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Testosterone

PubChem CID
6013
Structure
Testosterone_small.png
Testosterone_3D_Structure.png
Molecular Formula
Synonyms
  • testosterone
  • 58-22-0
  • Testosteron
  • Androderm
  • Testim
Molecular Weight
288.4 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2004-09-16
  • Modify:
    2025-01-18
Description
Testosterone is an androstanoid having 17beta-hydroxy and 3-oxo groups, together with unsaturation at C-4-C-5.. It has a role as an androgen, a human metabolite, a Daphnia magna metabolite and a mouse metabolite. It is a 17beta-hydroxy steroid, an androstanoid, a C19-steroid and a 3-oxo-Delta(4) steroid.
Testosterone is a steroid sex hormone indicated to treat primary hypogonadism and hypogonadotropic hypogonadism. Testosterone antagonizes the androgen receptor to induce gene expression that causes the growth and development of masculine sex organs and secondary sexual characteristics. Testosterone was isolated from samples and also synthesized in 1935.
Testosterone is an Androgen. The mechanism of action of testosterone is as an Androgen Receptor Agonist.
See also: Testosterone Propionate (is active moiety of); Testosterone Enanthate (active moiety of); Testosterone Cypionate (active moiety of) ... View More ...

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Testosterone.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(8R,9S,10R,13S,14S,17S)-17-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C19H28O2/c1-18-9-7-13(20)11-12(18)3-4-14-15-5-6-17(21)19(15,2)10-8-16(14)18/h11,14-17,21H,3-10H2,1-2H3/t14-,15-,16-,17-,18-,19-/m0/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

MUMGGOZAMZWBJJ-DYKIIFRCSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)CCC4=CC(=O)CC[C@]34C
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C19H28O2
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

58-22-0

2.3.2 Deprecated CAS

1050678-68-6

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DrugBank ID

2.3.8 DSSTox Substance ID

2.3.9 HMDB ID

2.3.10 KEGG ID

2.3.11 Lipid Maps ID (LM_ID)

2.3.12 Metabolomics Workbench ID

2.3.13 NCI Thesaurus Code

2.3.14 Nikkaji Number

2.3.15 PharmGKB ID

2.3.16 Pharos Ligand ID

2.3.17 RXCUI

2.3.18 Wikidata

2.3.19 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 17 beta Hydroxy 4 Androsten 3 one
  • 17 beta Hydroxy 8 alpha 4 Androsten 3 one
  • 17-beta-Hydroxy-4-Androsten-3-one
  • 17-beta-Hydroxy-8 alpha-4-Androsten-3-one
  • 8 Isotestosterone
  • 8-Isotestosterone
  • Androderm
  • AndroGel
  • Andropatch
  • Androtop
  • Histerone
  • Sterotate
  • Sustanon
  • Testim
  • Testoderm
  • Testolin
  • Testopel
  • Testosterone
  • Testosterone Sulfate

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
288.4 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
3.3
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
0
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
288.208930132 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
288.208930132 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
37.3 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
21
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
508
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
6
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Solid
White or slightly cream-white crystals or crystalline powder.

3.2.2 Color / Form

White needles from dilute acetone
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1702
Needles from dilute acetone
Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-304
White or slightly cream-white crystals or crystalline powder
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. 1313

3.2.3 Odor

Odorless
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. 1313

3.2.4 Melting Point

155 °C
PhysProp
151.0 °C
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. 3-304
MP: 153-157 °C
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. 1313
MP: 140-141 °C /Testosterone acetate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1702
Crystals. MP: 36-37.5 °C. Very soluble in ether; soluble in vegetable oils. Insoluble in water /Enanthate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1702
155 °C
311 °F

3.2.5 Solubility

23.4 mg/L (at 25 °C)
YALKOWSKY,SH & HE,Y (2003)
In water, 23.4 mg/L at 25 °C
Yalkowsky, S.H., He, Yan, Jain, P. Handbook of Aqueous Solubility Data Second Edition. CRC Press, Boca Raton, FL 2010, p. 1205
Freely soluble in dehydrogenated alcohol, chloroform; soluble in vegetable oils, alcohol, dioxane and other organic solvents; slightly soluble in ether
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1702
Insoluble in water
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. 3-304
Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-304
In ethanol: 1 in 5; in chloroform: 1 in 2; in diethyl ether: 1 in 100; in ethyl oleate: 1 in 150. Sol in acetone, dioxane and fixed oils
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V21: 520 (1979)
0.0234 mg/mL

3.2.6 Vapor Pressure

1.7x10-8 mmHg (est)

3.2.7 LogP

3.32
HANSCH,C ET AL. (1995)
log Kow = 3.32
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 164
3.32
HANSCH,C ET AL. (1995)

3.2.8 Stability / Shelf Life

Stable under recommended storage conditions.
Sigma-Aldrich; Safety Data Sheet for Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
Easily oxidized
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V21 520 (1979)
Stable in air.
Troy, D.B. (Ed); Remmington The Science and Practice of Pharmacy. 21 st Edition. Lippincott Williams & Williams, Philadelphia, PA 2005, p. 1472

3.2.9 Optical Rotation

Specific optical rotation: +109 deg at 24 °C/D (c = 4 in alcohol)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1702
Dextrorotatory in dioxane solution
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. 1313

3.2.10 Decomposition

When heated to decomposition it emits acrid smoke and irritating fumes.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3365

3.2.11 Ionization Efficiency

Ionization mode
Positive
logIE
2.13
pH
2.91
Instrument
Sciex API4000
Ion source
Electrospray ionization
Additive
formic acid (10nM)
Organic modifier
MeCN (90%)
Reference

3.2.12 Caco2 Permeability

-4.34
ADME Research, USCD

3.2.13 Collision Cross Section

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

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

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

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

Ross et al. JASMS 2022; 33; 1061-1072. DOI:10.1021/jasms.2c00111

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

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

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

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

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

172.37 Ų [M+H]+
S61 | UJICCSLIB | Collision Cross Section (CCS) Library from UJI | DOI:10.5281/zenodo.3549476

3.2.14 Other Experimental Properties

Crystals from methanolacetone; mp: 250-255 °C (decomposition); specific optical rotation: +73 deg at 19 °C/D (concentration by volume = 0.992 g in 100 ml methanol); freely sol in water /Testosterone beta-maltoside/
Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 1446
White or creamy white crystals or crystalline powder. Odorless or has slight odor. Practically insoluble in water; freely soluble in alcohol, chloroform, dioxane, ether /Testosterone cypionate/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 933
Specific optical rotation: +87 deg at 25 °C/D (CHCl3); MP: 101-102 °C. Freely soluble in alcohol, chloroform, dioxane, ether; soluble in vegetable oils. Insoluble in water /Testosterone 17beta-cyclopentaneproprionate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1702
White or creamy white crystals or crystalline powder. Odorless or has faint odor characteristic of enanthic acid. Practically insoluble in water. 1 g in about 0.3 mL ether. Soluble in vegetable oils /Testosterone enanthate/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 933
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V21: 522 (1978)
White or creamy white crystals or crystalline powder. Odorless. Practically insoluble in water; soluble in vegetable oils. Freely soluble in alcohol, dioxane, ether; freely soluble in organic solvents /Testosterone propionate/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 933
Stout prisms from alcohol and water, MP: 118-122 °C. Specific optical rotation: +83.0 to 90 deg at 25 C/D (100 mg in 10 ml dioxane). Freely soluble in pyridine and other organic solvents. Soluble in vegetable oils. Insoluble in water /Testosterone propionate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1702
MW: 456.71 /Testosterone undecanate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1702

3.3 SpringerMaterials Properties

3.4 Chemical Classes

Hormone

3.4.1 Drugs

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds
S58 | PSYCHOCANNAB | Synthetic Cannabinoids and Psychoactive Compounds | DOI:10.5281/zenodo.3247723
Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
3.4.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Androgens; Hormones
Human drug -> Discontinued
Human drug -> Prescription; None (Tentative Approval); Discontinued; Active ingredient (TESTOSTERONE)
Human drug -> Prescription
Human drugs -> Sex hormones and modulators of the genital system -> Human pharmacotherapeutic group -> EMA Drug Category
Paediatric drug
Androgens
3.4.1.2 Animal Drugs
Active Ingredients (Testosterone) -> FDA Greenbook
Pharmaceuticals -> Animal Drugs -> Approved in Taiwan
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

3.4.2 Endocrine Disruptors

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

3.4.3 Lipids

Lipids -> Sterol Lipids [ST] -> Steroids [ST02] -> C19 steroids (androgens) and derivatives [ST0202]

4 Spectral Information

4.1 1D NMR Spectra

1D NMR Spectra
SADTLER REFERENCE NUMBER: 727 (IR, PRISM); 13203 (IR, PRISM), 3128 (NMR)
1D NMR Spectra
NMR: 11900 (Sadtler Research Laboratories Spectral Collection)

4.1.1 1H NMR Spectra

1 of 4
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Spectra ID
Instrument Type
Varian
Frequency
500 MHz
Solvent
CDCl3
pH
7.00
Shifts [ppm]:Intensity
2.37:12.48, 2.09:4.47, 2.10:4.92, 2.13:1.98, 1.60:11.38, 1.35:3.72, 1.58:6.63, 0.99:8.01, 1.48:6.05, 2.31:6.14, 1.07:3.24, 1.62:6.57, 1.31:6.11, 0.91:3.55, 7.27:66.46, 2.29:6.39, 2.47:2.71, 1.64:5.99, 1.68:3.15, 1.44:3.44, 1.10:6.79, 2.44:8.06, 1.55:2.64, 1.28:2.20, 0.80:99.20, 3.66:6.09, 3.69:2.95, 1.69:3.27, 1.44:7.79, 2.27:4.14, 1.86:8.92, 2.07:4.81, 1.47:4.44, 1.50:2.13, 1.57:6.52, 1.51:2.41, 2.06:5.17, 2.33:2.46, 2.33:3.88, 2.04:5.41, 1.37:10.66, 2.43:8.02, 2.08:5.26, 1.34:6.79, 2.38:9.05, 1.02:4.93, 1.21:100.00, 1.73:4.21, 1.86:10.66, 3.64:3.12, 2.30:7.87, 2.06:7.29, 1.12:3.96, 1.00:8.04, 2.03:6.34, 1.74:3.90, 1.11:7.06, 1.62:10.66, 1.85:8.38, 1.43:5.43, 5.74:10.02, 1.29:2.46, 2.30:7.59, 1.40:2.08, 0.94:5.92, 2.41:11.35, 1.66:2.35, 1.72:6.59, 1.89:4.46, 2.36:7.00, 1.61:6.01, 2.05:4.35, 2.46:2.99, 1.05:2.55, 1.84:5.60, 2.44:3.95, 0.98:7.41, 1.88:8.28, 1.46:10.04, 1.88:8.07, 1.56:32.34, 1.13:3.94, 2.27:4.93, 1.33:6.70, 1.06:2.43, 1.29:2.16, 1.03:4.75, 3.67:6.06, 2.27:4.61, 1.71:6.39, 1.60:13.70, 1.83:2.66, 2.03:5.82, 1.50:2.73, 1.63:9.36, 2.11:4.09, 1.66:2.65, 2.43:6.29, 1.64:5.02, 1.41:2.24, 2.34:2.91, 1.49:7.48, 0.92:3.84, 1.02:5.01, 0.94:5.91, 2.40:10.90, 0.96:5.50, 0.97:6.97, 1.67:2.23, 1.45:8.26, 2.02:4.55, 1.08:3.77, 2.12:2.42, 2.26:3.67, 1.30:5.98, 1.36:10.48
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Spectra ID
Instrument Type
JEOL
Frequency
400 MHz
Solvent
CDCl3
Shifts [ppm]:Intensity
2.36:98.00, 1.85:71.00, 0.96:118.00, 1.69:64.00, 0.95:106.00, 2.05:88.00, 5.73:185.00, 1.70:66.00, 0.79:1000.00, 2.04:79.00, 2.29:73.00, 1.56:60.00, 5.73:187.00, 2.40:111.00, 1.65:50.00, 2.40:61.00, 2.30:72.00, 1.01:63.00, 1.44:44.00, 2.09:52.00, 2.37:95.00, 1.88:69.00, 2.02:135.00, 1.64:49.00, 1.62:85.00, 2.03:95.00, 2.39:69.00, 1.47:50.00, 1.86:80.00, 2.30:63.00, 1.28:61.00, 1.06:60.00, 2.43:82.00, 1.61:96.00, 1.58:79.00, 1.05:58.00, 1.62:80.00, 1.49:52.00, 1.50:62.00, 1.32:69.00, 1.46:69.00, 1.90:48.00, 0.99:88.00, 2.42:83.00, 2.29:64.00, 2.06:83.00, 1.03:51.00, 2.01:106.00, 1.63:71.00, 2.04:74.00, 2.08:45.00, 1.49:54.00, 2.05:73.00, 1.60:102.00, 1.59:113.00, 1.01:56.00, 0.93:58.00, 2.02:148.00, 1.85:94.00, 1.57:82.00, 1.45:56.00, 1.83:52.00, 2.36:109.00, 1.02:51.00, 0.92:53.00, 2.07:61.00, 2.39:71.00, 1.09:70.00, 1.86:85.00, 1.42:54.00, 1.89:71.00, 1.08:65.00, 1.61:75.00, 2.35:94.00, 2.04:59.00, 1.45:60.00, 2.44:52.00, 0.98:93.00, 2.38:98.00, 0.93:88.00, 2.08:57.00, 1.46:64.00, 1.60:71.00, 1.41:51.00, 2.36:91.00, 2.36:90.00, 2.40:56.00, 1.20:966.00, 1.33:72.00, 2.42:55.00, 1.73:44.00, 3.65:61.00, 1.30:65.00, 2.43:51.00, 2.13:114.00
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4.1.2 13C NMR Spectra

