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Diethylstilbestrol

PubChem CID
448537
Structure
Diethylstilbestrol_small.png
Diethylstilbestrol_3D_Structure.png
Diethylstilbestrol__Crystal_Structure.png
Molecular Formula
Synonyms
  • diethylstilbestrol
  • 56-53-1
  • Stilbestrol
  • Stilboestrol
  • Distilbene
Molecular Weight
268.3 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2004-09-16
  • Modify:
    2025-01-18
Description
Diethylstilbestrol (DES) can cause cancer according to California Labor Code. It can cause developmental toxicity according to state or federal government labeling requirements.
Diethylstilbestrol is an odorless tasteless white crystalline powder. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Diethylstilbestrol is an olefinic compound that is trans-hex-3-ene in which the hydrogens at positions 3 and 4 have been replaced by p-hydroxyphenyl groups. It has a role as an antineoplastic agent, a carcinogenic agent, a xenoestrogen, an EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor, an antifungal agent, an endocrine disruptor, an EC 1.1.1.146 (11beta-hydroxysteroid dehydrogenase) inhibitor, an autophagy inducer and a calcium channel blocker. It is a polyphenol and an olefinic compound.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Diethylstilbestrol.png

1.2 3D Conformer

1.3 Crystal Structures

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

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

4-[(E)-4-(4-hydroxyphenyl)hex-3-en-3-yl]phenol
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C18H20O2/c1-3-17(13-5-9-15(19)10-6-13)18(4-2)14-7-11-16(20)12-8-14/h5-12,19-20H,3-4H2,1-2H3/b18-17+
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

RGLYKWWBQGJZGM-ISLYRVAYSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

CC/C(=C(/CC)\C1=CC=C(C=C1)O)/C2=CC=C(C=C2)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C18H20O2
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

56-53-1
22610-99-7
6898-97-1

2.3.3 Deprecated CAS

8026-45-7, 8028-09-9, 8030-34-0, 8049-42-1, 8053-00-7

2.3.4 European Community (EC) Number

2.3.5 UNII

2.3.6 UN Number

2.3.7 ChEBI ID

2.3.8 ChEMBL ID

2.3.9 DrugBank ID

2.3.10 DSSTox Substance ID

2.3.11 HMDB ID

2.3.12 KEGG ID

2.3.13 Metabolomics Workbench ID

2.3.14 NCI Thesaurus Code

2.3.15 Nikkaji Number

2.3.16 NSC Number

2.3.17 PharmGKB ID

2.3.18 Pharos Ligand ID

2.3.19 RXCUI

2.3.20 Wikidata

2.3.21 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Agostilben
  • Apstil
  • Diethylstilbestrol
  • Diethylstilbestrol, (Z)-Isomer
  • Diethylstilbestrol, Disodium Salt
  • Distilbène
  • Estrogen, Stilbene
  • Stilbene Estrogen
  • Stilbestrol
  • Tampovagan

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
268.3 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
5.1
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
2
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
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
268.146329876 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
268.146329876 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
40.5 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
20
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
286
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
1
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

Diethylstilbestrol is an odorless tasteless white crystalline powder. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

3.2.2 Color / Form

White crystalline powder
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 380
Small plates from benzene
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 529

3.2.3 Odor

Odorless
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 380

3.2.4 Melting Point

336 to 342 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
172
Adler, E.,Gie, G.J. and von Euler, H.; US. Patent 2,421,401; June 3, 1947; assigned to Hoffmann-La Roche, Inc.
169-172 °C
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 529

3.2.5 Solubility

less than 1 mg/mL at 68 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
12 mg/L (at 25 °C)
YALKOWSKY,SH & DANNENFELSER,RM (1992)
Soluble in alcohol, ether, chloroform, fatty oils, dil hydroxides.
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 529
SOL @ 25 °C IN 95% ETHANOL (1 IN 5); SOL @ 25 °C IN CHLOROFORM (1 IN 200), ETHER (1 IN 3); SOL IN ACETONE, DIOXANE, ETHYL ACETATE, METHYL ALCOHOL, SOL IN VEGETABLE OILS & AQUEOUS SOLN OF ALKALI HYDROXIDES
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. V6 56 (1974)
In water, 12 mg/l @ 25 °C
Yalkowsky SH, Dannenfelser RM; The AQUASOL dATAbASE of Aqueous Solubility. Fifth ed, Tucson, AZ: Univ AZ, College of Pharmacy (1992)

3.2.6 LogP

5.07
HANSCH,C ET AL. (1995)
log Kow= 5.07
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 156

3.2.7 LogS

-4.35
ADME Research, USCD

3.2.8 Decomposition

When heated to decomposition it emits acrid smoke and fumes.
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1196

3.2.9 Refractive Index

INDEX OF REFRACTION: 1.594 (ALPHA), 1.611 (BETA), 1.73 (GAMMA)
Association of Official Analytical Chemists. Official Methods of Analysis. 10th ed. and supplements. Washington, DC: Association of Official Analytical Chemists, 1965. New editions through 13th ed. plus supplements, 1982., p. 13/932 52.024

3.2.10 Collision Cross Section

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

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

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

Ross et al. JASMS 2022; 33; 1061-1072. DOI:10.1021/jasms.2c00111
175.64 Ų [M-H]-
S61 | UJICCSLIB | Collision Cross Section (CCS) Library from UJI | DOI:10.5281/zenodo.3549476

3.2.11 Kovats Retention Index

Standard non-polar
2298

3.2.12 Other Experimental Properties

CIS-ISOMER TENDS TO REVERT TO TRANS-FORM
Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 493

3.3 SpringerMaterials Properties

3.4 Chemical Classes

Hormone

3.4.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
3.4.1.1 Human Drugs
Human drug -> Discontinued; Active ingredient (DIETHYLSTILBESTROL)
Human drug -> Discontinued
3.4.1.2 Animal Drugs
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

4 Spectral Information

4.1 1D NMR Spectra

1D NMR Spectra

4.1.1 1H NMR Spectra

1 of 2
Instrument Name
Varian A-60
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Instrument Name
Varian CFT-20
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.1.2 13C NMR Spectra

1 of 2
Source of Sample
MCB Manufacturing Chemists, Norwood, Ohio
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
218944
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 5
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NIST Number
234131
Library
Main library
Total Peaks
203
m/z Top Peak
268
m/z 2nd Highest
107
m/z 3rd Highest
239
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NIST Number
75977
Library
Replicate library
Total Peaks
105
m/z Top Peak
107
m/z 2nd Highest
145
m/z 3rd Highest
268
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4.2.2 LC-MS

1 of 11
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Authors
Schulze T, Krauss M, Department of Effect-Directed Analysis, Helmholtz Centre for Environmental Research - UFZ GmbH, Leipzig, Germany
Instrument
LTQ Orbitrap XL Thermo Scientific
Instrument Type
LC-ESI-ITFT
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
55 (nominal)
Fragmentation Mode
HCD
Column Name
Kinetex Core-Shell C18 2.6 um, 3.0 x 100 mm, Phenomenex
Retention Time
24.897 min
Precursor m/z
269.1536
Precursor Adduct
[M+H]+
Top 5 Peaks

107.0489 999

199.075 355

135.0802 318

121.0645 239

173.0594 118

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License
CC BY
2 of 11
View All
Authors
Schulze T, Krauss M, Department of Effect-Directed Analysis, Helmholtz Centre for Environmental Research - UFZ GmbH, Leipzig, Germany
Instrument
LTQ Orbitrap XL Thermo Scientific
Instrument Type
LC-ESI-ITFT
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
80 (nominal)
Fragmentation Mode
HCD
Column Name
Kinetex Core-Shell C18 2.6 um, 3.0 x 100 mm, Phenomenex
Retention Time
24.897 min
Precursor m/z
269.1536
Precursor Adduct
[M+H]+
Top 5 Peaks

107.0489 999

181.0646 107

121.0646 91

199.0751 69

91.0541 67

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License
CC BY

4.3 UV Spectra

MAX ABSORPTION (ACID): 232 NM (E= 530); (BASE): 245 NM (E= 510)
Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969., p. 261
UV: 1-566 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York)
Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985., p. V2 301
UV max (0.1 N NaOH): 259 nm; E(1%, 1 cm)= 764
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 529

4.3.1 UV-VIS Spectra

1 of 2
Copyright
Copyright © 2008-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Copyright
Copyright © 2008-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4 IR Spectra

4.4.1 FTIR Spectra

1 of 2
Technique
KBr WAFER
Source of Sample
Merck & Company, Inc., Rahway, New Jersey
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Technique
KBr WAFER
Source of Sample
Chemetron Corporation
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4.2 ATR-IR Spectra

Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II) ground
Source of Spectrum
Forensic Spectral Research
Source of Sample
Steraloids Inc.
Catalog Number
D0400-000
Lot Number
G477
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4.3 Vapor Phase IR Spectra

Instrument Name
DIGILAB FTS-14
Technique
Vapor Phase
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.5 Raman Spectra

1 of 2
Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Steraloids Inc.
Catalog Number
D0400-000
Lot Number
G477
Copyright
Copyright © 2013-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Catalog Number
218944
Copyright
Copyright © 2017-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2017-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.6 Other Spectra

Intense mass spectral peaks: 107 m/z, 145 m/z, 159 m/z, 239 m/z, 268 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. 454

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Used in the treatment of prostate cancer. Previously used in the prevention of miscarriage or premature delivery in pregnant women prone to miscarriage or premature delivery.

