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Cysteine

PubChem CID
5862
Structure
Cysteine_small.png
Cysteine_3D_Structure.png
Cysteine__Crystal_Structure.png
Molecular Formula
Synonyms
  • L-cysteine
  • 52-90-4
  • cysteine
  • Cystein
  • (R)-2-Amino-3-mercaptopropanoic acid
Molecular Weight
121.16 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2004-09-16
  • Modify:
    2025-01-04
Description
L-cysteine is an optically active form of cysteine having L-configuration. It has a role as a flour treatment agent, a human metabolite and an EC 4.3.1.3 (histidine ammonia-lyase) inhibitor. It is a serine family amino acid, a proteinogenic amino acid, a cysteine and a L-alpha-amino acid. It is a conjugate base of a L-cysteinium. It is a conjugate acid of a L-cysteinate(1-). It is an enantiomer of a D-cysteine. It is a tautomer of a L-cysteine zwitterion.
A thiol-containing non-essential amino acid that is oxidized to form cystine.
L-Cysteine is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
See also: Cysteine Hydrochloride (has salt form) ... View More ...

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Cysteine.png

1.2 3D Conformer

1.3 Crystal Structures

1 of 16
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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-Cys-OH
Sequence
C
PLN
H-C-OH
HELM
PEPTIDE1{C}$$$$
IUPAC
L-cysteine

3 Names and Identifiers

3.1 Computed Descriptors

3.1.1 IUPAC Name

(2R)-2-amino-3-sulfanylpropanoic acid
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

3.1.2 InChI

InChI=1S/C3H7NO2S/c4-2(1-7)3(5)6/h2,7H,1,4H2,(H,5,6)/t2-/m0/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.3 InChIKey

XUJNEKJLAYXESH-REOHCLBHSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.4 SMILES

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

3.2 Molecular Formula

C3H7NO2S
Computed by PubChem 2.2 (PubChem release 2021.10.14)

3.3 Other Identifiers

3.3.1 CAS

52-90-4
3374-22-9

3.3.3 Deprecated CAS

1404190-35-7, 154605-72-8, 4371-52-2
154605-72-8, 4371-52-2

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 FEMA Number

3.3.11 HMDB ID

3.3.12 JECFA Number

1419

3.3.13 KEGG ID

3.3.14 Metabolomics Workbench ID

3.3.15 NCI Thesaurus Code

3.3.16 Nikkaji Number

3.3.17 PharmGKB ID

3.3.18 RXCUI

3.3.19 Wikidata

3.3.20 Wikipedia

3.4 Synonyms

3.4.1 MeSH Entry Terms

  • Cysteine
  • Cysteine Hydrochloride
  • Half Cystine
  • Half-Cystine
  • L Cysteine
  • L-Cysteine
  • Zinc Cysteinate

3.4.2 Depositor-Supplied Synonyms

4 Chemical and Physical Properties

4.1 Computed Properties

Property Name
Molecular Weight
Property Value
121.16 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
-2.5
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
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
121.01974964 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
121.01974964 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
64.3 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
7
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
75.3
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

Colorless or white solid; [HSDB] Colorless crystalline solid; [Sigma-Aldrich MSDS]
White powder with a sulfurous odor; [Acros Organics MSDS]
Solid
White crystals; Sulferous aroma

4.2.2 Color / Form

Colorless crystals
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 329
White crystals
Ashford, R.D. Ashford's Dictionary of Industrial Chemicals. London, England: Wavelength Publications Ltd., 1994., p. 255

4.2.3 Melting Point

240 dec °C
PhysProp
260 °C decomposes
Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-140
220 °C

4.2.4 Solubility

277000 mg/L (at 25 °C)
BEILSTEIN
Freely soluble in water
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 486
Freely soluble in alcohol, acetic acid, ammonia water; insoluble in ether, acetone, ethyl acetate, benzene, carbon disulfide, carbon tetrachloride
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 486
Water solubility (per g/100 g H2O): 28 g/100 mL of solution at 25 °C; 16 g/100 mL of solution at 20 °C
Drauz K et al; Amino Acids. Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (1999-2016). New York, NY: John Wiley & Sons. Online Posting Date: 15 Apr 2007
277 mg/mL at 25 °C
BEILSTEIN
Very soluble in water and acetic acid; Insoluble in ether, acetone and benzene
Soluble (in ethanol)

4.2.5 Vapor Pressure

0.00000207 [mmHg]

4.2.6 LogP

-2.49
HANSCH,C ET AL. (1995)
log Kow = -2.49
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 6
-2.49
HANSCH,C ET AL. (1995)

4.2.7 Stability / Shelf Life

Stable under recommended storage conditions.
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html
In neutral or slightly alkaline aq solns it is oxidized to cystine by air. More stable in acidic solns.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 497

4.2.8 Optical Rotation

Decomposes 175-178 °C; soluble in water, alcohol, acetone; the aqueous solution is acid; decomposes and oxidizes slowly; hygroscopic. Specific optical rotation: +5.0 °C (5 N HCl) at 25 °C/D; +10.0 °C at 25 °C/D (glacial acetic acid) /Cysteine hydrochloride/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 486
Specific optical rotation: +6.5 deg at 25 °C/D (5 N HCl); +13.0 deg at 25 °C/D (glacial acetic acid)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 486
Specific optical rotation: +9.7 deg (c = 8 in 1M HCl) at 25 °C/D
Drauz K et al; Amino Acids. Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (1999-2016). New York, NY: John Wiley & Sons. Online Posting Date: 15 Apr 2007

4.2.9 Decomposition

When heated to decomposition it emits very toxic fumes of /sulfur oxides and nitrogen oxides/.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1059

4.2.10 Ionization Efficiency

Ionization mode
Positive
logIE
1.24
pH
2.7
Instrument
Agilent XCT
Ion source
Electrospray ionization
Additive
formic acid (5.3nM)
Organic modifier
MeCN (80%)

4.2.11 Dissociation Constants

pKa
1.71
MERCK INDEX (1996); pK1
pK1 1.71 /carboxylic/; pK2 8.33 /amine/; pK3 10.78 /sulfide/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 486

4.2.12 Collision Cross Section

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

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

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

113 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine]

144 Ų [M-H]-

148.6 Ų [M+H]+

150.4 Ų [M+Na]+

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

4.2.13 Other Experimental Properties

Readily oxidizes to form a dimeric amino acid, cystine, in which the two cysteines are linked via a disulfide bridge, a common structural feature in proteins. Amino Acids and Proteins, D.M. Greenberg, Ed. (Charles C. Thomas, Springfield, IL, 1951) 950 pp.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 486
In neutral or slightly alkaline aqueous solution it is oxidized to cystine by air. More stable in acidic solutions.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 486
MP (anhydrous): 178 °C (decomposes). Specific optical rotation: +6.53 deg at 25 °C/D (calculated as cysteine) (c = 2 in 5M HCl); solubility >100 (20 °C) g/100 g H2O /L-Cysteine hydrochloride monohydrate/
Drauz K et al; Amino Acids. Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (1999-2016). New York, NY: John Wiley & Sons. Online Posting Date: 15 Apr 2007

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
Pharmaceuticals -> Metabolite of Acetylcysteine
S113 | SWISSPHARMA24 | 2024 Swiss Pharmaceutical List with Metabolites | DOI:10.5281/zenodo.10501043

4.3.2 Cosmetics

Cosmetic ingredients (Cysteine) -> CIR (Cosmetic Ingredient Review)
Reducing; Hair conditioning; Antioxidant; 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

DOUGH STRENGTHENER, FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT, FLOUR TREATING AGENT, NUTRIENT SUPPLEMENT -> FDA Substance added to food

4.3.4 Pesticides

Agrochemicals -> Pesticide active substances
Active substance -> EU Pesticides database: Approved

5 Spectral Information

5.1 1D NMR Spectra

1 of 2
1D NMR Spectra
1H NMR: SAD 16992 (Sadtler Research Laboratories spectral collection)
2 of 2
1D NMR Spectra

