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Tryptophan

PubChem CID
6305
Structure
Tryptophan_small.png
Tryptophan_3D_Structure.png
Tryptophan__Crystal_Structure.png
Molecular Formula
Synonyms
  • L-tryptophan
  • tryptophan
  • 73-22-3
  • h-Trp-oh
  • L-Tryptophane
Molecular Weight
204.22 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2004-09-16
  • Modify:
    2025-01-18
Description
L-tryptophan is a white powder with a flat taste. An essential amino acid; occurs in isomeric forms. (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-tryptophan is the L-enantiomer of tryptophan. It has a role as an antidepressant, a nutraceutical, a micronutrient, a plant metabolite, a human metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite and a mouse metabolite. It is an erythrose 4-phosphate/phosphoenolpyruvate family amino acid, a proteinogenic amino acid, a tryptophan and a L-alpha-amino acid. It is a conjugate base of a L-tryptophanium. It is a conjugate acid of a L-tryptophanate. It is an enantiomer of a D-tryptophan. It is a tautomer of a L-tryptophan zwitterion.
An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor of indole alkaloids in plants. It is a precursor of serotonin (hence its use as an antidepressant and sleep aid). It can be a precursor to niacin, albeit inefficiently, in mammals.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Tryptophan.png

1.2 3D Conformer

1.3 Crystal Structures

1 of 2
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CCDC Number
Crystal Structure Data
Crystal Structure Depiction
Crystal Structure Depiction

2 Biologic Description

SVG Image
SVG Image
IUPAC Condensed
H-Trp-OH
Sequence
W
PLN
H-W-OH
HELM
PEPTIDE1{W}$$$$
IUPAC
L-tryptophan

3 Names and Identifiers

3.1 Computed Descriptors

3.1.1 IUPAC Name

(2S)-2-amino-3-(1H-indol-3-yl)propanoic acid
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

3.1.2 InChI

InChI=1S/C11H12N2O2/c12-9(11(14)15)5-7-6-13-10-4-2-1-3-8(7)10/h1-4,6,9,13H,5,12H2,(H,14,15)/t9-/m0/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.3 InChIKey

QIVBCDIJIAJPQS-VIFPVBQESA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.4 SMILES

C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)N
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

3.2 Molecular Formula

C11H12N2O2
Computed by PubChem 2.2 (PubChem release 2021.10.14)

3.3 Other Identifiers

3.3.1 CAS

54-12-6
73-22-3

3.3.3 Deprecated CAS

154635-35-5, 2416148-24-6, 6912-86-3, 80206-30-0
154635-35-5, 2416148-24-6, 2831375-12-1, 6912-86-3, 80206-30-0
154635-35-5, 80206-30-0

3.3.4 European Community (EC) Number

3.3.5 UNII

3.3.6 ChEBI ID

3.3.7 ChEMBL ID

3.3.8 DrugBank ID

3.3.9 DSSTox Substance ID

3.3.10 HMDB ID

3.3.11 KEGG ID

3.3.12 Metabolomics Workbench ID

3.3.13 NCI Thesaurus Code

3.3.14 Nikkaji Number

3.3.15 NSC Number

3.3.16 PharmGKB ID

3.3.17 Pharos Ligand ID

3.3.18 RXCUI

3.3.19 Wikidata

3.3.20 Wikipedia

3.4 Synonyms

3.4.1 MeSH Entry Terms

  • Ardeydorm
  • Ardeytropin
  • L Tryptophan
  • L Tryptophan ratiopharm
  • L-Tryptophan
  • L-Tryptophan-ratiopharm
  • Levotryptophan
  • Lyphan
  • Naturruhe
  • Optimax
  • PMS Tryptophan
  • PMS-Tryptophan
  • ratio Tryptophan
  • ratio-Tryptophan
  • Trofan
  • Tryptacin
  • Tryptan
  • Tryptophan
  • Tryptophan Metabolism Alterations

3.4.2 Depositor-Supplied Synonyms

4 Chemical and Physical Properties

4.1 Computed Properties

Property Name
Molecular Weight
Property Value
204.22 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
-1.1
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
204.089877630 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
204.089877630 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
79.1 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
15
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
245
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
1
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)

4.2 Experimental Properties

4.2.1 Physical Description

L-tryptophan is a white powder with a flat taste. An essential amino acid; occurs in isomeric forms. (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.
Solid; [Merck Index] White to slightly yellowish-white odorless solid; [HSDB] White powder; [Sigma-Aldrich MSDS]
Solid

4.2.2 Color / Form

Leaflets or plates from dilute alcohol
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1682
White to slightly yellowish-white ... crystals or crystalline powder
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 61

4.2.3 Odor

Odorless
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 61

4.2.4 Taste

FLAT TASTE
Sax, N.I. and R.J. Lewis, Sr. (eds.). Hawley's Condensed Chemical Dictionary. 11th ed. New York: Van Nostrand Reinhold Co., 1987., p. 1197
Slightly bitter
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 61

4.2.5 Melting Point

554 to 558 °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.
290.5 dec °C
PhysProp
282 °C (decomposes)
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-514
230 °C

4.2.6 Solubility

1 to 5 mg/mL at 68 °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.
13400 mg/L (at 25 °C)
YALKOWSKY,SH & DANNENFELSER,RM (1992)
Slightly soluble in acetic acid, ethanol; insoluble in ethyl ether
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-514
Solubility in water: 0.23 g/L at 0 °C, 11.4 g/L at 25 °C, 17.1 g/L at 50 °C, 27.95 g/L at 75 °C, 49.9 g/L at 100 °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. 1682
Soluble 1 in 100 of water; very slightly soluble in alcohol; practically insoluble chloroform and ether; soluble in hot alcohol and solutions of dilute acids and alkali hydroxides.
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 61
13.4 mg/mL at 25 °C
YALKOWSKY,SH & DANNENFELSER,RM (1992)

4.2.7 LogP

-1.06
HANSCH,C ET AL. (1995)
log Kow = -1.06
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 84
-1.06
HANSCH,C ET AL. (1995)

4.2.8 LogS

-1.23
ADME Research, USCD

4.2.9 Optical Rotation

Specific optical rotation: -31.5 deg at 23 °C/D (water, 1%), +2.4 deg at 20 °C/D (hydrochloric acid, 0.5 N); +0.15 deg at 20 °C/D (sodium hydroxide, 2.43% in 0.5 N)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1682
Specific optical rotation: +6.1 deg at 20 °C/D (In Sodium hydroxide, 11%)
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V5: 5159

4.2.10 Decomposition

When heated to decomposition it emits toxic fumes of /nitric oxide/.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3632

4.2.11 pH

A 1% solution in water has a pH of 5.5 to 7.
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 61

4.2.12 Ionization Efficiency

1 of 2
Ionization mode
Positive
logIE
2.62
pH
2.7
Instrument
Agilent XCT
Ion source
Electrospray ionization
Additive
formic acid (5.3nM)
Organic modifier
MeCN (80%)
2 of 2
Ionization mode
Negative
logIE
-0.05
pH
10.5
Instrument
Agilent XCT
Ion source
Electrospray ionization
Additive
ammonia (10nM)
Organic modifier
MeCN (80%)

4.2.13 Dissociation Constants

Acidic pKa
2.36
Comparison of the accuracy of experimental and predicted pKa values of basic and acidic compounds. Pharm Res. 2014; 31(4):1082-95. DOI:10.1007/s11095-013-1232-z. PMID:24249037
Basic pKa
9.42
Comparison of the accuracy of experimental and predicted pKa values of basic and acidic compounds. Pharm Res. 2014; 31(4):1082-95. DOI:10.1007/s11095-013-1232-z. PMID:24249037
pKa
7.38 (at 25 °C)
KORTUM,G ET AL (1961)
pK1 = 2.38 /SRC: carboxylic acid/; pK2 = 9.39 /SRC: primary amine/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1682

4.2.14 Collision Cross Section

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

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

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

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

Ross et al. JASMS 2022; 33; 1061-1072. DOI:10.1021/jasms.2c00111
145 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine]

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

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

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

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

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

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

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

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

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

151.3 Ų [M+H]+

147.2 Ų [M+Na]+

149.1 Ų [M-H]-

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

4.2.15 Other Experimental Properties

Decomposes at 289 °C (rapid heating)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1683
Needles from methanol, decomposes at 251 °C /Tryptophan hydrochloride/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1682
UV: 3453 (Sadtler Research Laboratories Spectral Collection) /Tryptophan (DL)/
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V5: 5158

4.3 Chemical Classes

Biological Agents -> Amino Acids and Derivatives

4.3.1 Drugs

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

4.3.2 Cosmetics

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

4.3.3 Food Additives

NUTRIENT SUPPLEMENT -> FDA Substance added to food

5 Spectral Information

5.1 1D NMR Spectra

1D NMR Spectra
1H NMR: 582 (Sadtler Research Laboratories Spectral Collection) /Tryptophan (DL)/
1D NMR Spectra
1H NMR: 582 (Sadtler Research Laboratories Spectral Collection) /Tryptophan (D)/
1D NMR Spectra
1H NMR: 582 (Sadtler Research Laboratories Spectral Collection)