7.2 FDA Approved Drugs

7.3 FDA Orange Book

7.4 FDA National Drug Code Directory

7.5 Drug Labels

Drug and label
Active ingredient and drug

7.6 Clinical Trials

7.6.1 ClinicalTrials.gov

7.6.2 EU Clinical Trials Register

7.7 Therapeutic Uses

...DES also have been used in the treatment of prostate cancer to reduce testicular androgen production secondary to inhibition of LH release from the pituitary.
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1421
... Two major uses are as a component of combination oral contraceptives and for hormone replacement therapy in postmenopausal women. /Estrogens/
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1421
Chemotherapeutic agents useful in neoplastic disease /of the/ breast, prostate /from table/
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1229
Antineoplastic Agents, Hormonal; Carcinogens; Contraceptives, Postcoital, Synthetic; Estrogens, Non-Steroidal
National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)
For more Therapeutic Uses (Complete) data for DIETHYLSTILBESTROL (14 total), please visit the HSDB record page.

7.8 Drug Warnings

Nausea & vomiting are an initial reaction...Fullness & tenderness of the breast & edema...Severe migraine in some...Reactivate or exacerbate endometriosis and its attendant pain. /Estrogens/
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1421
DIETHYLSTILBESTROL TAKEN DURING PREGNANCY HAS BEEN SHOWN TO BE CAUSALLY ASSOC WITH INCR IN VAGINAL AND CERVICAL CLEAR-CELL ADENOCARCINOMA IN DAUGHTERS, PRIMARILY IN THOSE BETWEEN THE AGES OF 10 AND 30 YR. THE RISK APPEARS TO BE IN THE ORDER OF 0.14-1.4/1000 EXPOSED DAUGHTERS UP TO THE AGE OF 24 YR.
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 209 (1977)
VET: TOXIC EFFECTS INCLUDE THROMBOCYTOPENIA, GYNECOMASTIA, AND FLUID RETENTION.
Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University Press, 1982., p. 796
... FIVE PATIENTS HAD SYMPTOMS OF PRESBYOPIA ASSOCIATED WITH USE OF DIETHYLSTILBESTROL & ... THESE SYMPTOMS ABATED ON DISCONTINUANCE OF DRUG.
Grant, W. M. Toxicology of the Eye. 2nd ed. Springfield, Illinois: Charles C. Thomas, 1974., p. 941
For more Drug Warnings (Complete) data for DIETHYLSTILBESTROL (24 total), please visit the HSDB record page.

8 Food Additives and Ingredients

8.1 Food Additive Classes

JECFA Functional Classes
Veterinary Drug -> GROWTH_PROMOTER;

8.2 Associated Foods

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

Chemical Name
alpha,alpha'-DIETHYLSTILBENEDIOL
Evaluation Year
1960
Comments
CCRVDF decision on DES (26 to 30 August 2013): The 5th JECFA noted that DES has carcinogenic properties. However, the information regarding carcinogenicity was not evaluated, a risk assessment was not performed, and a conclusion regarding the safety of DES or stilbenes in food was not provided. Since IARC follows comparable principles and procedures regarding transparency, convening of independent international expert groups and evaluating the scientific evidence, the latest IARC evaluation of DES, being the model compound for stilbenes, was used on an exceptional basis for risk management recommendations rather than requesting a JECFA evaluation. IARC's updated evaluation of DES (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, 2012, Volume 100A, WHO Press) stated that DES is carcinogenic to humans (Group 1), based on evidence linking exposure to DES with clear cell adenoma in the vagina and cervix in women who were exposed to DES in utero, as well as breast cancer in women who exposed to DES while pregnant. In addition, positive associations were observed between exposure to DES and cancer of the endometrium, and between in utero exposure to DES and squamous cell carcinoma of the cervix and cancer of the testis. DES exposure similarly resulted in increased incidences of ovarian, endometrial and cervical tumours, as well as mammary adenocarcinomas in female mice. In male rasH2 and XPa/p53 mice DES exposure increased the incidence of osteosarcomas and Leydig cell tumors, respectively. In view of the available scientific information, CCRVDF concluded that there is no safe level of residues of stilbenes or their metabolites in food that represents an acceptable risk to consumers. For this reason, competent authorities should prevent residues of stilbenes in food. This can be accomplished by not using stilbenes in food producing animals.

9 Pharmacology and Biochemistry

9.1 Pharmacodynamics

Diethylstilbestrol is a synthetic estrogen that was developed to supplement a woman's natural estrogen production. In 1971, the Food and Drug Administration (FDA) issued a Drug Bulletin advising physicians to stop prescribing DES to pregnant women because it was linked to a rare vaginal cancer in female offspring.

9.2 MeSH Pharmacological Classification

Carcinogens
Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. (See all compounds classified as Carcinogens.)
Estrogens, Non-Steroidal
Non-steroidal compounds with estrogenic activity. (See all compounds classified as Estrogens, Non-Steroidal.)

9.3 ATC Code

L - Antineoplastic and immunomodulating agents

L02 - Endocrine therapy

L02A - Hormones and related agents

L02AA - Estrogens

L02AA01 - Diethylstilbestrol

G - Genito urinary system and sex hormones

G03 - Sex hormones and modulators of the genital system

G03C - Estrogens

G03CC - Estrogens, combinations with other drugs

G03CC05 - Diethylstilbestrol

G - Genito urinary system and sex hormones

G03 - Sex hormones and modulators of the genital system

G03C - Estrogens

G03CB - Synthetic estrogens, plain

G03CB02 - Diethylstilbestrol

9.4 Absorption, Distribution and Excretion

ONLY TRACES ... COULD BE FOUND IN TISSUES 24 HR AFTER ADMIN TO SHEEP & GOATS.
Garner's Veterinary Toxicology. 3rd ed., rev. by E.G.C. Clarke and M.L. Clarke. Baltimore: Williams and Wilkins, 1967., p. 179
... SMALL AMT EXCRETED UNCHANGED. STILBESTROL LABELLED WITH (14)C IN TWO METHYLENE GROUPS, INJECTED IN SMALL DOSES INTO RATS, IS MOSTLY EXCRETED IN BILE ... ONLY 5% OF DOSE IS EXCRETED IN URINE. NO (14)CO2 IS EXCRETED IN EXPIRED AIR, SO PRESUMABLY MOLECULE IS STABLE.
Parke, D. V. The Biochemistry of Foreign Compounds. Oxford: Pergamon Press, 1968., p. 170
DES is readily absorbed from the GI tract following oral administration. The drug is slowly inactivated in the liver and excreted in urine and feces, principally as the glucuronide.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 1999. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1999 (Plus Supplements)., p. 2693

9.5 Metabolism / Metabolites

Hepatic.
IN SMALL DOSES, ABOUT 70% IS CONJUGATED WITH GLUCURONIC ACID AT ONE OF TWO HYDROXYL GROUPS, VERY LITTLE SULFATE CONJUGATION OCCURS, & ONLY SMALL AMT ARE EXCRETED UNCHANGED.
Parke, D. V. The Biochemistry of Foreign Compounds. Oxford: Pergamon Press, 1968., p. 170
MAJOR METABOLITES OF DES IN SEVERAL SPECIES (RAT, MOUSE, HAMSTER, PRIMATES) ARE DIENOESTROL AND OMEGA-HYDROXYDIENOESTROL ... .
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 197 (1979)
OXIDATIVE METABOLISM OF DES WAS MEASURED IN MALE & FEMALE GENITAL TRACTS OF FETAL MOUSE IN ORGAN CULTURE. MAJOR OXIDATIVE METABOLITE WAS Z,Z-DIENESTROL, WHOSE FORMATION APPEARED TO BE TIME DEPENDENT IN ISOLATED FETAL GENITAL TRACT OF BOTH SEXES. IN ADDN, FETAL GENITAL TRACTS WERE CAPABLE OF O-METHYLATION OF DES. A NEW METABOLITE, 4'-O-METHYL-DES, WAS FORMED IN FETAL GENITAL TISSUES BUT NOT IN LIVER CULTURES. CONJUGATION OF DES OCCURRED EXTENSIVELY IN FETAL LIVER & PLACENTA BUT NOT IN FETAL GENITAL TISSUES.
MAYDL R ET AL; ENDOCRINOLOGY 113 (1): 146 (1983)
Microsomes were prepared from livers of untreated male hamsters (8 wk old) by differential centrifugation. Microsome-mediated reactions were carried out using 10 to 250 uM diethylstilbestrol (DES) with (0.5 to 2.0 mM) cumene hydroperoxide or 100 uM DES with 1 to 5 mM nicotinamide adenine dinucleotide phosphate. Diethylstilbestrol-4',4''-quinone formation by fetal liver homogenate was carried out by incubating 100 uM DES, 1.5 mM cumene hydroperoxide and fetal homogenate (4 mg/ml protein) for 10 min. In vitro, the time dependent formation of diethylstilbestrol-4',4''-quinone as a function of microsomal protein, cofactor or substrate concn was demonstrated. Quinone formation was time dependent and increased in linear fashion for up to 10 min, then remained at a plateau level when incubation times were further increased. Diethylstilbestrol-4',4''-quinone was also formed by fetal liver homogenate. The microsome mediated oxidation of DES to quinone was inhibited 93% by 500 uM 2(3-t-butyl-4-hydroxyanisole), 96% by 500 uM N,N,N',N'-tetramethyl-p-phenylenediamine, 83% by 500 uM n-octylamine, 97% by 500 uM potassium cyanide, and 6% by 1 mM cyclohexene oxide. In microsomal incubations with nicotinamide-adenine dinucleotide phosphate, quinone formation was below detection limits (< 0.005 nmol/mg protein/min).
Roy D, Liehr JG; Carcinogenesis 10 (7): 1241-5 (1989)
For more Metabolism/Metabolites (Complete) data for DIETHYLSTILBESTROL (7 total), please visit the HSDB record page.