5.1.1 1H NMR Spectra

1 of 4
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Spectra ID
Instrument Type
Varian
Frequency
500 MHz
Solvent
Water
pH
5.00
Shifts [ppm]:Intensity
3.01:45.61, 3.09:93.74, 3.03:100.00, 3.97:85.99, 3.97:82.72, 3.08:92.22, 3.98:67.50, 3.00:43.43, 3.11:40.74, 3.04:98.88, 3.96:71.83, 3.12:42.42
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Spectra ID
Instrument Type
Bruker
Solvent
D2O
pH
7.4
Shifts [ppm]:Intensity
3.95:10.70, 3.00:7.07, 3.95:12.43, 3.02:15.00, 3.09:6.76, 3.96:12.10, 3.96:10.26, 3.00:7.27, 3.06:14.31, 3.03:14.61, 3.07:14.49, 3.10:6.95
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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
-0.00:1.58, 58.80:12.68, 175.39:2.64, 27.80:19.00
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Spectra ID
Frequency
400 MHz
Solvent
H2O
Shifts [ppm]
58.80, 175.39, 27.80
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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)
3.95:3.06, 3.95:3.09, 3.05:3.05, 3.95:3.00, 3.04:3.06, 3.95:3.05, 3.06:3.10, 3.95:3.03, 3.05:3.03, 3.95:3.93, 3.95:3.96, 3.04:3.94, 3.95:3.10, 3.03:2.99
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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
3.95:58.88:1.00, 3.05:27.79:0.01
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5.3 Mass Spectrometry

5.3.1 GC-MS

1 of 19
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Spectra ID
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

218.1 100

146.1 59.84

266.15 31.93

147.15 30.14

100.1 28.86

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Notes
instrument=GCMS-2010 Plus, Shimadzu
2 of 19
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Spectra ID
Instrument Type
GC-EI-TOF
Ionization Mode
positive
Top 5 Peaks

218.0 100

146.0 91.99

100.0 52.05

147.0 51.25

148.0 20.72

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

5.3.2 MS-MS

1 of 6
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Spectra ID
Instrument Type
QqQ
Ionization Mode
negative
Top 5 Peaks
33.0 100
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Notes
adduct_type [M-H]- original_collision_energy -14 CannabisDB spectra from MoNa 2020 June API 2000 ReSpect
2 of 6
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Spectra ID
Ionization Mode
Positive
Top 5 Peaks

76.02084 100

58.99469 97

86.98946 30.67

105.00021 21.56

122.02696 16.60

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5.3.3 LC-MS

1 of 10
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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
0.604 min
Precursor m/z
122.027
Precursor Adduct
[M+H]+
Top 5 Peaks

76.0208 999

86.9894 167

105 137

122.0264 75

125.0257 1

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License
CC BY
2 of 10
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
20
Fragmentation Mode
CID
Column Name
BEH C18 1.7um, 2.1x100mm, Waters
Retention Time
0.604 min
Precursor m/z
122.027
Precursor Adduct
[M+H]+
Top 5 Peaks

76.0209 999

86.9895 128

104.9997 19

77.0237 13

62.9893 7

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License
CC BY

5.3.4 Other MS

1 of 6
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Other MS
MASS: NIST 63547 (NIST/EPA/MCDC Mass Spectral Database 1990 version)
2 of 6
View All
Authors
Miyagawa H, Akimoto S, Yamasaki K, GL Sciences Inc.
Instrument
GCMS-2010 Plus, Shimadzu
Instrument Type
EI-B
MS Level
MS
Ionization Mode
POSITIVE
Column Name
InertCap 5MS/NP 0.25 mmI.D. x 30 m, df=0.25 um
Retention Time
941.58
Top 5 Peaks

218.1 999

146.1 598

266.15 319

147.15 301

100.1 288

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License
CC BY-SA

5.4 UV Spectra

UV: OES 2-10 (Phillip et al; Organic Electronic Spectral Data. NT, NY: John Wiley and Sons)
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. V3: 2407

5.5 IR Spectra

IR Spectra
IR: SADP 13419 (Sadtler Research Laboratories IR prism collection)

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
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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5.5.2 ATR-IR Spectra

1 of 2
Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Sigma-Aldrich Company Llc
Catalog Number
<a href=https://www.sigmaaldrich.com/US/en/product/sigma/C7755>C7755</a>
Lot Number
38C-0297
Copyright
Copyright © 2014-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Source of Sample
Aldrich
Catalog Number
168149
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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5.6 Raman Spectra

1 of 2
Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Sigma-Aldrich Inc.
Catalog Number
C7755
Lot Number
38C-0297
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Instrument Name
Bruker MultiRAM Stand Alone FT-Raman Spectrometer
Source of Spectrum
Zenodo
Copyright
Copyright © 2023-2024 John Wiley & Sons, Inc. All Rights Reserved.
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7 Chemical Vendors

8 Drug and Medication Information

8.1 Drug Indication

For the prevention of liver damage and kidney damage associated with overdoses of acetaminophen

8.2 FDA National Drug Code Directory

8.3 Drug Labels

Homeopathic product and label

8.4 Clinical Trials

8.4.1 ClinicalTrials.gov

8.4.2 NIPH Clinical Trials Search of Japan

8.5 Therapeutic Uses

/EXPL THER/ Acetaminophen-cysteine adducts (APAP-CYS) are a serum biomarker of acetaminophen exposure, formed when the oxidative metabolite of acetaminophen binds to cysteine residues of hepatic proteins. APAP-CYS adducts become elevated in cases of acute liver failure following acetaminophen overdose and have been proposed as a diagnostic tool to identify acetaminophen-induced acute liver failure when standard testing is inconclusive.
Frey SM et al; J Med Toxicol 11 (2): 218-22 (2015)
/EXPL THER/ Lead is a toxic heavy metal that adversely affects nervous tissues; it often occurs as an environmental pollutant. We investigated histological changes in the cerebral cortex, hippocampus and cerebellum of adult albino mice following exposure to lead acetate. We also studied the possible ameliorative effect of the chelating agent, L-cysteine, on lead-induced neurotoxicity. We divided albino mice into six groups: 1) vehicle-only control, 2) L-cysteine control, 3 and 4) treated for 7 days with 20 and 40 mg/kg lead acetate, respectively, and 5 and 6) treated for 7 days with 20 and 40 mg/kg lead acetate, respectively, followed by 50 mg/kg L-cysteine for 7 days. Lead acetate administration caused disorganization of cell layers, neuronal loss and degeneration, and neuropil vacuolization. Brain sections from lead-intoxicated mice treated with L-cysteine showed fewer pathological changes; the neuropil showed less vacuolization and the neurons appeared less damaged. L-cysteine at the dose we used only marginally alleviated lead-induced toxicity.
Mahmoud YI, Sayed SS; Biotech Histochem 1-6 (2016) (Epub ahead of print)
/EXPL THER/ In hamster lung cell cultures addn of l-Cysteine or vit C to media protects against or reverses abnormal growth & malignant transformation in aged controls (1-2 yr old) or young (3-6 mo) after repeated exposure to smoke of tobacco or marijuana cigarettes.
Leuchtenberger C; Br J Exp Pathol 58 (6): 625-34 (1977)
/EXPL THER/ L-Cysteine admin orally or ip to rats protected against acute toxicity of methylmercury chloride, reducing mercury content in kidney & brain but not in liver.
Sugiyama et al; Toho Igakkai Zasshi 22 (1): 78-85 (1975)
For more Therapeutic Uses (Complete) data for CYSTEINE (7 total), please visit the HSDB record page.

8.6 Biomarker Information

9 Food Additives and Ingredients

9.1 Food Additive Classes

Flavoring Agents
JECFA Functional Classes
Flavouring Agent -> FLAVOURING_AGENT;

9.2 FEMA Flavor Profile

Savory

9.3 FDA Substances Added to Food

Substance
Used for (Technical Effect)
DOUGH STRENGTHENER, FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT, FLOUR TREATING AGENT, NUTRIENT SUPPLEMENT
Document Number (21 eCFR)
FEMA Number
3263
GRAS Number
5
JECFA Flavor Number
1419

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

Chemical Name
L-CYSTEINE
Evaluation Year
2004
ADI
No safety concern at current levels of intake when used as a flavouring agent
Comments
Not evaluated using the Procedure for the Safety Evaluation of Flavouring Agents; the substance is a macronutrient and a normal component of protein and, as such, human exposure through food is orders of magnitude higher than the anticipated level of exposure from use as a flavouring agent
Tox Monograph

10 Agrochemical Information

10.1 Agrochemical Category

Pesticide active substances

10.2 EU Pesticides Data

Active Substance
l-cysteine
Status
Approved [Reg. (EC) No 1107/2009]
Legislation
Reg. (EU) 2020/642

11 Pharmacology and Biochemistry

11.1 Pharmacodynamics

Due to this ability to undergo redox reactions, cysteine has antioxidant properties. Cysteine is an important source of sulfur in human metabolism, and although it is classified as a non-essential amino acid, cysteine may be essential for infants, the elderly, and individuals with certain metabolic disease or who suffer from malabsorption syndromes. Cysteine may at some point be recognized as an essential or conditionally essential amino acid.

