelengths >290 nm and therefore may be susceptible to direct photolysis by sunlight. If released to soil, L-ascorbic acid is expected to have very high mobility based upon an estimated Koc of 10. The pKa of L-ascorbic acid is 4.70, 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 acid exists as an anion and anions do not volatilize. L-Ascorbic acid may not volatilize from dry soil surfaces based upon its vapor pressure. L-Ascorbic acid exhibited moderate biodegradation using an enriched consortia derived from domestic sewage, suggesting that biodegradation is an important environmental fate process. If released into water, L-ascorbic acid is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. A pKa of 4.70 indicates L-ascorbic 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 expected to be an important environmental fate process since this compound contains functional groups that hydrolyze under environmental conditions. L-Ascorbic acid is easily oxidized in aqueous solution in the presence of air. Occupational exposure to L-ascorbic acid may occur through inhalation and dermal contact with this compound at workplaces where L-ascorbic acid is produced or used. Use data indicate that the general population is exposed to L-ascorbic acid via ingestion of food, medicines, and other consumer products containing L-ascorbic acid. (SRC)

14.2.4 Natural Pollution Sources

L-Ascorbic acid is widely distributed in the plant and animal kingdom(1). Food sources of L-ascorbic acid include acerola (West Indian cherry); citrus fruits, tomatoes; potatoes, and green leafy vegetables(2). It has been isolated from the adrenal cortex of ox and later from lemons and paprika(1).
(1) O'Neil MJ, ed; The Merck Index. 14th ed. Whitehouse Station, NJ: Merck and Co., Inc., p. 136 (2006)
(2) Lewis RJ Sr; Hawley's Condensed Chemical Dictionary., 15th ed., New York, NY: John Wiley & Sons, Inc., p. 103 (2007)
VITAMIN C IS FOUND IN ALL LIVING PLANT CELLS, IS SYNTHESIZED DURING GERMINATION OF SEEDS & IS...CONCENTRATED IN RAPIDLY GROWING PARTS OF PLANT. IT IS PRESENT IN ALL ANIMAL TISSUES...ONLY GUINEA PIGS, PRIMATES...FEW EXOTIC ANIMAL SPECIES, & MAN ARE UNABLE TO MEET...NEEDS BY SYNTHESIS...RELY UPON DIETARY SOURCE.
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 948
Recent speculations on the loss and retention of the ability to synthesize L-ascorbic acid (vitamin C) during evolution of animals have been based on few data, often for limited numbers of species. Published reports for the Mammalia deal mostly with domesticated and laboratory species, and there is little information on ascorbate biosynthesis in wild populations. The status of knowledge on bats typifies this paucity of data. It has been reported that two species of bats (of approximately 850 species), like anthropoid primates and guinea pigs, are unable to synthesize vitamin C because they lack L-gulonolactone oxidase. When present, this enzyme catalyzes the final step in the biosynthesis of L-ascorbic acid from glucose. These species are Pteropus medius (= P. giganteus), a fructivore of the suborder Megachiroptera, and Vesperugo abramus (presumably Pipistrellus coromandrd), an insectivore of the only other chiropteran suborder, the Microchiroptera. We have assayed livers of 34 species of New World microchiropteran bats for L-gulonolactone oxidase .... These species represent six families, temperate and tropical environments, and a wide variety of food habits and life histories. Within the limits of our assay, we could not detect L-gulonolactone oxidase in livers of any of the species examined. This greatly strengthens the hypothesis that all members of the Chiroptera lack the ability to synthesize vitamin C, which is surprising considering the diversity of bats and their many highly specialized diets.
Birney EC et al; Nature 260: 626-8 (1976). Available from, as of Aug 19, 2010: https://www.nature.com/nature/journal/v260/n5552/abs/260626a0.html