9.6 Mechanism of Action

Estrogens diffuse into their target cells and interact with a protein receptor, the estrogen receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. The effect of Estrogen binding their receptors causes downstream increases the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).
The precise mechanism(s) of action of DES as a postcoital contraceptive is not fully understood; however, the drug appears to inhibit nidation (implantation) of the fertilized ovum in the endometrium when administered within 72 hours following coitus. The postcoital contraceptive activity of the drug may involve effects mediated via decreased concentrations of circulating progesterone, effects on tubal motility resulting in accelerated passage of the ovum into the uterus, and inhibition of synthesis of carbonic anhydrase in the endometrium.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 1999. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1999 (Plus Supplements)., p. 2693
... DES ... inhibited the postcastration rise in plasma FSH amd LH levels ... . In addition, DES stimulated large increases in prolactin secretion ...
Thomas, J.A., K.S. Korach, J.A. McLachlan. Endocrine Toxicology. New York, NY: Raven Press, Ltd., 1985., p. 372

9.7 Transformations

10 Use and Manufacturing

10.1 Uses

Therap Cat: Estrogen
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 529
Therap Cat (Vet): Formerly in estrogenic hormone therapy.
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 529
Biochemical research, medicine (prevents spontaneous abortion), veterinary medicine.
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 380
Used in the treatment of prostate cancer. Previously used in the prevention of miscarriage or premature delivery in pregnant women prone to miscarriage or premature delivery.

10.1.1 Use Classification

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients
Veterinary Drug -> GROWTH_PROMOTER; -> JECFA Functional Classes
Hazard Classes and Categories -> Carcinogens, Mutagens, Teratogens
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

REACTION OF SODIUM AMALGAM & SODIUM HYDROXIDE WITH P-HYROXYPROPIOPHENONE AND REARRANGEMENT OF RESULTING INTERMEDIATE; REARRANGEMENT OF ETHYL DESOXYANISOIN.
SRI
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 380

10.3 Formulations / Preparations

Grade: USP
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 380

10.4 U.S. Production

(1978) GREATER THAN 4.54X10+5 G (DIPHOSPHATE)
SRI

10.5 U.S. Imports

(1978) 7.83X10+6 G (PRINCPL CUSTMS DISTS)
SRI
(1982) 1.31X10+5 G (PRINCPL CUSTMS DISTS)
SRI

10.6 General Manufacturing Information

EPA TSCA Commercial Activity Status
Phenol, 4,4'-[(1E)-1,2-diethyl-1,2-ethenediyl]bis-: ACTIVE
EPA TSCA Regulatory Flag
S - indicates a substance that is identified in a final Significant New Use Rule.
Non-steroid, synthetic estrogen, always in trans form. It is most active of commonly used stilbene cmpd.
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 380

11 Identification

11.1 Analytic Laboratory Methods

AOAC Method 956.10. Diethylstilbestrol in feeds. Spectrophotometric method.
Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC: Association of Analytical Chemists, 1990, p. 97
AOAC Method 960.61. Diethylstilbestrol in drugs. Spectrophotometric method.
Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC: Association of Analytical Chemists, 1990, p. 1609
Thin layer chromatography is used for determination of diethylstilbestrol in feeds. Sensitivity of this method is 0.07 mg/kg.
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 182 (1979)
Ultra-violet spectrometry at a wavelength of 418 nm can be used for determination of diethylstilbestrol in drugs and vegetable 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 182 (1979)

11.2 Clinical Laboratory Methods

FLUORIMETRIC METHOD USED TO DETECT DIETHYLSTILBESTROL AT 1 PPB IN ANIMAL TISSUES & URINE.
VERBEKE R, VANHEE P; J CHROMATOGR 265 (2): 239 (1983)
DES AT PICOGRAM LEVEL IN BOVINE URINE WAS IDENTIFIED BY CAPILLARY GAS CHROMATOGRAPHY WITH NEGATIVE CHEMICAL IONIZATION MASS SPECTROMETRY USING METHANE OR METHANE-NITROUS OXIDE (4:1) AS REAGENT GAS.
DIEDERIK H ET AL; ARCH TOXICOL SUPPL 6: 315 (1983)
MODIFIED ELECTRON CAPTURE GAS-LIQ CHROMATOGRAPHIC METHOD USED FOR DETECTION OF DES IN CATTLE URINE.
TIRPENOU AE ET AL; J ASSOC OFF ANAL CHEM 66 (5): 1230 (1983)
Column chromotography/flame ionization detection is used for determination of diethylstilbestrol in biological fluids and animal tissues. Sensitivity of this method is 8 ug/l ml sample.
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 182 (1979)

12 Safety and Hazards

12.1 Hazards Identification

12.1.1 GHS Classification

1 of 3
View All
Pictogram(s)
Irritant
Health Hazard
Environmental Hazard
Signal
Danger
GHS Hazard Statements

H315 (88.9%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (88.9%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (88.9%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

H350 (88.9%): May cause cancer [Danger Carcinogenicity]

H360 (93.3%): May damage fertility or the unborn child [Danger Reproductive toxicity]

H400 (88.9%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

H410 (88.9%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

Precautionary Statement Codes

P203, P261, P264, P264+P265, P271, P273, P280, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P332+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501

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

ECHA C&L Notifications Summary

Aggregated GHS information provided per 45 reports by companies from 5 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

Skin Irrit. 2 (88.9%)

Eye Irrit. 2A (88.9%)

STOT SE 3 (88.9%)

Carc. 1B (88.9%)

Repr. 1B (93.3%)

Aquatic Acute 1 (88.9%)

Aquatic Chronic 1 (88.9%)

Skin Irrit. 2 (100%)

Eye Irrit. 2 (100%)

Carc. 1A (100%)

Aquatic Chronic 2 (100%)

12.1.3 Health Hazards

SYMPTOMS: Symptoms of exposure to this compound via ingestion include dysmenorrhea, premenstrual-like syndrome, amenorrhea (during and after), increase in size of uterine fibromyomata, vaginal candidiasis, change in cervical eversion and of cervical secretion, cystitis-like syndrome; tenderness, enlargement and secretion of the breasts; abdominal cramps, bloating, cholestatic jaundice, chloasma or melasma, erythema multiforme, erythema nodosum, loss of scalp hair hemorrhagic eruptions, hirsutism, steepening of corneal curvature, intolerance to contact lenses, headache, migraine, dizziness, mental depression, chorea, decrease or increase in weight, reduced carbohydrate tolerance, aggravation of porphyria, edema and changes in libido. Gynaecomastia is the main side effect in the male. Exposure may also cause proliferation and withdrawal bleeding, sodium retention, nitrogen retention, alterations in liver function, jaundice, nausea and vomiting. It can cause male impotence and transsexual changes. It may also cause congenital malformation in the fetus. Human reproductive effects by ingestion include abnormal spermatogenesis, changes in the testes, epididymis and sperm duct; menstrual cycle changes or disorders, changes in female fertility, developmental abnormalities of the fetal urogenital system, germ cell effects in offspring and delayed effects in the newborn.