11.2 Bionecessity

L-Cysteine is the central compound in sulfur metabolism in the human body. In proteins the formation of disulfide bonds between the thiol groups of cysteine plays an important role for tertiary structure and enzymatic activity ... .
European Chemicals Agency (ECHA); Registered Substances, L-cysteine (CAS Number: 52-90-4) (EC Number: 200-158-2) (Last updated: May 17, 2016). Available from, as of May 24, 2016: https://echa.europa.eu/
Amino acid catabolism is essential for adjusting pool sizes of free amino acids and takes part in energy production as well as nutrient remobilization. The carbon skeletons are generally converted to precursors or intermediates of the tricarboxylic acid cycle. In the case of cysteine, the reduced sulfur derived from the thiol group also has to be oxidized in order to prevent accumulation to toxic concentrations. ...
Hofler S et al; Physiol Plant doi: 10.1111/ppl.12454 (2016) (Epub ahead of print)

11.3 Metabolism / Metabolites

L-Cysteine is the central compound in sulfur metabolism in the human body. In proteins the formation of disulfide bonds between the thiol groups of cysteine plays an important role for tertiary structure and enzymatic activity; cysteine is however always incorporated in the polypeptide chain as cysteine. L-Cysteine is degraded to pyruvate in two steps: one is removal of sulfur and the other is a transamination. Cysteine can be metabolized to form taurine and carbon dioxide through the cysteinsulfinate pathway, where the initial step is oxidation of cysteine to cysteine sulfinate. This step is catalyzed by cysteine dioxygenase. Cysteine sulfinate may then be decarboxylated to form taurine or it may be metabolized via the putative intermediate beta-sulfinylpyruvate to pyruvate and sulfite and then to carbon dioxide and sulfate.
European Chemicals Agency (ECHA); Registered Substances, L-cysteine (CAS Number: 52-90-4) (EC Number: 200-158-2) (Last updated: May 17, 2016). Available from, as of May 24, 2016: https://echa.europa.eu/
Amino acid catabolism is essential for adjusting pool sizes of free amino acids and takes part in energy production as well as nutrient remobilization. The carbon skeletons are generally converted to precursors or intermediates of the tricarboxylic acid cycle. In the case of cysteine, the reduced sulfur derived from the thiol group also has to be oxidized in order to prevent accumulation to toxic concentrations. Here we present a mitochondrial sulfur catabolic pathway catalyzing the complete oxidation of L-cysteine to pyruvate and thiosulfate. After transamination to 3-mercaptopyruvate the sulfhydryl group from L-cysteine is transferred to glutathione by sulfurtransferase 1 and oxidized to sulfite by the sulfur dioxygenase ETHE1. Sulfite is then converted to thiosulfate by addition of a second persulfide group by sulfurtransferase 1. This pathway is most relevant during early embryo development and for vegetative growth under light limiting conditions. Characterization of a double mutant produced from Arabidopsis thaliana T-DNA insertion lines for ETHE1 and sulfurtransferase 1 revealed that an intermediate of the ETHE1 dependent pathway, most likely a persulfide, interferes with amino acid catabolism and induces early senescence.
Hofler S et al; Physiol Plant doi: 10.1111/ppl.12454 (2016) (Epub ahead of print)
Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.

11.4 Mechanism of Action

Cysteine can usually be synthesized by the human body under normal physiological conditions if a sufficient quantity of methionine is available. Cysteine is typically synthesized in the human body when there is sufficient methionine available. Cysteine exhibits antioxidant properties and participates in redox reactions. Cysteine's antioxidant properties are typically expressed in the tripeptide glutathione, which occurs in humans as well as other organisms. Glutathione (GSH) typically requires biosynthesis from its constituent amino acids, cysteine, glycine, and glutamic acid, due to its limited systemic availability. Glutamic acid and glycine are readily available in the diets of most industrialized countries, but the availability of cysteine can be the limiting substrate. In human metabolism, cysteine is also involved in the generation of sulfide present in iron-sulfur clusters and nitrogenase by acting as a precursor. In a 1994 report released by five top cigarette companies, cysteine is one of the 599 additives to cigarettes. Its use or purpose, however, is unknown, like most cigarette additives. Its inclusion in cigarettes could offer two benefits: Acting as an expectorant, since smoking increases mucus production in the lungs; and increasing the beneficial antioxidant glutathione (which is diminished in smokers).

11.5 Human Metabolite Information

11.5.1 Tissue Locations

  • Adrenal Cortex
  • Epidermis
  • Fibroblasts
  • Intestine
  • Kidney
  • Liver
  • Neuron
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Spleen
  • Testis
  • Thyroid Gland

11.5.2 Cellular Locations

  • Cytoplasm
  • Extracellular
  • Mitochondria

11.5.3 Metabolite Pathways

11.6 Biochemical Reactions

12 Use and Manufacturing

12.1 Uses

Cosmetic Ingredient Review Link
CIR ingredient: Cysteine
EPA CPDat Chemical and Product Categories
The Chemical and Products Database, a resource for exposure-relevant data on chemicals in consumer products, Scientific Data, volume 5, Article number: 180125 (2018), DOI:10.1038/sdata.2018.125
Sources/Uses
Cysteine is a non-essential amino acid that has been used as a dough conditioner and veterinary detoxicant; [Merck Index] Used as a flavoring agent, dough strengthener, nutritional supplement, and flour treating agent for foods; [FDA] Used for biochemical and nutritional research and as a medication; [HSDB]
Merck Index - O'Neil MJ, Heckelman PE, Dobbelaar PH, Roman KJ (eds). The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th Ed. Cambridge, UK: The Royal Society of Chemistry, 2013.
Sources/Uses
Cysteine is a non-essential amino acid that has been used as a dough conditioner and veterinary detoxicant; [Merck Index]
Merck Index - O'Neil MJ, Heckelman PE, Dobbelaar PH, Roman KJ (eds). The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th Ed. Cambridge, UK: The Royal Society of Chemistry, 2013.

Reported uses (ppm):

Table: Reported uses (ppm): (Flavor and Extract Manufacturers' Association, 1994)

Food Category
Breakfast cereals
Usual
100.00
Max.
100.00
Food Category
Condiments, relishes
Usual
100.00
Max.
100.00
Food Category
Meat products
Usual
100.00
Max.
100.00
Food Category
Milk products
Usual
100.00
Max.
100.00

Burdock, G.A. (ed.). Fenaroli's Handbook of Flavor Ingredients. 6th ed.Boca Raton, FL 2010, p. 370
Biochemical and nutrition research, reducing agent in bread doughs (up to 90 ppm).
Larranaga, M.D., Lewis, R.J. Sr., Lewis, R.A.; Hawley's Condensed Chemical Dictionary 16th Edition. John Wiley & Sons, Inc. Hoboken, NJ 2016., p. 408
MEDICATION
MEDICATION (VET)
Treatment with cysteine reduced seedling injury caused by gamma-irradiation of sorghum seed. Cysteine effects were most pronounced in primary root elongation.
Reddy CS, JD Smith; Environ Exp Bot 18 (4): 241-3 (1978)

Use (kg) in Switzerland (2009): >10000

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

Use (kg; exact) in Germany (2009): 132069

Use (kg) in France (2004): 96759

Consumption (g per capita) in Switzerland (2009): 1.3

Consumption (g per capita; approx.) in Germany (2009): 1.2

Consumption (g per capita; exact) in Germany (2009): 1.6

Consumption (g per capita) in France (2004): 1.6

Excretion rate: 0.3

Calculated removal (%): 92.1

For the prevention of liver damage and kidney damage associated with overdoses of acetaminophen

12.1.1 Use Classification

Food additives -> Flavoring Agents
Flavouring Agent -> FLAVOURING_AGENT; -> JECFA Functional Classes
Flavoring Agents -> JECFA Flavorings Index
Cosmetics -> Reducing; Hair conditioning; Antioxidant; Antistatic
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

12.1.2 Household Products

Household & Commercial/Institutional Products

Information on 4 consumer products that contain Cysteine in the following categories is provided:

• Personal Care

12.2 Methods of Manufacturing

By addition of a thiol compound to an unsaturated amino acid derivative; by hydrolysis of proteins in the presence of carbon dioxide; by treating in HCl hydrolysis of proteins in the presence of carbon dioxide; by treating an HCl hydrolysate of hair with CuO2, followed by the decomposition of the resulting copper-cysteine complex with hydrogen sulfide; by the addition of thioacetic acid to alpha-acetamido acrylic acid; by treatment of a keratine HCl hydrolysate with zinc to reduce the cystine present to cysteine; by electrolytic reduction of cystine.
Burdock, G.A. (ed.). Fenaroli's Handbook of Flavor Ingredients. 6th ed.Boca Raton, FL 2010, p. 370
L-Cysteine used to be produced almost exclusively by hydrolysis of hair or other keratins. The amino acid isolated was l-cystine, which was reduced electrolytically to l-cysteine. L-Cysteine has also been prepared from beta-chloro-d,l-alanine and sodium sulfide with cysteine desulfhydrase, an enzyme obtained from, e.g., Citrobacterium freundii. Today, however, the main processes for cysteine production are biological. A direct fermentation process has been developed for the manufacture of l-cystine, using a modified Escherichia coli bacterium. The technology has been extended to prepare other modified l-cysteine analogues. An enzymatic process for l-cysteine has been successfully developed using microorganisms capable to hydrolyze 2-amino-delta2-thiazoline 4-carboxylic acid (ATC) which is readily available from methyl alpha-chloroacrylate and thiourea. A mutant of Pseudomonas thiazolinophilum converts d,l-ATC to l-cysteine in 95% molar yield at product concentrations higher than 30 g/L.
Drauz K et al; Amino Acids. Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2016). NY, NY: John Wiley & Sons. Online Posting Date: April 15, 2007

12.3 Formulations / Preparations

Available commercially as L(+)-cysteine hydrochloride.
Larranaga, M.D., Lewis, R.J. Sr., Lewis, R.A.; Hawley's Condensed Chemical Dictionary 16th Edition. John Wiley & Sons, Inc. Hoboken, NJ 2016., p. 408

12.4 U.S. Production

Non-confidential 2012 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: L-Cysteine. National Production Volume: 28,660 lb/yr.
USEPA/Pollution Prevention and Toxics; 2012 Chemical Data Reporting Database. L-Cysteine (52-90-4). Available from, as of July 12, 2016: https://java.epa.gov/oppt_chemical_search/

12.5 General Manufacturing Information

EPA TSCA Commercial Activity Status
L-Cysteine: ACTIVE
A non-essential amino acid in human development.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 486
An amino acid derived from cystine, occurring naturally in the L-form ...
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 12th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2012., p. V2: 1292

13 Identification

13.1 Analytic Laboratory Methods

The near-infrared (NIR) fluorescence sensor for rapid, selective, and sensitive detection of cysteine (Cys) is of great importance in both biological and environmental sciences. Herein, we report a specific probe with turn-on fluorescence property, visible color change with naked-eye, and large wavelength shift on UV spectra for highly selective detection of Cys over homocysteine (Hcy) and glutathione (GSH) in both HEPES buffer (10 mM, pH 7.4) and diluted human serum. The probe based on the conjugate addition-cyclization reaction has a low limit of detection to Cys (0.16 uM as NIR fluorescence sensor and 0.13 uM as UV sensor). Kinetic study indicated that the probe has a very rapid response to Cys, owing to the much higher pseudo-first-order reaction constant with Cys (299/M/s) than with Hcy (1.29/M/s) or GSH (0.53/M/s). Upon addition of Cys to a solution of the probe, the color changed from purple to cyan, with the maximum wavelength shifting from 582 to 674 nm in the UV spectrum and a fluorescence emission at 697 nm appearing. It has been successfully applied for determination of Cys in diluted serum and bioimaging of Cys in living cells with low cell toxicity.
Zhang J et al; Anal Chem 87 (9): 4856-63 (2015)
Gold nanoparticles (AuNPs) were synthesized at room temperature following a simple, rapid, and green route using fresh-squeezed apple juice as a reducing reagent. The optimal AuNPs, based on the particle color, stability, and color change suitable for colorimetric detection of cysteine (Cys), are synthesized using 5 mL of 10% apple juice, 1 mL of 10 mM gold precursor solution, and 1 mL of 0.1 M NaOH. Under this set of parameters, the AuNPs are synthesized within 30 min at room temperature. The average size (11.1 +/- 3.2 nm) and zeta potential (-36.5 mV) of the AuNPs synthesized were similar to those of AuNPs prepared via the conventional citrate-reduction method. In the presence of Cys, unlike with any other amino acid, the AuNPs aggregated, possibly due to the gold-sulfur covalent interaction, yielding red-to-purple color change of the sample solution. The red-shift of the localized surface plasmon resonance peak of the AuNPs responsible for the color change was recorded by UV-vis spectrometer. The effect of other potential interferents such as glucose, ascorbic acid, K(+) , Na(+) , Ca(2+) , Zn(2+) , Ag(+) , Ni(2+) , Cu(2+) , Co(2+) , and Hg(2+) were also examined. The results show that AuNPs can be used to selectively detect and measure Cys with a linear dependency in the range of 2 to 100 uM and a limit of detection (signal-to-noise ratio > 3) of 50 nM. The results suggest that the green-synthesized AuNPs are useful for simple, rapid, and sensitive colorimetric detection of Cys, which is an essential amino acid in food and biological systems.
Bagci PO et al; J Food Sci 80 (9): N2071-8 (2015)

13.2 Clinical Laboratory Methods

A new fluorescent probe based on an ensemble of gold nanoclusters (AuNCs) and polymer protected gold nanoparticles (AuNPs) for turn-on sensing of L-cysteine was designed and prepared. The AuNCs were protected by bovine serum albumin and had strong fluorescence. The polymer protected AuNPs were synthesized by a facile in situ strategy at room temperature and could quench the fluorescence of AuNCs due to the Forster resonance energy transfer. Interestingly, it has been observed that the quenched fluorescence of AuNCs was recovered by L-cysteine, which could induce the aggregation of polymer protected AuNPs by sulfur group. Then the prepared fluorescent probe was successfully used for determination of L-Cys in human urines ... .
Xu X et al; Anal Chim Acta 879: 97-103 (2015)
A chlorinated coumarin-aldehyde was developed as a colorimetric and ratiometric fluorescent probe for distinguishing glutathione (GSH), cysteine (Cys) and homocysteine (Hcy). The GSH-induced substitution-cyclization and Cys/Hcy-induced substitution-rearrangement cascades lead to the corresponding thiol-coumarin-iminium cation and amino-coumarin-aldehyde with distinct photophysical properties. The probe can be used to simultaneously detect GSH and Cys/Hcy by visual determination based on distinct different colors - red and pale-yellow in PBS buffer solution by two reaction sites. From the linear relationship of fluorescence intensity and biothiols concentrations, it was determined that the limits of detection for GSH, Hcy and Cys are 0.08, 0.09 and 0.18 uM, respectively. Furthermore, the probe was successfully used in living cell imaging with low cell toxicity.
Dai X et al; Anal Chim Acta 900: 103-10 (2015)
A highly sensitive and selective turn on fluorescent probe P-acid-aldehyde (P-CHO) is developed for the determination of cysteine (Cys) and homocysteine (Hcy). The probe is designed and synthesized by incorporating the specific functional group aldehyde group for thiols into a stable ?-conjugated material 4,4'-(2,5-dimethoxy-1,4-phenylene) bis(ethyne-2,1-diyl) dibenzoic acid (P-acid). The probe fluorescence is quenched through donor photoinduced electron transfer (d-PET) between the fluorophore (P-acid) and the recognition group (aldehyde group). In the presence of thiols, Cys and Hcy can selectively react with aldehyde group of the probe because the inhibition of d-PET between fluorophore and recognition group. Therefore, a turn-on fluorescent sensor was established for the fluorescence recovery. Under the optimized conditions, the fluorescence response of probe is directly proportional to the concentration of Cys in the range of 4-95 nM/L, with a detection limit 3.0 nM. In addition, the sensing system exhibits good selectively toward Cys and Hcy in the presence of other amino acids. It has been successfully applied for bioimaging of Cys and Hcy in living cells with low cell toxicity.
Yang C et al; Biosens Bioelectron 80: 17-23 (2016)

14 Safety and Hazards

14.1 Hazards Identification

14.1.1 GHS Classification

1 of 4
View All
Note
Pictograms displayed are for 68.6% (350 of 510) of reports that indicate hazard statements. This chemical does not meet GHS hazard criteria for 31.4% (160 of 510) of reports.
Pictogram(s)
Irritant
Signal
Warning
GHS Hazard Statements

H302 (57.6%): Harmful if swallowed [Warning Acute toxicity, oral]

H315 (12.4%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (12.4%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (12.4%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

Precautionary Statement Codes

P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 510 reports by companies from 14 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 160 of 510 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 12 notifications provided by 350 of 510 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.