5.1.1 1H NMR Spectra

1 of 3
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Spectra ID
Instrument Type
Varian
Frequency
600 MHz
Solvent
Water
pH
7.01
Shifts [ppm]:Intensity
7.18:28.34, 7.29:26.36, 3.49:28.18, 3.29:30.90, 7.54:57.52, 3.31:40.03, 7.73:56.45, 3.30:39.12, 4.05:46.99, 7.20:35.67, 3.46:37.67, 4.04:48.48, 7.20:37.75, 4.04:44.05, 3.48:28.24, 7.72:59.68, 3.27:29.68, 7.26:30.43, 7.31:100.00, 7.27:54.19, 7.26:33.07, 4.06:41.14, 7.29:27.35, 3.46:36.33, 7.19:60.66, 7.52:64.21
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Copyright
Database Compilation Copyright © 2021-2024 John Wiley & Sons, Inc. All Rights Reserved.
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5.1.2 13C NMR Spectra

1 of 4
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Spectra ID
Instrument Type
Bruker
Frequency
125 MHz
Solvent
Water
pH
7.00
Shifts [ppm]:Intensity
121.12:9.80, 122.12:9.70, 110.32:2.97, 127.84:7.10, 139.13:2.78, 177.16:4.10, 124.78:9.80, 114.66:9.10, 29.15:8.45, 57.93:7.86, -0.00:0.83, 129.36:2.67
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Spectra ID
Frequency
400 MHz
Solvent
H2O
Shifts [ppm]
122.12, 29.15, 121.12, 57.93, 124.78, 177.16, 139.13, 114.66, 127.84, 129.36, 110.32
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5.2 2D NMR Spectra

5.2.1 1H-1H NMR Spectra

2D NMR Spectra Type
1H-1H TOCSY
Spectra ID
Shifts [ppm] (F2:F1)
7.20:7.54, 3.46:7.30, 7.20:7.26, 4.18:4.81, 3.46:3.28, 3.30:4.04, 7.07:7.07, 4.04:3.32, 7.72:7.17, 7.27:7.52, 7.72:7.54, 7.53:7.26, 4.44:4.79, 4.81:4.81, 7.53:7.29, 4.04:4.04, 7.72:7.28, 7.27:7.19, 3.30:3.30, 7.53:7.18, 7.30:7.30, 7.72:7.52, 3.46:3.32, 4.04:3.46, 3.30:3.45, 7.27:7.21, 4.04:3.50, 7.30:7.34, 7.20:7.28, 7.20:7.17, 3.30:3.26, 7.27:7.71, 7.72:7.71, 3.30:3.32, 3.47:3.46, 7.20:7.73, 4.04:3.30, 7.53:7.19, 7.53:7.71, 7.27:7.54, 3.47:3.49, 7.27:7.26, 4.34:4.79, 7.72:7.21, 7.53:7.52, 7.72:7.26, 3.30:7.30, 3.46:3.26, 7.27:7.28, 4.81:4.96, 4.98:4.80, 7.53:7.73, 7.27:7.73, 7.72:7.19, 7.72:7.73, 7.53:7.21, 4.04:3.28, 4.04:3.26, 7.20:7.19, 4.24:4.79, 7.53:7.28, 7.20:7.21, 3.88:4.81, 7.20:7.52, 3.30:3.29, 3.46:4.04, 7.20:7.71, 7.72:7.29, 3.46:3.30, 2.97:4.81
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5.2.2 1H-13C NMR Spectra

2D NMR Spectra Type
1H-13C HSQC
Spectra ID
Instrument Type
Bruker
Frequency
600 MHz
Solvent
Water
pH
7.00
Shifts [ppm] (F2:F1):Intensity
7.72:121.19:0.30, 7.19:122.18:0.52, 7.53:114.73:0.29, 7.31:127.92:1.00, 3.46:29.13:0.16, 4.04:57.92:0.47, 7.27:124.88:0.32, 3.29:29.13:0.18
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5.3 Mass Spectrometry

5.3.1 GC-MS

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Spectra ID
Instrument Type
GC-MS
Top 5 Peaks

130.0 1

131.0 0.15

77.0 0.08

132.0 0.06

103.0 0.05

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Spectra ID
Instrument Type
GC-MS
Top 5 Peaks

202.0 1

203.0 0.23

291.0 0.11

204.0 0.07

218.0 0.06

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5.3.2 MS-MS

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Spectra ID
Instrument Type
Quattro_QQQ
Ionization Mode
Positive
Top 5 Peaks

187.876 100

145.929 25.88

204.892 17.06

158.96 4.93

143.914 4.12

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Notes
delivery=Flow_Injectionanalyzer=Triple_Quad
2 of 6
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Spectra ID
Instrument Type
Quattro_QQQ
Ionization Mode
Positive
Top 5 Peaks

117.837 100

145.913 60.47

143.243 19.57

131.953 18.80

142.087 17.25

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Notes
delivery=Flow_Injectionanalyzer=Triple_Quad

5.3.3 LC-MS

1 of 64
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Authors
da Silva KM, Iturrospe E, van de Lavoir M, Robeyns R, University of Antwerp, Belgium
Instrument
Agilent 6530 QTOF
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
10 eV
Fragmentation Mode
CID
Retention Time
0.219 min
Precursor m/z
205.0972
Precursor Adduct
[M+H]+
Top 5 Peaks

188.0715 999

146.0606 726

118.0656 267

144.0814 165

159.0905 74

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License
CC BY
2 of 64
View All
Authors
BGC, Helmholtz Zentrum Muenchen
Instrument
maXis plus UHR-ToF-MS, Bruker Daltonics
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
10
Fragmentation Mode
CID
Column Name
BEH C18 1.7um, 2.1x100mm, Waters
Retention Time
2.369 min
Precursor m/z
205.0972
Precursor Adduct
[M+H]+
Top 5 Peaks

188.0699 999

205.0965 153

146.0598 40

159.0909 15

144.0805 4

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License
CC BY

5.3.4 Other MS

1 of 7
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Other MS
MASS: 1229 (National Bureau of Standards EPA-NIH Mass Spectra Data Base, NSRDS-NBS-63) /Tryptophan (DL)/
Other MS
MASS: 1229 (National Bureau of Standards EPA-NIH Mass Spectra Data Base, NSRDS-NBS-63) /Tryptophan (D)/
Other MS
MASS: 25370 (NIST/EPA/MSDC Mass Spectral Database, 1990 version); 1707 (National Bureau of Standards)
2 of 7
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Authors
YAMAMOTO M, DEP. CHEMISTRY, FAC. SCIENCE, NARA WOMEN'S UNIV.
Instrument
HITACHI M-2500
Instrument Type
EI-B
MS Level
MS
Ionization Mode
POSITIVE
Ionization
ENERGY 70 eV
Top 5 Peaks

130 999

131 125

204 84

103 53

129 40

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License
CC BY-NC-SA

5.4 UV Spectra

MAX ABSORPTION (WATER): 280 NM (LOG E= 3.72)
Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-534
UV: 17157 (Sadtler Research Laboratories Spectral Collection)
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V5: 5159

5.5 IR Spectra

IR Spectra
IR: 8612 (Sadtler Research Laboratories IR Grating Collection) /Tryptophan (DL)/

5.5.1 FTIR Spectra

1 of 2
Technique
KBr WAFER
Source of Sample
Fluka Chemie AG, Buchs, Switzerland
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Technique
Mull
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Aldrich
Catalog Number
T90204
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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5.5.2 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
Calbiochem, EMD Chemicals, Inc., an Affiliate of Merck KGaA, Darmstadt, Germany
Catalog Number
6540
Lot Number
101772
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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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/T0254>T0254</a>
Lot Number
64H0331
Copyright
Copyright © 2014-2024 John Wiley & Sons, Inc. All Rights Reserved.
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5.6 Raman Spectra

1 of 2
Instrument Name
Bruker MultiRAM Stand Alone FT-Raman Spectrometer
Source of Spectrum
Zenodo
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Copyright © 2023-2024 John Wiley & Sons, Inc. All Rights Reserved.
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Bruker MultiRAM Stand Alone FT-Raman Spectrometer
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7 Chemical Vendors

8 Drug and Medication Information

8.1 Drug Indication

Tryptophan may be useful in increasing serotonin production, promoting healthy sleep, managing depression by enhancing mental and emotional well-being, managing pain tolerance, and managing weight.

8.2 FDA National Drug Code Directory

8.3 Drug Labels

Active ingredient and drug
Homeopathic product and label

8.4 Clinical Trials

8.4.1 ClinicalTrials.gov

8.4.2 EU Clinical Trials Register

8.4.3 NIPH Clinical Trials Search of Japan

8.5 Therapeutic Uses

Tryptophan is a precursor of serotonin. Because CNS depletion of serotonin is considered to be involved in depression, tryptophan has been used in its treatment. Although it has been given alone, evidence of effectiveness is scant and tryptophan has generally been used as adjunctive therapy in depression. It has sometimes been given with pyridoxine and ascorbic acid, which are involved in its metabolism to serotonin
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.427.
/EXPTL USE/: Inhibition of Walker 256 intramuscular carcinoma in rats by admin of l-tryptophan.
Gold J; Oncology 24 (4): 291-303 (1970)
(L)-Tryptophan decreases sleep latency and slightly increases sleeping time without altering qualitative characteristics of polygraphic patterns during sleep in normal subjects. In insomniac patients, it increases sleeping time and decreases both sleep latency and number of awakenings.
Hartmann E et al; Psychopharmacologia 19 (2): 114 (1971)
Beneficial effects were observed when L-tryptophan was administered to 2 patients with myoclonus. In each case suspension of methylcellulose and water containing 1 g of (L)-tryptophan/15 mL was prepared and administered orally at a level of 10 g daily in 5 divided doses.
Delean J, Richardson JC; Lancet 2 (7940): 870-1 (1975)
For more Therapeutic Uses (Complete) data for (L)-Tryptophan (11 total), please visit the HSDB record page.