ACUTE/CHRONIC HAZARDS: This chemical may be harmful if swallowed or inhaled. It may cause irritation of the skin, eyes, mucous membranes and upper respiratory tract. When heated to decomposition it emits toxic fumes of carbon monoxide and carbon dioxide. (NTP, 1992)

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

12.1.4 Fire Hazards

Flash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.1.5 Hazards Summary

The major hazards encountered in the use and handling of diethylstilbestrol stem from its toxicologic properties. Toxic by all routes (ie, inhalation, ingestion, dermal absorption), exposure to this white, crystalline substance may occur from its production, handling, and use as a veterinary drug. Effects from exposure may include headache, dizziness, nausea, leg cramps, and hypersensitivity reactions. More importantly, the International Agency for Research on Cancer (IARC) has designated diethylstilbestrol as a Group 1 carcinogen, meaning, "The agent is carcinogenic to humans." Mechanical ventilation which employs a high efficiency particulate arrestor (HEPA) should be used to minumize airborne levels of diethylstilbestrol. In activities and situations where over-exposure may occur, wear a protective suit and a carefully fitted respirator. Smoking, drinking, and eating should be prohibited in diethylstilbestrol work areas, and cleanliness following the handling of diethylstilbestrol should be emphasized. Diethylstilbestrol should be stored in a securely sealed, watertight container, which should be enclosed in a second, unbreakable, leakproof container. Diethylstilbestrol is a good candidate for rotary kiln or fluidized bed forms of incineration.

12.1.6 EPA Hazardous Waste Number

U089; A toxic waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or manufacturing chemical intermediate.

12.2 First Aid Measures

12.2.1 First Aid

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

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

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.

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

OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992)

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

12.3 Fire Fighting

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

12.4 Accidental Release Measures

12.4.1 Isolation and Evacuation

Excerpt from ERG Guide 171 [Substances (Low to Moderate Hazard)]:

IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.

SPILL: Increase the immediate precautionary measure distance, in the downwind direction, as necessary.

FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024)

12.4.2 Cleanup Methods

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/
Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 15

12.4.3 Disposal Methods

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U089, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.
40 CFR 240-280, 300-306, 702-799 (7/1/89)
Diethylstilbestrol is a waste chemical stream constituent which may be subjected to ultimate disposal by controlled incineration.
USEPA; Engineering Handbook for Hazardous Waste Incineration p.2-4 (1981) EPA 68-03-3025
A good candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A good candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.
USEPA; Engineering Handbook for Hazardous Waste Incineration p.3-13 (1981) EPA 68-03-3025
The following wastewater treatment technologies have been investigated for 2,2'-diethylstilbenediol: Concentration process: Biological treatment.
USEPA; Management of Hazardous Waste Leachate, EPA Contract No.68-03-2766 p.E-3-E-22 (1982)
For more Disposal Methods (Complete) data for DIETHYLSTILBESTROL (9 total), please visit the HSDB record page.

12.4.4 Preventive Measures

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/
Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 8
PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/
Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 8
PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/
Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 8
PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/
Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 9
For more Preventive Measures (Complete) data for DIETHYLSTILBESTROL (9 total), please visit the HSDB record page.

12.5 Handling and Storage

12.5.1 Nonfire Spill Response

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

STORAGE PRECAUTIONS: You should protect this material from exposure to light, and store it in a refrigerator. (NTP, 1992)

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

12.5.2 Storage Conditions

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/
Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 13

12.6 Exposure Control and Personal Protection

12.6.1 Personal Protective Equipment (PPE)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/
Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 8

12.7 Stability and Reactivity

12.7.1 Air and Water Reactions

Insoluble in water.

12.7.2 Reactive Group

Hydrocarbons, Aliphatic Unsaturated

Phenols and Cresols

12.7.3 Reactivity Profile

DIETHYLSTILBESTROL is incompatible with strong oxidizing agents, strong bases, acid chlorides and acid anhydrides (NTP, 1992).
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.8 Transport Information

12.8.1 Shipment Methods and Regulations

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/
Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 13
PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/
Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 13

12.8.2 DOT Label

Class 9

12.9 Regulatory Information

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

12.9.1 State Drinking Water Guidelines

(FL) FLORIDA 100 ug/l
USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present

12.9.2 CERCLA Reportable Quantities

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 1 lb or 0.454 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).
40 CFR 302.4 (7/1/99)

12.9.3 RCRA Requirements

U089; As stipulated in 40 CFR 261.33, when diethylstilbestrol, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).
40 CFR 261.33 (7/1/99)

12.9.4 FDA Requirements

Drug products withdrawn or removed from the market for reasons of safety or effectiveness. Diethylstilbestrol: All oral and parenteral drug products containing 25 milligrams or more of diethylstilbestrol per unit dose.
21 CFR 216.24 (4/1/99)
Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).
21 CFR 200-299, 300-499, 820, and 860 (4/1/99)

12.10 Other Safety Information

Chemical Assessment

IMAP assessments - Phenol, 4,4'-(1,2-diethyl-1,2-ethenediyl)bis-, (E)-: Human health tier I assessment

IMAP assessments - Phenol, 4,4'-(1,2-diethyl-1,2-ethenediyl)bis-, (E)-: Environment tier I assessment

12.10.1 Special Reports

National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Diethylstilbestrol (56-53-1) is listed as known to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s071diet.pdf]

13 Toxicity

13.1 Toxicological Information

13.1.1 Toxicity Summary

Estrogens diffuse into their target cells and interact with a protein receptor, the estrogen receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. The effect of Estrogen binding their receptors causes downstream increases the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).

13.1.2 RAIS Toxicity Values

Inhalation Unit Risk (IUR) (ug/m^3)^-1
0.1
Inhalation Unit Risk Reference
CALEPA
Oral Slope Factor (CSFo)(mg/kg-day)^-1
350
Oral Slope Factor Reference
CALEPA

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

Chemical
trans-Diethylstilbestrol
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

13.1.4 Evidence for Carcinogenicity

The Human Health Assessment Group in EPA's Office of Health and Environmental Assessment has evaluated diethylstilbestrol for carcinogenicity. According to their analysis, the weight-of-evidence for diethylstilbestrol is group A, which is based on sufficient evidence in humans and sufficient evidence in animals. As a group A chemical, diethylstilbestrol is considered carcinogenic to humans.
USEPA; Methodology for Evaluating Potential Carcinogenicity in Support of Reportable Quantity Adjustments Pursuant to Cercla Section 102 (Final) p.39 (1988) EPA/600/8-89/053
Classification of carcinogenicity: 1) evidence in humans: sufficient; 2) evidence in animals: sufficient. Overall summary evaluation of carcinogenic risk to humans is Group 1: The agent is carcinogenic to humans. /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. S7 68 (1987)
Diethylstilbestrol: known to be a human carcinogen.
DHHS/National Toxicology Program; Eleventh Report on Carcinogens: Diethylstilbestrol (56-53-1) (January 2005). Available from, as of July 31, 2009: https://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s071diet.pdf

13.1.5 Carcinogen Classification

1 of 2
IARC Carcinogenic Agent
Diethylstilbestrol
IARC Carcinogenic Classes
Group 1: Carcinogenic to humans
IARC Monographs

Volume 21: (1979) Sex Hormones (II)

Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)

Volume 100A: (2012) Pharmaceuticals

2 of 2
Carcinogen Classification
1, carcinogenic to humans. (L135)

13.1.6 Symptoms

Symptoms of overdose include nausea and vomiting, and withdrawal bleeding may occur in females.

13.1.7 Acute Effects

13.1.8 Interactions

BILIARY EXCRETION OF METABOLITES OF ... STILBESTROL ... IN RATS WAS SHOWN ... TO BE INCR BY PRE-TREATMENT WITH HEPATIC-MICROSOMAL-ENZYME INDUCERS, & TO BE DECR BY ENZYME INHIBITORS AFTER DOSING WITH PARENT CMPD, BUT NO EFFECT WAS OBSERVED AFTER DOSING WITH METABOLITES.
The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 2: A Review of the Literature Published Between 1970 and 1971. London: The Chemical Society, 1972., p. 436
Male and timed pregnant female Syrian hamsters received vitamin C (1% w/v) in drinking water for 4 days or 40 mg/kg alpha-naphthoflavone in corn oil by ip injection daily for 4 days. Male hamsters (1, 20, 85 or 240 days old) then received a single ip injection of diethylstilbestrol (DES, 20 mg/kg containing 250 uCi (3)H-DES). Pregnant hamsters received the same dose of DES ip on the 14th day of gestation. 30 min later animals were killed. Formation of diethylstilbestrol-4',4''-quinone occurred in all tissues investigated, livers and kidneys of male and female adult hamsters, neonates and fetuses, and in uterus and placenta. After injection of 75 umol/kg DES, diethylstilbestrol-4',4''-quinone was identified in liver and kidney extracts of male hamsters (12 wk old) at levels of 76 + or - 14 and 20 + or - 3 pmol/g tissue respectively. In neonates and fetuses, concn of diethylstilbestrol-4',4''-quinone after the same dose of DES were markedly less than those in adults (0.026 and 0.47% of adult levels in neonatal liver and kidney and 0.013 and 0.016% of adult levels in fetal liver and kidney respectively). Quinone metabolite levels were cut in half in response to vitamin C (44 to 60% of controls in kidneys and 41 to 65% of controls in livers). alpha-Naphthoflavone pretreatment decr renal and hepatic diethylstilbestrol-4',4''-quinone concn by 70 and 17% respectively.
Roy D, Liehr JG; Carcinogenesis 10 (7): 1241-5 (1989)
Estrogens may interfere with the effects of bromocriptine; dosage adjustment may be necessary. /Estrogens/
USP. Convention. USPDI - Drug Information for the Health Care Professional. 19th ed. Volume I.Micromedex, Inc. Englewood, CO., 1999. Content Prepared by the U.S. Pharmacopieal Convention, Inc., p. 1385
Concurrent use with estrogens may increase calcium absorption and exacerbate nephrolithiasis in susceptible individuals; this can be used to therapeutic advantage to increase bone mass. /Estrogens/
USP. Convention. USPDI - Drug Information for the Health Care Professional. 19th ed. Volume I.Micromedex, Inc. Englewood, CO., 1999. Content Prepared by the U.S. Pharmacopieal Convention, Inc., p. 1385
For more Interactions (Complete) data for DIETHYLSTILBESTROL (11 total), please visit the HSDB record page.