14.1.2 Hazard Classes and Categories

Acute Tox. 4 (57.6%)

Skin Irrit. 2 (12.4%)

Eye Irrit. 2 (12.4%)

STOT SE 3 (12.4%)

Acute Tox. 4 (93.5%)

14.1.3 Hazards Summary

Safe when used as a flavoring agent in food; [JECFA] May cause irritation; Harmful by ingestion; [Sigma-Aldrich MSDS]
Causes other liver changes and effects on phosphatases and dehydrogenases in 2-day intermittent intraperitoneal studies of mice; [RTECS] May cause irritation; [Acros Organics MSDS]

14.1.4 Skin, Eye, and Respiratory Irritations

... A single ocular application of the test item L-Cysteine to rabbits at a dose of 0.1 g produced slight irritant effects, which were fully reversible within 48 hours. ...
European Chemicals Agency (ECHA); Registered Substances, L-cysteine (CAS Number: 52-90-4) (EC Number: 200-158-2) (Last updated: May 17, 2016). Available from, as of May 24, 2016: https://echa.europa.eu/
... The single dermal application of the test item L-Cysteine to three rabbits at a dose of 0.5 g showed neither irritant nor corrosive effects. ...
European Chemicals Agency (ECHA); Registered Substances, L-cysteine (CAS Number: 52-90-4) (EC Number: 200-158-2) (Last updated: May 17, 2016). Available from, as of May 24, 2016: https://echa.europa.eu/
... Single dermal application of the test item L-Cysteine to rats at a dose of 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity but signs of irritation. ...
European Chemicals Agency (ECHA); Registered Substances, L-cysteine (CAS Number: 52-90-4) (EC Number: 200-158-2) (Last updated: May 17, 2016). Available from, as of May 24, 2016: https://echa.europa.eu/

14.2 Fire Fighting

14.2.1 Fire Fighting Procedures

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html
Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html

14.3 Accidental Release Measures

14.3.1 Cleanup Methods

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html

14.3.2 Disposal Methods

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.
Product: Offer surplus and non-recyclable solutions to a licensed disposal company; Contaminated packaging: Dispose of as unused product.
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html

14.3.3 Preventive Measures

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Avoid breathing dust. Environmental precautions: Do not let product enter drains.
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html
Precautions for safe handling: Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html
Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html
Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html
SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

14.4 Handling and Storage

14.4.1 Storage Conditions

Keep container tightly closed in a dry and well-ventilated place. Store under inert gas. Air sensitive. Storage class (TRGS 510): Non Combustible Solids.
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html

14.5 Exposure Control and Personal Protection

14.5.1 Allowable Tolerances

Residues of cysteine 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 July 12, 2016: https://www.ecfr.gov

14.5.2 Personal Protective Equipment (PPE)

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html
Skin protection: Handle with gloves.
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html
Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html
Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html

14.6 Stability and Reactivity

14.6.1 Hazardous Reactivities and Incompatibilities

Incompatible materials: Strong oxidizing agents.
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html

14.7 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: L-Cysteine
Status Regulation (EC)
Reg. (EU) 2020/642
REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
Cysteine: Does not have an individual approval but may be used under an appropriate group standard

14.7.1 FIFRA Requirements

Residues of cysteine 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 July 12, 2016: https://www.ecfr.gov

14.7.2 FDA Requirements

Cysteine used as a nutrient and/or dietary supplement in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice.
21 CFR 582.5271 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of July 12, 2016: https://www.ecfr.gov
Substance added directly to human food affirmed as generally recognized as safe (GRAS).
21 CFR 184.1271 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of July 12, 2016: https://www.ecfr.gov
The food additive amino acids may be safely used as nutrients added to foods in accordance with the following conditions: (a) The food additive consists of one or more of the following individual amino acids in the free, hydrated, or anhydrous form, or as the hydrochloride, sodium, or potassium salts. L-Cysteine is included on this list.
21 CFR 172.320 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of July 12, 2016: https://www.ecfr.gov

14.8 Other Safety Information

Chemical Assessment

IMAP assessments - Cysteine and its salts: Human health tier II assessment

IMAP assessments - L-Cysteine: Environment tier I assessment

14.8.1 Toxic Combustion Products

Special hazards arising from the substance or mixture: Carbon oxides, nitrogen oxides (NOx), sulphur oxides
Sigma-Aldrich; Safety Data Sheet for L-Cysteine. Product Number: 168149, Version 4.5 (Revision Date 08/26/2015). Available from, as of May 18, 2016: https://www.sigmaaldrich.com/safety-center.html

15 Toxicity

15.1 Toxicological Information

15.1.1 Toxicity Summary

IDENTIFICATION AND USE: Cysteine forms white or colorless crystals. It is used in biochemical and nutrition research, as a reducing agent in bread doughs (up to 90 ppm). It is also used as flavor enhancer and medication, including veterinary medication. HUMAN EXPOSURE AND TOXICITY: Cysteine solution (3%) was not irritating for human eyes. ANIMAL STUDIES: A single ocular application of L-cysteine to rabbits at a dose of 0.1 g produced slight irritant effects, which were fully reversible within 48 hours. The single dermal application of L-cysteine to three rabbits at a dose of 0.5 g showed neither irritant nor corrosive effects. Decreased litter size observed in rats receiving high-dose cysteine, which was related to the degeneration and/or death of ovulated unfertilized oocytes and embryos with changes in the zona pellucida, which was already affected in the ovary. Pregnant mice and rats were treated s.c. with 1.2 mg per g on the last day of pregnancy and brain degeneration was observed one day later in the fetus. L-Cysteine is considered to be non-mutagenic in the HPRT locus using V79 cells of the Chinese Hamster. L-Cysteine did not induce structural chromosomal aberrations in the V79 Chinese hamster cell line. ECOTOXICITY STUDIES: The objective of the study was to determine the effects of cysteine on postthaw sperm motility, duration of sperm motility, DNA damage, and fertility in the common carp (Cyprinus carpio). Supplementation with cysteine increased the fertilization and hatching rate and decreased DNA damage.
Uremic toxins such as cysteine are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (A7868). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (A7869). Although classified as a non-essential amino acid cysteine may be essential for infants, the elderly, and individuals with certain metabolic disease or who suffer from malabsorption syndromes. Cysteine can usually be synthesized by the human body under normal physiological conditions if a sufficient quantity of methionine is available. Due to the ability of thiols to undergo redox reactions, cysteine has antioxidant properties. Cysteine's antioxidant properties are typically expressed in the tripeptide glutathione, which occurs in humans as well as other organisms. The systemic availability of oral glutathione (GSH) is negligible; so it must be biosynthesized from its constituent amino acids, cysteine, glycine, and glutamic acid. Glutamic acid and glycine are readily available in the diets of most industrialized countries, but the availability of cysteine can be the limiting substrate. Cysteine is also an important source of sulfide in human metabolism. The sulfide in iron-sulfur clusters and in nitrogenase is extracted from cysteine, which is converted to alanine in the process. In a 1994 report released by five top cigarette companies, cysteine is one of the 599 additives to cigarettes. Its use or purpose, however, is unknown, like most cigarette additives. Its inclusion in cigarettes could offer two benefits: Acting as an expectorant, since smoking increases mucus production in the lungs; and increasing the beneficial antioxidant glutathione (which is diminished in smokers).
A7868: Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. PMID:25041433
A7869: Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. PMID:22419041

15.1.2 Drug Induced Liver Injury

Compound
l-cysteine
DILI Annotation
Ambiguous DILI-concern
Severity Grade
3
Label Section
Warnings and precautions
References

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

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

15.1.3 Carcinogen Classification

Carcinogen Classification
No indication of carcinogenicity to humans (not listed by IARC).

15.1.4 Health Effects

Chronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.

15.1.5 Exposure Routes

Endogenous, Ingestion, Dermal (contact)

15.1.6 Symptoms

As a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.

15.1.7 Acute Effects

15.1.8 Treatment

Kidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored.