14.2.5 Artificial Pollution Sources

L-Ascorbic acid's production and use in nutrition, color fixing, flavoring and preservative in meats and other foods, as an oxidant in bread dough, in abscission of citrus fruit in harvesting, as a reducing agent in analytical chemistry(1) and as an antimicrobial and antioxidant in foodstuffs(2) may result in its release to the environment through various waste streams(SRC).
(1) Lewis RJ Sr; Hawley's Condensed Chemical Dictionary 15th ed. New York, NY: John Wiley & Sons, Inc., p. 103 (2007)
(2) O'Neil MJ, ed; The Merck Index. 14th ed., Whitehouse Station, NJ: Merck and Co., Inc., p. 136 (2006)

14.2.6 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a log Kow of -1.85(2) and a regression-derived equation(3), indicates that L-ascorbic acid is expected to have very high mobility in soil(SRC). The pKa of L-ascorbic acid is 4.70(4), 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(5). Volatilization from moist soil is not expected because the acid exists as an anion and anions do not volatilize. L-Ascorbic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.8X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(6). L-Ascorbic acid exhibited moderate biodegradation using an enriched consortia derived from domestic sewage(7), suggesting that biodegradation is an important environmental fate process in soil(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Avdeef A; Seminar on Ionization and Lipophilicity. Log P values measured by pION Inc., Brookline, MA (1997)
(3) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm as of Feb 18, 2010.
(4) Kortum G et al; Dissociation Constants of Organic Acids in Aqueous Solution. International Union of Pure and Applied Chemistry. London: Butterworth (1961)
(5) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(6) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(7) Sharma A et al; Bull Environ Contam Toxicol 57: 34-40 (1996)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a log Kow of -1.85(2) and a regression-derived equation(3), indicates that L-ascorbic acid is not expected to adsorb to suspended solids and sediment(SRC). A pKa of 4.70(4) indicates L-ascorbic acid will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water and moist soil surfaces is not expected to be an important fate process(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). L-Ascorbic acid is easily oxidized in aqueous solution in the presence of air(8). L-Ascorbic acid exhibited moderate biodegradation using an enriched consortia derved from domestic sewage(9), suggesting that biodegradation is an important environmental fate process in water(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Avdeef A; Seminar on Ionization and Lipophilicity. Log P values measured by pION Inc., Brookline, MA (1997)
(3) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm as of Feb 18, 2010.
(4) Kortum G et al; Dissociation Constants of Organic Acids in Aqueous Solution. International Union of Pure and Applied Chemistry. London: Butterworth (1961)
(5) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds, Boca Raton, FL: Lewis Publ (2000)
(6) Franke C et al; Chemosphere 29: 1501-14 (1994)
(7) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
(8) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, DC: Taylor and Francis (1989)
(9) Sharma A et al; Bull Environ Contam Toxicol 57: 34-40 (1996)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), L-ascorbic acid, which has an estimated vapor pressure of 9.8X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase L-ascorbic acid may be removed from the air by wet or dry deposition(SRC). L-Ascorbic acid contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)

14.2.7 Environmental Biodegradation

AEROBIC: Using a mixed microbial consortia enriched from untreated sewage samples collected in the vicinity of a primary treatment plant in Delhi, India, L-ascorbic acid exhibited 36.7 mg/L BOD, suggesting moderate susceptibility to biodegradation(1).
(1) Sharma A et al; Bull Environ Contam Toxicol 57: 34-40 (1996)

14.2.8 Environmental Abiotic Degradation

L-Ascorbic acid is expected to undergo hydrolysis in the environment due to the presence of functional groups that hydrolyze under environmental conditions(1). L-Ascorbic acid is stable in the dry state but is easily oxidized in aqueous solution in the presence of air. Oxidation is accelerated by heat, light, alkalies, oxidative enzymes, and traces of copper and iron(2). L-Ascorbic acid contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC). The half-lives of L-ascorbic acid in surface water and at a meter depth exposed to continuous June sunlight and adjusted to pH 8.0. was reported as 3.5 and 9.0 hours, respectively. Samples were obtained from the Greifensee, a polluted alpine lake in Switzerland. The half-life in the top meter of the Greifensee was 1.0 days, study conducted on July 25, 1985(4).
(1) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5 (1990)
(2) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, DC: Taylor and Francis (1989)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)
(4) Faust BC, Hoigne J; Environ Sci Technol 21: 957-64 (1987)