1 of 4
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13C NMR Spectra
13C NMR: 483 FT (Johnson and Jankowski, Carbon 13 NMR Spectra, John Wiley and Sons, NY)
2 of 4
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Spectra ID
Instrument Type
JEOL
Frequency
100.54 MHz
Solvent
CDCl3
Shifts [ppm]:Intensity
35.67:1000.00, 81.56:738.00, 30.41:848.00, 35.73:921.00, 31.55:920.00, 33.94:880.00, 38.67:740.00, 32.80:846.00, 53.93:950.00, 11.06:909.00, 17.42:973.00, 171.35:567.00, 20.65:853.00, 50.49:855.00, 199.60:359.00, 123.85:818.00, 42.82:807.00, 36.44:884.00, 23.34:872.00
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4.2 2D NMR Spectra

4.2.1 1H-13C NMR Spectra

2D NMR Spectra Type
1H-13C HSQC
Spectra ID
Instrument Type
Bruker
Frequency
600 MHz
Solvent
CDCl3
pH
7.00
Shifts [ppm] (F2:F1):Intensity
1.70:35.69:0.19, 2.42:33.93:0.25, 1.63:23.28:0.30, 1.87:36.32:0.24, 5.73:123.83:1.00, 1.85:31.48:0.39, 0.79:11.15:0.09, 1.31:23.49:0.16, 0.97:50.41:0.31, 1.20:17.53:0.51, 2.28:32.74:0.29, 3.65:81.66:0.52, 1.61:20.61:0.33, 2.03:35.83:0.21, 1.01:31.48:0.22, 1.43:20.61:0.20, 1.09:36.46:0.27, 2.09:30.36:0.23, 1.47:30.43:0.25, 1.57:35.62:0.28, 2.38:32.74:0.24, 2.34:33.86:0.18, 0.93:53.85:0.38
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4.3 Mass Spectrometry

4.3.1 GC-MS

1 of 17
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Spectra ID
Instrument Type
GC-MS
Top 5 Peaks

129.0 1

91.0 0.22

105.0 0.16

79.0 0.16

130.0 0.14

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Spectra ID
Instrument Type
GC-MS
Top 5 Peaks

432.0 1

91.0 0.57

209.0 0.51

433.0 0.41

105.0 0.39

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4.3.2 MS-MS

1 of 6
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Spectra ID
Ionization Mode
Positive
Top 5 Peaks

289.2159 100

123.0796 89.29

253.1944 78.88

147.1157 56.76

159.1155 56.26

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Spectra ID
Ionization Mode
Positive
Top 5 Peaks

123.0796 100

145.1004 64.46

131.0845 63.46

129.0684 51.75

133.1001 50.25

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4.3.3 LC-MS

1 of 45
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Authors
da Silva KM, Iturrospe E, van de Lavoir M, Robeyns R, University of Antwerp, Belgium
Instrument
Agilent 6560 QTOF
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
20 eV
Fragmentation Mode
CID
Column Name
Direct injection
Retention Time
0.152 min
Precursor m/z
289.2162
Precursor Adduct
[M+H]+
Top 5 Peaks

97.0653 999

109.0652 708

289.2164 87

81.0704 68

123.0804 55

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License
CC BY
2 of 45
View All
Authors
da Silva KM, Iturrospe E, van de Lavoir M, Robeyns R, University of Antwerp, Belgium
Instrument
Agilent 6560 QTOF
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
10 eV
Fragmentation Mode
CID
Column Name
Direct injection
Retention Time
0.157 min
Precursor m/z
289.2162
Precursor Adduct
[M+H]+
Top 5 Peaks

289.2162 999

97.0646 916

109.0643 680

271.2063 128

253.1943 85

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CC BY

4.3.4 Other MS

1 of 7
View All
Other MS
MASS: 62026 (NIST/EPA/MSDC Mass Spectral Data Base, 1990 Version)
2 of 7
View All
Authors
KOGA M, UNIV. OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH
Instrument
JEOL JMS-01-SG-2
Instrument Type
EI-B
MS Level
MS
Ionization Mode
POSITIVE
Ionization
ENERGY 75 eV
Top 5 Peaks

124 999

41 414

246 368

91 361

79 350

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License
CC BY-NC-SA

4.4 UV Spectra

UV Max absorption: 238 nm
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1702
UV: 7-851 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York)
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V1: 238

4.5 IR Spectra

IR Spectra
IR: 5450 (Coblentz Society Spectral Collection)

4.5.1 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
Instrument Name
Bio-Rad FTS
Technique
KBr1 0.65mg
Source of Spectrum
Forensic Spectral Research
Source of Sample
Steraloids
Catalog Number
A6950-000
Lot Number
H508
Copyright
Copyright © 2008-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.5.2 ATR-IR Spectra

Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Steraloids Inc.
Catalog Number
A6950-000
Lot Number
H508
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.6 Raman Spectra

Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Steraloids Inc.
Catalog Number
A6950-000
Lot Number
H508
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.7 Other Spectra

Intense mass spectral peaks: 124 m/z, 246 m/z, 288 m/z
Pfleger, K., H. Maurer and A. Weber. Mass Spectral and GC Data of Drugs, Poisons and their Metabolites. Parts I and II. Mass Spectra Indexes. Weinheim, Federal Republic of Germany. 1985., p. 499

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Testosterone is indicated to treat primary hypogonadism and hypogonadotropic hypogonadism.
Intrinsa is indicated for the treatment of hypoactive sexual desire disorder (HSDD) in bilaterally oophorectomised and hysterectomised (surgically induced menopause) women receiving concomitant estrogen therapy.

7.2 Drug Classes

Breast Feeding; Lactation; Milk, Human; Androgens; Hormones

7.3 FDA Medication Guides

1 of 6
View All
Drug
Active Ingredient
TESTOSTERONE
Form;Route
GEL, METERED;TRANSDERMAL
Company
ABBVIE
Date
5/30/19
Drug
Active Ingredient
TESTOSTERONE
Form;Route
GEL;TRANSDERMAL
Company
ABBVIE
Date
5/30/19
Drug
Active Ingredient
TESTOSTERONE
Form;Route
GEL;TRANSDERMAL
Company
ABBVIE
Date
5/30/19
Drug
Active Ingredient
TESTOSTERONE
Form;Route
GEL, METERED;TRANSDERMAL
Company
ABBVIE
Date
5/30/19
2 of 6
View All
Drug
Active Ingredient
TESTOSTERONE
Form;Route
SOLUTION, METERED;TRANSDERMAL
Company
ELI LILLY AND CO
Date
7/13/17
3 of 6
View All
Drug
Active Ingredient
TESTOSTERONE
Form;Route
GEL, METERED;TRANSDERMAL
Company
ENDO PHARMS
Date
6/30/20

7.4 WHO Essential Medicines

Drug
Drug Classes
Androgens
Formulation
Parenteral - General injections - IM: 200 mg per mL in 1 mL ampoule (enantate)
Indication
Testicular dysfunction or testosterone-related disorders

7.5 FDA Approved Drugs

7.6 FDA Orange Book

7.7 FDA National Drug Code Directory

7.8 FDA Green Book

7.9 Drug Labels

Drug and label
Active ingredient and drug
Homeopathic product and label

7.10 Clinical Trials

7.10.1 ClinicalTrials.gov

7.10.2 EU Clinical Trials Register

7.10.3 NIPH Clinical Trials Search of Japan

7.11 DEA Drug and Chemical Information

7.11.1 DEA Controlled Substances

1 of 3
Non-Proprietary Name
TESTOSTERONE
DEA Substances Act Schedule
Schedule III
2 of 3
Non-Proprietary Name
TESTOSTERONE GEL, 1%
DEA Substances Act Schedule
Schedule III
3 of 3
Non-Proprietary Name
TESTOSTERONE,
DEA Substances Act Schedule
Schedule III

7.12 EMA Drug Information

1 of 7
View All
Medicine
Category
Human drugs
Therapeutic area
Sexual Dysfunctions, Psychological
Active Substance
Testosterone
INN/Common name
testosterone
Pharmacotherapeutic Classes
Sex hormones and modulators of the genital system
Status
Withdrawn
Company
Warner Chilcott UK Ltd.
Market Date
2006-07-28
2 of 7
View All
Medicine
Category
Human drugs
Therapeutic area
Sexual Dysfunctions, Psychological
Active Substance
Testosterone
INN/Common name
testosterone
Pharmacotherapeutic Classes
Sex hormones and modulators of the genital system
Status
Withdrawn
Company
Warner Chilcott  Deutschland GmbH
Market Date
2006-07-28

7.13 Therapeutic Uses

Androgens
National Library of Medicine's Medical Subject Headings. Testosterone. Online file (MeSH, 2016). Available from, as of November 28, 2016: https://www.nlm.nih.gov/mesh/2016/mesh_browser/MBrowser.html
/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Testosterone is included in the database.
NIH/NLM; ClinicalTrials.Gov. Available from, as of February 1, 2017: https://clinicaltrials.gov/ct2/results?term=testosterone&Search=Search
In males, testosterone is used for the management of congenital or acquired primary hypogonadism such as that resulting from orchiectomy or from testicular failure caused by cryptorchidism, bilateral torsion, orchitis, or vanishing testis syndrome. Testosterone also is used in males for the management of congenital or acquired hypogonadotropic hypogonadism such as that resulting from idiopathic gonadotropin or gonadotropin-releasing hormone (luteinizing hormone releasing hormone) deficiency or from pituitary-hypothalamic injury caused by tumors, trauma, or radiation. If any of these conditions occur before puberty, androgen replacement therapy will be necessary during adolescence for the development of secondary sexual characteristics and prolonged therapy will be required to maintain these characteristics. Prolonged androgen therapy also is required to maintain sexual characteristics in other males who develop testosterone deficiency after puberty. /Included in US product labeling/
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3131
When the diagnosis is well established, testosterone may be used to stimulate puberty in carefully selected males with delayed puberty. These males usually have a family history of delayed puberty that is not caused by a pathologic disorder. Brief treatment with conservative doses of an androgen may occasionally be justified in these males if they do not respond to psychologic support. Because androgens may adversely affect bone maturation in these prepubertal males, this potential risk should be fully discussed with the patient and his parents prior to initiation of androgen therapy. If androgen therapy is initiated in these prepubertal males, radiographs of the hand and wrist should be obtained at 6-month intervals to determine the effect of therapy on the epiphyseal centers. Testosterone is designated an orphan drug by the FDA for use in this condition. /Included in US product labeling/
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3132
For more Therapeutic Uses (Complete) data for Testosterone (17 total), please visit the HSDB record page.