8.6 Drug Warnings

Since serotonin plays a role in inducing and maintaining sleep, l-tryptophan has been administered orally to increase brain levels of serotonin. Although a dose of 1 g significantly decreased sleep latency and total time awake without altering sleep patterns, the hypnotic action is observed only during the early part of the sleep cycle, is unpredictable, and is not characterized by a satisfactory dose-response relationship. Because the hypnotic action has not been confirmed in other studies, this use of l-tryptophan must be considered investigational and the drug is not recommended in routine clinical practice. In order to avoid central serotonergic toxicity, tryptophan should not be used in patients also receiving a monoamine oxidase inhibitor or the serotonin uptake inhibitor, fluoxetine (Prozac).
American Medical Association. AMA Drug Evaluations Annual 1991. Chicago, IL: American Medical Association, 1991., p. 215
Tryptophan-containing products have been associated with the eosinophilia-myalgia syndrome. Other adverse effects that have been reported include nausea, headache, lightheadedness, and drowsiness.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.427.
An increased incidence of bladder tumours has been reported in mice given l-tryptophan orally as well as in cholesterol pellets embedded in the bladder lumen. However, there was no increase in tumour incidence when only high-dose, oral tryptophan was given.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.427.
Tryptophan has been associated with eosinophilia-myalgia syndrome; caution is advised in patients receiving the drug who develop some, but not all, of the symptoms of this syndrome. It should not be used in those with a history of eosinophilia-myalgia syndrome associated with tryptophan treatment.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.427.
For more Drug Warnings (Complete) data for (L)-Tryptophan (7 total), please visit the HSDB record page.

8.7 Drug Idiosyncrasies

The concomitant admin of tryptophan and a monoamine oxidase inhibitor may provoke a reaction likened to inebriation and may enhance the effects of the monoamine oxidase inhibitor. If concomitant admin is desired the initial dose of tryptophan should be 500 mg daily, gradually increased after one week. Such treatment should be initiated in hospital.
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 61

8.8 Biomarker Information

9 Food Additives and Ingredients

9.1 FDA Substances Added to Food

Substance
Used for (Technical Effect)
NUTRIENT SUPPLEMENT
Document Number (21 eCFR)

10 Pharmacology and Biochemistry

10.1 Pharmacodynamics

Tryptophan is critical for the production of the body's proteins, enzymes and muscle tissue. It is also essential for the production of niacin, the synthesis of the neurotransmitter serotonin and melatonin. Tryptophan supplements can be used as natural relaxants to help relieve insomnia. Tryptophan can also reduce anxiety and depression and has been shown to reduce the intensity of migraine headaches. Other promising indications include the relief of chronic pain, reduction of impulsivity or mania and the treatment of obsessive or compulsive disorders. Tryptophan also appears to help the immune system and can reduce the risk of cardiac spasms. Tryptophan deficiencies may lead to coronary artery spasms. Tryptophan is used as an essential nutrient in infant formulas and intravenous feeding. Tryptophan is marketed as a prescription drug (Tryptan) for those who do not seem to respond well to conventional antidepressants. It may also be used to treat those afflicted with seasonal affective disorder (a winter-onset depression). Tryptopan serves as the precursor for the synthesis of serotonin (5-hydroxytryptamine, 5-HT) and melatonin (N-acetyl-5-methoxytryptamine).

10.2 MeSH Pharmacological Classification

Antidepressive Agents, Second-Generation
A structurally and mechanistically diverse group of drugs that are not tricyclics or monoamine oxidase inhibitors. The most clinically important appear to act selectively on serotonergic systems, especially by inhibiting serotonin reuptake. (See all compounds classified as Antidepressive Agents, Second-Generation.)

10.3 ATC Code

N - Nervous system

N06 - Psychoanaleptics

N06A - Antidepressants

N06AX - Other antidepressants

N06AX02 - Tryptophan

10.4 Bionecessity

... Skin is an optically inhomogeneous medium; reflection, refraction, scattering, and absorption all modify the radiation that reaches deeper structures. Important UV absorbers within the epidermis incl melanin, which varies greatly in content and location between individuals and races; urocanic acid, a deamination product of histidine found in sweat; and for shorter wavelengths, proteins containing tryptophan and tyrosine. The net optical effect is that shorter wavelengths are selectively absorbed in the superficial layers, although a biologically significant amt of UV-B reaches the dermis ... .
Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991., p. 476
An essential amino acid for human development; precursor of serotonin.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1682
...Tryptophan is a significant precursor of niacin for humans. It is for this reason that high corn diets result in clinical deficiency (pellagra) of niacin, corn being particularly deficient in tryptophan.
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 89
Corn and cereal grains contain fairly adequate quantities of niacin, but the vitamin is in a bound and unavailable form. They are also low in tryptophan. The combination of low tryptophan and unavailable dietary niacin results in a niacin deficiency. In current feeding practice in intensive agriculture situations, niacin or tryptophan should be added to high-concentrate diets of poultry and pigs.
Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University Press, 1982., p. 637
For more Bionecessity (Complete) data for (L)-Tryptophan (30 total), please visit the HSDB record page.

10.5 Absorption, Distribution and Excretion

(L)-Tryptophan with plant oils in soft gelatin capsules permitted lower dosage than with usual dosage form. Max of free tryptophan in serum was achieved in 1st hr whereas 4-5 times as much would be required with tablets or hard gelatin capsules.
Klosa J; Ger Offen Patent NO 2824362 12/13/79
Absorption and Fate. Tryptophan is readily absorbed from the gastro-intestinal tract. Tryptophan is extensively bound to serum albumin. It is metabolized to serotonin and other metabolites, incl kynurenine derivatives, and excreted in the urine. Pyridoxine and ascorbic acid appear to be concerned in its metabolism.
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 61
Although the free amino acids dissolved in the body fluids are only a very small proportion of the body's total mass of amino acids, they are very important for the nutritional and metabolic control of the body's proteins. ... Although the plasma compartment is most easily sampled, the concentration of most amino acids is higher in tissue intracellular pools. Typically, large neutral amino acids, such as leucine and phenylalanine, are essentially in equilibrium with the plasma. Others, notably glutamine, glutamic acid, and glycine, are 10- to 50-fold more concentrated in the intracellular pool. Dietary variations or pathological conditions can result in substantial changes in the concentrations of the individual free amino acids in both the plasma and tissue pools. /Amino acids/
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 596, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
After ingestion, proteins are denatured by the acid in the stomach, where they are also cleaved into smaller peptides by the enzyme pepsin, which is activated by the increase in stomach acidity that occurs on feeding. The proteins and peptides then pass into the small intestine, where the peptide bonds are hydrolyzed by a variety of enzymes. These bond-specific enzymes originate in the pancreas and include trypsin, chymotrypsins, elastase, and carboxypeptidases. The resultant mixture of free amino acids and small peptides is then transported into the mucosal cells by a number of carrier systems for specific amino acids and for di- and tri-peptides, each specific for a limited range of peptide substrates. After intracellular hydrolysis of the absorbed peptides, the free amino acids are then secreted into the portal blood by other specific carrier systems in the mucosal cell or are further metabolized within the cell itself. Absorbed amino acids pass into the liver, where a portion of the amino acids are taken up and used; the remainder pass through into the systemic circulation and are utilized by the peripheral tissues. /Amino acids/
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 599, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
For more Absorption, Distribution and Excretion (Complete) data for (L)-Tryptophan (9 total), please visit the HSDB record page.

10.6 Metabolism / Metabolites

Hepatic.
In Hartnup disease ... tryptophane appear/s/ in urine due to defective renal and intestinal absorption of tryptophane ... It is an intermediary metabolite in the synthesis of serotonin (5-hydroxytryptamine) and 5-hydroxyindole acetic acid (HIAA).
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 590
Patients with bladder cancer excreted significantly more kynurenic acid, acetylkynurenine, kynurenine, and 3-hydroxykynurenine after ingesting a loading dose of L-tryptophan than did control subjects with no known disease.
Searle, C. E. (ed.). Chemical Carcinogens. ACS Monograph 173. Washington, DC: American Chemical Society, 1976., p. 443
Tryptophan is metabolized in the liver by tryptophan pyrrolase and tryptophan hydroxylase. Metabolites include hydroxytryptophan, which is then converted to serotonin, and kynurenine derivatives. Some tryptophan is converted to nicotinic acid and nicotinamide. Pyridoxine and ascorbic acid are cofactors in the decarboxylation and hydroxylation, respectively, of tryptophan; pyridoxine apparently prevents the accumulation of the kynurenine metabolites.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.427.
Yields indole-3-pyruvic acid in man ... and in rats; yields tryptamine in guinea pigs. /From table/
Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. T-38
For more Metabolism/Metabolites (Complete) data for (L)-Tryptophan (21 total), please visit the HSDB record page.

