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Chloral Hydrate

PubChem CID
2707
Structure
Chloral Hydrate_small.png
Chloral Hydrate_3D_Structure.png
Molecular Formula
Synonyms
  • chloral hydrate
  • 302-17-0
  • 2,2,2-Trichloroethane-1,1-diol
  • Trichloroacetaldehyde hydrate
  • Noctec
Molecular Weight
165.40 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-25
  • Modify:
    2025-01-04
Description
Chloral Hydrate can cause cancer according to California Labor Code.
Transparent colorless crystals or white crystalline solid. Aromatic penetrating slightly acrid odor and a slightly bitter caustic taste. Alcoholic solution (1 in 20) does not at once redden moistened blue litmus paper. (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.
Chloral hydrate is an organochlorine compound that is the hydrate of trichloroacetaldehyde. It has a role as a sedative, a general anaesthetic, a mouse metabolite and a xenobiotic. It is an organochlorine compound, an aldehyde hydrate and an ethanediol.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Chloral Hydrate.png

1.2 3D Conformer

1.3 Crystal Structures

COD records with this CID as component

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

2,2,2-trichloroethane-1,1-diol
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C2H3Cl3O2/c3-2(4,5)1(6)7/h1,6-7H
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

RNFNDJAIBTYOQL-UHFFFAOYSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C(C(Cl)(Cl)Cl)(O)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C2H3Cl3O2
Computed by PubChem 2.2 (PubChem release 2021.10.14)

C2H3Cl3O2

Cl3CCH(OH)2

2.3 Other Identifiers

2.3.1 CAS

302-17-0

2.3.2 Deprecated CAS

109128-19-0
1178760-67-2

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 UN Number

2.3.6 ChEBI ID

2.3.7 ChEMBL ID

2.3.8 DEA Code Number

2465 (DEA schedule IV controlled substance)

2.3.9 DrugBank ID

2.3.10 DSSTox Substance ID

2.3.11 HMDB ID

2.3.12 ICSC Number

2.3.13 KEGG ID

2.3.14 Metabolomics Workbench ID

2.3.15 NCI Thesaurus Code

2.3.16 Nikkaji Number

2.3.17 NSC Number

2.3.18 PharmGKB ID

2.3.19 Wikidata

2.3.20 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Chloral Hydrate
  • Hydrate, Chloral
  • Noctec

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
165.40 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
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
0
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
163.919862 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
163.919862 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
7
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
56.4
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
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Transparent colorless crystals or white crystalline solid. Aromatic penetrating slightly acrid odor and a slightly bitter caustic taste. Alcoholic solution (1 in 20) does not at once redden moistened blue litmus paper. (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.
Colorless transparent solid with a penetrating, slightly acrid odor; [Hawley] Colorless or white solid; Colorless liquid; [HSDB] Crystalline solid; [MSDSonline]
TRANSPARENT COLOURLESS CRYSTALS WITH CHARACTERISTIC ODOUR.

3.2.2 Color / Form

COLORLESS OR WHITE CRYSTALS
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 796
Transparent, colorless crystals
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 257
Large, monoclinic plates
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 342

3.2.3 Odor

Aromatic, penetrating and slightly acrid odor
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 342
Characteristic: sweet
Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. 2001, p. V1: 452

3.2.4 Taste

Slightly bitter, caustic taste
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 342

3.2.5 Boiling Point

207.5 °F at 760 mmHg (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.
98 °C
PhysProp
96 °C (decomposes)
Lide, D.R. CRC Handbook of Chemistry and Physics 86TH Edition 2005-2006. CRC Press, Taylor & Francis, Boca Raton, FL 2005, p. 3-90

3.2.6 Melting Point

135 °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.
57 °C
PhysProp
57 °C
Lide, D.R. CRC Handbook of Chemistry and Physics 86TH Edition 2005-2006. CRC Press, Taylor & Francis, Boca Raton, FL 2005, p. 3-90
MP: 57 °C when heated in an open vessel. BP 98 °C with dissociation into chloral and water.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 342
57-60 °C

3.2.7 Solubility

greater than or equal to 10 mg/mL at 68.9 °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.
793000 mg/L (at 25 °C)
YALKOWSKY,SH & HE,Y (2003)
Freely soluble in acetone, methyl ethyl ketone. Moderately or sparingly soluble in turpentine, petroleum ether, carbon tetrachloride, benzene, toluene.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 342
Very soluble in benzene, ethyl ether, and ethanol.
Lide, D.R. CRC Handbook of Chemistry and Physics 86TH Edition 2005-2006. CRC Press, Taylor & Francis, Boca Raton, FL 2005, p. 3-90
In water, 7.93X10+5 mg/L at 25 °C
Yalkowsky, S.H., He, Yan., Handbook of Aqueous Solubility Data: An Extensive Compilation of Aqueous Solubility Data for Organic Compounds Extracted from the AQUASOL dATAbASE. CRC Press LLC, Boca Raton, FL. 2003.
Solubility in water: very good

3.2.8 Density

1.9081 at 68 °F (NTP, 1992) - Denser than water; will sink
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
1.9081 g/cu m at 20 °C/4 °C
Lide, D.R. CRC Handbook of Chemistry and Physics 86TH Edition 2005-2006. CRC Press, Taylor & Francis, Boca Raton, FL 2005, p. 3-90
1.9 g/cm³

3.2.9 Vapor Density

5.1 (Air= 1)
Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. 2001, p. V1: 452

3.2.10 Vapor Pressure

5 mmHg at 50 °F ; 10 mmHg at 67.1 °F; 60 mmHg at 115.2 °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.
15.0 [mmHg]
15 mm Hg at 25 °C
Perry RH, Green D; Perry's Chemical Engineers's Handbook. Physical and Chemical Data. New York, NY: McGraw-Hill 6th ed (1984)

3.2.11 LogP

0.99
HANSCH,C ET AL. (1995)
log Kow = 0.99
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 4
0.99

3.2.12 Stability / Shelf Life

SLOWLY VOLATILIZES ON EXPOSURE TO AIR.
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 343
Aqueous solutions of chloral hydrate decomposed rapidly when exposed to ultraviolet light, with the formation of hydrochloric acid, trichloroacetic acid, and formic acid. ... A 1% solution lost about 5% of its strength after storage at room temperature for 20 weeks.
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 796
Aqueous solutions are likely to develop mold growth.
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 796

3.2.13 Decomposition

When heated to decomposition it emits toxic fumes of /hydrogen chloride/.
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 705
97 °C

3.2.14 Corrosivity

... Corrosive to the skin and mucous membrane unless well diluted
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 796

3.2.15 pH

3.5-4.4 (10% soln in water)
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 1999. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1999 (Plus Supplements)., p. 2097

3.2.16 Kovats Retention Index

Standard non-polar
698 , 698 , 705 , 695

3.2.17 Other Experimental Properties

Decomposed by sodium hydroxide into chloroform; reduces ammoniacal silver nitrate /Monohydrate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 342
One gram of chloral hydrate dissolves in 1.3 mL alcohol, in 2 mL chloroform, in 1.5 mL ether, in 1.4 mL olive oil, in 0.5 glycerol, in 68 g carbon disulfide. /Monohydrate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 342
Chloral hydrate slowly volatilizes when exposed to air. Aqueous solutions of chloral hydrate are incompatible with alkaline substances, are decomposed by light, and may develop mold growth if a preservative is not present.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 2610
Incompatible with soluble barbiturates, tannin, oxidizing agents, and alcohol (chloral alcoholate may crystallize out), phenazone, phenol, thymol, and quinine salts
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 796
For more Other Experimental Properties (Complete) data for CHLORAL HYDRATE (8 total), please visit the HSDB record page.

3.3 SpringerMaterials Properties

3.4 Chemical Classes

Other Classes -> Halogenated Alcohols

3.4.1 Drugs

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds
S58 | PSYCHOCANNAB | Synthetic Cannabinoids and Psychoactive Compounds | DOI:10.5281/zenodo.3247723
Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
Pharmaceuticals -> Antiepileptics
S57 | GREEKPHARMA | Suspect Pharmaceuticals from the National Organization of Medicine, Greece | DOI:10.5281/zenodo.3248883
Pharmaceuticals -> unsed in Switzerland 2014-2016
S113 | SWISSPHARMA24 | 2024 Swiss Pharmaceutical List with Metabolites | DOI:10.5281/zenodo.10501043
Pharmaceuticals
S10 | SWISSPHARMA | Pharmaceutical List with Consumption Data | DOI:10.5281/zenodo.2623484
3.4.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Hypnotics and Sedatives
3.4.1.2 Animal Drugs
Active Ingredients (Chloral Hydrate) -> FDA Greenbook

4 Spectral Information

4.1 1D NMR Spectra

1 of 2
1D NMR Spectra
1H NMR: 10362 (Sadtler Research Laboratories Spectral Collection)
2 of 2
1D NMR Spectra

4.1.1 1H NMR Spectra

Copyright
Copyright © 2022-2024 Chemical Block, Russia, Leninsky Prospect 47 - Database Compilation Copyright © 2022-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.1.2 13C NMR Spectra

1 of 2
Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
Thumbnail
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2 of 2
Instrument Name
Varian CFT-20
Copyright
Copyright © 2002-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.1.3 17O NMR Spectra

1 of 2
Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
Thumbnail
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2 of 2
Instrument Name
SF = 060 MHz
Copyright
Copyright © 2002-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 6
View All
NIST Number
118677
Library
Main library
Total Peaks
55
m/z Top Peak
82
m/z 2nd Highest
84
m/z 3rd Highest
47
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2 of 6
View All
NIST Number
228873
Library
Replicate library
Total Peaks
74
m/z Top Peak
82
m/z 2nd Highest
29
m/z 3rd Highest
47
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4.2.2 Other MS

Other MS
MASS: 75231 (NIST/EPA/MSDC Mass Spectral database, 1990 version)

4.3 IR Spectra

IR Spectra
IR: 5423 (Coblentz Society Spectral Collection)

4.3.1 FTIR Spectra

Instrument Name
Bruker IFS 85
Technique
KBr-Pellet
Source of Sample
Riedel de Haen AG, Seelze
Copyright
Copyright © 1989, 1990-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.3.2 ATR-IR Spectra

Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Alltech Associates, Inc., Grace Davison Discovery Sciences
Catalog Number
01836
Lot Number
51198
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4 Raman Spectra

Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Alltech Associates, Inc., Grace Davison Discovery Sciences
Catalog Number
01836
Lot Number
51198
Copyright
Copyright © 2013-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.5 Other Spectra

Intense mass spectral peaks: 82 m/z, 111 m/z, 146 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. 200

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Mainly used as a hypnotic in the treatment of insomnia; however, it is only effective as a hypnotic for short-term use. May be used as a routine sedative preoperatively to decrease anxiety and cause sedation and/or sleep with respiration depression or cough reflex.