7.14 Drug Warnings

/BOXED WARNING/ WARNING: SECONDARY EXPOSURE TO TESTOSTERONE. Virilization has been reported in children who were secondarily exposed to testosterone gel. Children should avoid contact with unwashed or unclothed application sites in men using testosterone gel. Healthcare providers should advise patients to strictly adhere to recommended instructions for use.
NIH; DailyMed. Current Medication Information for Androgel (Testosterone Gel) (Updated: January 2015). Available from, as of April 5, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a8253ce7-77df-49d4-8077-816cf4dc234f
Cardiovascular events, including MI or stroke, have been reported during postmarketing experience with testosterone transdermal system (Androderm). Testosterone should be used with caution in patients at high risk for cardiovascular disease (e.g., older men, those with diabetes mellitus or obesity). Patients should be advised to immediately report symptoms suggestive of MI or stroke (e.g., chest pain, shortness of breath, unilateral weakness, difficulty talking) to their clinician.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3135-6
Venous thromboembolic events, including deep-vein thrombosis (DVT) and pulmonary embolism (PE), have been reported during postmarketing experience with testosterone preparations, including testosterone transdermal system (Androderm). Patients reporting symptoms of pain, edema, warmth, and erythema in a lower extremity or presenting with acute shortness of breath should be evaluated for possible DVT or PE, respectively. If venous thromboembolism is suspected, testosterone therapy should be discontinued and appropriate evaluation and management should be initiated.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3136
Testosterone should be used with caution in patients with cardiac, renal, and/or hepatic dysfunction since edema may occur as a result of sodium and water retention. Edema, with or without congestive heart failure, may be a serious complication in patients with preexisting cardiac, renal, and/or hepatic disease. If edema occurs during testosterone therapy and it is considered a serious complication, the drug should be discontinued; diuretic therapy may also be necessary.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3136
For more Drug Warnings (Complete) data for Testosterone (34 total), please visit the HSDB record page.

7.15 Biomarker Information

8 Food Additives and Ingredients

8.1 Food Additive Classes

JECFA Functional Classes
Veterinary Drug -> PRODUCTION_AID;

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

Chemical Name
TESTOSTERONE
Evaluation Year
2000
ADI
0-0.002 mg/kg bw
Comments
The Committee established an ADI of 0-2 µg/kg bw for testosterone on the basis of the NOEL of 100 mg/day (1.7 mg/kg bw/day) in the study of eunuchs and a safety factor of 1000. The large safety factor was used in order to protect sensitive populations and because of the small number of subjects in the study from which the NOEL was identified. Based on a calculated excess intake of testosterone of 60 ng/p/d (0.05% of ADI), the Committee concluded that there was no need to specify MRL values when the drug was used in accordance with good veterinary practices.
Tox Monograph

9 Pharmacology and Biochemistry

9.1 Pharmacodynamics

Testosterone antagonizes the androgen receptor to induce gene expression that causes the growth and development of masculine sex organs and secondary sexual characteristics. The duration of action of testosterone is variable from patient to patient with a half life of 10-100 minutes. The therapeutic index is wide considering the normal testosterone levels in an adult man range from 300-1000ng/dL. Counsel patients regarding the risk of secondary exposure of testosterone topical products to children.

9.2 MeSH Pharmacological Classification

Androgens
Compounds that interact with ANDROGEN RECEPTORS in target tissues to bring about the effects similar to those of TESTOSTERONE. Depending on the target tissues, androgenic effects can be on SEX DIFFERENTIATION; male reproductive organs, SPERMATOGENESIS; secondary male SEX CHARACTERISTICS; LIBIDO; development of muscle mass, strength, and power. (See all compounds classified as Androgens.)

9.3 FDA Pharmacological Classification

1 of 4
FDA UNII
3XMK78S47O
Active Moiety
TESTOSTERONE
Pharmacological Classes
Established Pharmacologic Class [EPC] - Androgen
Pharmacological Classes
Mechanisms of Action [MoA] - Androgen Receptor Agonists
Pharmacological Classes
Chemical Structure [CS] - Androstanes
FDA Pharmacology Summary
Testosterone is an Androgen. The mechanism of action of testosterone is as an Androgen Receptor Agonist.
2 of 4
Non-Proprietary Name
TESTOSTERONE
Pharmacological Classes
Androstanes [CS]; Androgen [EPC]; Androgen Receptor Agonists [MoA]
3 of 4
Non-Proprietary Name
TESTOSTERONE GEL, 1%
Pharmacological Classes
Androstanes [CS]; Androgen [EPC]; Androgen Receptor Agonists [MoA]
4 of 4
Non-Proprietary Name
TESTOSTERONE,
Pharmacological Classes
Androgen Receptor Agonists [MoA]; Androgen [EPC]; Androstanes [CS]

9.4 ATC Code

G03BA03
S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

G - Genito urinary system and sex hormones

G03 - Sex hormones and modulators of the genital system

G03B - Androgens

G03BA - 3-oxoandrosten (4) derivatives

G03BA03 - Testosterone

9.5 Bionecessity

Androgens are responsible for the growth spurt that occurs during adolescence and for the eventual termination of linear growth that results from fusion of the epiphyseal growth centers. ...
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3137
Testosterone, like other androgenic anabolic hormones, also produces retention of nitrogen, potassium, sodium, and phosphorus; increases protein anabolism; and decreases amino acid catabolism and urinary calcium concentrations. Nitrogen balance is improved only when there is sufficient intake of calories and protein.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3137
Testosterone is the principal endogenous androgen. Endogenous androgens are essential hormones that are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics, including the growth and maturation of the prostate, seminal vesicles, penis, and scrotum; development of male hair distribution, such as beard, pubic, chest, and axillary hair; laryngeal enlargement and thickening of the vocal cords; and alterations in body musculature and fat distribution.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3137
Testosterone is a key hormone in the pathology of metabolic diseases such as obesity. Low testosterone levels are associated with increased fat mass (particularly central adiposity) and reduced lean mass in males. These morphological features are linked to metabolic dysfunction, and testosterone deficiency is associated with energy imbalance, impaired glucose control, reduced insulin sensitivity and dyslipidaemia. A bidirectional relationship between testosterone and obesity underpins this association indicated by the hypogonadal-obesity cycle and evidence weight loss can lead to increased testosterone levels. Androgenic effects on enzymatic pathways of fatty acid metabolism, glucose control and energy utilization are apparent and often tissue specific with differential effects noted in different regional fat depots, muscle and liver to potentially explain the mechanisms of testosterone action. Testosterone replacement therapy demonstrates beneficial effects on measures of obesity that are partially explained by both direct metabolic actions on adipose and muscle and also potentially by increasing motivation, vigour and energy allowing obese individuals to engage in more active lifestyles. The degree of these beneficial effects may be dependent on the treatment modality with longer term administration often achieving greater improvements. Testosterone replacement may therefore potentially be an effective adjunctive treatment for weight management in obese men with concomitant hypogonadism.
Kelly DM, Jones TH; Obes Rev 16 (7): 581-606 (2015)

9.6 Absorption, Distribution and Excretion

Absorption
A single 100mg topical dose of testosterone has an AUC of 10425±5521ng\*h/dL and a Cmax of 573±284ng/dL. Testosterone is approximately 10% bioavailable topically.
Route of Elimination
90% of an intramuscular dose is eliminated in urine, mainly as glucuronide and sulfate conjugates. 6% is eliminated in feces, mostly as unconjugated metabolites.
Volume of Distribution
The volume of distribution of testosterone in elderly men is 80.36±24.51L.
Clearance
The mean metabolic clearance in middle aged men is 812±64L/day.
Testosterone is absorbed systemically through the skin following topical application as a gel or transdermal system. Following topical application of a hydroalcoholic gel formulation of testosterone (AndroGel, Testim) to the skin, the gel quickly dries on the skin surface, which serves as a reservoir for sustained release of the hormone into systemic circulation. Approximately 10% of a testosterone dose applied topically to the skin as a 1% gel is absorbed percutaneously into systemic circulation. The manufacturer of AndroGel states that increases in serum testosterone concentrations were apparent within 30 minutes of topical application of a 100-mg testosterone dose of the 1% gel, with physiologic concentrations being achieved in most patients within 4 hours (pretreatment concentrations were not described); percutaneous absorption continues for the entire 24-hour dosing interval. Serum testosterone concentrations approximate steady-state levels by the end of the initial 24 hours and are at steady state by the second or third day of dosing of the 1% gel. With daily topical application of the 1% gel (AndroGel), serum testosterone concentrations 30, 90, and 180 days after initiating treatment generally are maintained in the eugonadal range. Administration of 10 or 5 g of AndroGel daily results in average daily serum testosterone concentrations of 794 or 566 ng/dL, respectively, at day 30. Following discontinuance of such topical therapy, serum testosterone concentrations remain within the normal range for 24-48 hours but return to pretreatment levels by the fifth day after the last application.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3137
With topical application of a transdermal preparation, the extent of percutaneous testosterone absorption varies according to the site of application, possibly secondary to regional differences in skin permeability, cutaneous blood flow, and/or degree of adhesion between the transdermal system and skin. In one study in which transdermal systems were applied to the abdomen, back, chest, shin, thigh, or upper arm, serum hormone profiles were qualitatively similar with each site, but steady-state serum concentrations showed significant differences, decreasing in order with the back, thigh, upper arm, abdomen, chest, and shin. Application of Androderm transdermal systems to the abdomen, back, thighs, or upper arms results in achievement of similar serum testosterone concentration profiles, and these sites are recommended as optimal for rotation of application sites during chronic therapy. Daily nighttime (at approximately 10 p.m.) application of Androderm transdermal system results in a serum testosterone concentration profile that mimics the endogenous diurnal pattern in healthy young men. In one study, showering 3 hours after application of Androderm decreased peak plasma concentrations of testosterone by 0.4% compared with not showering 3 hours after application of the transdermal system. In addition, showering 3 hours after transdermal system application did not substantially alter the systemic exposure of testosterone.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3137-8
Following topical application of transdermal systems of testosterone, the hormone is absorbed percutaneously into systemic circulation. Although interindividual variation in percutaneous testosterone absorption occurs, serum testosterone concentrations achieved with recommended dosages of transdermal systems of the drug generally reach the normal range during the first day of dosing and are maintained during continuous dosing without accumulation. Average daily serum testosterone concentrations in patients receiving Androderm reportedly are 498 ng/dL at steady state. Mean ratios of testosterone to DHT are within the normal range.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3137
Esterification of testosterone generally results in less polar compounds. The enanthate ester of testosterone is absorbed slowly from the lipid tissue phase at the IM injection site, achieving peak serum concentrations about 72 hours after IM injection; thus, this preparation has a prolonged duration of action (i.e., up to 2-4 weeks) following IM administration. Because IM injection of testosterone esters causes local irritation, the rate of absorption may be erratic. /Testosterone esters/
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3137
For more Absorption, Distribution and Excretion (Complete) data for Testosterone (9 total), please visit the HSDB record page.