10.7 Biological Half-Life

The biological half-life of tryptophan was reported to be 15.8 hr.
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 61

10.8 Mechanism of Action

A number of important side reactions occur during the catabolism of tryptophan on the pathway to acetoacetate. The first enzyme of the catabolic pathway is an iron porphyrin oxygenase that opens the indole ring. The latter enzyme is highly inducible, its concentration rising almost 10-fold on a diet high in tryptophan. Kynurenine is the first key branch point intermediate in the pathway. Kynurenine undergoes deamniation in a standard transamination reaction yielding kynurenic acid. Kynurenic acid and metabolites have been shown to act as antiexcitotoxics and anticonvulsives. A second side branch reaction produces anthranilic acid plus alanine. Another equivalent of alanine is produced further along the main catabolic pathway, and it is the production of these alanine residues that allows tryptophan to be classified among the glucogenic and ketogenic amino acids. The second important branch point converts kynurenine into 2-amino-3-carboxymuconic semialdehyde, which has two fates. The main flow of carbon elements from this intermediate is to glutarate. An important side reaction in liver is a transamination and several rearrangements to produce limited amounts of nicotinic acid, which leads to production of a small amount of NAD+ and NADP+.
Findings indicate that enhanced rates of serotonin turnover produced by (L)-tryptophan and physical restraint are associated with inhibition of thyroid-stimulating hormone (TSH) and stimulation of prolactin release from anterior pituitary in rats.
Mueller GP et al; Life Sci 18 (7): 715-24 (1976)
L-Tryptophan, an indispensable amino acid, serves as a precursor for several small molecules of functional significance including the vitamin niacin, the neurotransmitter serotonin, the metabolite tryptamine, and the pineal hormone melatonin. Increases in tryptophan have been shown to increase synthesis of the neurotransmitters in brain, blood, and other body organs.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 731, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
Amino acids are selected for protein synthesis by binding with transfer RNA (tRNA) in the cell cytoplasm. The information on the amino acid sequence of each individual protein is contained in the sequence of nucleotides in the messenger RNA (mRNA) molecules, which are synthesized in the nucleus from regions of DNA by the process of transcription. The mRNA molecules then interact with various tRNA molecules attached to specific amino acids in the cytoplasm to synthesize the specific protein by linking together individual amino acids; this process, known as translation, is regulated by amino acids (e.g., leucine), and hormones. Which specific proteins are expressed in any particular cell and the relative rates at which the different cellular proteins are synthesized, are determined by the relative abundances of the different mRNAs and the availability of specific tRNA-amino acid combinations, and hence by the rate of transcription and the stability of the messages. From a nutritional and metabolic point of view, it is important to recognize that protein synthesis is a continuing process that takes place in most cells of the body. In a steady state, when neither net growth nor protein loss is occurring, protein synthesis is balanced by an equal amount of protein degradation. The major consequence of inadequate protein intakes, or diets low or lacking in specific indispensable amino acids relative to other amino acids (often termed limiting amino acids), is a shift in this balance so that rates of synthesis of some body proteins decrease while protein degradation continues, thus providing an endogenous source of those amino acids most in need. /Amino acids/
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 601-602, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
The mechanism of intracellular protein degradation, by which protein is hydrolyzed to free amino acids, is more complex and is not as well characterized at the mechanistic level as that of synthesis. A wide variety of different enzymes that are capable of splitting peptide bonds are present in cells. However, the bulk of cellular proteolysis seems to be shared between two multienzyme systems: the lysosomal and proteasomal systems. The lysosome is a membrane-enclosed vesicle inside the cell that contains a variety of proteolytic enzymes and operates mostly at acid pH. Volumes of the cytoplasm are engulfed (autophagy) and are then subjected to the action of the protease enzymes at high concentration. This system is thought to be relatively unselective in most cases, although it can also degrade specific intracellular proteins. The system is highly regulated by hormones such as insulin and glucocorticoids, and by amino acids. The second system is the ATP-dependent ubiquitin-proteasome system, which is present in the cytoplasm. The first step is to join molecules of ubiquitin, a basic 76-amino acid peptide, to lysine residues in the target protein. Several enzymes are involved in this process, which selectively targets proteins for degradation by a second component, the proteasome.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 602, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
For more Mechanism of Action (Complete) data for (L)-Tryptophan (7 total), please visit the HSDB record page.

10.9 Human Metabolite Information

10.9.1 Tissue Locations

  • Fibroblasts
  • Neuron
  • Placenta
  • Prostate

10.9.2 Cellular Locations

Extracellular

10.9.3 Metabolite Pathways

10.10 Biochemical Reactions

10.11 Transformations

11 Use and Manufacturing

11.1 Uses

Cosmetic Ingredient Review Link
CIR ingredient: Tryptophan
Sources/Uses
An essential amino acid; Used in biochemical research; [Merck Index] Used as a nutritional supplement for foods; [FDA] Used as a dietary supplement, for research, cereal enrichment, and as a medication; [HSDB] 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.
Nutrition and research; medicine; dietary supplement; cereal enrichment /Tryptophan/
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 1292
Probe for studying protein structure and dynamics
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1683
Nutritional supplement (amino acid) in drugs and foods
SRI
BIOLOGICAL ACTIVITIES: Analgesic; Antidementia; Antidepressant; Antidyskinetic; Antihypertensive; Antiinsomniac; Antimanic; Antimenopausal; Antimigraine; Antioxidant; Antiparkinsonian; Antiphenylketonuric; Antiprostaglandin; Antipsychotic; Antirheumatic; Antiscolioticn;;Carcinogenic; Essential; Hypnotic; Hypoglycemic; Hypotensive; Insulinase-Inhibitor; Insulinotonic;Monoamine-Precursor; Prolactinogenic; Sedative; Serotoninergic; Tumor-Promoter /Tryptophan/
Dr. Duke's Phytochemical and Ethnobotanical Databases. Plants with a chosen chemical. Tryptophan. Washington, DC: US Dept Agric, Agric Res Service. Available from, as of August 13, 2010: https://www.ars-grin.gov/duke/
For more Uses (Complete) data for (L)-Tryptophan (6 total), please visit the HSDB record page.

Use (kg; approx.) in Germany (2009): >5000

Consumption (g per capita; approx.) in Germany (2009): 0.0611

Calculated removal (%): 75.1

Tryptophan may be useful in increasing serotonin production, promoting healthy sleep, managing depression by enhancing mental and emotional well-being, managing pain tolerance, and managing weight.

11.1.1 Use Classification

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

11.2 Methods of Manufacturing

Fermentation of natural or biologically available substances with Corynebacterium glutamicum; enzymatically from indole, pyruvic acid, and ammonia using microbial tryptophanase
SRI
Synthesis starting with beta-indolylaldehyde and hippuric acid; ... from hydantoin; alternate route starting with 3-indoleacetonitrile.
Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 1540

11.3 Formulations / Preparations

Grades: Reagent; Technical; Food Chemicals Codex /Tryptophan/
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 1292
(L)-Tryptophan with plant oils in soft gelatin capsules.
Klosa J; Ger Offen Patent No 2824362 12/13/79

11.4 U.S. Production

(1977) Not produced commercially in USA
SRI
(1979) Not produced commercially in USA
SRI
Production volumes for non-confidential chemicals reported under the Inventory Update Rule.
Year
1986
Production Range (pounds)
10 thousand - 500 thousand
Year
1990
Production Range (pounds)
No Reports
Year
1994
Production Range (pounds)
No Reports
Year
1998
Production Range (pounds)
No Reports
Year
2002
Production Range (pounds)
No Reports
US EPA; Non-confidential Production Volume Information Submitted by Companies for Chemicals Under the 1986-2002 Inventory Update Rule (IUR). L-Tryptophan (73-22-3). Available from, as of March 23, 2010: https://www.epa.gov/oppt/iur/tools/data/2002-vol.html

11.5 U.S. Imports

(1977) 2.34 X 10+7 g (Princpl Custms Dists)
SRI
(1979) 2.47 X 10+7 g (Princpl Custms Dists)
SRI

11.6 General Manufacturing Information

EPA TSCA Commercial Activity Status
Tryptophan: ACTIVE
EPA TSCA Commercial Activity Status
L-Tryptophan: ACTIVE
An essential amino acid for human development; precursor of serotonin.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1682
60 mg of tryptophan is approx equiv to 1.0 mg of niacin. /Tryptophan/
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 89
The amino acids that are incorporated into mammalian protein are alpha-amino acids, with the exception of proline, which is an alpha-imino acid. This means that they have a carboxyl group, an amino nitrogen group, and a side chain attached to a central alpha-carbon. Functional differences among the amino acids lie in the structure of their side chains. In addition to differences in size, these side groups carry different charges at physiological pH (e.g., nonpolar, uncharged but polar, negatively charged, positively charged); some groups are hydrophobic (e.g., branched chain and aromatic amino acids) and some hydrophilic (most others). These side chains have an important bearing on the ways in which the higher orders of protein structure are stabilized and are intimate parts of many other aspects of protein function.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 592, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html

12 Identification

12.1 Analytic Laboratory Methods

Method: AOAC 960.47; Procedure: microbiological, turbidimetric and titrimetric methods; Analyte: tryptophan; Matrix: vitamin preparations; Detection Limit: not provided.
Official Methods of Analysis of AOAC International, 18th Edition Online. Tryptophan (73-22-3). Available from, as of March 25, 2010: https://www.aoac.org
Method: AOAC 988.15; Procedure: ion exchange chromatographic method; Analyte: tryptophan; Matrix: foods and food & feed ingredients; Detection Limit: not provided.
Official Methods of Analysis of AOAC International, 18th Edition Online. Tryptophan (73-22-3). Available from, as of March 25, 2010: https://www.aoac.org
TECHNIQUE OF DOUBLE-BEAM FLUORESCENCE SPECTROPHOTOMETRY FOR DETERMINATION OF TRYPTOPHAN IN PROTEINS.
PORRO TJ, TERHAAR DA; ANAL CHEM 48 (13): 1103 (1976)
Determination of tryptophan in foods by isocratic reversed-phase HPLC.
Hagen SR, Augustin J; J Micronutr Anal 5 (4): 303-9 (1989)