14.2.9 Environmental Bioconcentration

An estimated BCF of 3 was calculated in fish for L-ascorbic acid(SRC), using a log Kow of -1.85(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 (1997)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm as of Feb 18, 2010.
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

14.2.10 Soil Adsorption / Mobility

The Koc of L-ascorbic acid is estimated as 10(SRC), using a log Kow of -1.85(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that L-ascorbic acid is expected to have very high mobility in soil. The pKa of L-ascorbic acid is 4.70(4), 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(5).
(1) Avdeef A; Seminar on Ionization and Lipophilicity. Log P values measured by pION Inc., Brookline, MA (1997)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. Available from https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm as of Feb 18, 2010.
(3) Swann RL et al; Res Rev 85: 17-28 (1983)
(4) Kortum G et al; Dissociation Constants of Organic Acids in Aqueous Solution. International Union of Pure and Applied Chemistry. London: Butterworth (1961)
(5) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)

14.2.11 Volatilization from Water / Soil

A pKa of 4.70(1) indicates L-ascorbic acid will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water and moist soil surfaces is not expected to be an important fate process(2). L-Ascorbic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.8X10-11 mm Hg(SRC), determined from a fragment constant method(3).
(1) Kortum G et al; Dissociation Constants of Organic Acids in Aqueous Solution. International Union of Pure and Applied Chemistry. London: Butterworth (1961)
(2) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(3) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)