9.7 Metabolism / Metabolites

Testosterone is metabolized to 17-keto steroids through two different pathways. The major active metabolites are estradiol and dihydrotestosterone (DHT). Testosterone can be hydroxylated at a number of positions by CYP3A4, CYP2B6, CYP2C9, and CYP2C19; glucuronidated by UGT2B17; sulfated; converted to estradiol by aromatase; converted to dihydrotestosterone (DHT) by 5α-reductase; metabolized to androstenedione by CYP3A4, CYP2C9, and CYP2C19; or converted to DHT glucuronide. Androstenedione undergoes metabolism by aromatase to form estrone, which undergoes a reversible reaction to form estradiol. Androstenedione can also be converted to 5α-androstanedione by 5α-reductase, which can be further metabolized to 5α-androsterone. DHT can be glucuronidated or sulfated, or metabolized to 5α-androstanediol, androstane-3α,17β-diol, or androstane-3β,17β-diol. DHT can also be reversibly converted to 5α-androstanedione.
Extensive reductive metabolism of testosterone occurs not only in the liver, but also in a variety of extrahepatic tissues, especially in target organs of the sex hormones; the ultimately effective physiological androgen is formed in the target tissues. Testosterone metabolism occurs not only in the prostate and seminal vesicles but also in rat uterus, rabbit placenta, rodent testis and primate brain. In rats, the small intestine is also capable of metabolizing testosterone.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V21 536 (1979)
It is transformed to 5-alpha-dehydrotestosterone in target organs such as the prostate, sebaceous glands and seminal vesicles; only the latter compound binds to the androgen-receptor site in these target organs.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V21 536 (1979)
Large quantitative differences in testosterone metabolism are evident between female and male rats. The reason for this phenomenon is that many steroid-metabolizing enzymes in rats are either androgen- or estrogen-dependent; the sex hormones thus act in an inductive or a repressive manner.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V21 536 (1979)
Esters of testosterone, such as the propionate, the heptanoate, the cypionate, the valerate, the isovalerate, the enanthate and the undecanoate, are partially cleaved in vivo to release the parent compound. This has been demonstrated by oral administration of testosterone undecanoate in oily solution to rats: most of the compound is converted within the intestinal wall, the first step being partial splitting off of the fatty acid moiety. The non-metabolized portion, however, and the metabolite 5-alpha-dihydrotestosterone undecanoate, are absorbed via the lymphatic system and made available for androgenic action to the organism. /Testosterone esters/
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V21 537 (1979)
For more Metabolism/Metabolites (Complete) data for Testosterone (6 total), please visit the HSDB record page.
Testosterone has known human metabolites that include 16beta-Hydroxytestosterone, 15beta-Hydroxytestosterone, Testosterone sulfate, Androstenedione, 2alpha-Hydroxytestosterone, 15-Hydroxytestosterone, 2beta-Hydroxytestosterone, 16-Hydroxytestosterone, and 6alpha-Hydroxytestosterone.
S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560
Testosterone is metabolized to 17-keto steroids through two different pathways. The major active metabolites are estradiol and dihydrotestosterone (DHT). Route of Elimination: About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6% of a dose is excreted in the feces, mostly in the unconjugated form. Half Life: 10-100 minutes

9.8 Biological Half-Life

The half life of testosterone is highly variable, ranging from 10-100 minutes.
The plasma half-life of testosterone reportedly ranges from 10-100 minutes. The plasma half-life of testosterone cypionate after IM injection is approximately 8 days. Following removal of an Androderm transdermal system, plasma testosterone concentrations decline with an apparent half-life of approximately 70 minutes ... .
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3138

9.9 Mechanism of Action

The androgen receptor exists in the cytoplasm bound to the heat shock proteins HSP90, HSP70, and other chaperones. After binding to an androgen, the androgen receptor dissociates from HSP90 and undergoes a conformational change to slow the rate of dissociation from the androgen receptor. The androgen-receptor complex is transported into the nucleus where it binds to DNA and recruits other transcriptional regulators to form a pre-initiation complex and eventually induce expression of specific genes. Testosterone and its active metabolite dihydrotestosterone (DHT) antagonize the androgen receptor to develop masculine sex organs including the prostate, seminal vesicles, penis, and scrotum. Antagonism of the androgen receptor is also responsible for the development of secondary sexual characteristics including facial and body hair, enlargement of the larynx, thickening of the vocal cords, and changes in muscle and fat distribution.
Low-grade chronic inflammation is commonly found in patients with polycystic ovary syndrome (PCOS) who exhibit hyperandrogenism or hyperandrogenemia. Clinical studies have shown that hyperandrogenemia is closely correlated with low-grade chronic inflammation. However, the mechanism underlying this correlation remains unclear. Recent studies have suggested that adipocytes increase the production of proinflammatory mediators such as interleukin-6 (IL-6) and macrophage chemotactic protein-1 (MCP-1) when the inflammatory signal transduction cascade system is activated by external stimuli. The present study aimed to evaluate the effects of testosterone on the innate signalling and expression of proinflammatory mediators in 3T3-L1 adipocytes, which were or were not induced by lipopolysaccharide (LPS). The effects of testosterone on the expression of proinflammatory mediators, nuclear factor-kappaB (NF-kappaB), and extracellular signal-regulated kinase 1/2 (ERK1/2) signalling pathways were investigated using an enzyme-linked immunosorbent assay, reverse transcriptase-polymerase chain reaction, western blot analysis and an electrophoresis mobility shift assay. Testosterone induces IL-6 and MCP-1, and enhances LPS-induction of IL-6 and MCP-1. However, the effects are not simply additive, testosterone significantly enhanced the effects of LPS-induced inflammation factors. Testosterone induces the phosphorylation of ERK1/2 and NF-kappaB. The effect of testosterone on the expression of IL-6 and MCP-1 is inhibited by PD98059, an ERK1/2 inhibitor, and PDTC, an NF-kappaB inhibitor. The results indicate that testosterone enhances LPS-induced IL-6 and MCP-1 expression by activating the ERK1/2/NF-kappaB signalling pathways in 3T3-L1 adipocytes.
Su C et al; Mol Med Rep 12 (1): 696-704 (2015)
Androgens reportedly stimulate the production of erythrocytes, apparently by enhancing the production of erythropoietic stimulating factor.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3137

9.10 Human Metabolite Information

9.10.1 Tissue Locations

  • Brain
  • Ovary
  • Semen
  • Skeletal Muscle
  • Testis

9.10.2 Cellular Locations

  • Cytoplasm
  • Endoplasmic reticulum
  • Extracellular
  • Membrane

9.10.3 Metabolite Pathways

9.11 Biochemical Reactions

9.12 Transformations

10 Use and Manufacturing

10.1 Uses

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
Androgens
National Library of Medicine's Medical Subject Headings. Testosterone. Online file (MeSH, 2016). Available from, as of November 28, 2016: https://www.nlm.nih.gov/mesh/2016/mesh_browser/MBrowser.html
Anabolic steroids are listed as Schedule III controlled substances (DEA Code #: 400). /Anabolic steroid means any drug or hormonal substance, chemically and pharmacologically related to testosterone (other than estrogens, progestins, corticosteroids, and dehydroepiandrosterone)/
21 CFR 1308.13(f) (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of February 27, 2017: https://www.ecfr.gov
Schedule III Controlled Substance: (A) The drug or other substance has a potential for abuse less than the drugs or other substances in schedules I and II. (B) The drug or other substance has a currently accepted medical use in treatment in the United States. (C) Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence.
US Department of Justice/Office of Diversion Control; Schedule of Controlled Substances. Available from, as of April 4, 2017: https://www.deadiversion.usdoj.gov/21cfr/21usc/812.htm
Biochemical research
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. 1313
For more Uses (Complete) data for Testosterone (6 total), please visit the HSDB record page.

Use (kg) in Switzerland (2009): >50

Use (kg; approx.) in Germany (2009): >500

Use (kg) in USA (2002): 1020

Consumption (g per capita) in Switzerland (2009): 0.0064

Consumption (g per capita; approx.) in Germany (2009): 0.0061

Consumption (g per capita) in the USA (2002): 0.0036

Excretion rate: 0.1

Calculated removal (%): 37.8

To be used as hormone replacement or substitution of diminished or absent endogenous testosterone. Use in males: For management of congenital or acquired hypogonadism, hypogonadism associated with HIV infection, and male climacteric (andopause). Use in females: For palliative treatment of androgen-responsive, advanced, inoperable, metastatis (skeletal) carcinoma of the breast in women who are 1-5 years postmenopausal; testosterone esters may be used in combination with estrogens in the management of moderate to severe vasomotor symptoms associated with menopause in women who do not respond to adequately to estrogen therapy alone.

10.1.1 Use Classification

Human drugs -> Sex hormones and modulators of the genital system -> Human pharmacotherapeutic group -> EMA Drug Category
Human Drugs -> EU pediatric investigation plans
Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients
Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients
Veterinary Drug -> PRODUCTION_AID; -> JECFA Functional Classes
Pharmaceuticals -> Animal Drugs -> Approved in Taiwan
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

10.2 Methods of Manufacturing

First isolated in crystalline form by Laquer in 1935 who obtained it from animal testes. Although small amounts of testosterone may be extracted from testicular material, the synthetic commercial supply is derived from cholesterol. The key intermediate in the synthesis is dehydroepiandrosterone, which can be treated further, by either chemical or microbiological processes, to yield testosterone.
Troy, D.B. (Ed); Remmington The Science and Practice of Pharmacy. 21 st Edition. Lippincott Williams & Williams, Philadelphia, PA 2005, p. 1472
Isolation from extract of testis, synthesis from cholesterol or from the plant steroid diosgenin.
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. 1313
Testosterone is synthesized from androstenolone acetate which is reduced to the 17beta-alcohol with Raney nickel and then esterified with benzoyl chloride in pyridine. This protecting ester group permits partial saponification of the 3-acetate with methanolic sodium hydroxide solution to yield the 3-hydroxy compound. Subsequent Oppenauer oxidation produces the testosterone benzoate, which is then subjected to alkaline hydrolysis to give testosterone.
Ullmann's Encyclopedia of Industrial Chemistry. 6th ed.Vol 1: Federal Republic of Germany: Wiley-VCH Verlag GmbH & Co. 2003 to Present, p. V16 627 (2003)

10.3 Formulations / Preparations

Parenteral: Injection (in oil): 200 mg/mL Delatestryl (C-III, with chlorobutanol), (Indevus and also available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name) /Testosterone enanthate/
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3138
Parenteral: Injection (in oil): 200 mg/mL Testosterone Cypionate, C-III (Watson and also available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name). /Testosterone cypionate/
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3138
Grade: National Formulary
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. 1313
Powder (C-III); (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name). /Testosterone propionate/
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3138
Table: Testosterone Preparations
Route of Administration
Buccal
Dosage Form
Tablets, extended-release
Strength
30 mg
Brand or Generic Form (Manufacturer)
Striant, C-III (Columbia)
Route of Administration
Topical
Dosage Form
Gel
Strength
1% (25 and 50 mg)
Brand or Generic Form (Manufacturer)
AndroGel, C-III (Abbott)
Route of Administration
Topical
Dosage Form
Gel
Strength
1% (25 and 30 mg)
Brand or Generic Form (Manufacturer)
(Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Route of Administration
Topical
Dosage Form
Gel
Strength
1% (50 mg)
Brand or Generic Form (Manufacturer)
Testin, C-III (Auxilium)
Route of Administration
Topical
Dosage Form
Gel
Strength
1% (50 mg)
Brand or Generic Form (Manufacturer)
(Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Route of Administration
Topical
Dosage Form
Transdermal System
Strength
2 mg/24 hours (9.7 mg/32 sq cm)
Brand or Generic Form (Manufacturer)
Androderm, C-III (Actavis)
Route of Administration
Topical
Dosage Form
Transdermal System
Strength
4 mg/24 hours (19.5 mg/39 sq cm)
Brand or Generic Form (Manufacturer)
Androderm, C-III (Actavis)
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3138

10.4 General Manufacturing Information

EPA TSCA Commercial Activity Status
Androst-4-en-3-one, 17-hydroxy-, (17.beta.)-: ACTIVE
An androgenic steroid; the male sex hormone produced by the testis. It has six times the androgenic activity of its metabolic product, androsterone.
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. 1313
Principal hormone of the testes, produced by the interstitial cells.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1702