7.2 LiverTox Summary

Chloral hydrate is a mild hypnotic that is used to treat simple insomnia. Despite many years of use, chloral hydrate has not been implicated in causing serum enzyme elevations or clinically apparent liver injury.

7.3 Drug Classes

Breast Feeding; Lactation; Milk, Human; Hypnotics and Sedatives
Sedatives and Hypnotics

7.4 FDA Green Book

7.5 Drug Labels

Homeopathic product and label

7.6 Clinical Trials

7.6.1 ClinicalTrials.gov

7.7 DEA Drug and Chemical Information

7.7.1 DEA Controlled Substances

Substance
Chloral hydrate
DEA Controlled Substances Code Number
2465
Controlled Substances Act Schedule
Schedule IV - Substances in the DEA Schedule IV have a low potential for abuse relative to substances in Schedule III.
Class
Depressants

7.8 Therapeutic Uses

Sedatives, Nonbarbiturate; Anesthetics, Intravenous
National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)
Chloral hydrate also has been used as an adjunct to opiates and analgesics in postoperative care and control of pain. However, it generally has been replaced by agents with better pharmacokinetic and pharmacodynamic profiles. /Included in US product labeling/
USP. Convention. USPDI - Drug Information for the Health Care Professional. 20th ed. Volume I. Micromedex, Inc. Englewood, CO., 2000. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 859
Chloral hydrate has been used as a routine sedative. However, it generally has been replaced by safer and more effective agents. /Included in US product labeling/
USP. Convention. USPDI - Drug Information for the Health Care Professional. 20th ed. Volume I. Micromedex, Inc. Englewood, CO., 2000. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 859
Chloral hydrate has been used for the treatment of insomnia. However, this medication is effective as a hypnotic only for short-term use; it has been shown to lose its effectiveness for both inducing and maintaining sleep after 2 weeks of administration. In addition, chloral hydrate generally has been replaced by agents with better pharmacokinetic and pharmacodynamic profiles. /Included in US product labeling/
USP. Convention. USPDI - Drug Information for the Health Care Professional. 20th ed. Volume I. Micromedex, Inc. Englewood, CO., 2000. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 859
For more Therapeutic Uses (Complete) data for CHLORAL HYDRATE (13 total), please visit the HSDB record page.

7.9 Drug Warnings

... /Chloral hydrate/ crosses the placenta and the effects of the drug on the fetus are unknown. The manufactures caution that the use of chloral hydrate durring pregnancy may cause withdrawal symptoms in neonates
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 2610
Prolonged use of chloral hydrate may produce tolerance and physical and/or psychologic dependence. Tolerance and psychological dependence may develop by the second week of continued therapy.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 2610
Cutaneous reactions to chloral hydrate are not common but have included scarlatiniform or erythematous rash, urticaria, angioedema, purpura, eczema, bullous lesions, and erythema multiforme. Sometimes cutaneous reactions have been accompanied by fever.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 2609
Gastric irritation manifested by nausea, vomiting, and diarrhea is the most frequent adverse effect of oral chloral hydrate administration. Gastric irritation may be minimized by diluting the oral solution with water or other liquid or administering other oral dosage forms with liquids. Flatulence and unpleasant taste may also occur.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 2609
For more Drug Warnings (Complete) data for CHLORAL HYDRATE (14 total), please visit the HSDB record page.

7.10 Drug Idiosyncrasies

Rarely, patients exhibit idiosyncratic reactions to chloral hydrate and may be disoriented and incoherent and show paranoid behavior.
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill, 2006., p. 421

7.11 Reported Fatal Dose

The lethal oral dose of chloral hydrate in adults is about 10 g; however, ingestion of 4 g has caused death, and some patients have survived ingestion of as much as 30 g.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 2610
Lethal doses /of chloral hydrate/ are between 5 and 10 g.
Gossel, T.A., J.D. Bricker. Principles of Clinical Toxicology. 3rd ed. New York, NY: Raven Press, Ltd., 1994., p. 315

7.12 Drug Tolerance

Tolerance may develop by the second week of continual therapy.
USP. Convention. USPDI - Drug Information for the Health Care Professional. 20th ed. Volume I. Micromedex, Inc. Englewood, CO., 2000. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 859
High-dose long-term use results in tolerance and physical dependence. Sudden withdrawal results in a serious abstinence syndrome similar to delirium tremens (seizures and psychosis) and responds to barbiturates or other sedative-hypnotic drugs.
Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 695

8 Pharmacology and Biochemistry

8.1 MeSH Pharmacological Classification

Hypnotics and Sedatives
Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety. (See all compounds classified as Hypnotics and Sedatives.)

8.2 ATC Code

N - Nervous system

N05 - Psycholeptics

N05C - Hypnotics and sedatives

N05CC - Aldehydes and derivatives

N05CC01 - Chloral hydrate

8.3 Absorption, Distribution and Excretion

Absorption
Rapidly absorbed in the GI tract following oral or rectal administration. Chloral hydrate and its active metabolite, trichloroethanol, have been detected in CSF, umbilical cord blood, fetal blood, and amniotic fluid.
Route of Elimination
Trichloroethanol, trichloroethanol glucuronide, and trichloroacetic acid are excreted in the urine. Some trichloroethanol glucuronide may be secreted into bile and excreted in the feces.
Following therapeutic doses of chloral hydrate, only small, clinically insignificant amounts of the active metabolite are distributed into milk.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 2610
Chloral hydrate is rapidly absorbed from the GI tract following oral or rectal administration. Plasma concentrations of chloral hydrate (or the major metabolite, trichloroethanol) required for sedative or hypnotic effects are unknown. Following administration of a single chloral hydrate dose of 15 mg/kg, peak plasma concentrations of trichloroethanol ranged from 7-10 ug/mL in one study.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 2610
After oral administration, chloral hydrate is rapidly absorbed from the gastrointestinal tract. Peak levels of trichloroethanol and trichloroethanol glucuronide were reached within 20- 60 min after oral administration of aqueous solutions.
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. V63 251 (1995)
The volume of distribution of chloral hydrate is 0.6 L/kg.
Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 586
For more Absorption, Distribution and Excretion (Complete) data for CHLORAL HYDRATE (11 total), please visit the HSDB record page.

8.4 Metabolism / Metabolites

Metabolized by the liver and erythrocytes to form trichloroethanol, an active metabolite. This reaction is catalyzed by alcohol dehydrogenase and other enzymes. Oxidation of chloral hydrate and trichloroethanol to trichloroacetic acid in the liver and kidneys also occurs to a lesser extent. Trichloroethanol also undergoes glucuronidation to produce an inactive metabolism.
/Chloral hydrate/ biotransformation to trichloroethanol must be rapid, since no parent compound could be detected in even the first samples taken 10 min after administration of 15 mg/kg bw to volunteers.
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. V63 251 (1995)
Chloral hydrate is metabolized by the liver and erythrocytes to form trichloroethanol (an active metabolite). The reduction of chloral hydrate to trichloroethanol (the major metabolite) is catalyzed by alcohol dehydrogenase and other enzymes. ... A small but variable amount of chloral hydrate and a larger portion of trichloroethanol are oxidized to trichloroacetic acid (an inactive metabolite), mainly in the liver and kidneys. Trichloroethanol may also be conjugated with glucuronic acid to form trichloroethanol glucuronide (urochloralic acid), an inactive metabolite. ... The quantities of metabolites excreted in the urine appear to be quite variable not only between different individuals but may even vary in the same individual on different days.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 2610
In mammalian species, chloral hydrate is rapidly reduced to trichloroethanol, the metabolite that appears to be responsible for the hypnotic properties of the drug. ... In rodents, a slightly different metabolic pattern is seen, as chloral hydrate is oxidized directly to trichloroacetic acid, and the oxidative pathway from trichloroethanol to trichloroacetate that is observed in humans seems to be absent.
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. V63 251 (1995)
As < 50% of an administered dose of chloral hydrate was recovered as metabolites in urine, yet unknown biotransformation reactions may exist for chloral hydrate in humans.
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. V63 251 (1995)
For more Metabolism/Metabolites (Complete) data for CHLORAL HYDRATE (10 total), please visit the HSDB record page.
Chloral hydrate is a known human metabolite of Trichloroethylene.
S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560