14.2.12 Food Survey Values

Dietary sources of L-ascorbic acid include citrus fruits, pototoes, peppers, leafy green vegetables such as broccoli, cabbage, and rose hips(1). It has also been identified in acerola (West Indian cherry) and tomatoes(2).
(1) O'Neil MJ, ed; The Merck Index. 14th ed. Whitehouse Station, NJ: Merck and Co., Inc., p. 136 (2006)
(2) Lewis RJ Sr; Hawley's Condensed Chemical Dictionary., 15th ed., New York, NY: John Wiley & Sons, Inc., p. 103 (2007)
Plants with the highest amount of Ascorbic acid(1).
Genus species
Myrciaria dubia (Kunth) MCVAUGH
Common name(s)
Araza de Agua (Sp.), Camo Camo (Peru), Camu- camu (Eng.,Peru,Scn.,Sp.), Camu-camu Negro (Peru), Guapuro Blanco (Bol.), Rumberry (Eng.)
Concentration
20,890 - 499,000 ppm
Area of Plant
Fruit
Genus species
Malpighia glabra L.
Common name(s)
Acerola
Concentration
16,228 - 172,231 ppm
Area of Plant
Fruit
Genus species
Momordica charantia L.
Common name(s)
Bitter Melon, Sorosi
Concentration
570 - 36,447 ppm
Area of Plant
Fruit
Genus species
Phyllanthus emblica L.
Common name(s)
Emblic, Myrobalan
Concentration
2,760 - 27,293 ppm
Area of Plant
Fruit
Genus species
Rosa canina L.
Common name(s)
Dog Rose, Dogbrier, Rose
Concentration
7,400 - 25,000 ppm
Area of Plant
Fruit
Genus species
Capsicum annuum L.
Common name(s)
Bell Pepper, Cherry Pepper, Cone Pepper, Green Pepper, Paprika, Sweet Pepper
Concentration
230 - 20,982 ppm
Area of Plant
Fruit
Genus species
Capsicum frutescens L.
Common name(s)
Cayenne, Chili, Hot Pepper, Red Chili, Spur Pepper, Tabasco
Concentration
350 - 19,992 ppm
Area of Plant
Fruit
Genus species
Armoracia rusticana GAERTN. ET AL.
Common name(s)
Horseradish
Concentration
1,220 - 18,200 ppm
Area of Plant
Plant
Genus species
Anacardium occidentale L.
Common name(s)
Cashew
Concentration
252 - 17,500 ppm
Area of Plant
Fruit
Genus species
Phytolacca americana L.
Common name(s)
Pokeweed
Concentration
1,360 - 16,184 ppm
Area of Plant
Shoot
Genus species
Juglans regia L.
Common name(s)
English Walnut
Concentration
4,500 - 15,000 ppm
Area of Plant
Fruit
Genus species
Basella alba L.
Common name(s)
Vinespinach
Concentration
1,020 - 14,785 ppm
Area of Plant
Leaf
Genus species
Psidium guajava L.
Common name(s)
Guava
Concentration
200 - 14,300 ppm
Area of Plant
Fruit
Genus species
Hippophae rhamnoides L.
Common name(s)
Sallow Thorn, Sea Buckthorn, Yellow Spine
Concentration
500 - 14,000 ppm
Area of Plant
Fruit
Genus species
Nasturtium officinale R. BR.
Common name(s)
Berro, Watercress
Concentration
430 - 13,690 ppm
Area of Plant
Herb
Genus species
Juglans regia L.
Common name(s)
English Walnut
Concentration
8,000 - 13,000 ppm
Area of Plant
Leaf
Genus species
Rosa rubiginosa L.
Common name(s)
Rosa Mosqueta
Concentration
12,500 ppm
Area of Plant
Seed
Genus species
Rosa spp
Common name(s)
Rose Hips
Concentration
1,000 - 12,500 ppm
Area of Plant
Fruit
Genus species
Momordica charantia L.
Common name(s)
Bitter Melon, Sorosi
Concentration
1,700 - 12,412 ppm
Area of Plant
Leaf
Genus species
Rumex acetosa L.
Common name(s)
Garden Sorrel
Concentration
630 - 12,400 ppm
Area of Plant
Leaf
Genus species
Cnidoscolus chayamansa McVAUGH
Common name(s)
Chaya
Concentration
1,960 - 12,200 ppm
Area of Plant
Leaf
Genus species
Rumex acetosella L.
Common name(s)
Sheep Sorrel
Concentration
500 - 12,000 ppm
Area of Plant
Leaf
Genus species
Citrus mitis BLANCO
Common name(s)
Calamansi, Calamondin
Concentration
884 - 11,130 ppm
Area of Plant
Fruit
Genus species
Brassica oleracea var. botrytis l. var. botrytis L.
Common name(s)
Cauliflower
Concentration
911 - 10,360 ppm
Area of Plant
Leaf
Genus species
Ribes nigrum L.
Common name(s)
Black Currant
Concentration
1,200 - 10,030 ppm
Area of Plant
Fruit
Genus species
Manihot esculenta CRANTZ
Common name(s)
Cassava, Tapioca, Yuca
Concentration
800 - 10,000 ppm
Area of Plant
Leaf
Genus species
Allium schoenoprasum L.
Common name(s)
Chives
Concentration
57 - 9,875 ppm
Area of Plant
Leaf
Genus species
Brassica chinensis L.
Common name(s)
Bok-Choy, Celery Cabbage, Celery Mustard, Chinese Cabbage, Chinese Mustard, Chinese White Cabbage, Pak-Choi
Concentration
450 - 9,713 ppm
Area of Plant
Leaf
Genus species
Luffa aegyptiaca MILLER
Common name(s)
Luffa, Smooth Loofah, Vegetable Sponge
Concentration
950 - 9,596 ppm
Area of Plant
Leaf
Genus species
Medicago sativa subsp. sativa
Common name(s)
Alfalfa, Lucerne
Concentration
1,470 - 9,364 ppm
Area of Plant
Plant
(1) USDA; Dr. Duke's Phytochemical and Ethnobotanical Databases. Plants with a chosen chemical. Ascorbic acid. Washington, DC: US Dept Agric, Agric Res Service. Available from, as of August 19, 2010: https://www.ars-grin.gov/duke/

14.2.13 Plant Concentrations

L-Ascorbic acid levels in six wild mushroom species, common to the Northeast and Beira Interior regions of Portugal, were as follows (mg/kg): Amanita caesarea, 2071.46; Boletus edulis, not detected; Gyroporus castaneus, not detected; Lactarius deliciosus, not detected to 972.81; Suillus collinitus, 92.40 to 3788.04; Xerocornus chrysenteron, not detected. Samples were collected in 2003(1).
(1) Valentao P et al; J Agric Food Chem 53: 3626-3630 (2005)