11 Identification

11.1 Analytic Laboratory Methods

Method: USGS-NWQL O-4434-12; Procedure: gas chromatography mass spectrometry/mass spectrometry; Analyte: testosterone; Matrix: unfiltered water; Detection Limit: 1.6 ng/L.
National Environmental Methods Index; Analytical, Test and Sampling Methods. Testosterone (58-22-0). Available from, as of March 2, 2017: https://www.nemi.gov
Method: EPA-OW/OST 1698; Procedure: high resolution gas chromatography combined with high resolution mass spectrometry; Analyte: testosterone; Matrix: multi-media environmental samples; Detection Limit: 20 ng/L.
National Environmental Methods Index; Analytical, Test and Sampling Methods. Testosterone (58-22-0). Available from, as of March 2, 2017: https://www.nemi.gov
A capillary separation method that incorporates pH-mediated stacking is employed for the simultaneous determination of circulating steroid hormones in plasma from Perca flavescens (yellow perch) collected from natural aquatic environments. The method can be applied to separate eight steroid standards: progesterone, 17alpha,20beta-dihydroxypregn-4-en-3-one, 17alpha-hydroxyprogesterone, testosterone, estrone, 11-ketotestosterone, ethynyl estradiol, and 17beta-estradiol. Based on screening of plasma, the performance of the analytical method was determined for 17alpha,20beta-dihydroxypregn-4-en-3-one, testosterone, 11-ketotestosterone, and 17beta-estradiol. The within-day reproducibility in migration time for these four steroids in aqueous samples was < or =2%. Steroid quantification was accomplished using a calibration curve obtained with external standards. Plasma samples from fish collected from the Choptank and Severn Rivers, Maryland, USA, stored for up to one year were extracted with ethyl acetate and then further processed with anion exchange and hydrophobic solid phase extraction cartridges. The recovery of testosterone and 17beta-estradiol from yellow perch plasma was 84 and 85%, respectively. Endogenous levels of testosterone ranged from 0.9 to 44 ng/mL, and when detected 17alpha,20beta-dihydroxypregn-4-en-3-one ranged from 5 to 34 ng/mL. The reported values for testosterone correlated well with the immunoassay technique. Endogenous concentrations of 17beta-estradiol were < or =1.7 ng/mL. 11-Ketotestosterone was not quantified because of a suspected interferant. Higher levels of 17alpha,20beta-dihydroxypregn-4-en-3-one were found in male and female fish in which 17beta-estradiol was not detected. Monitoring multiple steroids can provide insight into hormonal fluctuations in fish.
Bykova L et al; Environ Toxicol Chem 29 (9): 1950-6 (2010)
An analytical procedure for the simultaneous determination of twelve endogenous steroids (testosterone, androstenedione, 17beta-estradiol, estrone, pregnenolone, progesterone, dihydroandrostenedione, dihydrotestosterone, 11alpha-ketotestosterone, 17alpha-hydroxyprogesterone, 17alpha-hydroxypregnenolone, 17alpha,20beta-dihydroxy-4-pregnen-3-one) in plasma and bile samples by solid-phase extraction (SPE) and gas chromatography/mass spectrometry (GC-MS) has been developed. After enzymatic hydrolysis for bile samples only, samples were concentrated and purified using two successive SPE (C(18) and NH(2)) cartridges. Analytes were derivatized with a mixture of N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) / mercaptoethanol / ammonium iodide (NH(4)I) and determined by GC-MS in selective ion monitoring mode. For most of the steroids monitored, recoveries were in the range 90-120% in plasma and in the range 60-70% in bile, and the reproducibility was below 10% for the complete procedure. Limits of detection obtained ranged from 0.1 to 0.4 ng/g in fish plasma and from 1.6 to 14 ng/g in fish bile. The developed method was successfully applied to the determination of plasma steroids in flounders (Platichthys flesus) collected from two French estuaries.
Budzinski H et al; Anal Bioanal Chem 386 (5): 1429-39 (2006)
For more Analytic Laboratory Methods (Complete) data for Testosterone (21 total), please visit the HSDB record page.

11.2 Clinical Laboratory Methods

Sample matrix: Bulk chemical. Sample preparation: Dissolve (ethanol). Assay procedure: UV at 240 nm. Limit of detection: 1.25 ug/ml. /From table/
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V21 526 (1979)
Sample matrix: Plasma. Sample preparation: Derivatize (heptafluorobutyrate); TLC. Assay procedure: GC/ECD. Limit of detection: 10 pg. /From table/
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V21 526 (1979)
Sample matrix: Urine. Sample preparation: TLC; oxidize [chromium (III)oxide]; derivatize (2,4-dinitrophenylhydrazone); TLC. Assay procedure: Colorimetry. Limit of detection: 0.5 ug. /From table/
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V21 529 (1979)
Sample matrix: Plasma. Sample preparation: Extract (diethyl ether); derivatize (heptafluorobutyrate). Assay procedure: GC/MS. Limit of detection: 0.21 ng/ml. /From table/
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V21 529 (1979)
For more Clinical Laboratory Methods (Complete) data for Testosterone (10 total), please visit the HSDB record page.

12 Safety and Hazards

12.1 Hazards Identification

12.1.1 GHS Classification

1 of 2
View All
Pictogram(s)
Irritant
Health Hazard
Environmental Hazard
Signal
Danger
GHS Hazard Statements

H302 (63.5%): Harmful if swallowed [Warning Acute toxicity, oral]

H350 (35.6%): May cause cancer [Danger Carcinogenicity]

H351 (64.9%): Suspected of causing cancer [Warning Carcinogenicity]

H360 (79.7%): May damage fertility or the unborn child [Danger Reproductive toxicity]

H361 (19.8%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

H362 (29.3%): May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]

H372 (16.2%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]

H400 (63.5%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

H410 (15.8%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

Precautionary Statement Codes

P203, P260, P263, P264, P270, P273, P280, P301+P317, P318, P319, P330, P391, 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 222 reports by companies from 16 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

12.1.2 Hazard Classes and Categories

Acute Tox. 4 (63.5%)

Carc. 1B (35.6%)

Carc. 2 (64.9%)

Repr. 1A (79.7%)

Repr. 2 (19.8%)

Lact. (29.3%)

STOT RE 1 (16.2%)

Aquatic Acute 1 (63.5%)

Aquatic Chronic 1 (15.8%)

12.2 Fire Fighting

12.2.1 Fire Fighting Procedures

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Sigma-Aldrich; Safety Data Sheet for Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: 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 Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html

12.3 Accidental Release Measures

12.3.1 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. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. 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 Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html

12.3.2 Disposal Methods

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product.
Sigma-Aldrich; Safety Data Sheet for Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html

12.3.3 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. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.
Sigma-Aldrich; Safety Data Sheet for Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. 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 Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: 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 Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
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 Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: 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.

12.4 Handling and Storage

12.4.1 Storage Conditions

Keep container tightly closed in a dry and well-ventilated place. Storage class (TRGS 510): Non-combustible, acute toxic Cat.3 / toxic hazardous materials or hazardous materials causing chronic effects.
Sigma-Aldrich; Safety Data Sheet for Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
Commercially available testosterone preparations should be stored at a temperature less than 40 °C, preferably between 15-30 °C; freezing of the sterile suspension and injections should be avoided. A precipitate may form if the injections are stored at a low temperature; however, this will dissolve after shaking and warming to room temperature. Use of a wet needle or syringe may cause the parenteral solutions to become cloudy; however, this will not affect potency.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3138

12.5 Exposure Control and Personal Protection

12.5.1 Personal Protective Equipment (PPE)

Eye/face protection: Safety glasses with side-shields conforming to EN166. 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 Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
Skin protection: Handle with gloves.
Sigma-Aldrich; Safety Data Sheet for Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
Body Protection: Complete suit protecting against chemicals. 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 Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Sigma-Aldrich; Safety Data Sheet for Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html

12.6 Stability and Reactivity

12.6.1 Hazardous Reactivities and Incompatibilities

Incompatible materials: Strong oxidizing agents.
Sigma-Aldrich; Safety Data Sheet for Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html

12.7 Regulatory Information

California Safe Cosmetics Program (CSCP) Reportable Ingredient

Hazard Traits - Carcinogenicity

Authoritative List - Prop 65

Report - regardless of intended function of ingredient in the product

REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
Testosterone: Does not have an individual approval but may be used under an appropriate group standard

12.7.1 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including testosterone, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of February 27, 2017: https://www.fda.gov/cder/ob/
The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including testosterone cypionate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Testosterone cypionate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of February 27, 2017: https://www.fda.gov/cder/ob/
The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including testosterone enanthate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Testosterone enanthate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of February 27, 2017: https://www.fda.gov/cder/ob/
The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including testosterone undecanoate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Testosterone undecanoate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of February 27, 2017: https://www.fda.gov/cder/ob/
For more FDA Requirements (Complete) data for Testosterone (10 total), please visit the HSDB record page.

12.8 Other Safety Information

Chemical Assessment

IMAP assessments - Androst-4-en-3-one, 17-hydroxy-, (17.beta.)-: Human health tier I assessment

IMAP assessments - Androst-4-en-3-one, 17-hydroxy-, (17.beta.)-: Environment tier I assessment

12.8.1 Toxic Combustion Products

Special hazards arising from the substance or mixture: Carbon oxides.
Sigma-Aldrich; Safety Data Sheet for Testosterone. Product Number: T1500, Version 3.10 (Revision Date 02/10/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html

13 Toxicity

13.1 Toxicological Information

13.1.1 Toxicity Summary

IDENTIFICATION AND USE: Testosterone is an anabolic steroid for systemic use. It consists of odorless or almost odorless crystals or crystalline powder. Naturally-occuring anabolic steroids are synthesized in the testis, ovary and adrenal gland. Anabolic steroids are listed as Schedule III controlled substances. HUMAN EXPOSURE AND TOXICITY: The main risks associated with testosterone are those of excessive androgens: menstrual irregularities and virilization in women and impotence, premature cardiovascular disease and prostatic hypertrophy in men. Both men and women can suffer liver damage with oral anabolic steroids containing a substituted 17-alpha-carbon. Psychiatric changes can occur during use or after cessation of these agents. Acute overdosage can produce nausea and gastrointestinal upset. Chronic usage is thought to cause an increase in muscle bulk, and can cause an exaggeration of male characteristics and effects related to male hormones. There is no clear evidence that anabolic steroids enhance overall athletic performance. Precocious prostatic cancer has been described after long-term anabolic steroid abuse. Cases where hepatic cancers have been associated with anabolic steroid abuse have been reported. Testosterone may cause fetal harm when administered to pregnant women due to the potential for virilization of a female fetus. Androgenic effects including clitoral hypertrophy, labial fusion of the external genital fold to form a scrotal-like structure, abnormal vaginal development, and persistence of a urogenital sinus have occurred in the female offspring of women who were given androgens during pregnancy. The degree of masculinization is related to the amount of drug given to the woman and the age of the fetus; masculinization is most likely to occur in a female fetus when exposure to androgens occurs during the first trimester. ANIMAL STUDIES: The effect of testosterone on the prostate of castrated rats was described as a significant increase in prostatic weight which occurred after 6 wk treatment with testosterone. In female mice injected subcutaneously with 25 ug testosterone daily for the first five days after birth, 7/9 developed hyperplastic epithelial lesions, resembling epidermoid carcinomas at about 71 weeks of age. Chronic treatment of rats with testosterone produced a low prostate carcinoma incidence. A high carcinoma incidence can only be produced by chronic treatment with testosterone following administration of carcinogens. Daily subcutaneous injections for 4-8 days of total doses of 0.5-80 mg testosterone into rats between days 10 and 20 of gestation and of total doses of 1-55 mg testosterone propionate between days 12 and 19 of gestation resulted in resorptions, necrosis, lethality, post-partum mortality and various degrees of masculinization in female offspring. Deposteron (testosterone cypionate) was genotoxic and cytotoxic in mice. Testosterone acted both as a mitogenic and genotoxic agent in L929 cells.
Testosterone is considered an anabolic steroid. It plays a key role in the development of male reproductive tissues such as the testis and prostate as well as promoting secondary sexual characteristics such as increased muscle, bone mass, and the growth of body hair. High levels of testosterone can lead to masculinization in females or premature puberty in young boys. Chronically high levels in adults increase the incidence of heart attack, stroke and blood clots by lowering the level of HDL (good cholesterol) and increasing the level of LDL (bad cholesterol). Chronic high use of anabolic steroids (such as testosterone) appears to lead to cardiac myopathy and weakening the left ventricle. The development of breast tissue in males, a condition called gynecomastia (which is usually caused by high levels of circulating estradiol), arises because of increased conversion of testosterone to estradiol by the enzyme aromatase. Reduced sexual function and temporary infertility can also occur in males. The mechanism of testosterone’s action is as follows: Free testosterone is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5-alpha reductase. DHT binds to the same androgen receptor even more strongly than testosterone, so that its androgenic potency is about 5 times that of testosterone. Once bound, the ligand-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects.

13.1.2 USGS Health-Based Screening Levels for Evaluating Water-Quality

Chemical
Testosterone
Chemical Classes
Hormone
Reference
Smith, C.D. and Nowell, L.H., 2024. Health-Based Screening Levels for evaluating water-quality data (3rd ed.). DOI:10.5066/F71C1TWP

13.1.3 Drug Induced Liver Injury

Compound
testosterone
DILI Annotation
Most-DILI-Concern
Severity Grade
8
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

13.1.4 Carcinogen Classification

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

13.1.5 Health Effects

In women, excess testosterone may cause decreased breast size, a deep voice, increased genital size, irregular periods, oily skin, and unnatural hair growth. In men, excess testosterone may cause aggression, breast tenderness or enlargement, decreased testes size, and urinary urgency. Chronically high levels of testosterone are associated with at least 2 inborn errors of metabolism including: Adrenal Hyperplasia Type 3 and Aromatase deficiency.