8.5 Biological Half-Life

The plasma half-life of trichloroethanol, the active metabolite, is about 7 to 10 hours.
USP. Convention. USPDI - Drug Information for the Health Care Professional. 20th ed. Volume I. Micromedex, Inc. Englewood, CO., 2000. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 859
The average half-life of trichloroethanol glucuronide was 6.7 hr. The average plasma half-life for chloral hydrate metabolites was 8.2 hr; the half-life of the third chloral hydrate metabolite, trichloroacetic acid, was about four days, as it binds extensively to plasma proteins.
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. V63 251 (1995)
The plasma half-life for therapeutic doses of chloral hydrate is 4 to 5 min, whereas for trichloroethanol /a metabolite/ is 8 to 12 hr and for trichloroacetic acid /a metabolite/, 67 hr.
Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 586
This study was designed to characterize the kinetics of chloral hydrate (CH) metabolism, and the formation and elimination of trichloroacetate (TCA), dichloroacetate (DCA), trichloroethanol (TCOH), and trichloroethanol glucuronide (TCOG) in male B6C3F1 mice. Mice were dosed with 67.8, 678, and 2034 umol/kg of CH through the tail vein. ... After intravenous administration, CH rapidly disappeared from blood with a terminal half-life ranging from 5 to 24 min. ... The terminal half-lives of TCOH and TCOG were similar, ranging from 0.2 to 0.7 hr. ...
Abbas R et al; Drug Metab Dispos 24 (12): 1340-6 (1996)

8.6 Mechanism of Action

Chloral hydrate has CNS depressant effects similar to those of paraldehyde and the barbiturates. The mechanism of action of the drug is not completely known. The CNS depressant effect of chloral hydrate is believed to result mainly from its metabolite, trichloroethanol, although some animal studies have indicated that the rapid onset of sedation and hypnosis that chloral hydrate produces may be due to chloral hydrate itself and that the prolonged duration of action may be due to trichloroethanol.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 2610

8.7 Transformations

9 Use and Manufacturing

9.1 Uses

Sources/Uses
Used as a drug (sedative and hypnotic), a rubefacient and liniment, a glue peptizing agent, and a chemical intermediate; [HSDB] Formed as by-product of drinking water chlorination; [IPCS]
Industrial Processes with risk of exposure
As glue peptizing agent
Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. V11 913 (1980)
Manufacture of DDT
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 342
Medicine (sedative), manufacture of DDT, linaments.
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 271
Hypnotic ... possesses anticonvulsant and muscle relaxant activities.
Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V13 1083
For more Uses (Complete) data for CHLORAL HYDRATE (10 total), please visit the HSDB record page.

Use (kg) in Switzerland (2009): >250

Use (kg; approx.) in Germany (2009): >1000

Consumption (g per capita) in Switzerland (2009): 0.032

Consumption (g per capita; approx.) in Germany (2009): 0.012

Excretion rate: 1

Calculated removal (%): 45.5

9.1.1 Use Classification

Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients
Hazard Classes and Categories -> Carcinogens

9.2 Methods of Manufacturing

Made by adding required amt of water to trichloroacetaldehyde.
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 343
Insoluble chloral hydrate forms from the reaction of chloral with water.
Gerhartz, W. (exec ed.). Ullmann's Encyclopedia of Industrial Chemistry. 5th ed.Vol A1: Deerfield Beach, FL: VCH Publishers, 1985 to Present., p. VA6 533
Chloral hydrate is formed by adding one molecule of water to the carbonyl group of chloral (2,2,2-trichloroacetaldehyde).
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill, 2006., p. 420

9.3 Formulations / Preparations

Dosage Forms-Capsules: 250 and 500 mg, and 1 g; Elixir: 500 mg/5 mL; Suppositories: 325, 500, and 650 mg. Syrup: 250 and 500 mg/5 mL.
GENNARO. REMINGTON'S PHARM SCI 17TH ED 1985 p.1070
Noctec capsules contain 500 mg chloral hydrate per capsule, Noctec syrup contains 500 mg chloral hydrate per 5 mL
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 2610
Grade: Technical, USP
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 271
Chloropent injection; Intravenous anesthetic; Each mL contains: chloral hydrate 42.5 mg; magnesium sulfate 21.2 mg; pentobarbital 8.86 mg; ethyl alcohol 14.25%; propylene glycol 33.8%; purified water, qs (for cattle & horses)
Aronson, C.E. (ed.). Veterinary Pharmaceuticals and Biologicals, 1982-1983. Edwardsville, Kansas: Veterinary Medicine Publishing Co., 1983., p. 16/109
For more Formulations/Preparations (Complete) data for CHLORAL HYDRATE (7 total), please visit the HSDB record page.

9.4 U.S. Production

(1972) 1.14X10+10 G (ANHYDROUS CHLORAL)
SRI
Production volumes for non-confidential chemicals reported under the Inventory Update Rule.
Year
1986
Production Range (pounds)
10 thousand - 500 thousand
Year
1990
Production Range (pounds)
No Reports
Year
1994
Production Range (pounds)
10 thousand - 500 thousand
Year
1998
Production Range (pounds)
No Reports
Year
2002
Production Range (pounds)
No Reports
US EPA; Non-confidential Production Volume Information Submitted by Companies for Chemicals Under the 1986-2002 Inventory Update Rule (IUR). 1,1-Ethanediol, 2,2,2-trichloro- (302-17-0). Available from, as of March 6, 2008: https://www.epa.gov/oppt/iur/tools/data/2002-vol.html

9.5 U.S. Imports

(1972) 2.83X10+7 G
SRI
(1975) 4.8X10+7 G
SRI
(1984) 5.41X10+6 g
BUREAU OF THE CENSUS. U.S. IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS 1984 p.1-366
(1986) 1.03X10+5 lb
BUREAU OF THE CENSUS. U.S. IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS 1986 P.1-533

9.6 General Manufacturing Information

EPA TSCA Commercial Activity Status
1,1-Ethanediol, 2,2,2-trichloro-: ACTIVE
Street names for chloral hydrate principally reflect its mixture with alcohol, which enhances its action, so we have such well known terms as "knock-out drops" and "Mickey Finn."
Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 836
This is a controlled substance (depressant): 21 CFR, 1308.14
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 342
Disinfection by-product
US EPA; Controlling Disinfection By-Products /DBP/ and Microbial Contaminants in Drinking Water. Washington DC; US EPA/600/R-01/110. Available from, as of Dec 23, 2008: https://www.epa.gov/nrmrl/pubs/600r01110/600r01110chap3.pdf
In industrial exposures ... The small quantities which can be tolerated by inhalation are usually metabolized so rapidly that no anesthetic symptons occur.
Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V1 935

10 Identification

10.1 Analytic Laboratory Methods

Chloral hydrate in drugs: Spectrophotometric method. Quinaldine ethyl iodide reacts with chloral hydrate to produce stable blue cyanine dye with A max at about 605 nm. Other polychlorinated compounds do not interfere.
Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC: Association of Analytical Chemists, 1990, p. VI 562
OSW Method 8240B-W. Determination of Volatile Organics Compounds by Gas Chromatography/Mass Spectrometry (GC/MS).
USEPA/Office of Solid Waste (OSW); Test Methods for Evaluating Solid Waste, Physical/ Chemical Methods, SW-846, 3rd Edition, Final Update II, September (1994)
OSW Method 8240B-S. Determination of Volatile Organic Compounds by Gas Chromatography/Mass Spectrometry (GC/MS).
USEPA/Office of Solid Waste (OSW); Test Methods for Evaluating Solid Waste, Physical/ Chemical Methods, SW-846, 3rd Edition, Final Update II, September (1994)
OSW Method 8260A. Determination of Volatile Organic Compounds by Gas Chromatography/Mass Spectrometry (GC/MS): Capillary Column Technique.
USEPA/Office of Solid Waste (OSW); Test Methods for Evaluating Solid Waste, Physical/ Chemical Methods, SW-846, 3rd Edition, Final Update II, September (1994)
For more Analytic Laboratory Methods (Complete) data for CHLORAL HYDRATE (15 total), please visit the HSDB record page.

10.2 Clinical Laboratory Methods

SPECTROPHOTOMETRIC METHOD FOR ANALYSIS OF BLOOD AND URINE HAS BEEN USED TO QUANTIFY TRICHLOROETHANOL IN FATAL CHLORAL HYDRATE POISONINGS. A 4 ML BLOOD SAMPLE IS EXTRACTED AT THE PH OF THE BLOOD WITH ETHER. A REACTION PRODUCT IS FORMED DURING HEATING OF THE ETHER PHASE WITH PYRIDINE AND SODIUM HYDROXIDE. A SPECTRUM OF THE REACTION PRODUCT HAS MAXIMA AT 368 AND 530 NM.
MCBAY AJ ET AL; J ANAL TOXICOL 4 (2): 99-101 (1980)
Analyte: chloral hydrate; matrix: blood (plasma); procedure: high-performance liquid chromatography with ultraviolet detection at 237 nm; limit of quantitation: 7000 ng/mL
Gupta RN; J Chromatogr 500: 655-659 (1990). As cited in: Lunn G; HPLC and CE Methods for Pharmaceutical Analysis. CD-ROM. New York, NY: John Wiley & Sons (2000)
Analyte: chloral hydrate; matrix: microsomal incubation; procedure: high-performance liquid chromatography with ultraviolet detection at 330 nm
Ni YC et al; Drug Metab Dispos 24: 81-90 (1996). As cited in: Lunn G; HPLC and CE Methods for Pharmaceutical Analysis. CD-ROM. New York, NY: John Wiley & Sons (2000)

11 Safety and Hazards

11.1 Hazards Identification

11.1.1 GHS Classification

1 of 5
View All
Pictogram(s)
Acute Toxic
Irritant
Signal
Danger
GHS Hazard Statements

H301 (99%): Toxic if swallowed [Danger Acute toxicity, oral]

H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (99%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

Precautionary Statement Codes

P264, P264+P265, P270, P280, P301+P316, P302+P352, P305+P351+P338, P321, P330, P332+P317, P337+P317, P362+P364, 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 97 reports by companies from 4 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.