12.2 Clinical Laboratory Methods

The plasma levels of 5-HT and its metabolites were determined by a HPLC system coupled with an amperometric detector. The HPLC system uses a reversed-phase column IRICA RP-18, with 4-hydroxyphenylacetic acid as internal std. The detection sensitivity of the HPLC system for 5-HTP, 5-HT, tryptophan, and 5-HIAA was 6.0, 7.1, 17.5, and 7.6 pg, resptively, with recovery rates of apprx 99% and intrassay relative standard deviations of <5%
Okatani Y, Sagara Y; Sanfujinka Chiryo 56 (2): 230 (1988)
An HPLC method for the determination of tryptophan and its metabolites in maternal and umbilical cord plasma is described. Chromatography was carried out on a column packed with 10 um IRICA RP-18 using as mobile phase a mixture of 0.1 M NaOAc, 0.1 M citric acid, 0.03 mM Na2EDTA, and 5-30% acetonitrile or 10-37% MeOH. Recovery range was99.0-100.7% for tryptophan and its metabolites. Interassay relative standard deviation was in the range of 1.5-5.7% for tryptophan and its metabolites. Detection limits were <150 pg/ml for 5-HTP, 177.5 pg/ml for 5-HT): 190 pg/ml for 5-HIAA, 437 pg/ml for tryptophan. The detection limits for 5-HT and 5-HIAA were sufficient for clinical determination of pregnancy. The method was applied to the determination of tryptophan and metabolites in maternal vein plasma and in umbilical artery and vein plasma.
Sagara Y et al; J Chromatogr 431 (1): 170-6 (1988)
A capillary electrophoresis method for separation and detection with time-of-flight mass spectrometry is described for tryptophan metabolites in the kynurenic pathway...
Arvidsson B et al; J Chromatog A 1159 (1-22): 154-8 (2007). Available from, as of March 17, 2010: https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17477928
A liquid chromatographic-tandem mass spectrometric method measures 3-hydroxykynurenine and 3-hydroxyanthranilic acid in addition to tryptophan and kynurenine both intra- and extracellularly. After reversed phase HPLC separation, the compounds were detected in the MS positive multiple reaction monitoring mode...
Yamada K et al; J Chromatog B 867 (1): 57-61 (2008). Available from, as of March 17, 2010: https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18395499

13 Safety and Hazards

13.1 Hazards Identification

13.1.1 GHS Classification

Note
This chemical does not meet GHS hazard criteria for 98.8% (238 of 241) of all reports. Pictograms displayed are for 1.2% (3 of 241) of reports that indicate hazard statements.
GHS Hazard Statements

Not Classified

Reported as not meeting GHS hazard criteria by 238 of 241 companies (only 1.2% companies provided GHS information). For more detailed information, please visit ECHA C&L website.

ECHA C&L Notifications Summary

Aggregated GHS information provided per 241 reports by companies from 5 notifications to the ECHA C&L Inventory.

Reported as not meeting GHS hazard criteria per 238 of 241 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 3 notifications provided by 3 of 241 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 Health Hazards

ACUTE/CHRONIC HAZARDS: When heated to decomposition this compound emits toxic 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.

13.1.4 Fire Hazards

Flash point data for this chemical are not available. 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.

13.1.5 Hazards Summary

Teratogenic effects observed in experimental animals at high doses; [Shepard's Catalog of Teratogenic Agents] No evidence of carcinogenicity in rats or mice; [NTP] May cause irritation; The FDA and CDC have established a possible link between L-tryptophan and eosinophilia-myalgia syndrome; [Sigma-Aldrich MSDS]

13.2 First Aid Measures

13.2.1 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.

13.3 Fire Fighting

Fires involving this material should be controlled using a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

13.4 Accidental Release Measures

13.4.1 Disposal Methods

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.
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: 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.

13.5 Handling and Storage

13.5.1 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 keep this material in a tightly-closed container under an inert atmosphere, and store it in a refrigerator. (NTP, 1992)

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

13.5.2 Storage Conditions

Protect from light
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 61

13.6 Exposure Control and Personal Protection

13.6.1 Allowable Tolerances

Residues of tryptophan are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. Use: synergist. Limit: maximum of 5% of formulation.
40 CFR 180.920 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 22, 2010: https://www.ecfr.gov

13.6.2 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 Stability and Reactivity

13.7.1 Air and Water Reactions

Slightly soluble in water.

13.7.2 Reactive Group

Salts, Acidic

13.7.3 Reactivity Profile

Acidic salts, such as L-TRYPTOPHAN, are generally soluble in water. The resulting solutions contain moderate concentrations of hydrogen ions and have pH's of less than 7.0. They react as acids to neutralize bases. These neutralizations generate heat, but less or far less than is generated by neutralization of inorganic acids, inorganic oxoacids, and carboxylic acid. They usually do not react as either oxidizing agents or reducing agents but such behavior is not impossible. Many of these compounds catalyze organic reactions.

13.8 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: Tryptophan
The Australian Inventory of Industrial Chemicals
Chemical: L-Tryptophan
REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
Tryptophan: Does not have an individual approval but may be used under an appropriate group standard
New Zealand EPA Inventory of Chemical Status
l-Tryptophan: Does not have an individual approval but may be used under an appropriate group standard

13.8.1 FIFRA Requirements

Residues of tryptophan are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. Use: synergist. Limit: maximum of 0.5% of formulation.
40 CFR 180.920 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 22, 2010: https://www.ecfr.gov

13.8.2 FDA Requirements

L-Tryptophan is a food additive permitted for direct addition to food for human consumption, as long as 1) the quantity of the substance added to food does not exceed the amount reasonably required to accomplish its intended physical, nutritive, or other technical effect in food, and 2) any substance intended for use in or on food is of appropriate food grade and is prepared and handled as a food ingredient.
21 CFR 172.320 (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: tryptophan 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 22, 2010: https://www.ecfr.gov

13.9 Other Safety Information

Chemical Assessment

IMAP assessments - DL-Tryptophan: Environment tier I assessment

Evaluation - Chemicals that are unlikely to require further regulation to manage risks to human health

Chemical Assessment

IMAP assessments - L-Tryptophan: Environment tier I assessment

Evaluation - Chemicals that are unlikely to require further regulation to manage risks to human health

13.9.1 History and Incidents

In late 1989 the first notification linking the eosinophilia-myalgia syndrome with the use of tryptophan-containing products was made in the USA. There followed a number of similar published case reports from the USA, Europe, and Japan. Reviews of tryptophan-associated eosinophilia-myalgia syndrome have noted that by early 1990 over 1500 cases were known in the USA. In early 1990 the CDC in the USA summarized the features and known reports concerning the syndrome. As the name implies the characteristic features are an intense eosinophilia together with disabling fatigue and muscle pain, although multisystem organ involvement and inflammatory disorders affecting the joints, skin, connective tissue, lungs, heart, and liver have also been recorded. Symptoms have generally developed over several weeks and the syndrome has occurred in patients who had been receiving tryptophan for many years previously with no untoward effect. In most patients slow and gradual improvement in the degree of eosinophilia and other clinical manifestations has followed the withdrawal of tryptophan, but in some patients the disease has progressed despite withdrawal and there have been fatalities. The inflammatory condition has necessitated the use of corticosteroids in some patients. The eosinophilia-myalgia syndrome has been reported in patients taking both tryptophan-containing prescription products for depression and non-prescription dietary supplements for a number of disorders including insomnia, the premenstrual syndrome, and stress; it does not appear to have occurred in patients receiving amino-acid preparations containing tryptophan as part of total parenteral nutrition regimens. The recognition of this syndrome led to the withdrawal of tryptophan-containing products or severe restrictions being imposed upon their use in many countries during 1990. Various theories were proposed as to the reason for the association of tryptophan with this syndrome. Confusion existed because the reports implicated a very wide range of products from different manufacturers. However, later evidence appeared to have confirmed that contaminated tryptophan had originated from a single manufacturer in Japan. Bulk tryptophan was imported from Japan for manufacture into finished pharmaceutical dosage forms and it was noted in one of these reports that a single product was often found to contain two or more lots of powdered tryptophan that were blended together during the production of tablets or capsules. Many trace contaminants have been found in batches of tryptophan associated with the syndrome. One contaminant has been identified as 1,1'-ethylidenebis(tryptophan). Its inclusion in bulk tryptophan powder appeared to coincide with alterations in the manufacturing conditions that involved a change in the strain of Bacillus amyloliquefaciens used in the fermentation process and a reduction in the amount of charcoal used for purification. Other investigations indicated the presence of bacitracin-like peptides in batches of the contaminated tryptophan. However, further work has provided only weak support for an association between the syndrome and any one particular contaminant and the causative agent remains to be confirmed. Nonetheless, since the syndrome only appeared to be associated with tryptophan from one manufacturer, tryptophan preparations were reintroduced in the UK in 1994 for restricted use under carefully monitored conditions. In January 2005, the UK requirement for patient registration and monitoring was removed.[Sweetman SC (ed), Martindale: The Complete Drug Reference.
online] London: Pharmaceutical Press. Available from, as of January 19, 2010: https://www.medicinescomplete.com/

13.9.2 Special Reports

NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C. (2009).[Available from, as of March 10, 2010: http://www.nap.edu/catalog/10490.html]
DHEW/NCI; Bioassay of L-Tryptophan for Possible Carcinogenicity CAS No. 73-22-3 (NCI-CG-TR-71) (1978) Technical Report Series No. 71 DHEW Pub No. (NIH) 78-1321[Available from, as of March 29, 2010: http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr071.pdf]

14 Toxicity

14.1 Toxicological Information

14.1.1 Toxicity Summary

A number of important side reactions occur during the catabolism of tryptophan on the pathway to acetoacetate. The first enzyme of the catabolic pathway is an iron porphyrin oxygenase that opens the indole ring. The latter enzyme is highly inducible, its concentration rising almost 10-fold on a diet high in tryptophan. Kynurenine is the first key branch point intermediate in the pathway. Kynurenine undergoes deamniation in a standard transamination reaction yielding kynurenic acid. Kynurenic acid and metabolites have been shown to act as antiexcitotoxics and anticonvulsives. A second side branch reaction produces anthranilic acid plus alanine. Another equivalent of alanine is produced further along the main catabolic pathway, and it is the production of these alanine residues that allows tryptophan to be classified among the glucogenic and ketogenic amino acids. The second important branch point converts kynurenine into 2-amino-3-carboxymuconic semialdehyde, which has two fates. The main flow of carbon elements from this intermediate is to glutarate. An important side reaction in liver is a transamination and several rearrangements to produce limited amounts of nicotinic acid, which leads to production of a small amount of NAD+ and NADP+.