14.2.14 Milk Concentrations

ENVIRONMENTAL: L-Ascorbic acid is distributed into milk. Milk of nursing mothers on a normal diet contains 40-70 ug of the vitamin per mL.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 2305

14.2.15 Probable Routes of Human Exposure

According to the 2006 TSCA Inventory Update Report, the number of workers reasonably likely to be exposed in the industrial manufacturing, processing, and use for L-ascorbic acid is 1 to 99 persons; the data may be greatly underestimated(1).
(1) US EPA; Inventory Update Reporting (IUR). Non-confidential 2006 IUR Records by Chemical, including Manufacturing, Processing and Use Information. Washington, DC: U.S. Environmental Protection Agency. Available from, as of Feb 18, 2010: https://cfpub.epa.gov/iursearch/index.cfm
NIOSH (NOES Survey 1981-1983) has statistically estimated that 137,698 workers (84,231 of these were female) were potentially exposed to L-ascorbic acid in the US(1). Occupational exposure to L-ascorbic acid may occur through inhalation and dermal contact with this compound at workplaces where L-ascorbic acid is produced or used. Use data indicate that the general population is exposed to L-ascorbic acid via ingestion of food, medicines, and other consumer products containing L-ascorbic 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 Feb 18, 2010: https://www.cdc.gov/noes/

14.2.16 Body Burden

Milk of nursing mothers on a normal diet contains 40-70 ug ... /L-ascorbic acid/ per mL.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993)., p. 2305

15 Associated Disorders and Diseases

Disease
Hyperoxalemia
References
PubMed: 15353324
Disease
Traumatic brain injury
References
Disease
Eosinophilic esophagitis
References
Mordechai, Hien, and David S. Wishart

16 Literature

16.1 Consolidated References

16.2 NLM Curated PubMed Citations

16.3 Springer Nature References

16.4 Thieme References

16.5 Wiley References

16.6 Nature Journal References

16.7 Chemical Co-Occurrences in Literature

16.8 Chemical-Gene Co-Occurrences in Literature

16.9 Chemical-Disease Co-Occurrences in Literature

17 Patents

17.1 Depositor-Supplied Patent Identifiers

17.2 WIPO PATENTSCOPE

17.3 FDA Orange Book Patents

17.4 Chemical Co-Occurrences in Patents

17.5 Chemical-Disease Co-Occurrences in Patents

17.6 Chemical-Gene Co-Occurrences in Patents

18 Interactions and Pathways

18.1 Protein Bound 3D Structures

18.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

18.2 Chemical-Target Interactions

18.3 Drug-Drug Interactions

18.4 Drug-Food Interactions

Avoid multivalent ions. Do not infuse with elemental compounds that can be reduced, such as copper.
Take on an empty stomach. Taking ferrous ascorbate with food reduces the absorption of iron.

18.5 Pathways

19 Biological Test Results

19.1 BioAssay Results

20 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
A metabolome atlas of the aging mouse brain. Nat Commun. 2021 Oct 15;12(1):6021. DOI:10.1038/s41467-021-26310-y. PMID:34654818; PMCID:PMC8519999.
The Metabolome Atlas of the Aging Mouse Brain: https://mouse.atlas.metabolomics.us
A metabolome atlas of the aging mouse brain. Nat Commun. 2021 Oct 15;12(1):6021. DOI:10.1038/s41467-021-26310-y. PMID:34654818; PMCID:PMC8519999.
The Metabolome Atlas of the Aging Mouse Brain: https://mouse.atlas.metabolomics.us