11.1.2 Hazard Classes and Categories

Acute Tox. 3 (99%)

Skin Irrit. 2 (100%)

Eye Irrit. 2 (99%)

Acute toxicity - category 3

Eye irritation - category 2

Skin irritation - category 2

11.1.3 Health Hazards

SYMPTOMS: Symptoms of exposure to this compound include general anesthesia, cardiac arrythmias and blood pressure depression. Other symptoms include hemorrhagic gastritis, enteritis, central nervous system depression, coma, severe respiratory depression, ventricular tachycardia and cardiac arrest. Dermatitis, swelling of the lids, hyperemia, edema of the conjuctiva and a sensation of irritation and tearing may also occur. Exposure may result in gastric irritation, rapid circulatory collapse, kidney and liver damage, heart damage, psychosis and leukopenia. Flatulence, abdominal distension, nausea, headache, giddiness, rashes and blood dyscrasias can occur.

ACUTE/CHRONIC HAZARDS: This compound is an irritant of the skin and eyes. When heated to decomposition it emits toxic fumes of chlorine. (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.

11.1.4 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.
Not combustible. Gives off irritating or toxic fumes (or gases) in a fire.

11.1.5 Hazards Summary

A skin, eye, and respiratory tract irritant; A CNS depressant; [ICSC] A skin and mucous membrane irritant; May cause eye injury; [HSDB] A skin and eye irritant; [eChemPortal: ERMA; ESIS] An irritant; [MSDSonline] Liver injury reported after lethal doses, but not after therapeutic doses; [INCHEM: CICADS]

11.1.6 Fire Potential

Combustible when exposed to heat or flame.
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 705

11.1.7 Skin, Eye, and Respiratory Irritations

... Chloral hydrate is irritating to the skin and mucous membranes and often causes gastric distress ...
World Health Organization/International Programme on Chemical Safety. Concise International Chemical Assessment Document No. 25 Chloral Hydrate p. 4-5 (2000)

11.2 First Aid Measures

Inhalation First Aid
Fresh air, rest. Artificial respiration may be needed. Refer immediately for medical attention.
Skin First Aid
Rinse skin with plenty of water or shower.
Eye First Aid
First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.
Ingestion First Aid
Rinse mouth. Do NOT induce vomiting. Refer immediately for medical attention.

11.2.1 First Aid

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

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

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

INGESTION: DO NOT INDUCE VOMITING. Volatile chemicals have a high risk of being aspirated into the victim's lungs during vomiting which increases the medical problems. 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. IMMEDIATELY transport the victim to a hospital. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

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

11.3 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.
In case of fire in the surroundings, use appropriate extinguishing media. In case of fire: keep drums, etc., cool by spraying with water.

11.4 Accidental Release Measures

11.4.1 Isolation and Evacuation

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]:

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)

11.4.2 Spillage Disposal

Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Carefully collect remainder. Then store and dispose of according to local regulations.

11.4.3 Disposal Methods

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
Chloral hydrate is a waste chemical stream constituent which may be subjected to ultimate disposal by controlled incineration. Preferably after mixing with another combustible fuel, care must be exercised to assure complete combustion to prevent the formation of phosgene; an acid scrubber is necessary to remove the halo acids produced.
USEPA; Engineering Handbook for Hazardous Waste Incineration EPA 68-03-3025 p.2-5 (1981)
The following wastewater treatment technology has been investigated for chloral hydrate: Concentration process: Solvent extraction.
USEPA; Management of Hazardous Waste Leachate, EPA Contract No.68-03-2766 p.E-6 (1982)

11.4.4 Preventive Measures

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

11.5 Handling and Storage

11.5.1 Nonfire Spill Response

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

STORAGE PRECAUTIONS: You should keep this material in a tightly closed container under an inert atmosphere, and store it at ambient temperatures. This compound is a Schedule IV DEA Controlled Substance and is to be stored according to State and Federal Regulations. Refer to Code of Federal Regulations Title 21 Part 1300 to End. (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.

11.5.2 Safe Storage

Separated from strong bases and food and feedstuffs.

11.5.3 Storage Conditions

Chloral hydrate oral solution should be stored in tight, light-resistant containers. Chloral hydrate capsules should be stored at 15-30 °C.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 2610

11.6 Exposure Control and Personal Protection

11.6.1 Inhalation Risk

A harmful contamination of the air will be reached rather slowly on evaporation of this substance at 20 °C.

11.6.2 Effects of Short Term Exposure

The substance is irritating to the eyes, skin and respiratory tract. The substance may cause effects on the central nervous system. This may result in disorientation, lowering of blood pressure and lowering of consciousness. Exposure at high levels could cause cardiac dysrhythmia and unconsciousness or death.

11.6.3 Effects of Long Term Exposure

The substance may have effects on the liver. This may result in addiction, behavioural effects and liver impairment. This substance is probably carcinogenic to humans. May cause heritable genetic damage to human germ cells.

11.6.4 Personal Protective Equipment (PPE)

RECOMMENDED RESPIRATOR: When working with this chemical, wear a NIOSH-approved full face chemical cartridge respirator equipped with the appropriate organic vapor cartridges. If that is not available, a half face respirator similarly equipped plus airtight goggles can be substituted. However, please note that half face respirators provide a substantially lower level of protection than do full face respirators. (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.

11.6.5 Preventions

Exposure Prevention
PREVENT DISPERSION OF DUST! IN ALL CASES CONSULT A DOCTOR!
Inhalation Prevention
Use local exhaust or breathing protection.
Skin Prevention
Protective gloves.
Eye Prevention
Wear safety spectacles or eye protection in combination with breathing protection if powder.
Ingestion Prevention
Do not eat, drink, or smoke during work. Wash hands before eating.

11.7 Stability and Reactivity

11.7.1 Air and Water Reactions

Water soluble.

11.7.2 Reactive Group

Alcohols and Polyols

Halogenated Organic Compounds

11.7.3 Reactivity Profile

CHLORAL HYDRATE is incompatible with alkalis, alkaline earth metals, alkali carbonates and soluble barbiturates. It is decomposed by sodium hydroxide. It reduces ammoniacal silver nitrate. It liquefies when triturated with an equal quantity of menthol, camphor or thymol. (NTP, 1992). Reaction of chloral hydrate with hydroxylamine produces toxic hydrogen cyanide gas, Org. Synth., 1941, Vol. 1, 377.
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.

11.8 Transport Information

11.8.1 DOT Label

Poison

11.8.2 Packaging and Labelling

Do not transport with food and feedstuffs.

11.8.3 EC Classification

Symbol: T; R: 25-36/38; S: (1/2)-25-45

11.8.4 UN Classification

UN Hazard Class: 6.1

11.9 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: 1,1-Ethanediol, 2,2,2-trichloro-
California Safe Cosmetics Program (CSCP) Reportable Ingredient

Hazard Traits - Carcinogenicity; Neurotoxicity

Authoritative List - IARC Carcinogens - 2A; IRIS Neurotoxicants; Prop 65

Report - regardless of intended function of ingredient in the product

DEA Controlled Substances
DEA schedule IV controlled substance
REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
Chloral hydrate: Does not have an individual approval but may be used under an appropriate group standard

11.9.1 Federal Drinking Water Guidelines

EPA 60 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

11.9.2 State Drinking Water Guidelines

(ME) MAINE 70 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

11.9.3 FDA Requirements

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: chloral hydrate is included in external analgesic drug products - analgesic and anesthetic drug products.
21 CFR 310.545((a) (10) (i) (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of July 30, 2008: https://www.ecfr.gov
Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: chloral hydrate is included in external analgesic drug products - counter irritant drug products.
21 CFR 310.545((a) (10) (ii) (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of July 30, 2008: https://www.ecfr.gov
Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: chloral hydrate is included in external analgesic drug products - fever blister and cold sore treatment drug products.
21 CFR 310.545((a) (10) (v) (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of July 30, 2008: https://www.ecfr.gov
Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: chloral hydrate is included in external analgesic drug products - poison ivy, poison oak, and poison sumac drug products.
21 CFR 310.545((a) (10) (vii) (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of July 30, 2008: https://www.ecfr.gov
For more FDA Requirements (Complete) data for CHLORAL HYDRATE (8 total), please visit the HSDB record page.

11.10 Other Safety Information

11.10.1 Other Hazardous Reactions

Slowly volatilizes when exposed to air.
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993, p. 257

11.10.2 Special Reports

DHHS/NIDA; Research Monograph Series 52: Testing Drugs for Physical Dependence Potential and Abuse Liability (1984) DHHS Pub No. (ADM)87-1332
DHHS/NIDA; Research Monograph Series 54: Mechanisms of Tolerance and Dependence (1984) DHHS Pub No. (ADM)88-1330
DHHS/NIDA; Research Monograph Series 56: Etiology of Drug Abuse: Implications for Prevention (1987) DHHS Pub No. (ADM)87-1335
DHHS/NIDA; Research Monograph Series 59: Current Research on the Consequences of Maternal Drug Abuse (1985) DHHS Pub No. (ADM)85-1400
For more Special Reports (Complete) data for CHLORAL HYDRATE (9 total), please visit the HSDB record page.