14.1.2 Carcinogen Classification

1 of 2
Substance
NTP Technical Report
TR-071: Bioassay of L-Tryptophan for Possible Carcinogenicity (CASRN 73-22-3) (1978 )
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
It is concluded that under the conditions of this bioassay, L-tryptophan was not carcinogenic for Fischer 344 rats or B6C3F1 mice.
2 of 2
Carcinogen Classification
No indication of carcinogenicity to humans (not listed by IARC).

14.1.3 Symptoms

Symptoms of overdose include agitation, confusion, diarrhea, fever, overactive reflexes, poor coordination, restlessness, shivering, sweating, talking or acting with excitement you cannot control, trembling or shaking, twitching, and vomiting.

14.1.4 Acute Effects

14.1.5 Interactions

Acetylsalicylic acid reduced serum-protein binding of tryptophan in man, causing rise in free serum tryptophan. Changes in metabolic pattern also occurred, with increased urinary excretion of xanthurenic acid and 3-hydroxylkynurenine and decreased excretion of 3-hydroxyanthranilic acid.
Searle, C. E. (ed.). Chemical Carcinogens. ACS Monograph 173. Washington, DC: American Chemical Society, 1976., p. 441
Although tryptophan has been given to patients receiving MAOIs in the belief that clinical efficacy may be improved, it should be noted that the adverse effects may also be potentiated.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.427.
Use of tryptophan with drugs that inhibit the reuptake of serotonin may exacerbate the adverse effects of the latter and precipitate the serotonin syndrome.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.427.
There have been occasional reports of sexual disinhibition in patients taking tryptophan with phenothiazines or benzodiazepines.
Sweetman SC (ed), Martindale: The Complete Drug Reference. London: Pharmaceutical Press (2009), p.427.
For more Interactions (Complete) data for (L)-Tryptophan (16 total), please visit the HSDB record page.

14.1.6 Antidote and Emergency Treatment

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

14.1.7 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ Serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in human blood and brain cerebrospinal fluid (CSF) increase /were found/ after tryptophan loading, which is similar to the effects of L-tryptophan in animals. ... Elevations in blood and 5-HIAA and CSF serotonin after single doses of 3 or 6 g of L-tryptophan. However, ... a double-blind, placebo-controlled trial in six normal men fed 3 g/day of L-tryptophan in divided doses with meals for 3 days, found a 113% elevation in plasma tryptophan, but no changes in platelet or plasma serotonin or in plasma catecholamines. ... No changes in urinary catecholamines /were found/. Additionally, no changes in blood pressure, heart rate, plasma sodium levels or 24-hour sodium excretion in urine /were found/.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 732, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
/HUMAN EXPOSURE STUDIES/ L-Tryptophan administration (2 g) as a single dose before a meal has been found to decrease subjective hunger ratings, food intake, and alertness in men, but not women.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 732, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
/HUMAN EXPOSURE STUDIES/ 15 humans /were tested/ only once with 0, 1, 2, and 3 g of L-tryptophan. Individuals receiving 2 and 3 g of L-tryptophan had decreased hunger and alertness and increased faintness and dizziness. Administration of 1 g of L-tryptophan with 10 g of carbohydrates before each meal (3 g L-tryptophan/d) for 3 months did not affect body weight of obese humans.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 732, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
/HUMAN EXPOSURE STUDIES/ Daily doses of 2.4 g of L-tryptophan for 2 weeks did not produce a significant reduction in the consumption of carbohydrate snacks in the majority of the 24 individuals.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 732-733, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
For more Human Toxicity Excerpts (Complete) data for (L)-Tryptophan (19 total), please visit the HSDB record page.

14.1.8 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ The hematologic and pathologic effects of orally administered L-tryptophan and indoleacetic acid and of L-tryptophan administered iv were studied in ponies. Sixteen adult Shetland ponies were allotted into 4 experimental groups. Group 1 consisted of 5 ponies (1-5) given 0.6 g of tryptophan/kg of body weight in a water slurry via stomach tube. Group 2 included 4 ponies (6-9) given 0.35 g of tryptophan/kg orally. Group 3 ponies (10-13) were given 0.35 g of indoleacetic acid/kg orally. Group 4 consisted of 3 ponies (14-16) given a single 4 hr iv infusion of 0.1 g of tryptophan/kg. Restlessness, increased respiratory rate, hemolysis, and hemoglobinuria were detected in 4 of the 5 group-1 ponies. Only pony 7 in group 2 developed hemolysis, hemoglobinuria, and a significant increase in respiratory rate. Renal pathologic lesions, consistent with hemoglobinuric nephrosis, were seen in ponies 2, 4, 5, and 7. Bronchiolar degeneration was evident in 4 of 9 ponies given tryptophan orally. The importance of these respiratory lesions was unknown. Clinical or pathologic abnormalities were not noticed in the ponies of groups 3 and 4. Mean plasma tryptophan values increased significantly in groups 1 and 2 at 6 hours after dosing. A second peak of tryptophan was detected in both groups at 12 hours. Values returned to predose values by 48 hours. Plasma indole and 3-methylindole concentrations were detectable in only 2 ponies (4 and 7). In vitro incubations of cecal fluid from ponies 6, 8, and 9 yielded a percentage conversion of tryptophan to indole of 16.75%, 5.84%, and 7.96% respectively. 3-Methylindole was not produced. These results suggested that indole was the major metabolite of orally administered tryptophan in these ponies.
Paradis MR et al; Am J Vet Res 52 (5): 742-7 (1991).
/LABORATORY ANIMALS: Acute Exposure/ High L-tryptophan concentrations, similar to those found in hypertryptophanemic patients were induced by three subcutaneous injections of saline-buffered tryptophan (2 umol/g body weight) to 30-day-old Wistar rats. The parameters were assessed 1 hr after the last injection. It was observed that tryptophan significantly increased thiobarbituric acid-reactive substances, 2',7'-dihydrodichlorofluorescein oxidation and reduced glutathione, whereas it reduced catalase activity. Pre-treatment with taurine (1.6 umol/g of body weight), or alpha-tocopherol plus ascorbic acid (40 and 100 ug/g body weight, respectively) prevented those effects of tryptophan, reinforcing the hypothesis that tryptophan induces oxidative stress in brain cortex of the rats...
Feksa LR et al; Metabol Brain Dis 23 (2): 221-33 (2008). Available from, as of March 17, 2010: https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18425567
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Several rodent studies have demonstrated that supplementation of low-protein diets with L-tryptophan (5%) reduces food intake and weight gain over a 4-day to 4-week period found that rats given a 20% casein diet supplemented with 14.3% tryptophan for 4 weeks developed scaly tails and thinning hair. However, no adverse effects were seen when the diets contained 1.4 or 2.9% L-tryptophan.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 732, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In pigs, supplementation with 0.1 or 1% L-tryptophan for up to 40 days did not affect weight gain, but 2 or 4% decreased weight gain and 4% also decreased food intake.
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 732, 2009. Available from, as of March 10, 2010: https://www.nap.edu/catalog/10490.html
For more Non-Human Toxicity Excerpts (Complete) data for (L)-Tryptophan (22 total), please visit the HSDB record page.

14.1.9 Non-Human Toxicity Values

LD50 Rat ip 1634 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. 3632
LD50 Mouse ip 4800 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. 3632

14.1.10 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=73-22-3]

14.1.11 National Toxicology Program Studies

A bioassay of the amino acid L-tryptophan for possible carcinogenicity was conducted by administering the test compound to Fischer 344 rats and B6C3F1 mice. Groups of 35 rats and 35 mice of each sex were administered the test compound at one of two doses, either 25,000 or 50,000 ppm, 5 day/wk for 78 wk, and then observed for 26 or 27 wk. Matched controls consisted of groups of 15 rats or 15 mice of each sex. All surviving rats and mice were sacrificed at 104 or 105 wk ... No neoplasms occurred in a statistically significant incidence among dosed rats when compared with controls. In both male and female mice, neoplasms of the hematopoietic system occurred at higher incidences in the low dose groups than in the matched control groups ... These incidences, however, are not statistically significant, ... therefore, no tumors are considered to be related to the administration of the test chemical ... It is concluded that under the conditions of this bioassay, L-tryptophan was not carcinogenic for Fischer 344 rats or B6C3F1 mice.
DHEW/NCI; Bioassay of L-Tryptophan for Possible Carcinogenicity p.vii (1978) Technical Rpt Series No. 071 DHEW Pub No. (NIH) 78-1321