13.1.9 Antidote and Emergency Treatment

Basic treatment: Establish a patent airway. 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 normal saline 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/
Bronstein, A.C., P.L. Currance; Emergency Care for Hazardous Materials Exposure. 2nd ed. St. Louis, MO. Mosby Lifeline. 1994., p. 139
Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/
Bronstein, A.C., P.L. Currance; Emergency Care for Hazardous Materials Exposure. 2nd ed. St. Louis, MO. Mosby Lifeline. 1994., p. 139

13.1.10 Medical Surveillance

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/
Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979., p. 23

13.1.11 Human Toxicity Excerpts

... VAGINAL ADENOSIS IN 13/34 FEMALE PATIENTS EXPOSED IN UTERO TO DES, & IN 7 THERE WERE TRANSVERSE CERVICAL OR VAGINAL RIDGES. SIMILAR LESIONS ... NOT PRESENT IN 275 GIRLS OF ... NO HISTORY OF DES EXPOSURE IN UTERO.
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. V6 68 (1974)
AMONG 24 FEMALE PATIENTS WITH GONADAL DYSGENESIS ... TREATED FOR 5 OR MORE YR WITH DES, ENDOMETRIAL CARCINOMA DEVELOPED IN 2 ... THREE OTHER CASES ... PREVIOUSLY ... REPORTED ... OF THE TOTAL OF 5 ... 3 WERE OF UNUSUAL MIXED OR ADENOSQUAMOUS TYPE.
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 205 (1979)
... PRIMARY CARCINOMA OF BREAST WITH PAGET'S DISEASE OF NIPPLE IN MAN WHO HAD RECEIVED LONG-TERM TREATMENT WITH DES FOR CARCINOMA OF PROSTATE.
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. V6 69 (1974)
STRUCTURAL CHANGES ... WERE REPORTED ... IN THE UTERUS AND FALLOPIAN TUBE OF 40 TO 60 FEMALES EXPOSED PRENATALLY TO DES. SMALL ENDOMETRIAL CAVITIES, 'T'-SHAPED UTERI AND DILATED CORNUAL AREAS WERE NOTED. THEY FOUND NO SIMILAR CHANGES IN ... UNEXPOSED FEMALES OF THE SAME 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 205 (1979)
For more Human Toxicity Excerpts (Complete) data for DIETHYLSTILBESTROL (14 total), please visit the HSDB record page.

13.1.12 Non-Human Toxicity Excerpts

TUMOR INDUCTION TIMES DECR ... WITH INCR DES CONCN. INTACT MALE C3H MICE ... DEVELOPED SIGNIFICANT INCIDENCE OF BREAST TUMORS (23/60) WHEN 500 PPB DES WERE GIVEN IN DIET, ALTHOUGH SOME ... DID OCCUR WITH LOWER CONCN. CASTRATED A STRAIN MALES WERE LESS SUSCEPTIBLE TO ALL DIETARY CONCN OF DES. NO BREAST TUMORS OCCURRED IN GROUPS OF 115 INTACT MALE C3H MICE OR IN 136 CASTRATED MALE A STRAIN CONTROLS.
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. V6 60 (1974)
NEWBORN MALE & FEMALE MICE WERE INJECTED SC WITH 2 MG DES IN SALINE SUSPENSION WITHIN THE FIRST 24 HR AFTER BIRTH; CANCERS OF THE CERVIX AND/OR VAGINA OCCURRED IN 6/17 FEMALE BALB/C MICE AGED 13-26 MO, IN 3/10 C3HF FEMALES AT 20-26 MO, & IN 1/4 CONTROLS. PRECANCEROUS LESIONS WERE FOUND IN 3 BALB/C MICE @ 13-21 MO & IN 4 FEMALE C3H MICE @ 24-26 MO. GRANULAR-CELL MYOBLASTOMAS OCCURRED IN 1/6 BALB/C FEMALES AGED 24-26 MO & IN 1/9 C3HF FEMALES @ 24-26 MO; HOWEVER, ONE OF THESE TUMORS ALSO OCCURRED IN 1/2 CONTROLS @ 26 MO. MALE MICE SHOWED NO UNUSUAL TUMORS IN ANY ORGAN; HOWEVER, 5/10 BALB/C AND 7/10 C3HF MICE SHOWED SINGLE OR MULTIPLE, OFTEN BILATERAL, EPIDIDYMAL CYSTS.
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 194 (1979)
WHEN 0.6 MG DES IN 0.2 ML OF 0.9% SALINE WAS INJECTED SUBCUTANEOUSLY EVERY OTHER DAY FOR 36 WK OR LONGER, 11/11 INTACT MALE GOLDEN HAMSTERS DEVELOPED KIDNEY TUMORS, COMPARED WITH 0/17 IN UNTREATED & 0/5 IN SALINE-TREATED CONTROLS.
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 188 (1979)
BITCHES IN KENNELS FED WITH EARS OF CATTLE WHICH HAD BEEN IMPLANTED WITH STILBESTROL FAILED TO CONCEIVE OR HAD DEAD FETUSES ... IN LACTATING CATTLE, PROLAPSE OF VAGINA & RECTUM ... RECORDED ... FOLLOWING ORAL ADMIN ... OTHER EFFECTS ... ABORTION IN PREGNANT ANIMALS, &, FOLLOWING SUBCUTANEOUS IMPLANTATION ... CHANGES IN PELVIC MORPHOLOGY ... .
Clarke, E.G., and M. L. Clarke. Veterinary Toxicology. Baltimore, Maryland: The Williams and Wilkins Company, 1975., p. 164
For more Non-Human Toxicity Excerpts (Complete) data for DIETHYLSTILBESTROL (21 total), please visit the HSDB record page.

13.1.13 Non-Human Toxicity Values

LD50 Rat oral >3 g/kg
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1196
LD50 Rat ip 34 mg/kg
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1196
LD50 Mouse oral >3 g/kg
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1196
LD50 Mouse ip 538 mg/kg
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1196
LD50 Mouse iv 300 mg/kg
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1196

13.1.14 Ongoing Test Status

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=56-53-1]