12 Toxicity

12.1 Toxicological Information

12.1.1 Toxicity Summary

IDENTIFICATION: Chloral hydrate is used in human and veterinary medicine as a sedative and hypnotic drug. HUMAN EXPOSURE: The major route of exposure of the general public is from drinking water, as chloral hydrate is formed when drinking water is disinfected with chlorine. Since chloral hydrate is a metabolite of trichloroethylene and tetrachloroethylene, people will be exposed to chloral hydrate if they are exposed to these chemicals. The public will be exposed to the metabolites of chloral hydrate, trichloroacetic acid and dichloroacetic acid, as these chemicals are also formed when drinking water is disinfected with chlorine. In its use as a sedative for people, the metabolite trichloroethanol is responsible for the pharmacologic effect. No quantitative information is available from occupational exposure. Chloral hydrate is irritating to the skin and mucous membranes and often causes gastric distress, nausea and vomiting at the recommended clinical dose. An overdose of this drug produces (in order of progression) ataxia, lethargy, deep coma, respiratory depression, hypotension and cardiac arrhythmia. There is some evidence of hepatic injury in people surviving near lethal acute overdoses. Despite its long use in human medicine there is no published information on toxicity in controlled studies in humans following extended exposure. Chloral hydrate is completely absorbed and rapidly metabolized following oral admin. In humans the half-life of trichloroethanol and its glucuronide is about 8 hr; the half-life of trichloroacetic acid is about 4 days. Some data suggest that half-life of trichloroethanol is incr several fold in pre-term and full term infants compared with toddlers and adults. The major routes of excretion of the metabolites of chloral hydrate is elimination in the urine.Chloral hydrate and its metabolites have been found in milk from women treated with this drug. There no carcinogenicity data from humans. ANIMAL STUDIES: Acute administration of chloral hydrate to mice causes loss of coordination (ataxia). A 90 day study in mice shows no evidence of behavioral changes or other neurotoxicity. Chronic studies in rats and mice show no evidence of behavioral changes and no evidence of histopathological changes in the nervous tissue. A slight detriment in humoral immunity was observed following exposure of mice for 90 days. This drug has been tested for developmental effects in rats and mice. No structural abnormalities were observed. In a neurodevelopmental study in mice, there was a slight effect in passive avoidance learning. Two bioassays in rats show no incr in tumors at any site. Three separate bioassays in male mice showed an incr incidence of liver tumors. The most definitive of these studies shows an incr incidence and multiplicity of liver tumors at each of three exposures. These data show suggestive evidence of carcinogenicity in male mice but are not considered appropriate for conducting a human health risk assessment with a linear response at low exposure. A variety of results show that chloral hydrate is a weak gene mutagen and clastogen. Chloral hydrate induces aneuploidy in a wide variety of cell types.
World Health Organization/International Programme on Chemical Safety. Concise International Chemical Assessment Document No. 25 Chloral Hydrate p. 4-5 (2000)

12.1.2 EPA IRIS Information

Toxicity Summary
EPA IRIS Summary PDF (Update: Sep-15-2000 )
Critical Effect Systems

Gastrointestinal

Nervous

Reference Dose (RfD), chronic
1 x 10 ^-1 mg/kg-day

12.1.3 RAIS Toxicity Values

Oral Chronic Reference Dose (RfDoc) (mg/kg-day)
0.1
Oral Chronic Reference Dose Reference
IRIS Current

12.1.4 Hepatotoxicity

Chloral hydrate has been in clinical use for many decades and has not been linked to serum enzyme elevations during therapy or instances of clinically apparent liver injury. While prospective studies of the effects of chloral hydrate on liver tests have not been done, the absence of reported instances of liver injury attributable to chloral hydrate suggests that it has little or no hepatic toxicity. Chloral hydrate has been linked to hypersensitivity reactions such as rash, fever and eosinophilia. Chloral hydrate also has major drug-drug interactions with oral anticoagulants, antidepressants and alcohol. In patients with cirrhosis and hepatic decompensation, chloral hydrate can trigger or worsen hepatic encephalopathy.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Drug Class: Sedatives and Hypnotics, Miscellaneous

12.1.5 Evidence for Carcinogenicity

WEIGHT-OF-EVIDENCE CHARACTERIZATION: Under the 1986 cancer guidelines (EPA), chloral hydrate is assigned to Group C, possible human carcinogen. Under the 1996 proposed guidelines (EPA) for carcinogen risk assessment, chloral hydrate shows suggestive evidence of human carcinogenicity by the oral route of exposure. There are no carcinogenicity data from humans. Two bioassays in rats in which chloral hydrate was administered by drinking water show no increase in tumors at any site. Because only minimal toxicity was observed in the livers of the rats in these bioassays, the tests were not conducted at the maximum tolerated dose. A chronic bioassay in female mice showed a slight increase in the severity grade of hyperplasia and a slight increase in the incidence of adenoma in the pituatary gland pars distalis at the highest exposure tested. There is some evidence that chloral hydrate causes hepatocellular tumors in male mice. An earlier study showing an increase of hepatocellular adenomas or trabecular carcinomas following a single bolus exposure could not be confirmed in a study using more animals and higher exposures. Three separate 2-year bioassays in male mice show an increased incidence of hepatocellular adenoma or carcinoma. There are no data identifying a lesion that is a precursor to the hepatocellular tumors. The strain of mice used has a very high spontaneous incidence of hepatocellular tumors. Two of the matabolites of chloral hydrate, trichloroacetic acid and dichloroacetic acid, have been shown to cause hepatocellular tumors in rodents. Trichloroacetic acid causes hepatocellular tumors only in mice. Dichloroacetic acid causes hepatocellular tumors in both rats and mice. There is an extensive database on genetic toxicity. A variety of results show that chloral hydrate is a weak gene mutagen and clastogen. Chloral hydrate induces aneuploidy in a wide variety of cell types. These latter effects are thought to arise by disruption of the spindle apparatus. A high concentration of chloral hydrate is required to cause observable effects. Although these data suggest that genotoxicity may play a role in the toxicity of chloral hydrate, the data indicate that these effects require concentrations that are unlikely to occur under physiological conditions at the exposures typically encountered from the environment. Collectively, these data provide suggestive evidence of carcinogenicity, but the weight of evidence is not sufficient to conduct a risk assessment assuming a linear response at low exposure. HUMAN CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: Limited.
U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS). Summary on Chloral Hydrate (302-17-0). Available from, as of September 15, 2000: https://www.epa.gov/iris/
Evaluation: There is inadequate evidence in humans for the carcinogenicity of chloral and chloral hydrate. There is inadequate evidence in experimental animals for the carcinogenicity of chloral. There is limited evidence in experimental animals for the carcinogenicity of chloral hydrate. Overall evaluation: Chloral and chloral hydrate are not classifiable as to their carcinogenicity to humans (Group 3).
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. 63 262 (1995)

12.1.6 Carcinogen Classification

IARC Carcinogenic Agent
Chloral hydrate
IARC Carcinogenic Classes
Group 2A: Probably carcinogenic to humans
IARC Monographs

Volume 63: (1995) Dry Cleaning, Some Chlorinated Solvents and Other Industrial Chemicals

Volume 84: (2004) Some Drinking-water Disinfectants and Contaminants, including Arsenic

Volume 106: (2014) Trichloroethylene, Tetrachloroethylene, and Some Other Chlorinated Agents

12.1.7 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Short-term or occasional use of chloral hydrate during breastfeeding is unlikely to adversely affect the breastfed infant, especially if the infant is older than 2 months. Because the active metabolite of chloral hydrate has a long half-life, other sedative-hypnotics are preferred for long-term use during breastfeeding, especially while nursing a neonate or preterm infant. Monitor the infant for sedation, poor feeding and poor weight gain.

◉ Effects in Breastfed Infants

An old review article states that if an infant is breastfed within 45 minutes of a maternal dose of chloral hydrate while she is taking 1.5 grams twice daily, the infant will fall into a prolonged, restless sleep.

A single maternal rectal dose of 1.3 grams chloral hydrate in 50 women was stated to not adversely affect their breastfed newborn infants.

Minimal morning sedation occurred in a 5-month-old breastfed infant whose mother was taking 1.3 grams of dichloralphenazone (equivalent to about 1 gram of chloral hydrate) every evening plus chlorpromazine 100 mg 3 times daily. The infant's overall development was said to be normal at 3 months of age.

◉ Effects on Lactation and Breastmilk

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

12.1.8 Exposure Routes

The substance can be absorbed into the body by inhalation of its vapour or dust and by ingestion.

12.1.9 Symptoms

Inhalation Exposure
Cough. Confusion. Drowsiness. Nausea. Unconsciousness.
Skin Exposure
Redness.
Ingestion Exposure
Abdominal pain. Vomiting. Further see Inhalation.

12.1.10 Target Organs

Gastrointestinal

Nervous

12.1.11 Adverse Effects

Neurotoxin - Acute solvent syndrome

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

IARC Carcinogen - Class 2: International Agency for Research on Cancer classifies chemicals as probable (2a), or possible (2b) human carcinogens.