21 Classification

21.1 MeSH Tree

21.2 NCI Thesaurus Tree

21.3 ChEBI Ontology

21.4 KEGG: Metabolite

21.5 KEGG: Drug

21.6 KEGG: USP

21.7 KEGG: ATC

21.8 KEGG: JP15

21.9 KEGG: Risk Category of Japanese OTC Drugs

21.10 KEGG: OTC drugs

21.11 KEGG: Animal Drugs

21.12 WHO ATC Classification System

21.13 FDA Pharm Classes

21.14 EPA Safer Choice

21.15 ChemIDplus

21.16 CAMEO Chemicals

21.17 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

21.18 ChEMBL Target Tree

21.19 UN GHS Classification

21.20 EPA CPDat Classification

21.21 NORMAN Suspect List Exchange Classification

21.22 CCSBase Classification

21.23 EPA DSSTox Classification

21.24 Consumer Product Information Database Classification

21.25 EPA TSCA and CDR Classification

21.26 LOTUS Tree

21.27 EPA Substance Registry Services Tree

21.28 MolGenie Organic Chemistry Ontology

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  27. ChEMBL
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    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
  28. ClinicalTrials.gov
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    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  29. 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
  30. 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
  31. IUPHAR/BPS Guide to PHARMACOLOGY
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    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  32. Therapeutic Target Database (TTD)
  33. 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/
  34. Cosmetic Ingredient Review (CIR)
  35. EPA Chemical and Products Database (CPDat)
  36. 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/
  37. DailyMed
  38. Drug Induced Liver Injury Rank (DILIrank) Dataset
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  39. IUPAC Digitized pKa Dataset
  40. Drugs and Lactation Database (LactMed)
  41. Drugs@FDA
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  42. WHO Model Lists of Essential Medicines
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    https://www.who.int/about/policies/publishing/copyright
  43. ECI Group, LCSB, University of Luxembourg
    LICENSE
    Data: CC-BY 4.0; Code: Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    L-ascorbic acid
  44. Natural Product Activity and Species Source (NPASS)
  45. West Coast Metabolomics Center-UC Davis
    Ascorbic acid (Vitamin C)
  46. EPA Safer Choice
    EPA Safer Chemical Ingredients Classification
    https://www.epa.gov/saferchoice
  47. FDA Orange Book
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  48. Joint FAO/WHO Expert Committee on Food Additives (JECFA)
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    https://www.who.int/about/policies/publishing/copyright
  49. EU Clinical Trials Register
  50. National Drug Code (NDC) Directory
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  51. FDA Substances Added to Food
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  52. Flavor and Extract Manufacturers Association (FEMA)
  53. FooDB
    LICENSE
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    https://foodb.ca/about
  54. SpectraBase
  55. MassBank of North America (MoNA)
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    https://mona.fiehnlab.ucdavis.edu/documentation/license
  56. Japan Chemical Substance Dictionary (Nikkaji)
  57. KEGG
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    https://www.kegg.jp/kegg/legal.html
    Therapeutic category of drugs in Japan
    http://www.genome.jp/kegg-bin/get_htext?br08301.keg
    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
    Classification of Japanese OTC drugs
    http://www.genome.jp/kegg-bin/get_htext?br08313.keg
  58. MarkerDB
    LICENSE
    This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
    https://markerdb.ca/
  59. Metabolomics Workbench
  60. Nature Chemical Biology
  61. NIPH Clinical Trials Search of Japan
  62. NLM RxNorm Terminology
    LICENSE
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    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  63. NTP Technical Reports
  64. Pharos
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    https://pharos.nih.gov/about
  65. Protein Data Bank in Europe (PDBe)
  66. RCSB Protein Data Bank (RCSB PDB)
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    https://www.rcsb.org/pages/policies
  67. Springer Nature
  68. SpringerMaterials
    (R)-5-(1,2-Dihydroxy-ethyl)-3,4-dihydroxy-5H-furan-2-one
    https://materials.springer.com/substanceprofile/docs/smsid_razupmjnphlkfvzc
  69. The Cambridge Structural Database
  70. Thieme Chemistry
    LICENSE
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    https://creativecommons.org/licenses/by-nc-nd/4.0/
  71. WHO Anatomical Therapeutic Chemical (ATC) Classification
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    https://www.whocc.no/copyright_disclaimer/
  72. Wikidata
  73. Wikipedia
  74. Wiley
  75. Medical Subject Headings (MeSH)
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    https://www.nlm.nih.gov/copyright.html
  76. PubChem
  77. GHS Classification (UNECE)
  78. EPA Substance Registry Services
  79. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  80. PATENTSCOPE (WIPO)
  81. NCBI
CONTENTS