13.1.6 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Limited data indicate that a low-dose (100 mg) subcutaneous testosterone pellet given to a nursing mother appears not to increase milk testosterone levels markedly. Subcutaneous testosterone cypionate does increase milk testosterone levels. However, testosterone has low oral bioavailability because of extensive first-pass metabolism, so it appears to not increase serum testosterone levels in breastfed infants. Breastfed infants appear not to be adversely affected by maternal or transgender paternal testosterone therapy. High doses of testosterone can suppress lactation.

◉ Effects in Breastfed Infants

After implantation of a 100 mg pellet of testosterone subcutaneously in a postpartum mother, her infant (age not stated) was breastfed (extent not stated). No adverse effects were noted in the infant over a 5-month period.

A transgender male began receiving subcutaneous testosterone cypionate 50 mg weekly 13.75 months after giving birth. The dose was increased to 80 mg weekly after 1 month. His male infant was partially “chestfed” (extent not stated) until the infant self-weaned at 137 days after initiation of testosterone (18 months of age). During this time, no adverse events or signs of virilization were noted by the infant’s pediatrician. The infant grew and developed normally.

◉ Effects on Lactation and Breastmilk

Supraphysiologic serum levels of testosterone, either from a tumor or from exogenously administered testosterone, reduces milk production in postpartum women. Testosterone alone reduces serum prolactin; however, when given in combination with estrogen and progestin, serum prolactin levels are not markedly reduced. Testosterone was previously used therapeutically to suppress lactation, usually in combination with an estrogen.

13.1.7 Exposure Routes

Endogenous, Injection

13.1.8 Symptoms

In women, testosterone may cause decreased breast size, a deep voice, increased genital size, irregular periods, oily skin, and unnatural hair growth. In men, excess testosterone may cause aggression, premature baldness, breast tenderness or enlargement, decreased testes size, and urinary urgency.

13.1.9 Acute Effects

13.1.10 Interactions

Concomitant use of anabolic androgenic steroids and cocaine has increased in the last years. However, the effects of chronic exposure to these substances during adolescence on cardiovascular function are unknown. Here, we investigated the effects of treatment for 10 consecutive days with testosterone and cocaine alone or in combination on basal cardiovascular parameters, baroreflex activity, hemodynamic responses to vasoactive agents, and cardiac morphology in adolescent rats. Administration of testosterone alone increased arterial pressure, reduced heart rate (HR), and exacerbated the tachycardiac baroreflex response. Cocaine-treated animals showed resting bradycardia without changes in arterial pressure and baroreflex activity. Combined treatment with testosterone and cocaine did not affect baseline arterial pressure and HR, but reduced baroreflex-mediated tachycardia. None of the treatments affected arterial pressure response to either vasoconstrictor or vasodilator agents. Also, heart to body ratio and left and right ventricular wall thickness were not modified by drug treatments. However, histological analysis of left ventricular sections of animals subjected to treatment with testosterone and cocaine alone and combined showed a greater spacing between cardiac muscle fibers, dilated blood vessels, and fibrosis. These data show important cardiovascular changes following treatment with testosterone in adolescent rats. However, the results suggest that exposure to cocaine alone or combined with testosterone during adolescence minimally affect cardiovascular function.
Engi SA et al; PLoS One 9 (8): e105172. (2014)
Topical administration of 0.1% triamcinolone cream prior to application of a testosterone transdermal system did not alter absorption of testosterone; however, pretreatment with topical administration of triamcinolone ointment substantially reduced absorption of testosterone.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3137
Administration of IM testosterone cypionate resulted in increased clearance of propranolol in one study. It is not known whether there is a potential for this interaction with topically administered testosterone gel. /Testosterone cypionate/
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3137
Testosterone may potentiate the action of oral anticoagulants, causing bleeding in some patients. When testosterone therapy is initiated in patients receiving oral anticoagulants, dosage reduction of the anticoagulant may be required to prevent an excessive hypoprothrombinemic response. In patients receiving concomitant therapy with testosterone and anticoagulants, more frequent monitoring of INR and prothrombin time is recommended, especially during initiation or discontinuance of therapy.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3137
For more Interactions (Complete) data for Testosterone (10 total), please visit the HSDB record page.

13.1.11 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

13.1.12 Medical Surveillance

SRP: Workers exposed to testosterone during its manufacture as well as patients receiving androgen therapy should be monitored for gynecomastia, hepatic, renal, and cardiac dysfunction, aggressive or antisocial behavior, lipoprotein profiles and priapism.

13.1.13 Human Toxicity Excerpts

/SIGNS AND SYMPTOMS/ Testosterone may cause fetal harm when administered to pregnant women due to the potential for virilization of a female fetus. Androgenic effects including clitoral hypertrophy, labial fusion of the external genital fold to form a scrotal-like structure, abnormal vaginal development, and persistence of a urogenital sinus have occurred in the female offspring of women who were given androgens during pregnancy. The degree of masculinization is related to the amount of drug given to the woman and the age of the fetus; masculinization is most likely to occur in a female fetus when exposure to androgens occurs during the first trimester. Since the risks clearly outweigh the possible benefits in women who are or may become pregnant, testosterone is contraindicated in such women. Women who become pregnant while receiving the drug should be informed of the potential hazard to the fetus.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3136
/SIGNS AND SYMPTOMS/ Cardiovascular events, including myocardial infarction or stroke, have been reported during postmarketing experience with testosterone transdermal system (Androderm). Testosterone should be used with caution in patients at high risk for cardiovascular disease (e.g., older men, those with diabetes mellitus or obesity). Patients should be advised to immediately report symptoms suggestive of MI or stroke (e.g., chest pain, shortness of breath, unilateral weakness, difficulty talking) to their clinician.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3135-6
/SIGNS AND SYMPTOMS/ Venous thromboembolic events, including deep-vein thrombosis (DVT) and pulmonary embolism (PE), have been reported during postmarketing experience with testosterone preparations, including testosterone transdermal system (Androderm). Patients reporting symptoms of pain, edema, warmth, and erythema in a lower extremity or presenting with acute shortness of breath should be evaluated for possible DVT or PE, respectively. If venous thromboembolism is suspected, testosterone therapy should be discontinued and appropriate evaluation and management should be initiated.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3136
/SIGNS AND SYMPTOMS/ Testosterone should be used with caution in patients with cardiac, renal, and/or hepatic dysfunction since edema may occur as a result of sodium and water retention. Edema, with or without congestive heart failure, may be a serious complication in patients with preexisting cardiac, renal, and/or hepatic disease. If edema occurs during testosterone therapy and it is considered a serious complication, the drug should be discontinued; diuretic therapy may also be necessary.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3136
For more Human Toxicity Excerpts (Complete) data for Testosterone (24 total), please visit the HSDB record page.

13.1.14 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ The effects of testosterone and (17) beta-estradiol on the prostate of castrated rats were investigated by histopathological and immunocytochemical procedures. A significant increase in prostatic weight occurred after 6 wk treatment with testosterone alone and in combination with (17) beta-estradiol. The greatest increase in prostatic weight occurred after the administration of testosterone plus (17) beta-estradiol. Histopathologically, glandular hyperplasia of the prostate was noted, and the number of bromodeoxyuridine-positive cells showed a significant increase over that induced by testosterone alone.
Murakoshi M et al; Tokai J Exp Clin Med 17 (3-4): 133-7 (1992)
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ N-acetylation participates in the biotransformation of hydrazine drugs and arylamine carcinogens to cytotoxic and carcinogenic products. Differences in acetylation capacity expressed in several mammalian species, including humans and mice, are associated with differences in toxicity and carcinogenicity from these chemicals. The present study examines the influence of genotype, age and sex on kidney N-acetyltransferase activity in C57BL/6J (B6) and A/J inbred mouse strains using p-aminobenzoic acid as a substrate. There were no strain differences in kidney p-aminobenzoic acid N-acetyltransferase activity. However, within these strains, males have greater kidney N-acetyltransferase activity than females. A 2 fold increase in kidney N-acetyltransferase activity of males was evident by 30 days postnatally and persisted into maturity (>200 days after birth), whereas the kidney N-acetyltransferase activity of females remained unchanged. Castration reduced male kidney N-acetyltransferase to female levels, whereas testosterone replacement restored original levels of activity. Ovariectomized females exhibited the same enzyme activity as intact females. Testosterone increased kidney N-acetyltransferase activity in females, but not in intact males. Estradiol decreased kidney N-acetyltransferase in males, but had no effect on female N-acetyltransferase activity. The data suggest that the increase in kidney N-acetyltransferase activity in male mice that accompanies development is under androgenic control. This idea is further supported by the finding that the kidney N-acetyltransferase activity of androgen-insensitive tfm/y mice is significantly less than the activity of either females or males sharing the same genetic background. These observations may explain, in part, the higher susceptibility of male mice to 2-acetylaminofluorene mutagenicity and carcinogenicity.
Smolen TN et al; J Pharmacol Exp Ther 264 (2): 854-8 (1993)
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Concomitant use of anabolic androgenic steroids and cocaine has increased in the last years. However, the effects of chronic exposure to these substances during adolescence on cardiovascular function are unknown. Here, we investigated the effects of treatment for 10 consecutive days with testosterone and cocaine alone or in combination on basal cardiovascular parameters, baroreflex activity, hemodynamic responses to vasoactive agents, and cardiac morphology in adolescent rats. Administration of testosterone alone increased arterial pressure, reduced heart rate (HR), and exacerbated the tachycardiac baroreflex response. Cocaine-treated animals showed resting bradycardia without changes in arterial pressure and baroreflex activity. Combined treatment with testosterone and cocaine did not affect baseline arterial pressure and HR, but reduced baroreflex-mediated tachycardia. None of the treatments affected arterial pressure response to either vasoconstrictor or vasodilator agents. Also, heart to body ratio and left and right ventricular wall thickness were not modified by drug treatments. However, histological analysis of left ventricular sections of animals subjected to treatment with testosterone and cocaine alone and combined showed a greater spacing between cardiac muscle fibers, dilated blood vessels, and fibrosis. These data show important cardiovascular changes following treatment with testosterone in adolescent rats. However, the results suggest that exposure to cocaine alone or combined with testosterone during adolescence minimally affect cardiovascular function.
Engi SA et al; PLoS One 9 (8): e105172. (2014)
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Of female BALB/cCrgl mice injected subcutaneously with 25 ug testosterone in water daily for the first five days after birth, 7/9 developed hyperplastic epithelial lesions, resembling epidermoid carcinomas (vaginal squamoua-cell tumors), at about 71 weeks of age.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V21 533 (1979)
For more Non-Human Toxicity Excerpts (Complete) data for Testosterone (25 total), please visit the HSDB record page.

13.1.15 Ongoing Test Status

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of December 8, 2016: http://actor.epa.gov/dashboard/]

13.1.16 Populations at Special Risk

Androgens should be used with extreme caution in children and only by specialists who are aware of the adverse effects of these drugs on bone maturation. Testosterone should be used cautiously to stimulate puberty, and only in carefully selected males with delayed puberty. In children, testosterone may accelerate bone maturation without producing compensatory gain in linear growth. This adverse effect may result in compromised adult stature.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3136
Testosterone is contraindicated in males with carcinoma of the breast or known or suspected carcinoma of the prostate. Testosterone also is contraindicated in women who are or may become pregnant or who are breastfeeding. Testosterone is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the respective formulation (e.g., soy, alcohol).
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3136
Testosterone should be used with caution in patients at high risk for cardiovascular disease (e.g., older men, those with diabetes mellitus or obesity).
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3135-6
Cardiovascular events, including MI or stroke, have been reported during postmarketing experience with testosterone transdermal system (Androderm). Testosterone should be used with caution in patients at high risk for cardiovascular disease (e.g., older men, those with diabetes mellitus or obesity). Patients should be advised to immediately report symptoms suggestive of MI or stroke (e.g., chest pain, shortness of breath, unilateral weakness, difficulty talking) to their clinician.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 3135-6
For more Populations at Special Risk (Complete) data for Testosterone (6 total), please visit the HSDB record page.