12.1.12 Acute Effects

12.1.13 Interactions

Prolonged concurrent use /with other addictive medications especially CNS depressants with habituating potential/ may increase the risk of habituation; caution is recommended.
USP. Convention. USPDI - Drug Information for the Health Care Professional. 20th ed. Volume I. Micromedex, Inc. Englewood, CO., 2000. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 860
Concurrent use /with alcohol or other CNS depression-producing medications/ may increase the CNS depressant effect of either these medications or chloral hydrate; caution is recommended and dosage of one or both agents should be reduced.
USP. Convention. USPDI - Drug Information for the Health Care Professional. 20th ed. Volume I. Micromedex, Inc. Englewood, CO., 2000. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 860
Hypoprothrombinemic effects may be increased when these medications /coumarin- or indandione-derivative anticoagulants/ are used concurrently with chloral hydrate, particularly during the first 2 weeks of concurrent therapy, because of displacement of the anticoagulant from its plasma protein binding sites; with continued concurrent use, anticoagulant activity may return to baseline level or be decreased; frequent prothrombin-time determinations may be required, especially during initiation of chloral hydrate therapy, to determine if dosage adjustment of the anticoagulant is necessary.
USP. Convention. USPDI - Drug Information for the Health Care Professional. 20th ed. Volume I. Micromedex, Inc. Englewood, CO., 2000. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 859
Administration of chloral hydrate followed by intravenous furosemide within 24 hours may result in diaphoresis, hot flashes, and variable blood pressure, including hypertension, due to a hypermetabolic state caused by displacement of thyroxine from its bound state.
USP. Convention. USPDI - Drug Information for the Health Care Professional. 20th ed. Volume I. Micromedex, Inc. Englewood, CO., 2000. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 860
For more Interactions (Complete) data for CHLORAL HYDRATE (13 total), please visit the HSDB record page.

12.1.14 Antidote and Emergency Treatment

Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. Treat coma, hypothermia, hypotension, and pulmonary edema if they occur. Monitor patients for at least 6 hours after ingestion, because delayed absorption may occur. Patients with chloral hydrate ingestion should be monitored 18 to 24 hours because of the risk of cardiac arrhythmias. Tachyarrhythmias caused by myocardial sensitization may be treated with propranolol or esmolol. ... Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. ... /Sedative-Hypnotic Agents/
Olson, K.R. (Ed.); Poisoning & Drug Overdose. 5th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2007., p. 338
Since chloral hydrate causes serious arrhythmias as well as respiratory depression, all significant ingestions should have careful evaluation of respiratory status, an intravenous line, oxygen, and a cardiac monitor.
Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 588
Hemodialysis effectively removes the active metabolite trichloroethanol at a rate of 120 to 162 mL/min. The plasma half-life decreased from 35 to 6 hours after hemodialysis of a patient who ingested 38 g chloral hydrate. The major indications are the failure of the patient to respond to supportive care or the presence of lethal drug levels. Resin hemoperfusion also effectively removes trichloroethanol at a rate similar to that of hemodialysis. Forced diuresis is ineffective. Exchange transfusion in an infant was not useful in removing substantial amounts of trichloroethanol.
Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 588
Hypotension should be treated with fluid challenges and alpha-adrenergic vasopressors (eg, levarterenol). Ventricular arrhythmias should be treated with lidocaine and then a beta-blocker drug (eg, propranolol). Watch for development of gastrointestinal hemorrhage, hepatic and renal dysfunction, and aspiration pneumonia as well as withdrawal symptoms.
Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 588

12.1.15 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ To test the hypothesis that chloral hydrate can cause direct hyperbilirubinemia in the newborn, two retrospective analyses of the medical records of patients admitted to a neonatal intensive care unit during an 18 month period were conducted. In one analysis of 14 newborns who had nonhemolytic direct hyperbilirubinemia, 10 did not have an identified cause of direct hyperbilirubinemia, and all 10 had received chloral hydrate. In the second retrospective study, all newborns who received chloral hydrate were divided into groups according to whether or not direct hyperbilirubinemia had developed. The newborns with direct hyperbilirubinemia, compared with those without direct hyperbilirubinemia, had received a higher total accumulative dose of chloral hydrate (1035 + or - 286 vs 183 + or - 33 mg/kg + or - 1 SEM, respectively). In the patients with direct hyperbilirubinemia, the direct serum bilirubin levels increased 6.8 + or - 0.8 days after the chloral hydrate administration began and resolved after the chloral hydrate was discontinued or markedly decreased. These data support the hypothesis that prolonged use of chloral hydrate in newborns can be associated with direct hyperbilirubinemia.
Lambert GH et al; Pediatrics 86 (2): 277-81 (1990)
/HUMAN EXPOSURE STUDIES/ Chloral hydrate is commonly used to sedate children before computed tomography. However, no prospective study has been published of the safety and efficacy of chloral hydrate at high dose levels for children undergoing computed tomography. High dose levels of oral chloral hydrate /are defined as/ 80-100 mg/kg, with a maximum total dose of 2 g. High dose chloral hydrate sedation was administered orally to 295 children for 326 computed tomographic examinations. Adverse reactions occurred in 7% of the children, with vomiting being the most common (4.3% of children). Hyperactivity and respiratory symptoms each occurred in less than 2% of children. Prolonged sedation ( >2 hr) was not encountered in this series. ...
Greenberg SB et al; J Comput Assist Tomogr 15 (3): 467-9 (1991)
/SIGNS AND SYMPTOMS/ ... In dangerous overdosage there may be mydriasis. Moderate doses ... affect eye movements, particularly interfering with convergence, and sometimes causing ptosis. ... Chloral hydrate ... may cause swelling of lids, hyperemia and edema of the conjunctivae, plus a sensation of irritation and tearing.
Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 199
/SIGNS AND SYMPTOMS/ Signs and symptoms of severe overdose are similar to those of barbiturate overdose, with respiratory depression and cardiovascular instability presenting the main threats to life. Symptoms begin with ataxia and lethargy and progress to deep coma often within 1 to 2 hours of ingestion. Pupils usually are miotic but dilate in the deeper stages of coma. The peculiar pearlike odor of chloral hydrate may help distinguish it from other sedative-hypnotics.
Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 587
For more Human Toxicity Excerpts (Complete) data for CHLORAL HYDRATE (22 total), please visit the HSDB record page.

12.1.16 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ The oral lethal dose in the horse is ... 100-150 g. ... Harmful effects are not seen when the drug is given iv until an amount equivalent to 370 mg/kg has been administered. The clinical signs observed in horses receiving toxic doses of chloral hydrate include relaxation of the voluntary muscles, staggering, dilatation of the pupils, lowering of the body temperature, and finally a condition of deep stupor. Death results from respiratory failure
Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988., p. 107
/LABORATORY ANIMALS: Acute Exposure/ Despite precaution, perivascular injection of chloral hydrate solution sometimes occurs, and it is quite irritating to the tissues, especially in the horse. Severe pain, swelling, and necrosis of tissues result, including sloughing and destruction of the external jugular vein. ... When higher concentration are injected at the usual rate until the desired effect is observed clinically, the animal will exhibit further depression within 10-15 minutes after injection is stopped.
Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University Press, 1982., p. 231
/LABORATORY ANIMALS: Acute Exposure/ Induction of gastric mucosal injury by chloral hydrate was studied in rats. Adult male rats, strain not specified, were injected ip with 0, 200, 300, 400, or 500 mg/kg chloral hydrate or sc with 0, 400, 500, 600, or 700 mg/kg chloral hydrate. Selected rats were killed 0, 3, 6, 12, or 24 hr after injection and the stomachs were removed. Strips of the gastric wall were cut from the forestomach to the pylorus through the entire glandular mucosa and examined for mucosal ulcers. Ulcer indices, the total length of all mucosal ulcers per rat, were computed. Ulcers were first detected 6 hr after dosing. The maximum values of the ulcer index, 12.6 mm for ip injection and 6.8 mm after sc injection, occurred at 12 hr. The minimum effective dose for inducing ulcers was 400 mg/kg for ip injection and 600 mg/kg for sc injection. In ip doses of 500 mg/kg or greater and sc doses of 700 mg/kg or greater caused mortality within 12 hr. The authors conclude that chloral hydrate induces gastric ulcers in rats when injected ip or sc. The mechanism of ulcer induction is unknown.
Ogino K et al; Toxicol Lett 52 (2): 129-133 (1990)
/LABORATORY ANIMALS: Acute Exposure/ Exposure of female CD1 mice to 100 ppm [603 mg/cu m] chloral for 6 hr induced deep anesthesia, which was fully reversible on cessation of exposure. Vacuolation of lung Clara cells, alveolar necrosis, desquamation of the bronchiolar epithelium and alveolar edema were observed. Cytochrome P450 enzyme activity was reduced, although the activities of ethoxycoumarin O-diethylase and glutathione S-transferase were unaffected
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. V63 252 (1995)
For more Non-Human Toxicity Excerpts (Complete) data for CHLORAL HYDRATE (28 total), please visit the HSDB record page.

12.1.17 Non-Human Toxicity Values

LD50 Rat oral 200-500 mg/kg
Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 837
LD50 Horse oral 100-150 g
Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988., p. 107
LD50 Rat oral 479 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. 705
LD50 Rat dermal 3030 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. 705
For more Non-Human Toxicity Values (Complete) data for CHLORAL HYDRATE (8 total), please visit the HSDB record page.