14.2 Ecological Information

14.2.1 Environmental Fate / Exposure Summary

(L)-Tryptophan's production and use in nutrition and research, in medicine, as a dietary supplement, and in cereal enrichment may result in its release to the environment through various waste streams. The compound is an essential amino acid for human development. If released to air, an estimated vapor pressure of 2.1X10-9 mm Hg at 25 °C indicates (L)-tryptophan will exist solely in the particulate phase in the atmosphere. Particulate-phase (L)-tryptophan will be removed from the atmosphere by wet or dry deposition. (L)-Tryptophan in aqueous solution is susceptible to direct photolysis by sunlight, with the oxidation products kynurenine and N-formylkynurenine accumulated most readily at pH 4-7.5. If released to soil, (L)-tryptophan is expected to have moderate mobility based upon an estimated Koc of 320. The pKa values of pKa1 2.38 (carboxylic acid) and pKa2 9.39 (primary amine) indicate that this compound will exist as a zwitterion which may affect its adsorption to soils and sediments. Volatilization from moist soil is not expected because ions do not volatilize. (L)-Tryptophan may not volatilize from dry soil surfaces based upon its vapor pressure. Using the Warburg respirometer test, theoretical BOD values of 4.6% in 24 hours suggest that biodegradation is not expected to be an important environmental fate process. If released into water, (L)-tryptophan may adsorb to suspended solids and sediment based upon the estimated Koc. The pKa values indicate (L)-tryptophan will exist as a zwitterion at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Occupational exposure to (L)-tryptophan may occur through inhalation and dermal contact with this compound at workplaces where (L)-tryptophan is produced or used. Use data indicate that the general population may be exposed to (L)-tryptophan via ingestion of food, medications and other consumer products containing (L)-tryptophan. (SRC)

14.2.2 Natural Pollution Sources

(L)-Tryptophan is an essential amino acid for human development and a precursor of serotonin(1).
(1) O'Neil MJ, ed; The Merck Index. 14th ed., Whitehouse Station, NJ: Merck and Co., Inc., p. 1683 (2006)
MILK & EGGS ... HAVE HIGH TRYPTOPHAN CONTENT.
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 89

14.2.3 Artificial Pollution Sources

(L)-Tryptophan's production and use in nutrition and research, in medicine, as a dietary supplement, and in cereal enrichment(1) 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. 1292 (2007)

14.2.4 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 320(SRC), determined from a log Kow of -1.06(2) and a regression-derived equation(3), indicates that (L)-tryptophan is expected to have moderate mobility in soil(SRC). The pKa values of pKa1 2.38 (carboxylic acid) and pKa2 9.39 (primary amine)(4) indicate that this compound will exist as a zwitterion which may affect its adsorption to soils and sediments(SRC). Volatilization from moist soil is not expected because ions do not volatilize(SRC). Volatilization from moist soil is not expected because the acid/base exists as an anion/cation and anions/cations do not volatilize. (L)-Tryptophan is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.1X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Using the Warburg respirometer test, a theoretical BOD value of 4.6% in 24 hours(6) suggests that biodegradation is not expected to be an important environmental fate process in soil(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 84 (1995)
(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 17, 2010.
(4) O'Neil MJ, ed; The Merck Index., 14th ed., Whitehouse Station, NJ: Merck and Co., Inc., p. 1683 (2006)
(5) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(6) Malaney GW, Gerhold RM; J Water Pollut Control Fed 41: R18-R33 (1969)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 320(SRC), determined from a log Kow of -1.06(2) and a regression-derived equation(3), indicates that (L)-tryptophan may adsorb to suspended solids and sediment(SRC). The pKa values of pKa1 2.38 (carboxylic acid) and pKa2 9.39 (primary amine)(4) indicate (L)-tryptophan will exist as a zwitterion at pH values of 5 to 9 and therefore volatilization from water 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). Using the Warburg respirometer test, a theoretical BOD value of 4.6% in 24 hours(8) suggests that biodegradation is not expected to be an important environmental fate process in water(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 84 (1995)
(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 17, 2010.
(4) O'Neil MJ, ed; The Merck Index.,14th ed. Whitehouse Station, NJ: Merck and Co., Inc., p. 1683 (2006)
(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) Malaney GW, Gerhold RM; J Water Pollut Control Fed 41: R18-R33 (1969)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), (L)-tryptophan, which has an estimated vapor pressure of 2.1X10-9 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)-tryptophan may be removed from the air by wet or dry deposition(SRC). Photooxidation proceeds primarily by a singlet-oxygen mechanism(3). The oxidation products kynurenine and N-formylkynurenine accumulated most readily at pH 4-7.5 following irradiation of solutions of tryptophan containing riboflavin(4).
(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) Nilsson R et al; Photochem Photobiol 16: 117-24 (1972)
(4) Kanner JD, Fennema O; J Agric Food Chem 35: 71-6 (1987)

14.2.5 Environmental Biodegradation

AEROBIC: At 500 ppm, theoretical BOD values of 0.6, 1.4, and 4.6% in 6, 12, and 24 hours, respectively, were measured for (L)-tryptophan after a 24-hr inoculation period in a Warburg respirometer using an activated sludge inocula, indicating a resistence to biodegradation(1).
(1) Malaney GW, Gerhold RM; J Water Pollut Control Fed 41: R18-R33 (1969)

14.2.6 Environmental Abiotic Degradation

(L)-Tryptophan is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). (L)-Tryptophan in aqueous solution was shown to photodegrade readily over six hours using both an HPLN-N 125 W Phillips lamp as a the near-UV source and natural sunlight(2). Photooxidation proceeds primarily by a singlet-oxygen mechanism(3). The oxidation products kynurenine and N-formylkynurenine accumulated most readily at pH 4-7.5 following irradiation of solutions of tryptophan containing riboflavin(4).
(1) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5 (1990)
(2) Jardim WF, Campos MLAM; Sci Total Environ 75: 243-8 (1988)
(3) Nilsson R et al; Photochem Photobiol 16: 117-24 (1972)
(4) Kanner JD, Fennema O; J Agric Food Chem 35: 71-6 (1987)

14.2.7 Environmental Bioconcentration

An estimated BCF of 3 was calculated in fish for (L)-tryptophan(SRC), using a log Kow of -1.06(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) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 84 (1995)
(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 17, 2010.
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

14.2.8 Soil Adsorption / Mobility

The Koc of (L)-tryptophan is estimated as 320(SRC), using a log Kow of -1.06(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that (L)-tryptophan is expected to have moderate mobility in soil. The pKa values of pKa1 2.38 (carboxylic acid) and pKa2 9.39 (primary amine)(4) indicate that this compound will exist as a zwitterion which may affect its adsorption to soils and sediments(SRC).
(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 84 (1995)
(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 17, 2010.
(3) Swann RL et al; Res Rev 85: 17-28 (1983)
(4) O'Neil MJ, ed; The Merck Index., 14th ed. Whitehouse Station, NJ: Merck and Co., Inc., p. 1683 (2006)

14.2.9 Volatilization from Water / Soil

The pKa values of pKa1 2.38 (carboxylic acid) and pKa2 9.39 (primary amine)(1) indicate (L)-tryptophan will exist as a zwitterion at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(2). (L)-Tryptophan is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.1X10-9 mm Hg(SRC), determined from a fragment constant method(3).
(1) O'Neil MJ, ed; The Merck Index., 14th ed. Whitehouse Station, NJ: Merck and Co., Inc., p. 1683 (2006)
(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)