15.1.9 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 revised edition, Elsevier Mosby, St. Louis, MO 2007, 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 revised edition, Elsevier Mosby, St. Louis, MO 2007, 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 TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. 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 revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160-1

15.1.10 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ ... Applied as a 3% near-neutral soln to ... human eyes ... no adverse effect is reported.
Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 300
/CASE REPORTS/ A 26-year-old female with history of unexplained, severe hepatitis presented with a second episode of severe hepatitis including coagulopathy and transaminase levels >10,000 U/L. The patient reported ingesting "only a couple" of acetaminophen tablets several days prior to her presentation. An acetaminophen concentration of 14 ug/mL at presentation aroused suspicion that acetaminophen might have caused the patient's liver failure, despite her adamant denial of overdose. ...
Frey SM et al; J Med Toxicol 11 (2): 218-22 (2015)

15.1.11 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ An eye irritation study according to OECD Guideline 405 was performed with L-Cysteine. 0.1 g of the pure test substance was administered into the conjunctival sac of the eye of three New Zealand White rabbits. The eyes were not rinsed after the application. After the application into the eyes of three female NZW rabbits the test item produced slight irritant but no corrosive ocular effects. Upon fluorescein examinations at the end of the observation period of 72 hours no corneal lesions were found in any animal. Conjunctival redness was observed in all animals, discharge in one animal. There were no significant body weight changes during the observation period. Under the conditions of the present study, a single ocular application of the test item L-Cysteine to rabbits at a dose of 0.1 g produced slight irritant effects, which were fully reversible within 48 hours. Neither mortalities nor significant clinical signs of toxicity were observed.
European Chemicals Agency (ECHA); Registered Substances, L-cysteine (CAS Number: 52-90-4) (EC Number: 200-158-2) (Last updated: May 17, 2016). Available from, as of May 24, 2016: https://echa.europa.eu/
/LABORATORY ANIMALS: Acute Exposure/ ... The single dermal application of the test item L-Cysteine to three rabbits at a dose of 0.5 g showed neither irritant nor corrosive effects. Neither mortalities nor significant clinical signs of toxicity were observed. ...
European Chemicals Agency (ECHA); Registered Substances, L-cysteine (CAS Number: 52-90-4) (EC Number: 200-158-2) (Last updated: May 17, 2016). Available from, as of May 24, 2016: https://echa.europa.eu/
/LABORATORY ANIMALS: Acute Exposure/ An actute dermal toxicity study was performed with L-Cysteine according to OECD Guideline 402. The substance was administered at a single dose, uniformly over an area which was approximately 10% of the total body surface. The test item was held in contact with the skin by a dressing throughout a 24-hour period. The dressing consisted of a gauze-dressing and non-irritating tape. Under the conditions of the present study, single dermal application of the test item L-Cysteine to rats at a dose of 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity but signs of irritation. The dermal LD50 was determined to be > 2000 mg L-Cysteine/kg body weight. No clear signs of toxicity were observed.
European Chemicals Agency (ECHA); Registered Substances, L-cysteine (CAS Number: 52-90-4) (EC Number: 200-158-2) (Last updated: May 17, 2016). Available from, as of May 24, 2016: https://echa.europa.eu/
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ L-Cysteine (CySH) is widely distributed throughout the body. A decrease in litter size was observed in female rats that received high-dose CySH before mating. The oocytes were assessed morphologically to investigate the cause of this effect of CySH. Ten-week-old female SD rats received CySH intravenously at a dosage of 1000 mg/kg/day for more than 1 week before mating. Rats in the control group received no treatment. The ovaries were stained with PAS and examined by light microscopy (n = 6) and an antral follicle exhibiting the effects of CySH was examined by electron microscopy (n = 1). Unfertilized oocytes (n = 10) collected from the ampulla of the uterine tube after ovulation and embryos (n = 10 to 13) collected from the oviduct on gestational day 2 (GD 2) were examined by stereomicroscopy. In light microscopic examination of the ovary in the CySH group, the zona pellucida (ZP) of follicles in almost all stages was thinned or indistinct. In addition, outflow of the ZP between the corona radiata (CR) and disarrangement of the CR were occasionally observed in the developing antral follicles. Electron microscopic examination of the antral follicles in the CySH group confirmed these findings, but no lesions were observed except for those related to the ZP. Fewer unfertilized oocytes were collected from the ampulla of the uterine tube in the CySH group than in the control group. Interestingly, ZP-lacking or partially ZPlacking oocytes were observed in the CySH group. On GD 2, embryos with changes in the ZP as well as unfertilized oocytes were observed, and most of the embryos were degenerative. It is known that the ZP plays several important roles in early embryogenesis. The oocytes in which the ZP was affected by CySH treatment were abnormal or nonviable. In conclusion, the findings of this study suggest that the decreased litter size observed in rats receiving high-dose CySH was related to the degeneration and/or death of ovulated unfertilized oocytes and embryos with changes in the ZP, which was already affected in the ovary.
Harada M et al; Congenit Anom Kyoto 42 (3): 271-2 (2002)
For more Non-Human Toxicity Excerpts (Complete) data for CYSTEINE (10 total), please visit the HSDB record page.

15.1.12 Non-Human Toxicity Values

LD50 Rat dermal >2000 mg/kg body weight
European Chemicals Agency (ECHA); Registered Substances, L-cysteine (CAS Number: 52-90-4) (EC Number: 200-158-2) (Last updated: May 17, 2016). Available from, as of May 24, 2016: https://echa.europa.eu/
LD50 Rat oral 1890 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. 1059
LD50 Rat ip 1620 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. 1059
LD50 Rat sc 1550 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. 1059
For more Non-Human Toxicity Values (Complete) data for CYSTEINE (7 total), please visit the HSDB record page.

15.2 Ecological Information

15.2.1 Ecotoxicity Values

LD50; Species: Oncorhynchus mykiss (Rainbow trout) weight 30 g; Conditions: freshwater, 15 °C, ip injection; Concentration: 4.5 mmol/kg bw for 4 hr (95% confidence interval: 3.7-5.3 mmol/kg bw) /formulation/
Yokoyama M, Sakaguchi M; Fish Sci 62 (4): 660-661 (1996)
LD50; Species: Oncorhynchus mykiss (Rainbow trout) weight 30 g; Conditions: freshwater, 15 °C, ip injection; Concentration: 4.8 mmol/kg bw for 3 hr (95% confidence interval: 4.5-5.7 mmol/kg bw) /formulation/
Yokoyama M, Sakaguchi M; Fish Sci 62 (4): 660-661 (1996)
LD50; Species: Oncorhynchus mykiss (Rainbow trout) weight 30 g; Conditions: freshwater, 15 °C, ip injection; Concentration: 7.5 mmol/kg bw for 2 hr (95% confidence interval: 6.3-9.6 mmol/kg bw) /formulation/
Yokoyama M, Sakaguchi M; Fish Sci 62 (4): 660-661 (1996)

15.2.2 Environmental Fate / Exposure Summary

Cysteine's production and use as a dough enhancer and in biochemical and nutritional research may result in its release to the environment through various waste streams. Cysteine is a non-essential amino acid for humans and also occurs in many plants. If released to air, an estimated vapor pressure of 6.7X10-7 mm Hg at 25 °C indicates cysteine will exist in both the vapor and particulate phases in the atmosphere. Vapor-phase cysteine will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 1.6 hours. Particulate-phase cysteine will be removed from the atmosphere by wet and dry deposition. Cysteine does not contain chromophores that absorb at wavelengths >290 nm and, therefore, is not expected to be susceptible to direct photolysis by sunlight. If released to soil, cysteine is expected to have very high mobility based upon a an estimated Koc of 3. The pKa values of cysteine are 1.71, 8.33 and 10.78, indicating that this compound will exist as a zwitterion in the environment and zwitterions generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil is not expected because the compound exists as an ion and ions do not volatilize. Cysteine is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Utilizing the Warburg test, 4.7% of the Theoretical BOD was reached in 24 hours indicating that biodegradation is not an important environmental fate process in soil and water. If released into water, cysteine is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. The pKa values indicate cysteine will exist almost entirely 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 (pH 5 to 9). Occupational exposure to cysteine may occur through inhalation and dermal contact with this compound at workplaces where cysteine is produced or used. Monitoring data indicate that the general population may be exposed to cysteine via ingestion of food. (SRC)