12.1.18 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=302-17-0]

12.1.19 National Toxicology Program Studies

2-YEAR STUDY: Groups of female B6C3F1 mice (regimens A, B, C and D) and groups of male B6C3F1 mice (regimen E) recieved chloral hydrate in distilled water by gavage; control groups recieved distilled water only. In regimen A, groups of 48 female mice received 0, 25, 50 or 100 mg chloral hydrate/kg body weight 5 days/wk for 104 wk beginning when they were 28 days old. In regimen B, 24 female mice received 0 mg/kg and three groups of 48 female mice 100 mg/kg 5 days/wk when they were 28 days old.Eight mice from the 0 and 100 mg/kg groups were killed at 3, 6 or 12 months. The remaining mice were held without further dosing for the duration of the 2 yr study. In regimen C, groups of 48 female mice received a single dose of 0, 10, 25 or 50 mg/kg when they were 28 days old and were held for 104 wk. In regimens D and E groups of 48 female and 48 male mice, respectively, received a single dose of 0, 10, 25, 50 mg/kg when they were 15 days old and were held for 104 wk. ... CONCLUSIONS: Under the conditions of this 2 yr gavage study, there was equivocal evidence of carcinogenic activity of chloral hydrate in female B6C3F1 mice treated continuously for 2 yr based on the incr incidences of pituitary gland pars distalis adenomas. No incr incidences of neoplams were seen in female B6C3F1 mice that recieved a single dose of chloral hydrate at 15 or 28 days of age or in male B6C3F1 mice that received a single dose of chloral hydrate at 15 days of age. No hepatocarcinogenicity was seen under any dosing condition.
Toxicology & Carcinogenesis Studies of Chloral hydrate in B6C3F1 Mice p.8-9 Technical Report Series No. 502 (2002) NIH Publication No. 02-4436 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709
GENETIC TOXICOLOGY: Chloral hydrate was mutagenic in vitro and in vivo. It induced mutations in Salmonella typhimurium strain TA100, with and without liver S9 activation; an equivocal response was obtained in S. typhimurium strain TA98 in the absence of S9, and no mutagenicity was detected with strain TA1535 or TA1537, with or without S9. Chloral hydrate was shown to produce chromosomal damage in mammalian cells. It induced significant increases in sister chromatid exchanges and chromosomal aberrations in cultured Chinese hamster ovary cells, with and without S9. Results of sexlinked recessive lethal (SLRL) tests in Drosophila melanogaster were inconclusive. Chloral hydrate, administered by feeding, produced an inconclusive increase in SLRL mutations in the germ cells of male flies. Results of an in vivo mouse bone marrow micronucleus test with chloral hydrate were positive.
Toxicology & Carcinogenesis Studies of Chloral hydrate in B6C3F1 Mice p.8-9 Technical Report Series No. 502 (2002) NIH Publication No. 02-4436 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709
2-YEAR STUDY IN MALE MICE: Groups of 120 male mice received chloral hydrate in distilled water by gavage at doses of 0, 25, 50, or 100 mg/kg 5 days per week for 104 to 105 weeks. Each dose group was divided into two dietary groups of 60 mice. The ad libitum-fed mice had free access to feed, and the dietary-controlled mice received feed in measured daily amounts calculated to maintain body weight on a previously computed idealized body weight curve. Twelve mice from each diet and dose group were evaluated at 15 months. ... CONCLUSIONS Under the conditions used in this 2-year gavage study, there was some evidence of carcinogenic activity of chloral hydrate in male B6C3F1 mice based on increased incidences of hepatocellular adenoma or carcinoma (combined) in ad libitum-fed mice and on increased incidences of hepatocellular carcinoma in dietary-controlled mice. In the dietary-controlled mice, induction of enzymes associated with peroxisome proliferation was observed at higher doses.
Toxicology & Carcinogenesis Studies of Chloral hydrate (ad libitum and dietary controlled) (Cas no. 302-17-0) in male B6C3F1 mice (gavage study) Technical Report Series No. 503 (2002) NIH Publication No. 03-4437 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709
For the range-finding studies, groups of eight male and eight female F344/N Nctr BR rats and B6C3F /Nctr BR 1 (C57BL/6NXC3H/HeN MTV ) mice were administered 0, 50, 100, 200, 400, or 800 mg chloral hydrate per -kg body weight in water by gavage 5 days per week for 17 days (rats) or 16 days (mice) for a total of 12 doses. One male rat receiving 800 mg/kg died after five doses. Two 800 mg/kg female rats died after dosing ended but before study termination. One male mouse in each group except the 400 mg/kg group died before the end of the study. Two 800 mg/kg female mice also died before the end of the study. The final mean body weight of 800 mg/kg male rats and the mean body weight gains of 400 and 800 mg/kg males were significantly less than those of the vehicle controls. The mean body weight gains of all groups of dosed male mice were significantly greater than that of the vehicle control group. The only clinical finding in rats and mice attributed to chloral hydrate treatment was light sedation in the 400 mg/kg groups and heavy sedation in the 800 mg/kg groups; sedation subsided within 30 minutes or 3 hours, respectively. The liver weights of 400 mg/kg male mice and 800 mg/kg male and female mice were significantly greater than those of the vehicle control groups. No chemical-related lesions were observed in rats or mice. ... In summary, due to the absence of chloral hydrate-induced histopathologic lesions in rats and mice, no-observed-adverse-effect levels (NOAELs) were based on body weights of rats and liver weights of mice. The NOAELs for rats and mice were 200 mg/kg.
NTP Technical Report on the Toxicity and Metabolism Studies of Chloral Hydrate (CAS No. 302-17-0) Administered by Gavage to F344/N Rats and B6C3F1 Mice. Technical Report Series No. 59 (1999). U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Available from: https://ntp.niehs.nih.gov/index.cfm?objectid=072DC149-B185-12F5-3E0C991CCBEDE100
For more National Toxicology Program Studies (Complete) data for CHLORAL HYDRATE (6 total), please visit the HSDB record page.

12.1.20 Populations at Special Risk

The margin of safety is too narrow to permit the drug to be used as a general anesthetic agent. ... In therapeutic doses, chloral hydrate has little effect on respiration and blood pressure. Toxic doses produce severe respiratory depression and hypotension. ... Chloral hydrate is contraindicated in patients with marked hepatic or renal impairment, and it should perhaps be avoided in patients with severe cardiac disease. If gastritis is present, the drug should not be given orally but may be admin in olive oil as a retention enema.
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 364

12.2 Ecological Information

12.2.1 Ecotoxicity Values

EC50; Species: Daphnia magna (Water flea); Conditions: freshwater; pH 8; Concentration: 630 mg/L for 24 hr; Effect: behavior, equilibrium /Conditions of bioassay not specified in source examined/
Bringmann G, Kuehn R; Z Wasser-Abwasser-Forsch 15 (1): 1-6 (1982) Available from, as of June 26, 2008
EC50; Species: Daphnia magna (Water flea); Conditions: freshwater; Concentration: 500 mg/L for 48 hr; Effect: intoxication, immobilization /Conditions of bioassay not specified in source examined/
Bringmann G, Meinck F; Gesundheits-Ingenieur 85: 229-60 (1964) Available from, as of June 26, 2008
LC50; Species: Daphnia magna (Water flea, age < or =24 hr); Conditions: freshwater; static, 20-22 °C, pH 7.6-7.7; Concentration: 510 mg/L for 24 hr
Bringmann G, Kuhn R; Z Wasser-Abwasser-Forsch 10 (5): 161-6 (1977) Available from, as of June 26, 2008
LC50; Species: Leuciscus idus melanotus (Carp); Conditions: freshwater; Concentration: 1720 mg/L for 48 hr /Conditions of bioassay not specified in source examined/
Bringmann G, Kuhn R; Z Wasser-Abwasser-Forsch 10 (5): 161-6 (1977) Available from, as of June 26, 2008

12.2.2 US EPA Regional Screening Levels for Chemical Contaminants

1 of 2
Resident Soil (mg/kg)
1.30e+06
Industrial Soil (mg/kg)
5.40e+06
Resident Air (ug/m3)
9.40e-01
Industrial Air (ug/m3)
3.90e+00
MCL (ug/L)
5.00e+00
Chronic Inhalation Reference Concentration (mg/m3)
9.00e-04
Volatile
Volatile
Mutagen
Mutagen
Fraction of Contaminant Absorbed in Gastrointestinal Tract
1
2 of 2
Resident Soil (mg/kg)
7.80e+03
Industrial Soil (mg/kg)
1.20e+05
Tapwater (ug/L)
2.00e+03
MCL (ug/L)
5.00e+00
Risk-based SSL (mg/kg)
4.00e-01
Chronic Oral Reference Dose (mg/kg-day)
1.00e-01
Volatile
Volatile
Mutagen
Mutagen
Fraction of Contaminant Absorbed in Gastrointestinal Tract
1

12.2.3 US EPA Regional Removal Management Levels for Chemical Contaminants

1 of 2
Resident Soil (mg/kg)
3.80e+06
Industrial Soil (mg/kg)
1.60e+07
Resident Air (ug/m3)
2.80e+00
Industrial Air (ug/m3)
1.20e+01
MCL (ug/L)
5.00e+00
Chronic Inhalation Reference Concentration (mg/m3)
9.00e-04
Volatile
Volatile
Mutagen
Mutagen
Fraction of Contaminant Absorbed in Gastrointestinal Tract
1
2 of 2
Resident Soil (mg/kg)
2.30e+04
Industrial Soil (mg/kg)
3.50e+05
Tapwater (ug/L)
5.90e+03
MCL (ug/L)
5.00e+00
Chronic Oral Reference Dose (mg/kg-day)
1.00e-01
Volatile
Volatile
Mutagen
Mutagen
Fraction of Contaminant Absorbed in Gastrointestinal Tract
1

12.2.4 ICSC Environmental Data

This substance may be hazardous to the environment. Special attention should be given to aquatic organisms.