14.2.10 Plant Concentrations

Plant species with highest amount of tryptophan(1). /Tryptophan/
Genus species
Oenothera biennis L.
Common name(s)
Evening-Primrose
Concentration
2,400 - 16,000 ppm
Area of Plant
Seed
Genus species
Helianthus annuus L.
Common name(s)
Girasol, Sunflower
Concentration
7,037 - 15,900 ppm
Area of Plant
Seed
Genus species
Psophocarpus tetragonolobus (L.) DC.
Common name(s)
Asparagus Pea, Goa Bean, Winged Bean
Concentration
7,620 - 8,313 ppm
Area of Plant
Seed
Genus species
Lablab purpureus (L.) SWEET
Common name(s)
Bonavist Bean, Hyacinth Bean, Lablab Bean
Concentration
880 - 7,255 ppm
Area of Plant
Seed
Genus species
Moringa oleifera LAM.
Common name(s)
Ben Nut, Benzolive Tree, Drumstick Tree, Horseradish Tree, Jacinto (Sp.), Moringa, West Indian Ben
Concentration
1,440 - 6,745 ppm
Area of Plant
Shoot
Genus species
Nasturtium officinale R. BR.
Common name(s)
Berro, Watercress
Concentration
300 - 6,000 ppm
Area of Plant
Herb
Genus species
Psophocarpus tetragonolobus (L.) DC.
Common name(s)
Asparagus Pea, Goa Bean, Winged Bean
Concentration
2,520 - 5,915 ppm
Area of Plant
Tuber
Genus species
Sinapis alba L.
Common name(s)
White Mustard
Concentration
5,260 - 5,628 ppm
Area of Plant
Seed
Genus species
Cucurbita foetidissima HBK.
Common name(s)
Buffalo Gourd
Concentration
1,840 - 5,472 ppm
Area of Plant
Seed
Genus species
Psophocarpus tetragonolobus (L.) DC.
Common name(s)
Asparagus Pea, Goa Bean, Winged Bean
Concentration
1,160 - 5,011 ppm
Area of Plant
Leaf
Genus species
Cicer arietinum L.
Common name(s)
Chickpea, Garbanzo
Concentration
1,850 - 4,970 ppm
Area of Plant
Seed
Genus species
Sesamum indicum L.
Common name(s)
Ajonjoli (Sp.), Beni, Benneseed, Sesame, Sesamo (Sp.)
Concentration
2,010 - 4,969 ppm
Area of Plant
Seed
Genus species
Phaseolus vulgaris subsp. var. vulgaris
Common name(s)
Black Bean, Dwarf Bean, Field Bean, Flageolet Bean, French Bean, Garden Bean, Green Bean, Haricot, Haricot Bean, Haricot Vert, Kidney Bean, Navy Bean, Pop Bean, Popping Bean, Snap Bean, String Bean, Wax Bean
Concentration
440 - 4,731 ppm
Area of Plant
Sprout Seedling
Genus species
Spinacia oleracea L.
Common name(s)
Spinach
Concentration
390 - 4,632 ppm
Area of Plant
Plant
Genus species
Cucurbita pepo L.
Common name(s)
Pumpkin
Concentration
4,310 - 4,630 ppm
Area of Plant
Seed
Genus species
Trigonella foenum-graecum L.
Common name(s)
Alholva (Sp.), Bockshornklee (Ger.), Fenugreek, Greek Clover, Greek Hay
Concentration
2,800 - 4,300 ppm
Area of Plant
Seed
Genus species
Basella alba L.
Common name(s)
Vinespinach
Concentration
280 - 4,060 ppm
Area of Plant
Leaf
Genus species
Corchorus olitorius L.
Common name(s)
Jew's Mallow, Mulukiya, Nalta Jute
Concentration
300 - 4,000 ppm
Area of Plant
Leaf
Genus species
Brassica nigra (L.) W. D. J. KOCH
Common name(s)
Black Mustard
Concentration
270 - 3,976 ppm
Area of Plant
Leaf
Genus species
Vigna radiata (L.) WILCZEK
Common name(s)
Green Gram, Mungbean
Concentration
370 - 3,886 ppm
Area of Plant
Sprout Seedling
Genus species
Allium schoenoprasum L.
Common name(s)
Chives
Concentration
310 - 3,875 ppm
Area of Plant
Leaf
Genus species
Asparagus officinalis L.
Common name(s)
Asparagus
Concentration
300 - 3,871 ppm
Area of Plant
Shoot
Genus species
Juglans cinerea L.
Common name(s)
Butternut
Concentration
3,660 - 3,786 ppm
Area of Plant
Seed
Genus species
Prunus dulcis (MILLER) D. A. WEBB
Common name(s)
Almond
Concentration
3,580 - 3,745 ppm
Area of Plant
Seed
Genus species
Amaranthus sp.
Common name(s)
Pigweed
Concentration
310 - 3,729 ppm
Area of Plant
Leaf
Genus species
Eryngium creticus
Common name(s)
Cretan culantro
Concentration
3,715 ppm
Area of Plant
Shoot
Genus species
Cichorium intybus L.
Common name(s)
Chicory, Succory, Witloof
Concentration
180 - 3,672 ppm
Area of Plant
Leaf
Genus species
Valerianella locusta (L.) LATERRADE
Common name(s)
Corn Salad, Lamb's Lettuce
Concentration
260 - 3,610 ppm
Area of Plant
Plant
Genus species
Portulaca oleracea L.
Common name(s)
Purslane, Verdolaga
Concentration
160 - 3,400 ppm
Area of Plant
Herb
Genus species
Brassica oleracea var. botrytis l. var. botrytis L.
Common name(s)
Cauliflower
Concentration
260 - 3,360 ppm
Area of Plant
Flower
(1) USDA; Dr. Duke's Phytochemical and Ethnobotanical Databases. Plants with a chosen chemical. Isoleucine. Washington, DC: US Dept Agric, Agric Res Service. Available from, as of August 13, 2010: https://www.ars-grin.gov/duke/

14.2.11 Milk Concentrations

Concentrations of tryptophan (free and protein bound) and its metabolites in ... breast milk were determined by high performance liquid chromatography. ... The colostrum contained a high level of total tryptophan. There were high ratios of free to total tryptophan in colostrum, transitional and mature milk. ...
Kamimira S et al; Acta Med Okayama Apr; 45(2): 101-6 (1991). Available from as of Aug 13, 2010:

14.2.12 Probable Routes of Human Exposure

NIOSH (NOES Survey 1981-1983) has statistically estimated that 24,809 workers (2,015 of these were female) were potentially exposed to (L)-tryptophan in the US(1). Occupational exposure to (L)-tryptophan may occur through inhalation and dermal contact with this compound at workplaces where (L)-tryptophan is produced or used. Use data indicate that the general population may be exposed to (L)-tryptophan via ingestion of food and other consumer products containing (L)-tryptophan(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 17, 2010: https://www.cdc.gov/noes/

14.2.13 Body Burden

Concentrations of tryptophan (free and protein bound) and its metabolites in plasma of maternal vein at delivery, umbilical vein, umbilical artery, neonatal vein and breast milk were determined by high performance liquid chromatography. The plasma levels of tryptophan and most of its metabolites in umbilical vein and artery were significantly higher than those in maternal vein. The concentration of total tryptophan in plasma of neonatal vein showed marked decrease at 24 h after birth in comparison with that at birth, but the total kynurenine concentration was not decreased in plasma of neonatal vein. The colostrum contained a high level of total tryptophan. There were high ratios of free to total tryptophan in colostrum, transitional and mature milk. In the blood, ratios of free to total of tryptophan and kynurenine were kept at constant level throughout the perinatal period.
Kamimira S et al; Acta Med Okayama Apr; 45(2): 101-6 (1991). Available from as of Aug 13, 2010:

15 Associated Disorders and Diseases

Disease
Colorectal cancer
References

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

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

Disease
Ovarian cancer
References
Disease
Obesity
References

PubMed: 15899597, 16253646, 2401584, 17264178, 1783639, 26505825, 17408529, 18997681, 24740590, 23108202, 26910390

Metabolomics reveals determinants of weight loss during lifestyle intervention in obese children

Disease
Nicotinamide Adenine Dinucleotide Deficiency
References
PubMed: 28792876
Disease
Hartnup disease
References
PubMed: 2472426
Disease
Leukemia
References
Disease
Olivopontocerebral atrophy
References
Disease
Hereditary spastic paraplegia
References
PubMed: 11383938
Disease
Hypothyroidism
References
Disease
Friedreich's ataxia
References
Disease
Irritable bowel syndrome
References
Disease
Rheumatoid arthritis
References

PubMed: 6589104, 16277678, 15338487, 10361015, 15249323

Tie-juan ShaoZhi-xing HeZhi-jun XieHai-chang LiMei-jiao WangCheng-ping Wen. Characterization of ankylosing spondylitis and rheumatoid arthritis using 1H NMR-based metabolomics of human fecal extracts. Metabolomics. April 2016, 12:70: https://link.springer.com/article/10.1007/s11306-016-1000-2

Disease
Perillyl alcohol administration for cancer treatment
References
Disease
Pancreatic cancer
References
Disease
Periodontal disease
References
PubMed: 20300169
Disease
Frontotemporal dementia
References
PubMed: 23857558
Disease
Lewy body disease
References
PubMed: 23857558
Disease
Attachment loss
References
PubMed: 31026179
Disease
Periodontal Probing Depth
References
PubMed: 31026179
Disease
Cachexia
References
Disease
Eosinophilic esophagitis
References
Mordechai, Hien, and David S. Wishart
Disease
Tryptophanuria with dwarfism
References
PubMed: 14055140

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 Chemical Co-Occurrences in Patents

17.4 Chemical-Disease Co-Occurrences in Patents

17.5 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 Conformer

18.2 Chemical-Target Interactions

18.3 Drug-Drug Interactions

18.4 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

21 Classification

21.1 MeSH Tree

21.2 NCI Thesaurus Tree

21.3 ChEBI Ontology

21.4 KEGG: Metabolite

21.5 KEGG: ATC

21.6 KEGG: JP15

21.7 KEGG: Risk Category of Japanese OTC Drugs

21.8 WHO ATC Classification System

21.9 ChemIDplus

21.10 CAMEO Chemicals

21.11 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

21.12 ChEMBL Target Tree

21.13 UN GHS Classification

21.14 NORMAN Suspect List Exchange Classification

21.15 CCSBase Classification

21.16 EPA DSSTox Classification

21.17 EPA TSCA and CDR Classification

21.18 LOTUS Tree

21.19 EPA Substance Registry Services Tree

21.20 MolGenie Organic Chemistry Ontology

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  26. Comparative Toxicogenomics Database (CTD)
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  27. Drug Gene Interaction database (DGIdb)
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  28. IUPHAR/BPS Guide to PHARMACOLOGY
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    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  29. Therapeutic Target Database (TTD)
  30. Cosmetic Ingredient Review (CIR)
  31. DailyMed
  32. ECI Group, LCSB, University of Luxembourg
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    https://creativecommons.org/licenses/by/4.0/
    L-tryptophan
  33. Natural Product Activity and Species Source (NPASS)
  34. EU Clinical Trials Register
  35. FDA Substances Added to Food
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    Anatomical Therapeutic Chemical (ATC) classification
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    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
  41. Kruve Lab, Ionization & Mass Spectrometry, Stockholm University
    tryptophan
  42. MarkerDB
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    https://markerdb.ca/
  43. Metabolomics Workbench
  44. National Drug Code (NDC) Directory
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  45. Nature Chemical Biology
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  47. Nature Synthesis
  48. NIPH Clinical Trials Search of Japan
  49. NLM RxNorm Terminology
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  52. Pharos
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  55. Springer Nature
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  58. WHO Anatomical Therapeutic Chemical (ATC) Classification
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  63. PubChem
  64. GHS Classification (UNECE)
  65. EPA Substance Registry Services
  66. MolGenie
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  67. PATENTSCOPE (WIPO)
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