13.1.15 National Toxicology Program Studies

Diethylstilbestrol (DES) ... was tested in Swiss mice using the RACB protocol. This study was one of the first RACB studies conducted. DES was chosen as a known positive, based on the extensive literature ... . There were two laboratories beginning to run RACB studies, & a DES study was performed at each of these laboratories to address the issue of interlaboratory variability. From the range finding study (Task 1), levels of 1.0, 10.0 & 50.0 ppb in feed were selected for the continuous breeding phase of the study. Based on body weights & measures of food consumption, the estimated average doses were approx 0.15, 1.5, & 7.70 mgm/kg/d. In Task 2, no adverse clinical signs were noted; one high dose female died of partner-inflicted wounds. Body weight was unaffected during Task 2. The mean number of litters/pair was reduced to nearly equal to 30% of control at the high dose, while the number of live pups/litter was reduced by 77% & 64% in the medium & high dose grups, respectively. Adjusted live pup weight was unaffected. The high dose group took longer to deliver each of the first 3 litters; no fourth or fifth litters were delivered at 50 ppb. Since adverse effects were noted in Task 2, Task 3 was conducted using the using the control & high dose mice. Compared to controls, only one-third as many exposed female mice delivered a litter, & these litters contained nearly equal to 60% fewer pups. Interestingly, for the exposed-female group, adjusted pup weight was reduced by nearly equal to 20%. The only adverse effect noted in the group containing exposed males was a 10% reduction in adjusted pup body weight. The larger adverse effects were clearly seen in exposed females. After the Task 3 litters were evaluated, the F0 control & high dose mice were killed & necropsied. For females, the only effect noted was a nearly equal to 30% incr in pituitary weight. For females, 25% of controls had an unclear estrous cycle, while more than 75% of treated females did not have a clear estrous cycle. In males, a significant incr in pituitary weight (nearly equal to 15%) was also seen, along with 13-18% reductions in the weight of epididymis, cauda epididymis, & prostate. There were no demonstrable sperm effects. Task 4, the F2 generation assessment, was not conducted. This study replicated all of the salient features of the other DES study: female as the much-more-sensitive gender in the absence of significant weight effects. Differences between the results of the two studies include effects in the middle dose group, different responses in adjusted pup weight (increased at one lab, decreased at the other), & an effect on pup number in the middle dose in Task 2 (unchanged at one lab, reduced by 11% at the other). Nonetheless, in broad strokes, these studies confirmed the general replicability of the data from two different laboratories, & provided a sense of the degree of variation that might be expected across labs.
Department of Health & Human Services/National Institute of Environmental Health Sciences, National Toxicology Program; Diethylstilbestrol (CAS #56-53-1): Fertility Assessment in CD-1 Mice When Administered in Feed, NTP Study No. RACB83046 (November 1984) Available from, as of August 14, 2002: https://ntp.niehs.nih.gov/index.cfm?objectid=0847F35A-0850-D1E7-B02ED4DDD150F990
Trans-diethylstilbestrol (DES) was evaluated as a model compound in a reproductive toxicology testing scheme which has been designated "Reproductive Assessment by Continuous Breeding". In the present DES study, ... dietary levels of 1, 10 & 50 ppb DES (/about/ 99% pure) were employed in Task 2. Continuous exposure of breeding pairs /of CD-1 mice/ to dietary DES led to rapid onset of infertility in the 50 ppb DES group, whereas fertility was unaffected in the 0, 1, & 10 ppb DES groups. In addition, the 50 ppb DES pairs produced fewer litters & had fewer live pups/litter & a lower proportion of pups born alive/litter than did the pairs in the other treatment groups. Therefore a crossover mating trial was conducted to determine which sex was adversely affected (Task 3). In the crossover mating trial the proportion of detected matings did not differ significantly among treatment groups, but fertility & the number of live pups/litter & the proportion of pups born alive were significantly reduced (p<0.05),in the control male x 50 ppb DES female group versus the control male x control female group. The proportion of fertile pairs in the 50 ppb DES male x control female group did not differ significantly from either of the above two groups. Hence, exposure to 50 ppb DES in the diet primarily affected fertility in female mice. The sex of pups born alive & the live pups weights, however, did not differ significantly among the three groups. Thus, these data support the conclusion that, under the conditions of this reproductive toxicity study, DES was a reproductive toxicant in female CD-l mice as evidenced by a decreased fertility index, decreased number of litters, decreased number of live pups/litter & a lower proportion of pups born alive/litter.
Department of Health & Human Services/National Institute of Environmental Health Sciences, National Toxicology Program; Reproductive and Fertility Assessment of Trans-Diethylstilbestrol (DES) (CAS No. 56-53-1) in CD-1 Mice When Administered in the Feed, NTP Study No. RACB83094 (November 1983) Available from, as of August 14, 2002: https://ntp.niehs.nih.gov/index.cfm?objectid=0847F35A-0850-D1E7-B02ED4DDD150F990
... Diethylstilbestrol (CAS No. 56-53-1 ) was administered subcutaneously in corn oil to mated Swiss (CD-1) mice (12/group) on gd 9 through 16 at levels of 0, 2.5, 5, 10, 50, or 100 mg/kg/day. A trioctanoin vehicle control group and 100 mg/kg/day diethylstilbestrol in trioctanoin group (12/group) were dosed concurrently to provide comparison of data using a different vehicle. Animals were observed daily for clinical signs of toxicity on gd 9-17. Food and water weights were recorded for the animals in each group on gd 0, 3, 6, 9, 12, 16, and 17. Body weights were taken on gd 0, 3, 6, and 9-17. All animals in the developmental toxicity study were killed on gd 17 and examined for maternal body and organ weights, implant status, fetal weight, sex, and morphological development (external, visceral and skeletal). For animals dosed with DES in corn oil, no maternal lethality was observed. Pregnancy rates were 100%, 100%, 100%, 83%, 100%, and 70% for the control through high dose groups. maternal body weight gain was decreased in the 50 and 100 mg/kg/day groups compared to the corn oil controls during the gestational period (gd 0-17), and in the high dose compared to the com oil controls during the treatment period (gd 9-16). Corrected maternal body weight gain was decreased in all the DES in corn oil-treated groups compared to the corn oil control group. No dose-related clinical signs were observed. maternal relative food and water consumption for the DES in com oil groups displayed little effect of treatment. At necropsy, relative maternal liver weight was increased in the high dose group, and gravid uterine weight was decreased. The number of implantation sites per dam exhibited a decreasing trend; the number of corpora lutea per dam was decreased at greater than 10 mg/kg/day. The percent resorptions per litter was increased 3, 4, and 5-fold in the 10, 50, and 100 mg/kg/day groups, respectively. Average live litter size was decreased at the high dose, with male and female fetuses equally affected. Live fetal body weight per litter was not affected by administration of diethylstilbestrol in corn oil. The incidence of malformations per litter was increased in the high dose group, with females more severely affected than males. This was due to an increase in the incidence of extemal malformations per litter, observed as an increase in the incidence of prominent nipples in the gd 17 fetuses, a characteristic effect of prenatal diethylstilbestrol exposure. No significant increase in the incidence of visceral or skeletal malformations or variations was observed for the diethylstilbestrol in corn oil-treated litters, except at 5 mg/kg/day diethylstilbestrol in corn oil where an increase in skeletal malformations was noted. Malformations included scrambled sternebrae, perforated sternum, and fused ribs, which have not been shown to be specific to diethylstilbestrol treatment. Failure to detect a statistically significant number of skeletal malformations in the 10, 50, and 100 mg/kg/day groups may have been influenced by a reduced number of fetuses available for examination in these groups, as a result of prenatal mortality. For animals dosed with diethylstilbestrol in trioctanoin, no maternal lethality was observed. Pregnancy rates were 92% and 100% for the control and 100 mg/kg/day dose group, respectively. Maternal body weight gain was decreased in the 100 mg/kg/day diethylstilbestrol in trioctanoin group compared to the trioctanoin control during the gestational period (gd 0-17), and during the treatment period (gd 9-16). Corrected maternal body weight gain was unaffected by treatment with diethylstilbestrol in trioctanoin. No treatment-related clinical signs were observed. Maternal relative food consumption was unaffected. Maternal relative water consumption for the DES in trioctanoin was decreased during the period of gd 9-12, but not at any other time interval during treatment. At necropsy, relative maternal liver weight was unaffected, while gravid uterine weight was decreased in the 100 mg/kg/day diethylstilbestrol in trioctanoin group. The percent resorptions per litter was increased 5-fold in the 100 mg/kg/day diethylstilbestrol in trioctanoin group compared to the trioctanoin control group. Average live litter size was decreased, with male and female fetuses equally affected. Live fetal body weight per litter was decreased by administration of diethylstilbestrol in trioctanoin. The incidence of malformations per litter was not increased by diethylstilbestrol in trioctanoin treatment. However, when external, visceral, and skeletal malformations were analyzed separately, the incidence of external malformations per litter was increased, due to an increase in the incidence of prominent nipples. No significant increase in the incidence of visceral or skeletal malformations or variations was observed for the DES in trioctanoin-treated litters. In summary, maternal toxicity was evident as decreased corrected maternal body weight at greater than 2.5 mg/kg/day DES in corn oil. Thus, for DES administered subcutaneously in corn oil to Swiss mice on gd 9-16, a No Observed Adverse Effect Level (NOAEL) for maternal toxicity was not determined. Gravid uterine weight and live litter size were decreased at the high dose (100 mg/kg/day). However, the incidence of resorptions (early embryo/fetal death) was increased at greater than 10 mg/kg/day. External malformations were increased at the 100 mg/kg/day, and were characterized by an increase in the incidence of prominent nipples, observed primarily in female fetuses. There was no evidence of altered skeletal development in the fetuses of any dose group. Thus, the LOAEL for developmental toxicity was 10 mg/kg/day and the NOAEL for developmental toxicity was 5 mg/kg/day. Comparison of the effects of 100 mg/kg/day diethylstilbestrol administered in corn oil and trioctanoin indicated there was no difference in corn oil or trioctanoin as vehicles for this compound.
Department of Health & Human Services/National Institute of Environmental Health Sciences, National Toxicology Program; Developmental Toxicity of Diethystilbestrol (CAS NO. 56-53-1) in Swiss (CD-1) Mice, NTP Study No. TER93137 (October, 1994) Available from, as of August 15, 2002: https://ntp.niehs.nih.gov/index.cfm?objectid=0847FF31-90CC-C685-88B4D7EAC975BD44