13.1.17 Protein Binding

Testosterone is 40% bound to sex hormone binding globulin, 2% unbound, and the remainder is bound to albumin and other proteins.

13.2 Ecological Information

13.2.1 Ecotoxicity Values

EC50; Species: Acartia tonsa (Calanoid Copepod) eggs; Conditions: saltwater, renewal; Concentration: 1500 ug/L for 5 days (95% confidence interval: 1400-1800 ug/L); Effect: development, decreased larval development, slowed, retarded, delayed or non-development
Andersen HR et al; Environ Toxicol Chem 20 (12): 2821-29 (2001) as cited in the ECOTOX database. Available from, as of January 30, 2017
LC50; Species: Acartia tonsa (Calanoid Copepod) adult age 10-12 days; Conditions: saltwater, static, 20 °C; Concentration: 5600 ug/L for 48 hr (95% confidence interval: 4700-6600 ug/L)
Andersen HR et al; Environ Toxicol Chem 20 (12): 2821-29 (2001) as cited in the ECOTOX database. Available from, as of January 30, 2017
LC50; Species: Neomysis integer (Opossum Shrimp) juvenile, length 2-4 mm; Conditions: saltwater, renewal, 15 °C; Concentration: 1950 ug/L for 96 hr (95% confidence interval: 550-9080 ug/L) /formulated product/
Verslycke T et al; Environ Toxicol Chem 23 (5): 1289-96 (2004) as cited in the ECOTOX database. Available from, as of January 30, 2017
LC50; Species: Dugesia japonica (Flatworm) 0.8 cm body length; Conditions: freshwater, static, 25 °C, pH 7.8, hardness 136.5 mg/L CaCO3; Concentration: 14800 ug/L for 24 hr />99% purity/
Li MH; Toxicol Environ Chem 95 (6): 984-991 (2013) as cited in the ECOTOX database. Available from, as of January 30, 2017
For more Ecotoxicity Values (Complete) data for Testosterone (7 total), please visit the HSDB record page.

13.2.2 Ecotoxicity Excerpts

/AQUATIC SPECIES/ Endocrine disruptors are known to alter endogenous free and esterified levels of androgenic and estrogenic steroid hormones in aquatic mollusks. The origin of steroids in these animals, however, remains controversial. In the present study, free and esterified testosterone concentrations were measured in the hermaphroditic aquatic gastropod Lymnaea stagnalis exposed to molecules known for their androgenic (testosterone and tributyltin), anti-androgenic (cyproterone-acetate), and estrogenic (chlordecone) properties, by reference to their mode of action in vertebrates. In parallel, snail oviposition and fecundity were followed over a 21-day exposure period. Testosterone exposure resulted in increased esterified testosterone levels, whereas free testosterone concentrations remained stable. In contrast, cyproterone-acetate significantly increased the free form of testosterone with no changes in the esterified form, whereas chlordecone showed a tendency to reduce (though not significantly) esterified testosterone concentrations without changing free testosterone levels. Finally, tributyltin did not alter testosterone homeostasis. The production of egg clutches and eggs was significantly reduced only in the snails exposed to the highest concentrations of chlordecone (19.6 ug/L) and tributyltin (94.2 ng Sn/L). Overall, the present study demonstrates that uptake of testosterone from the exposure medium occurs in L. stagnalis. Moreover, it shows that cyproterone-acetate and, to a lesser extent, chlordecone can alter endogenous testosterone levels in this freshwater snail. However, the relationship between hormonal changes and snail reproduction has not been established.
Giusti A et al; Environ Toxicol Chem 32 (8): 1740-45 (2013)

13.2.3 Environmental Fate / Exposure Summary

Testosterone's production and use as a steroid, in biochemical research and possible use as a performance enhancement drug in athletes may result in its release to the environment through various waste streams. Testosterone is a principal hormone of the testes produced in interstitial cells. If released to air, an estimated vapor pressure of 1.7X10-8 mm Hg at 25 °C indicates testosterone will exist solely in the particulate phase in the ambient atmosphere. Particulate-phase testosterone will be removed from the atmosphere by wet and dry deposition. Testosterone contains chromophores that absorb at wavelengths >290 nm and, therefore, may be susceptible to direct photolysis by sunlight. If released to soil, testosterone is expected to have low mobility based upon a Koc of 2200. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 3.5X10-9 atm-cu m/mole. A 63% mineralization in 5 days using a sandy soil suggests that biodegradation may be an important environmental fate process in soil. However, it has been reported that when both swine slurry or municipal slurry is added to a loam soil at 10% v/w, mineralization of testosterone is suppressed. If released into water, testosterone is expected to adsorb to suspended solids and sediment based upon the Koc. A biodegradation half-life of 32 days in four municipal treatment plants exhibiting 55-65% mineralization of testosterone in 24 hours suggests that biodegradation may be a moderate environmental fate process in water. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 72 suggests the potential for bioconcentration in aquatic organisms is moderate. 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 testosterone may occur through dermal contact with this compound at workplaces where testosterone is produced or used. Testosterone is a major circulating androgen and required for normal male sexual differentiation. Increased exposure to testosterone among the general population may be limited to those administered the drug, an androgenic steroid. Intentional human exposure may have occurred from testosterone use as a possible performance enhancement drug in athletes. (SRC)

13.2.4 Natural Pollution Sources

Testosterone is a principal hormone of the testes produced in interstitial cells and required for male sexual differentiation(1).
(1) O'Neil MJ, ed; The Merck Index. 15th ed., Cambridge, UK: Royal Society of Chemistry, p. 1702 (2013)

13.2.5 Artificial Pollution Sources

Testosterone's production and use as a steroid, in biochemical research(1) and possible use as a performance enhancement drug(2) may result in its release to the environment through various waste streams(SRC).
(1) Larranaga MD et al; Hawley's Condensed Chemical Dictionary 16th ed. Hoboken, NJ: John Wiley & Sons, Inc., p 1313 (2016)
(2) Donahue JL, Lowenthal DT; Am J Ther 7: 365-73 (2000)

13.2.6 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), a measured log Koc range of 3.25-3.52(2), corresponding to an average Koc of 2200(SRC), indicates that testosterone is expected to have low mobility in soil(SRC). Volatilization of testosterone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.5X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Testosterone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). A 63% mineralization in 5 days using a sandy soil(5) suggests that biodegradation may be an important environmental fate process in soil(SRC). However, it has been reported that when swine slurry or municipal slurry is added to a loam soil at 10% v/w, mineralization of testosterone is suppressed(6).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Lee LS et al; Environ Sci Technol 37: 4098-05 (2003)
(3) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(4) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Dec 8, 2016: https://www2.epa.gov/tsca-screening-tools
(5) Fan Z et al; Chemosphere 67: 886-95 (2007)
(6) Jacobsen A-M et al; J Environ Qual 34: 861-871 (2005)]
AQUATIC FATE: Based on a classification scheme(1), a measured log Koc range of 3.25-3.52(2), corresponding to an average Koc of 2200(SRC), indicates that testosterone is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.5X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 72(SRC), from its log Kow of 3.32(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). A biodegradation half-life of 32 days in four municipal treatment plants exhibiting 55-65% mineralization of testosterone in 24 hours(8) suggests that biodegradation may be a moderate environmental fate process in water(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Lee LS et al; Environ Sci Technol 37: 4098-05 (2003)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)
(4) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(5) Franke C et al; Chemosphere 29: 1501-14 (1994)
(6) 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. 164 (1995)
(7) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Dec 8, 2016: https://www2.epa.gov/tsca-screening-tools
(8) Layton AC et al; Environ Sci Technol 34: 3925-3931 (2000)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), testosterone, which has an estimated vapor pressure of 1.7X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase testosterone may be removed from the air by wet and dry deposition(SRC). Testosterone contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may 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 Dec 8, 2016: https://www2.epa.gov/tsca-screening-tools
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)

13.2.7 Environmental Biodegradation

AEROBIC: Testosterone, at a starting concentration of 99 ug/L, was mineralized over 24 hours to 14CO2 in four municipal treatment plants in the southeastern United States in amounts ranging from 55-65%; total removal from the aqueous phase of treatment was greater than 95%(1). The first order rate constant of 0.0152/min for this process(1) corresponds to a biodegradation half-life of 32 days(SRC). Similar results, up to 58% mineralization, were obtained using industrial biosolids(1). Testosterone concentrations ranging from 0.8-1.1 nmol/L in raw sewage samples from Tel Aviv, Israel, were decreased to 0.2-0.5 nmol/L using anaerobic and aerobic digestion in a sewage disposal plant, corresponding to a 60-77% removal efficiency(2). 14C-Ring-labeled testosterone, present at 0.052 mg/L, reached 63% mineralization in 5 days using a Hamar sandy soil (2.23% organic matter; 14.0% clay; 10.0% silt, 67% sand) inoculum(3). It has been reported that when swine slurry or municipal slurry is added to a loam soil at 10% v/w), mineralization of testosterone is suppressed. The % 14C mineralization recovered was 44, 18 and 31 for unamended, swine- and biosolid-amended loam soil, respectively(4).
(1) Layton AC et al; Environ Sci Technol 34: 3925-3931 (2000)
(2) Shore LS et al Bull Environ Contam Toxicol 51: 361-366 (1993)
(3) Fan Z et al; Chemosphere 67: 886-95 (2007)
(4) Jacobsen A-M et al; J Environ Qual 34: 861-871 (2005)
AEROBIC: % Mineralization of ring-labeled 14C-testosterone, present a concentration of 39 ng/g dry weight, in sediments collected upstream and downstream from respective wastewater treatment plants(1).
Location
Fourmile Creek (Ankeny, IA)
%mineralization upstream
35
%mineralization downstream
30
Location
Boulder Creek (Boulder, CO)
%mineralization upstream
45
%mineralization downstream
55
Location
South Platte River (Denver, CO)
%mineralization upstream
30
%mineralization downstream
60
(1) Bradley PM et al; Environ Sci Technol 43: 1902-10 (2009)
ANAEROBIC: Ring-labeled 14C-testosterone, present at 0.052 mg/L, reached 63% mineralization in 5 days using a Hamar sandy soil (2.23% organic matter; 14.0% clay; 10.0% silt, 67% sand) inoculum(1).
(1) Fan Z et al; Chemosphere 67: 886-95 (2007)

13.2.8 Environmental Abiotic Degradation

Testosterone is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(1). Testosterone contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).
(1) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990)

13.2.9 Environmental Bioconcentration

An estimated BCF of 72 was calculated for testosterone(SRC), using a log Kow of 3.32(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(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. 164 (1995)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Dec 8, 2016: https://www2.epa.gov/tsca-screening-tools
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

13.2.10 Soil Adsorption / Mobility

The soil absorption of testosterone was measured in several different soil samples(1). Log Koc values ranging from 3.25-3.52 were measured; the average log Koc was 3.32(1), corresponding to a Koc value of 2,188(SRC). According to a classification scheme(2), this Koc value suggests that testosterone is expected to have low mobility in soil. In another study, 69-74% of applied C14-testosterone (0.406 and 0.738 mg/L) was retained in the top 5 cm of soil in a column experiment using an undisturbed, agricultural soil (Hamar sandy soil: 2.23% organic matter; 14.0% clay; 10.0% silt, 67% sand)(3).
(1) Lee LS et al Environ Sci Technol 37: 4098-105 (2003)
(2) Swann RL et al; Res Rev 85: 17-28 (1983)
(3) Fan Z, et al; J Environ Qual 36: 864-873 (2007)

13.2.11 Volatilization from Water / Soil

The Henry's Law constant for testosterone is estimated as 3.5X10-9 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that testosterone is expected to be essentially nonvolatile from water and moist soil surfaces(2). Testosterone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-8 mm Hg(SRC), determined from a fragment constant method(3).
(1) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)
(3) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Dec 8, 2016: https://www2.epa.gov/tsca-screening-tools