15.2.3 Natural Pollution Sources

Cysteine is a non-essential amino acid for human development(1). Cysteine also occurs in many plants(2).
(1) O'Neil MJ, ed; The Merck Index. 15th ed., Cambridge, UK: Royal Society of Chemistry, p. 486 (2013)
(2) US Dept Agric; US Dept Agric, Agric Res Service. 1992-2016. Dr. Duke's Phytochemical and Ethnobotanical Databases. Cysteine. Available from, as of Sept 28, 2016: https://phytochem.nal.usda.gov/phytochem/search

15.2.4 Artificial Pollution Sources

Cysteine's production and use as a dough enhancer(1) and in biochemical and nutritional research(2) may result in its release to the environment through various waste streams(SRC).
(1) O'Neil MJ, ed; The Merck Index. 15th ed., Cambridge, UK: Royal Society of Chemistry, p. 486 (2013)
(2) Larranaga MD et al; Hawley's Condensed Chemical Dictionary 16th ed., Hoboken, NJ: John Wiley & Sons, Inc. p. 408 (2016)

15.2.5 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3(SRC), determined from a structure estimation method(2), indicates that cysteine is expected to have very high mobility in soil(SRC). The pKa values of cysteine are 1.71, 8.33 and 10.78(3), indicating that this compound will exist as a zwitterion in the environment and zwitterions generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as an ion and ions do not volatilize. Cysteine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.7X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Utilizing the Warburg test, 4.7% of the Theoretical BOD was reached in 24 hours(5) indicating that biodegradation is not an important environmental fate process in soil(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Jul 13, 2016: https://www2.epa.gov/tsca-screening-tools
(3) O'Neil MJ, ed; The Merck Index. 15th ed., Cambridge, UK: Royal Society of Chemistry p. 486 (2013)
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(5) 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 3(SRC), determined from a structure estimation method(2), indicates that cysteine is not expected to adsorb to suspended solids and sediment(SRC). The pKa values of 1.71, 8.33 and 10.78(3) indicates cysteine 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(SRC). According to a classification scheme(4), an estimated BCF of 3(SRC), from its log Kow of -2.49(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Utilizing the Warburg test, 4.7% of the Theoretical BOD was reached in 24 hours(6) indicating that biodegradation is not an important environmental fate process in water(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Jul 13, 2106: https://www2.epa.gov/tsca-screening-tools
(3) O'Neil MJ, ed; The Merck Index. 15th ed., Cambridge, UK: Royal Society of Chemistry p. 486 (2013)
(4) Franke C et al; Chemosphere 29: 1501-14 (1994)
(5) 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. 6 (1995)
(6) 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), cysteine, which has an estimated vapor pressure of 6.7X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase cysteine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 1.6 hours(SRC), calculated from its rate constant of 8.0X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase cysteine may be removed from the air by wet and dry deposition(SRC). Cysteine does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Jul 13, 2016: https://www2.epa.gov/tsca-screening-tools
(3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(4) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)

15.2.6 Environmental Biodegradation

AEROBIC: Cysteine, present at 500 mg/L, reached 1.5, 2.4 and 4.7% of its theoretical BOD in 6, 12, and 24 hours, respectively, using an activated sludge inoculum at 2500 mg/L in the Warburg test. It is one of the more resistant of the amino acids(1).
(1) Malaney GW, Gerhold RM; J Water Pollut Control Fed 41: R18-R33 (1969)
PURE CULTURE: Alcaligenes faecalis, isolated from activated sludge, was able to oxidize 500 mg/L cysteine, exhibiting an O2 uptake of 575 mg/L in 130 hours in the Warburg test at 20 °C(1).
(1) Marion CV, Malaney GW; J Water Pollut Control Fed 35: 1269-84 (1963)
ANAEROBIC: An enrichment culture capable of degrading cysteine was isolated from sediment from a stream in Charleston, WV that received industrial wastewater effluent(1).
(1) Jessee JA et al; Appl Environ Microbiol 45: 97-102 (1983)

15.2.7 Environmental Abiotic Degradation

The rate constant for the vapor-phase reaction of cysteine with photochemically-produced hydroxyl radicals has been estimated as 8.0X10-22 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.6 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the estimated OH radical reaction of cysteine with hydroxyl radicals in aqueous solutions at pH 7 is 3.5X10-10 L/mol-sec(2); this corresponds to an aquatic half-life of 1 hour at an aquatic concentration of 1X10-17 hydroxyl radicals per liter(3). Cysteine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(4). Cysteine does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(2) Buxton GV et al; J Phys Chem Ref Data 17: 513-882 (1988)
(3) Mill T et al; Science 207: 886-887 (1980)
(4) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990)

15.2.8 Environmental Bioconcentration

An estimated BCF of 3 was calculated in fish for cysteine(SRC), using a log Kow of -2.49(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. 6 (1995)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Jul 13, 2016: https://www2.epa.gov/tsca-screening-tools
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

15.2.9 Soil Adsorption / Mobility

Using a structure estimation method based on molecular connectivity indices(1), the Koc of cysteine can be estimated to be 3(SRC). According to a classification scheme(2), this estimated Koc value suggests that cysteine is expected to have very high mobility in soil. The pKa values of cysteine are 1.71, 8.33 and 10.78(3) indicating that this compound will exist as a zwitterion in the environment and zwitterions generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).
(1) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Jul 13, 2016: https://www2.epa.gov/tsca-screening-tools
(2) Swann RL et al; Res Rev 85: 17-28 (1983)
(3) O'Neil MJ, ed; The Merck Index. 15th ed., Cambridge, UK: Royal Society of Chemistry p. 486 (2013)
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)

15.2.10 Volatilization from Water / Soil

The pKa values of cysteine are 1.71, 8.33 and 10.78(1), indicating that this compound will exist as a zwitterion at pH values of 5 to 9; therefore, volatilization from water surfaces is not expected to be an important fate process. Cysteine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.7X10-7 mm Hg(SRC), determined from a fragment constant method(2).
(1) O'Neil MJ, ed; The Merck Index. 15th ed., Cambridge, UK: Royal Society of Chemistry p. 486 (2013)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Jul 13, 2016: https://www2.epa.gov/tsca-screening-tools

15.2.11 Environmental Water Concentrations

SURFACE WATER: Cysteine was tested for but not detected in grab samples from the Huron River at the Ann Arbor, Michigan Water Treatment Plant intake, sampled in June 2004(1).
(1) Lee JH et al; Environ Sci Technol 40: 1478-1484 (2006)

15.2.12 Effluent Concentrations

Cysteine was present at 5.0, 1.5 and 0.8 nmol/g in three consecutive horizon samples from an active landfill in a low permeability clay soil, located in Conica-Montemarta, Sevilla, Spain; sampling was conducted following 3 years of use(1).
(1) Gonzalez-Vila FJ et al; Chemosphere 31: 2817-25 (1995)

15.2.13 Food Survey Values

Cysteine in fruit juices purchased in supermarkets in Davis, CA(1).
Juice
prune, with pulp
Concn (mg/L juice)
4
Juice
prune, no pulp
Concn (mg/L juice)
not determined
Juice
prune, concentrated extracts of dried
Concn (mg/L juice)
not determined
Juice
prune, frozen juice from fresh
Concn (mg/L juice)
76
Juice
prune, fresh French
Concn (mg/L juice)
27
Juice
plum
Concn (mg/L juice)
55
Juice
peach
Concn (mg/L juice)
53
Juice
cherry
Concn (mg/L juice)
90
Juice
nectarine
Concn (mg/L juice)
86
Juice
pear
Concn (mg/L juice)
38
Juice
apple
Concn (mg/L juice)
1
Juice
grape
Concn (mg/L juice)
23
Juice
kiwi fruit
Concn (mg/L juice)
46
Juice
strawberry
Concn (mg/L juice)
not detected
(1) van Gorsel H et al; J Agric Food Chem 40: 784-789 (1992)