13.1.16 TSCA Test Submissions

Diethylstilbestrol (CAS # 56-53-1) was evaluated for reproductive effects in sexually mature male Dutch Belted rabbits (6/group) fed 5 doses of 0.1 or 1.0 mg/kg in oil by oral gavage. Semen specimens were collected twice weekly over 12 weeks following dosing for comparison of sperm volume, motility, density, and morphology to baseline values from specimens collected for 4 weeks prior to dosing. Two or more consecutive measurements outside the "normal range", defined as within 2 standard deviations, indicated an effect on semen quality. Total doses of 0.5 mg/kg (5 x 0.1 mg/kg) were associated with slightly increased sperm volume and wider variations of sperm counts, while 5.0 mg/kg dose totals induced a marked increase in abnormal sperm and decreased sperm numbers, volume, and motility. These changes coincided for approximately 7 weeks post-dosing with all returning to near normalcy, except diminished sperm motility which persisted for 10 weeks. Evaluation of time to changes in sperm count or morphology revealed that nonlethal doses affected primarily spermatocytes and spermatogonia rather than epididymal sperm, spermatids and testicular sperm; only a dose of 20 mg/kg (5 x 4 mg/kg) affected the quality of epididymal sperm. Sperm morphology was the most sensitive indicator of reproductive toxicity.
E I Dupont De Nemours & Co; Laboratory Tests for Testicular Function; 11/25/80; EPA Document No. 88-920010617; Fiche No. OTS0555886
Clastogenic activity was evaluated in 3 cultures of RL1 rat liver cells per dose, exposed for 22 hours to diethylstilbestrol at concentrations of 0, 5.0, 10.0, or 20.0 ug/ml of culture medium. Test concentrations were chosen to be 1/4, 1/2, and 1x the GI50 (concentration at which 50% growth inhibition is achieved). Both positive (methylmethanesulfonate) and solvent (dimethylsulfoxide) controls were used. No metabolic activation system was used. Cell division was arrested, and at least 225 metaphases from each test concentration were examined. Neither chromatid aberrations nor chromosome aberrations were increased significantly. The proportions of cells with chromatid aberrations were 0.2%, 0.0%, 0.0%, and 0.6% at 0.0, 5.0, 10.0, and 20.0 ug/ml, respectively. The proportions of cells with chromosome aberrations were 0.0%, 0.0%, 0.3%, and 0.3% at 0.0, 5.0, 10.0, and 20.0 ug/ml, respectively. Although the positive control compound induced chromatid aberrations in 5.4% of cells, no chromosomal aberrations were induced.
Shell Chem. Co.; The Activity of 27 Coded Compounds in the RL1 Chromosome Assay (1989), EPA Document No. 86-890000950, Fiche No. OTS0520388

13.2 Ecological Information

13.2.1 US EPA Regional Screening Levels for Chemical Contaminants

Resident Soil (mg/kg)
1.60e-03
Industrial Soil (mg/kg)
6.60e-03
Resident Air (ug/m3)
2.8e-05
Industrial Air (ug/m3)
1.20e-04
Tapwater (ug/L)
5.1e-05
MCL (ug/L)
5.00e+00
Risk-based SSL (mg/kg)
2.8e-05
Oral Slope Factor (mg/kg-day)-1
3.50e+02
Inhalation Unit Risk (ug/m3)-1
1.00e-01
Volatile
Volatile
Mutagen
Mutagen
Fraction of Contaminant Absorbed in Gastrointestinal Tract
1
Fraction of Contaminant Absorbed Dermally from Soil
0.1

13.2.2 US EPA Regional Removal Management Levels for Chemical Contaminants

Resident Soil (mg/kg)
1.60e-01
Industrial Soil (mg/kg)
6.60e-01
Resident Air (ug/m3)
2.80e-03
Industrial Air (ug/m3)
1.20e-02
Tapwater (ug/L)
5.10e-03
MCL (ug/L)
5.00e+00
Oral Slope Factor (mg/kg-day)-1
3.50e+02
Inhalation Unit Risk (ug/m3)-1
1.00e-01
Volatile
Volatile
Mutagen
Mutagen
Fraction of Contaminant Absorbed in Gastrointestinal Tract
1
Fraction of Contaminant Absorbed Dermally from Soil
0.1

13.2.3 Environmental Fate / Exposure Summary

Diethylstilbestrol's production and use in biochemical research, medicine, and also in veterinary medicine may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 1.4X10-8 mm Hg at 25 °C indicates diethylstilbestrol will exist solely in the particulate phase in the ambient atmosphere. If released to soil, diethylstilbestrol is expected to be immobile based upon an estimated Koc of 570,000. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 5.8X10-12 atm-cu m/mole. Diethylstilbestrol is not expected to volatilize from dry soil surfaces based upon its vapor pressure. If released into water, diethylstilbestrol is expected to adsorb to suspended solids and sediment in water based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. Hydrolysis is not expected to occur due to the lack of hydrolyzable functional groups. An estimated BCF of 1600 suggests the potential for bioconcentration in aquatic organisms is very high if diethylstilbestrol is not metabolized. Occupational exposure to diethylstilbestrol may occur through inhalation and dermal contact with this compound at workplaces where diethylstilbestrol is produced or used. (SRC)

13.2.4 Natural Pollution Sources

Diethylstilbestrol (DES) is not known to occur naturally(1).
(1) IARC; Diethylstilbestrol and Diethylstilbestrol dipropionate 21: 173-80 (1979)

13.2.5 Artificial Pollution Sources

Diethylstilbestrol's production and use in biochemical research, medicine, and also in veterinary medicine(1) may result in its release to the environment through various waste streams(SRC).
(1) Lewis RJ Sr, ed; Hawley's Condensed Chemical Dictionary. 13th ed. NY, NY: John Wiley and Sons p. 380 (1997)

13.2.6 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 570,000(SRC), determined from a structure estimation method(2), indicates that diethylstilbestrol is expected to be immobile in soil(SRC). Volatilization of diethylstilbestrol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law of 5.8X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Diethylstilbestrol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.4X10-8 mm Hg(SRC), determined from a fragment constant method(4).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992)
(3) Meylan WM, Howard PH; Environ Toxicol Chem 10:1283-93 (1991)
(4) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 570,000(SRC), determined from an estimation method(2), indicates that diethylstilbestrol is expected to adsorb to suspended solids and sediment in water(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.8X10-12 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Hydrolysis is not expected to occur due to the lack of hydrolyzable functional groups(3). According to a classification scheme(5), an estimated BCF of 1600(SRC), from its log Kow of 5.07(8) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is very high if diethylstilbestrol is not metabolized.
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9, 7-4, 7-5, 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) Meylan WM, Howard PH; J Pharm Sci 84: 83-92 (1995)
(7) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
(8) 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. 156 (1995)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), diethylstilbestrol, which has an estimated vapor pressure of 1.4X10-8 mm Hg at 25 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase diethylstilbestrol may be removed from the air by wet and dry deposition(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)

13.2.7 Environmental Biodegradation

AEROBIC: Over a period of 6 days under aerobic conditions at 20 °C, 500 mg/l diethylstilbestrol was resistant to biodegradation in two activated sludge samples and was slightly inhibitory in a third sample(1). Biodegradation studies of diethylstilbestrol have indicated this hormone is persistant in soil and feces(2).
(1) Lutin PA et al; Purdue Univ Eng Bull Ext Ser 118: 131-45 (1965)
(2) Halling-Sorensen B et al; Chemosphere 36: 357-93 (1998)

13.2.8 Environmental Abiotic Degradation

Diethylstilbestrol is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(1).
(1) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5 (1990)

13.2.9 Environmental Bioconcentration

An estimated BCF of 1600 was calculated for diethylstilbestrol(SRC), using a log Kow of 5.07(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is very high if diethylstilbestrol is not metabolized.
(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. 156 (1995)
(2) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

13.2.10 Soil Adsorption / Mobility

Using a structure estimation method based on molecular connectivity indices(1), the Koc for diethylstilbestrol can be estimated to be 570,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that diethylstilbestrol is expected to be immobile in soil.
(1) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992)
(2) Swann RL etal; Res Rev 85: 17-28 (1983)

13.2.11 Volatilization from Water / Soil

The Henry's Law constant for diethylstilbestrol is estimated as 5.8X10-8 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that diethylstilbestrol is expected to be essentially nonvolatile from water surfaces(2). Diethylstilbestrol's Henry's Law constant(1) indicates that volatilization from moist soil surfaces is not expected to occur(SRC). Diethylstilbestrol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.4X10-8 mm Hg(3), determined from a fragment constant method(SRC).
(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) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)

13.2.12 Environmental Water Concentrations

DRINKING WATER: Diethylstilbestrol was detected in German drinking water samples at a concentration of 0.11-0.26 ng/l(1,2).
(1) IARC; Diethylstilbestrol and diethylstilbestrol dipropionate 21: 173-89 (1979)
(2) Rurainski RD et al; Gas-Wasserfach, Wasser-Abwasser 118: 288-91 (1977)