13.2.12 Environmental Water Concentrations

GROUNDWATER: Testosterone has been detected at a concentration of 1.0 ng/L in groundwater from drilled sampling wells on farms that had used chicken manure fertilizer for over 5 years(1).
(1) Drewes JE, Shore LS; Amer Chem Soc, ACS Symp Ser 791: 206-228 (2001)
DRINKING WATER: Testosterone was reported at a median concentration of 1.1 ng/L in source water (2 of 19 samples) from 19 US water utilities analyzed between 2006 and 2007. It was not detected in finished water or tap water sampled during the same time period(1). Testosterone concentrations ranged from 15.6-0.2 ng/L and not detected to 26.4 ng/L in influents and effluents, respectively, of 8 French drinking water plants. Sampling was conducted in March-April 2007, January 2008 and September-October 2008; detection limit = 0.02 ng/L(2).
(1) Benotti MJ et al; Environ Sci Technol 43: 597-603 (2009)
(2) Vulliet E et al; Environ Sci Technol 9(1): 103-114 (2011)
SURFACE WATER: A US Geological Survey measured 95 organic waste contaminants in water samples from 139 streams across 30 states during 1999 and 2000(1). Testosterone was detected in 2.8% of the 70 samples studied with a median concentration of 0.116 ug/L(1). Testosterone was detected in Lake Michigan samples offshore from the South Shore Water Reclamation Facility, Milwaukee WI. Mean concentrations of below the detection limit of 1.1 ng/L to a maximum of 9.1 ng/L in samples were reported in and around the treatment plant outflow. Sampling was conducted from May 16, 2009 to June 16, 2010(2). The compound was detected, not quantified in the Bow Creek watershed, Nebraska, an area predominated by beef cattle and row crop agriculture; sampling was conducted in June of 2008 and 2009(3). Testosterone was detected at a concentration range of 0.031 to 0.069 nmol/L in Lake Kinneret, Israel, sampled from 1991-1992(4). Testosterone was detected at <0.50 ng/L in 6 surface water samples from the Han River; it was not detected in 4 samples from an effluent dominated creek water that flows into the Han River in Seoul, South Korea. Samples were collected Sept 30, 2008(5).
(1) Kolpin DW et al; Environ Sci Technol 36: 1202-11 (2002)
(2) Blair BD et al; Chemosphere 93(9): 2116-2123 (2013)
(3) Sellin Jeffries MK, et al; Environ Toxicol Chem 30(10): 2253-2260 (2011)
(4) Shore LS et al; Bull Environ Contam Toxicol 51: 361-366 (1993)
(5) Yoon Y et al; Sci Total Environ 408: 636-643 (2010)

13.2.13 Effluent Concentrations

Testosterone was detected in constructed water treatment plant effluents in Maryland in concentrations of 2.1 and 1.6 ng/L for wetland effluent and peat effluent, respectively(1). Testosterone was detected in raw sewage effluent water sampled in Tel Aviv, Israel in 1991 at concentrations ranging from 208-320 ng/L (third year of a drought); lower concentrations were measured in 1992 after the drought was over(2). The testosterone level in secondary effluent from a Tel Aviv, Israel treatment plant was 50 ng/L(2).
(1) Drewes JE, Shore LS; Amer Chem Soc, ACS Symp Ser 791: 206-228 (2001)
(2) Shore LS et al; Bull Environ Contam Toxicol 51: 361-6 (1993)

13.2.14 Sediment / Soil Concentrations

SEDIMENT: Testosterone was sampled for but not detected in Lake Michigan sediment samples offshore from the South Shore Water Reclamation Facility, Milwaukee WI. Sampling was conducted from May 16, 2009 to June 16, 2010(1).
(1) Blair BD et al; Chemosphere 93(9): 2116-23 (2013)

13.2.15 Other Environmental Concentrations

Testosterone has been detected in the manures of immature broilers, laying hens, and roosters at concentrations of 133, 254, and 670 ng/g dry weight, respectively(1).
(1) Drewes JE, Shore LS; Amer Chem Soc, ACS Symp Ser 791: 206-228 (2001)

13.2.16 Probable Routes of Human Exposure

Occupational exposure to testosterone may occur through dermal contact with this compound at workplaces where testosterone is produced or used(SRC). Male workers who are exposed to testosterone during manufacturing and packing have shown effects from testosterone(1). Increased exposure to testosterone among the general population may be limited to those administered the drug, an androgenic steroid(SRC). Intentional human exposure may have occurred from testosterone use as a possible performance enhancement drug in athletes(2).
(1) Lewis RJ, ed; Sax's Dangerous Properties of Industrial Materials. 12th ed. Vol 1-5. New York, NY: John Wiley & Sons Inc., V5: 4153 (2012)
(2) Donahue JL, Lowenthal DT; Am J Ther 7: 365-73 (2000)

14 Associated Disorders and Diseases

Disease
11-beta-Hydroxylase deficiency
References
Disease
21-Hydroxylase deficiency
References

PubMed: 16551734, 25850025, 10857554, 11038205, 11826238, 26336836

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

Disease
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
References
Disease
Cadmium exposure
References
PubMed: 11939709
Disease
Hypogonadism
References

PubMed: 10468933

http://en.wikipedia.org/wiki/Testosterone: http://en.wikipedia.org/wiki/Testosterone

Disease
Congenital Adrenal Hyperplasia, due to 17-Hydroxylase-Deficiency
References
Disease
Adrenal insufficiency, congenital, with 46,XY sex reversal, partial or complete
References
PubMed: 18182448
Disease
Aromatase deficiency
References
PubMed: 9177373
Disease
Lipoid Congenital Adrenal Hyperplasia
References
Disease
Woodhouse-Sakati syndrome
References
PubMed: 6876115
Disease
X-linked ichthyosis
References
PubMed: 3864567

15 Literature

15.1 Consolidated References

15.2 NLM Curated PubMed Citations

15.3 Springer Nature References

15.4 Thieme References

15.5 Wiley References

15.6 Nature Journal References

15.7 Chemical Co-Occurrences in Literature

15.8 Chemical-Gene Co-Occurrences in Literature

15.9 Chemical-Disease Co-Occurrences in Literature

16 Patents

16.1 Depositor-Supplied Patent Identifiers

16.2 WIPO PATENTSCOPE

16.3 FDA Orange Book Patents

16.4 Chemical Co-Occurrences in Patents

16.5 Chemical-Disease Co-Occurrences in Patents

16.6 Chemical-Gene Co-Occurrences in Patents

17 Interactions and Pathways

17.1 Protein Bound 3D Structures

17.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

17.2 Chemical-Target Interactions

17.3 Drug-Drug Interactions

17.4 Pathways

18 Biological Test Results

18.1 BioAssay Results

19 Taxonomy

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

20 Classification

20.1 MeSH Tree

20.2 NCI Thesaurus Tree

20.3 ChEBI Ontology

20.4 LIPID MAPS Classification

20.5 KEGG: Metabolite

20.6 KEGG: Lipid

20.7 KEGG: Phytochemical Compounds

20.8 KEGG: USP

20.9 KEGG: ATC

20.10 KEGG: Target-based Classification of Drugs

20.11 KEGG: Risk Category of Japanese OTC Drugs

20.12 KEGG: OTC drugs

20.13 KEGG: Drug Groups

20.14 WHO ATC Classification System

20.15 FDA Pharm Classes

20.16 ChemIDplus

20.17 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

20.18 ChEMBL Target Tree

20.19 UN GHS Classification

20.20 EPA CPDat Classification

20.21 NORMAN Suspect List Exchange Classification

20.22 CCSBase Classification

20.23 EPA DSSTox Classification

20.24 EPA TSCA and CDR Classification

20.25 LOTUS Tree

20.26 EPA Substance Registry Services Tree

20.27 MolGenie Organic Chemistry Ontology

21 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
    Androst-4-en-3-one, 17-hydroxy-, (17.beta.)-
    https://services.industrialchemicals.gov.au/search-assessments/
  2. CAS Common Chemistry
    LICENSE
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    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
    Androst-4-en-3-one, 17-hydroxy-, (17.beta.)-
    https://www.epa.gov/chemicals-under-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
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    https://echa.europa.eu/web/guest/legal-notice
  8. FDA Global Substance Registration System (GSRS)
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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
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    LICENSE
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    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  12. Occupational Safety and Health Administration (OSHA)
    LICENSE
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    https://www.dol.gov/general/aboutdol/copyright
  13. BindingDB
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    https://www.bindingdb.org/rwd/bind/info.jsp
    (1S,2R,10R,11S,14S,15S)-14-hydroxy-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
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  14. ChEMBL
    LICENSE
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    http://www.ebi.ac.uk/Information/termsofuse.html
  15. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  16. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  17. IUPHAR/BPS Guide to PHARMACOLOGY
    LICENSE
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    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  18. Therapeutic Target Database (TTD)
  19. Toxin and Toxin Target Database (T3DB)
    LICENSE
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    http://www.t3db.ca/downloads
  20. California Safe Cosmetics Program (CSCP) Product Database
  21. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  22. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    Testosterone
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  23. ChEBI
  24. FDA Pharm Classes
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  25. LOTUS - the natural products occurrence database
    LICENSE
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    https://lotus.nprod.net/
  26. NCI Thesaurus (NCIt)
    LICENSE
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    https://www.cancer.gov/policies/copyright-reuse
  27. Open Targets
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    https://platform-docs.opentargets.org/licence
  28. ClinicalTrials.gov
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    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  29. DailyMed
  30. Drug Induced Liver Injury Rank (DILIrank) Dataset
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  31. European Medicines Agency (EMA)
    LICENSE
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    https://www.ema.europa.eu/en/about-us/legal-notice
  32. Drugs and Lactation Database (LactMed)
  33. Drugs@FDA
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  34. WHO Model Lists of Essential Medicines
    LICENSE
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    https://www.who.int/about/policies/publishing/copyright
  35. ECI Group, LCSB, University of Luxembourg
    LICENSE
    Data: CC-BY 4.0; Code: Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    testosterone
  36. Natural Product Activity and Species Source (NPASS)
  37. EPA Chemical and Products Database (CPDat)
  38. EU Clinical Trials Register
  39. FDA Approved Animal Drug Products (Green Book)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  40. FDA Orange Book
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  41. Joint FAO/WHO Expert Committee on Food Additives (JECFA)
    LICENSE
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    https://www.who.int/about/policies/publishing/copyright
  42. WHO Anatomical Therapeutic Chemical (ATC) Classification
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    https://www.whocc.no/copyright_disclaimer/
  43. FDA Medication Guides
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  44. National Drug Code (NDC) Directory
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  45. SpectraBase
    17-BETA-HYDROXY-ANDROST-4-EN-3-ONE,(TESTOSTERON)
    https://spectrabase.com/spectrum/Fmq3LHfzp04
  46. MassBank Europe
  47. 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
  48. NIST Mass Spectrometry Data Center
    LICENSE
    Data covered by the Standard Reference Data Act of 1968 as amended.
    https://www.nist.gov/srd/public-law
  49. Japan Chemical Substance Dictionary (Nikkaji)
  50. KEGG
    LICENSE
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    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
    Risk category of Japanese OTC drugs
    http://www.genome.jp/kegg-bin/get_htext?br08312.keg
    Classification of Japanese OTC drugs
    http://www.genome.jp/kegg-bin/get_htext?br08313.keg
  51. Kruve Lab, Ionization & Mass Spectrometry, Stockholm University
    testosterone
  52. LIPID MAPS
    Lipid Classification
    https://www.lipidmaps.org/
  53. MarkerDB
    LICENSE
    This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
    https://markerdb.ca/
  54. Metabolomics Workbench
  55. Nature Chemistry
  56. NIPH Clinical Trials Search of Japan
  57. NLM RxNorm Terminology
    LICENSE
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    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  58. PharmGKB
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  59. Pharos
    LICENSE
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  60. Protein Data Bank in Europe (PDBe)
  61. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
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    https://www.rcsb.org/pages/policies
  62. Rhea - Annotated Reactions Database
    LICENSE
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    https://www.rhea-db.org/help/license-disclaimer
  63. Springer Nature
  64. SpringerMaterials
  65. Thieme Chemistry
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  66. USGS Health-Based Screening Levels for Evaluating Water-Quality Data
  67. Wikidata
  68. Wikipedia
  69. Wiley
  70. Medical Subject Headings (MeSH)
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  72. GHS Classification (UNECE)
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  75. PATENTSCOPE (WIPO)
  76. NCBI
CONTENTS