15.2.14 Plant Concentrations

Cysteine has been reported in 30 plants(1).
Genus species
Helianthus annuus
Family
Asteraceae
Common name(s)
Girasol; Sunflower
Part
Seed
Concn (ppm)
16000.0
Genus species
Glycine max
Family
Fabacaea
Common name(s)
Soybean
Part
Seed
Concn (ppm)
6430.0
Genus species
Citrullus lanatus
Family
Cucurbitaceae
Common name(s)
Watermelon
Part
Seed
Concn (ppm)
5742.0
Genus species
Opuntia ficusindica
Family
Castaceae
Common name(s)
Nopal; Indian Fig; Prickly Pear; Nopalito
Part
Seed
Concn (ppm)
5740.0
Genus species
Cucurbita foetidissima
Family
Cucurbitaceae
Common name(s)
Buffalo Gourd
Part
Seed
Concn (ppm)
3080.0
Genus species
Phaseolus acutifolius
Family
Fabaceae
Common name(s)
Tepary Bean
Part
Seed
Concn (ppm)
2920.0
Genus species
Senna obtusifolia
Family
Fabaceae
Common name(s)
Sicklepod
Part
Seed
Concn (ppm)
244.0
Genus species
Triticum aestivum
Family
Poaceae
Common name(s)
Wheat
Part
Seed
Concn (ppm)
1449.0
Genus species
Phoenix dactylifera
Family
Arecaceae
Common name(s)
Date Palm
Part
Fruit
Concn (ppm)
1140.0
Genus species
Citrullus lanatus
Family
Cucurbitaceaea
Common name(s)
Watermelon
Part
Fruit
Concn (ppm)
236.0
(1) US Dept Agric; US Dept Agric, Agric Res Service. 1992-2016. Dr. Duke's Phytochemical and Ethnobotanical Databases. Cysteine. Available from, as of Sept 28, 2016: https://phytochem.nal.usda.gov/phytochem/search

15.2.15 Probable Routes of Human Exposure

According to the 2012 TSCA Inventory Update Reporting data, 1 reporting facility estimated the number of persons reasonably likely to be exposed in the manufacturing, processing, or use of cysteine in the United States may be in the range of 25-49 workers per plant; the data may be greatly underestimated due to confidential business information (CBI) or unknown values(1).
(1) US EPA; Chemical Data Reporting (CDR). Non-confidential 2012 Chemical Data Reporting information on chemical production and use in the United States. Available from, as of July 13, 2016: https://java.epa.gov/chemview
Occupational exposure to cysteine may occur through inhalation and dermal contact with this compound at workplaces where cysteine is produced or used. Monitoring data indicate that the general population may be exposed to cysteine via ingestion of food. (SRC)

16 Associated Disorders and Diseases

Disease
Uremia
References

PubMed: 11865086, 10509899, 9607216, 7482520, 6520173, 22626821, 21359215, 2026685, 9573551, 24023812, 15353324, 19309105, 8087979, 17132244, 12675874

Merck Manual of Diagnosis and Therapy.

David F. Putnam Composition and Concentrative Properties of Human Urine. NASA Contractor Report. July 1971

Geigy Scientific Tables, 8th Rev edition, pp. 130. Edited by C. Lentner, West Cadwell, N.J.: Medical education Div., Ciba-Geigy Corp. Basel, Switzerland c1981-1992.

Geigy Scientific Tables, 8th Rev edition, pp. 165-177. Edited by C. Lentner, West Cadwell, N.J.: Medical education Div., Ciba-Geigy Corp., Basel, Switzerland c1981-1992.

National Health and Nutrition Examination Survey (NHANES Survey) 2013

Geigy Scientific Tables, 8th Rev edition, pp. 80-82. Edited by C. Lentner, West Cadwell, N.J.: Medical education Div., Ciba-Geigy Corp., Basel, Switzerland c1981-1992.

Disease
Sulfite oxidase deficiency, ISOLATED
References

PubMed: 10682307, 27289259, 23452914, 15558695

Clinical and Laboratory Barriers to the Timely Diagnosis of Sulphite Oxidase Deficiency. Proceedings of Singapore Healthcare, 19(2), 94-100.

Disease
Stroke
References
Disease
Peripheral neuropathy
References
Disease
Dementia
References
Disease
Colorectal cancer
References

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

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

Disease
Eosinophilic esophagitis
References
Mordechai, Hien, and David S. Wishart
Disease
Cystinylglycinuria
References
PubMed: 10384375

17 Literature

17.1 Consolidated References

17.2 NLM Curated PubMed Citations

17.3 Springer Nature References

17.4 Thieme References

17.5 Wiley References

17.6 Nature Journal References

17.7 Chemical Co-Occurrences in Literature

17.8 Chemical-Gene Co-Occurrences in Literature

17.9 Chemical-Disease Co-Occurrences in Literature

18 Patents

18.1 Depositor-Supplied Patent Identifiers

18.2 WIPO PATENTSCOPE

18.3 Chemical Co-Occurrences in Patents

18.4 Chemical-Disease Co-Occurrences in Patents

18.5 Chemical-Gene Co-Occurrences in Patents

19 Interactions and Pathways

19.1 Protein Bound 3D Structures

19.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Conformer

19.2 Chemical-Target Interactions

19.3 Pathways

20 Biological Test Results

20.1 BioAssay Results

21 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

22 Classification

22.1 MeSH Tree

22.2 NCI Thesaurus Tree

22.3 ChEBI Ontology

22.4 KEGG: Metabolite

22.5 KEGG: Drug

22.6 KEGG: JP15

22.7 KEGG: Risk Category of Japanese OTC Drugs

22.8 KEGG: OTC drugs

22.9 ChemIDplus

22.10 ChEMBL Target Tree

22.11 UN GHS Classification

22.12 EPA CPDat Classification

22.13 NORMAN Suspect List Exchange Classification

22.14 CCSBase Classification

22.15 EPA DSSTox Classification

22.16 Consumer Product Information Database Classification

22.17 EPA TSCA and CDR Classification

22.18 LOTUS Tree

22.19 EPA Substance Registry Services Tree

22.20 MolGenie Organic Chemistry Ontology

23 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
  2. CAS Common Chemistry
    LICENSE
    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  3. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  4. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  5. EPA Chemicals under the TSCA
    EPA TSCA Classification
    https://www.epa.gov/tsca-inventory
  6. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  7. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
  8. FDA Global Substance Registration System (GSRS)
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  9. Hazardous Substances Data Bank (HSDB)
  10. Human Metabolome Database (HMDB)
    LICENSE
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    http://www.hmdb.ca/citing
  11. New Zealand Environmental Protection Authority (EPA)
    LICENSE
    This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International licence.
    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
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    CCSbase Classification
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    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
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    NORMAN Suspect List Exchange Classification
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    The code for LOTUS is released under the GNU General Public License v3.0.
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    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
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    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
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    LICENSE
    T3DB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (T3DB) and the original publication.
    http://www.t3db.ca/downloads
  21. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
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    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
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    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
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    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
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    Copyright (c) 2024 DeLima Associates. All rights reserved. Unless otherwise indicated, all materials from CPID are copyrighted by DeLima Associates. No part of these materials, either text or image may be used for any purpose other than for personal use. Therefore, reproduction, modification, storage in a retrieval system or retransmission, in any form or by any means, electronic, mechanical or otherwise, for reasons other than personal use, is strictly prohibited without prior written permission.
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    Copyright (c) 2022 Haz-Map(R). All rights reserved. Unless otherwise indicated, all materials from Haz-Map are copyrighted by Haz-Map(R). No part of these materials, either text or image may be used for any purpose other than for personal use. Therefore, reproduction, modification, storage in a retrieval system or retransmission, in any form or by any means, electronic, mechanical or otherwise, for reasons other than personal use, is strictly prohibited without prior written permission.
    https://haz-map.com/About
  30. DailyMed
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    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  32. Joint FAO/WHO Expert Committee on Food Additives (JECFA)
    LICENSE
    Permission from WHO is not required for the use of WHO materials issued under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Intergovernmental Organization (CC BY-NC-SA 3.0 IGO) licence.
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    Data: CC-BY 4.0; Code: Artistic-2.0
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  35. Natural Product Activity and Species Source (NPASS)
  36. EU Food Improvement Agents
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    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  40. Flavor and Extract Manufacturers Association (FEMA)
  41. MassBank Europe
  42. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
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  44. NIST Mass Spectrometry Data Center
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    Data covered by the Standard Reference Data Act of 1968 as amended.
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    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
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    https://www.pharmgkb.org/page/policies
  57. Protein Data Bank in Europe (PDBe)
  58. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
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    https://www.rcsb.org/pages/policies
  59. Springer Nature
  60. The Cambridge Structural Database
  61. Thieme Chemistry
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    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
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  62. Wikidata
  63. Wikipedia
  64. Wiley
  65. Medical Subject Headings (MeSH)
    LICENSE
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  67. GHS Classification (UNECE)
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  69. MolGenie
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  70. PATENTSCOPE (WIPO)
  71. NCBI
CONTENTS