13.2.13 Food Survey Values

In 1972 and 1973, diethylstilbestrol was detected in beef livers at the following concentration, number of samples not reported: <2 ug/kg, 2 and 0.5% pos, respectively(1); in 1972 and 1973, sheep livers, 1900 samples, residual levels, <2% pos(1); from 1973 to June 1976, beef livers, 9426 samples, greater than or equal to 0.5 ug/kg, 0.6% pos(1).
(1) IARC; Diethylstilbestrol and diethylstilbestrol dipropionate 21: 173-80 (1979)

13.2.14 Probable Routes of Human Exposure

... food contaminant ... in beef ... chickens
Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 2908
NIOSH (NOES Survey 1981-1983) has statistically estimated that 1,478 workers (920 of these are female) are potentially exposed to diethylstilbestrol in the US(1). Occupational exposure to diethylstilbestrol may occur through dermal contact with this compound at workplaces where diethylstilbestrol is produced or used(SRC). Air samples collected inside the plastic suits of full-time workers in a plant manufacturing diethylstilbestrol contained 0.4-1.8 ug/cu m diethylstilbestrol(2). Two sets of air samples collected in areas outside the main work room contained 0.2 ug/cu m and 12.8 ug/cu m(2). An air sample from a finishing room contained 24 ug/cu m diethylstilbestrol(2). Ambient air samples in three plants where diethylstilbestrol was mixed with animal feed contained 0.002-1.03 ug/cu m diethylstilbestrol(2).
(1) NIOSH; National Occupational Exposure Survey (NOES) (1983)
(2) IARC; Diethylstilbestrol and diethylstilbestrol dipropionate 21: 173-80 (1979)

14 Associated Disorders and Diseases

15 Literature

15.1 Consolidated References

15.2 NLM Curated PubMed Citations

15.3 Springer Nature References

15.4 Thieme References

15.5 Nature Journal References

15.6 Chemical Co-Occurrences in Literature

15.7 Chemical-Gene Co-Occurrences in Literature

15.8 Chemical-Disease Co-Occurrences in Literature

16 Patents

16.1 Depositor-Supplied Patent Identifiers

16.2 WIPO PATENTSCOPE

16.3 Chemical Co-Occurrences in Patents

16.4 Chemical-Disease Co-Occurrences in Patents

16.5 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

18 Biological Test Results

18.1 BioAssay Results

19 Classification

19.1 MeSH Tree

19.2 NCI Thesaurus Tree

19.3 ChEBI Ontology

19.4 KEGG: ATC

19.5 KEGG: Target-based Classification of Drugs

19.6 KEGG: Risk Category of Japanese OTC Drugs

19.7 KEGG: Drug Groups

19.8 WHO ATC Classification System

19.9 ChemIDplus

19.10 CAMEO Chemicals

19.11 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

19.12 ChEMBL Target Tree

19.13 UN GHS Classification

19.14 NORMAN Suspect List Exchange Classification

19.15 CCSBase Classification

19.16 EPA DSSTox Classification

19.17 International Agency for Research on Cancer (IARC) Classification

19.18 EPA TSCA and CDR Classification

19.19 MolGenie Organic Chemistry Ontology

20 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
    Phenol, 4,4'-(1,2-diethyl-1,2-ethenediyl)bis-, (E)-
    https://services.industrialchemicals.gov.au/search-assessments/
  2. CAMEO Chemicals
    LICENSE
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    https://cameochemicals.noaa.gov/help/reference/terms_and_conditions.htm?d_f=false
    CAMEO Chemical Reactivity Classification
    https://cameochemicals.noaa.gov/browse/react
  3. CAS Common Chemistry
    LICENSE
    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  4. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  5. 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
  6. DTP/NCI
    LICENSE
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    https://www.cancer.gov/policies/copyright-reuse
  7. EPA Chemicals under the TSCA
    Phenol, 4,4'-[(1E)-1,2-diethyl-1,2-ethenediyl]bis-
    https://www.epa.gov/chemicals-under-tsca
    EPA TSCA Classification
    https://www.epa.gov/tsca-inventory
  8. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  9. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
  10. FDA Global Substance Registration System (GSRS)
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  11. Hazardous Substances Data Bank (HSDB)
  12. New Zealand Environmental Protection Authority (EPA)
    LICENSE
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    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  13. NJDOH RTK Hazardous Substance List
  14. Risk Assessment Information System (RAIS)
    LICENSE
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    https://rais.ornl.gov/
  15. BindingDB
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    https://www.bindingdb.org/rwd/bind/info.jsp
  16. ChEMBL
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    http://www.ebi.ac.uk/Information/termsofuse.html
  17. Comparative Toxicogenomics Database (CTD)
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    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  18. Drug Gene Interaction database (DGIdb)
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    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  19. IUPHAR/BPS Guide to PHARMACOLOGY
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    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  20. Therapeutic Target Database (TTD)
  21. Toxin and Toxin Target Database (T3DB)
    LICENSE
    T3DB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (T3DB) and the original publication.
    http://www.t3db.ca/downloads
  22. California Office of Environmental Health Hazard Assessment (OEHHA)
  23. ChEBI
  24. NCI Thesaurus (NCIt)
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    https://www.cancer.gov/policies/copyright-reuse
  25. Open Targets
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    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  26. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  27. 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/
    Diethylstilbestrol
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  28. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  29. Crystallography Open Database (COD)
    LICENSE
    All data in the COD and the database itself are dedicated to the public domain and licensed under the CC0 License. Users of the data should acknowledge the original authors of the structural data.
    https://creativecommons.org/publicdomain/zero/1.0/
  30. DailyMed
  31. Drugs@FDA
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  32. EPA Regional Screening Levels for Chemical Contaminants at Superfund Sites
  33. EU Clinical Trials Register
  34. NITE-CMC
    Diethylstilbestrol - FY2009 (New/original classication)
    https://www.chem-info.nite.go.jp/chem/english/ghs/09-mhlw-0224e.html
  35. FDA Orange Book
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  36. Joint FAO/WHO Expert Committee on Food Additives (JECFA)
    LICENSE
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    https://www.who.int/about/policies/publishing/copyright
  37. FooDB
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    https://foodb.ca/about
  38. Human Metabolome Database (HMDB)
    LICENSE
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    http://www.hmdb.ca/citing
  39. International Agency for Research on Cancer (IARC)
    LICENSE
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    https://publications.iarc.fr/Terms-Of-Use
    IARC Classification
    https://www.iarc.fr/
  40. Japan Chemical Substance Dictionary (Nikkaji)
  41. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    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
  42. MassBank Europe
  43. 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
  44. Metabolomics Workbench
  45. National Drug Code (NDC) Directory
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  46. Nature Chemical Biology
  47. 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
  48. SpectraBase
    trans-alpha,alpha'-DIETHYL-4,4'-STILBENEDIOL
    https://spectrabase.com/spectrum/GdHuoU67EiS
    Diethylstilbestrol, mixture of cis and trans
    https://spectrabase.com/spectrum/GGqATSLnhFy
    trans-alpha,alpha'-diethyl-4,4'-stilbenediol
    https://spectrabase.com/spectrum/1I8yZimKwE5
    alpha,alpha'-diethyl-4,4'-stilbenediol
    https://spectrabase.com/spectrum/LQZIuhlvwJK
    trans-alpha,alpha'-DIETHYL-4,4'-STILBENEDIOL
    https://spectrabase.com/spectrum/J7imWFnEO5W
    trans-alpha,alpha'-diethyl-4,4'-stilbenediol
    https://spectrabase.com/spectrum/L1uF128iJzR
    trans-alpha,alpha'-diethyl-4,4'-stilbenediol
    https://spectrabase.com/spectrum/2YuULNc6Src
    STILBENDIOL, 4,4'-, A,A'-DIETHYL-,
    https://spectrabase.com/spectrum/A0H2Awb8LoH
    Diethylstilbestrol, mixture of cis and trans
    https://spectrabase.com/spectrum/EjFOHsnSPkV
  49. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  50. NMRShiftDB
  51. PharmGKB
    LICENSE
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    https://www.pharmgkb.org/page/policies
  52. Pharos
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    https://pharos.nih.gov/about
  53. Protein Data Bank in Europe (PDBe)
  54. RCSB Protein Data Bank (RCSB PDB)
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    https://www.rcsb.org/pages/policies
  55. Springer Nature
  56. SpringerMaterials
  57. The Cambridge Structural Database
  58. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  59. USGS Health-Based Screening Levels for Evaluating Water-Quality Data
  60. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  61. Wikidata
  62. Wikipedia
  63. Medical Subject Headings (MeSH)
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    https://www.nlm.nih.gov/copyright.html
  64. PubChem
  65. GHS Classification (UNECE)
  66. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  67. PATENTSCOPE (WIPO)
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