12.2.5 Environmental Fate / Exposure Summary

Chloral hydrate is a disinfection by-product formed as a result of water treatment using chlorine with ozone or chloramine with ozone which may result in its release to the environment through various waste streams. Chloral hydrate's production in organic synthesis and use as a sedative may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 15 mm Hg at 25 °C indicates chloral hydrate will exist solely as a vapor in the atmosphere. Vapor-phase chloral hydrate will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 8 days. The related aldehyde chloral is readily photolyzed in sunlight based on its atmospheric half-life of 4.5-6 hours; therefore, atmospheric photolysis of chloral hydrate may be a major degradation pathway. If released to soil, chloral hydrate is expected to have high mobility based upon an estimated Koc of 82. Volatilization from moist soil surfaces is expected to be an important fate process based upon an estimated Henry's Law constant of 5.7X10-9 atm-cu m/mole. Biodegradation data for chloral hydrate were not available. In water, chloral hydrate is formed from the exothermic reaction of chloral with water, in which chloral hydrate is in equilibrium. Chloral hydrate hydrolyzes to form chloroform at high pH. Chloral hydrate is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Chloral hydrate hydrolyzes to form chloroform at high pH. Occupational exposure to chloral hydrate may occur through inhalation and dermal contact with this compound at workplaces where chloral hydrate is produced or used. Monitoring data indicate that the general population may be exposed to chloral hydrate via ingestion of chlorinated drinking water, and dermal contact with this compound when swimming in chlorinated pools; limited exposure is expected from its use as a sedative. (SRC)

12.2.6 Artificial Pollution Sources

Chloral hydrate is a disinfection by-product formed as a result of water treatment using chlorine with ozone or chloramine with ozone(1) which may result in its release to the environment through various waste streams(SRC). Chloral hydrate's production in organic synthesis(2) and use as a sedative(3) may result in its release to the environment through various waste streams(SRC).
(1) Richardson SD et al; Environ Sci Technol 33: 3368-77 (1999)
(2) Verschueren K; Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY., 1: 452 (2001)
(3) O'Neil MJ, ed; The Merck Index. 14th ed., Whitehouse Station, NJ: Merck and Co., Inc., p. 342 (2006)

12.2.7 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 82(SRC), determined from a log Kow of 0.99(2) and a regression-derived equation(3), indicates that chloral hydrate is expected to have high mobility in soil(SRC). Volatilization of chloral hydrate from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.7X10-9 atm-cu m/mole(SRC) derived from its vapor pressure, 15 mm Hg(4), and water solubility, 7.93X10+5 mg/L(5). Chloral hydrate is expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). Biodegradation data for chloral hydrate were not available(5).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 4 (1995)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9 (1990)
(4) Perry RH, Green D; Perry's Chemical Engineers's Handbook. Physical and Chemical Data. New York, NY: McGraw-Hill 6th ed (1984)
(5) Yalkowsky SH, He Y; Handbook of Aqueous Solubility Data. CRC Press LLC, Boca Raton, FL. p. 21 (2003)
(6) van Argteren MH et al; Handbook on Biodegradation and Biological Treatment of Hazardous Organic Compounds. Kluwer Acad Pub, Norwell, MA (1998)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 82(SRC), determined from a log Kow of 0.99(2) and a regression-derived equation(3), indicates that chloral hydrate is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 4.1X10-9 atm-cu m/mole(SRC), derived from its vapor pressure, 15 mm Hg(4), and water solubility, 7.93X10+5 mg/L(5). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 12 days and 88 days, respectively(SRC). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data for chloral hydrate were not available(8).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 4 (1995)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9, 15-1 to 15-29 (1990)
(4) Perry RH, Green D; Perry's Chemical Engineers's Handbook. Physical and Chemical Data. New York, NY: McGraw-Hill 6th ed (1984)
(5) Yalkowsky SH, He Y; Handbook of Aqueous Solubility Data. CRC Press LLC, Boca Raton, FL. p. 21 (2003) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(6) Franke C et al; Chemosphere 29: 1501-14 (1994)
(7) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
(8) van Argteren MH et al; Handbook on Biodegradation and Biological Treatment of Hazardous Organic Compounds. Kluwer Acad Pub, Norwell, MA (1998)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), chloral hydrate, which has a vapor pressure of 15 mm Hg at 25 deg(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase chloral hydrate is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 8 days(SRC), calculated from its rate constant of 1.9X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). The related aldehyde chloral is readily photolyzed in sunlight based on an atmospheric half-life of 4.5-6 hours for this compound under conditions representing the solar flux during summer months(4).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Perry RH, Green D; Perry's Chemical Engineers's Handbook. Physical and Chemical Data. New York, NY: McGraw-Hill 6th ed (1984)
(3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(4) Wenger JC et al; Environ Sci Technol 38: 831-7 (2004)

12.2.8 Environmental Biodegradation

AEROBIC: Biodegradation data for chloral hydrate were not available(1).
(1) van Argteren MH et al; Handbook on Biodegradation and Biological Treatment of Hazardous Organic Compounds. Kluwer Acad Pub, Norwell, MA (1998)

12.2.9 Environmental Abiotic Degradation

The rate constant for the vapor-phase reaction of chloral hydrate with photochemically-produced hydroxyl radicals has been estimated as 1.9X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 8 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Chloral hydrate hydrolyzes to form chloroform at high pH(2). The rate constant for the reaction of chloral hydrate with hydroxyl radicals in aqueous solutions at pH 11.3 is 1.2X10+10 L/mol-sec(3).
(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(2) Stevens AA et al; J Amer Water Works Assoc 81: 54-60 (1989)
(3) Wenger JC et al; Environ Sci Technol 38: 831-7 (2004)
It should be mentioned that chloral hydrate was degraded via reductive dehalogenation by carbonate green rust, a corrosion product on unlined iron or steel pipe surfaces, which readily interacts with some disinfection by-products; at an initial concentration of 88 and 84.8 uM overall reaction rates were 3.2X10-3/hr and 1.9X10-3/hr using MOPS and carbonate buffers, respectively(1); corresponding half-lives were 9 days and 15 days, respectively(SRC). Hydrolysis rates were 1.0X10-3/hr and 1.8X10-3/hr, respectively; reductive dehalogenation rates were 2.2X10-3 and 8,5X10-5/hr, respectively; ratio of MOPS to carbonate buffer = 25.9(1).
(1) Chun CL et al; Environ Sci Technol 41: 1615-21 (2007)

12.2.10 Environmental Bioconcentration

An estimated BCF of 3 was calculated in fish for chloral hydrate(SRC), using a log Kow of 0.99(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).
(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 4 (1995)
(2) Franke C et al; Chemosphere 29: 1501-14 (1994)

12.2.11 Soil Adsorption / Mobility

The Koc of chloral hydrate is estimated as 82(SRC), using a log Kow of 0.99(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that chloral hydrate is expected to have high mobility in soil.
(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. 4 (1995)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9 (1990)
(3) Swann RL et al; Res Rev 85: 17-28 (1983)

12.2.12 Volatilization from Water / Soil

The Henry's Law constant for chloral hydrate is estimated as 4.1X10-9 atm-cu m/mole(SRC) derived from its vapor pressure, 15 mm Hg(1), and water solubility, 7.9X10+5 mg/L(2). This Henry's Law constant indicates that chloral hydrate is expected to volatilize from water surfaces(3). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(3) is estimated as 11 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(3) is estimated as 88 days(SRC). Chloral hydrate's estimated Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). The potential for volatilization of chloral hydrate from dry soil surfaces may exist(SRC) based upon its vapor pressure(1).
(1) Perry RH, Green D; Perry's Chemical Engineers's Handbook. Physical and Chemical Data. New York, NY: McGraw-Hill 6th ed (1984)
(2) Yalkowsky SH, He Y; Handbook of Aqueous Solubility Data. CRC Press LLC, Boca Raton, FL. p. 21 (2003)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)

12.2.13 Environmental Water Concentrations

SURFACE WATER: A sample of lake water from West Palm Beach FL (pH 7.2) chlorinated for 70 minutes with 12 ppm of chlorine resulted in the formation of 30 ppb chloral hydrate; a Gainsville, FL lake (pH 7.6) chlorinated for 70 minutes with 20 ppm chlorine resulted in 35 ppb chlroine(1).
(1) Trehy ML et al; Environ Sci Technol 20: 1117-22 (1986)
DRINKING WATER: Chloral hydrate was one of the major disinfection by-products identified as a result of a survey of drinking water from 53 Canadian treatment facilities(1). The compound is often present at greater than 10 ug/L(2). A yearly mean of monthly values from a plant employing chlorine-chloramine treatment was 2.2 ug/L, minimum of <0.1 ug/L and a maximum concentration of 6.6 ug/L(1). A yearly mean of monthly values from a plant employing chlorine-chloramine treatment was 3.4 ug/L, minimum of 0.6 ug/L and a maximum concentration of 10.5 ug/L(1). A yearly mean of monthly values from a plant employing ozone-chlorine treatment was 8.9 ug/L, minimum of 1.0 ug/L and a maximum concentration of 23.4 ug/L(1). Disinfection by-product occurrence in 12 US drinking water plants surveyed from 2000 to 2002 was conducted, with samples tested in fall 2000 (Oct-Dec); winter through early Spring (Jan-Apr); summer (Jul-Sept); and fall 2001(3). Chloral hydrate concentrations ranged from 13 ug/L after chlorine-chloramine disinfection to 0.3 ug/L following zone-chloramine disinfection (sampled 12/11/00)(3).
(1) LeBel GL et al; Chemosphere 34: 2301-17 (1997)
(2) Young MS, Uden C; in Amer Chem Soc, Div Environ Chem, 206th ACS Natl Mtg, 33: 187-90 (1993)
(3) Krasner SW et al; Environ Sci Technol 40: 7175-85 (2006)

12.2.14 Effluent Concentrations

Using pilot-plant studies of disinfection by-products, it was found that the concentration of chloral hydrate increased with time for pH 5 and 7(1). The compound leveled off at both pH values (5 ug/L at 4 hr and 25 ug/L at 7 days) and was initially formed most rapidly at pH 9.4 (10 ug/L in 4 hr). However, the rate of hydrolysis at pH 9.4 exceeded rate of formation, resulting in <2 ug/L after 7 days(1). A concentration range of 20 to 38 ppb chloral hydrate were measured in samples of chlorinated wastewater from an extended aeration treatment plant, collected in two separate days(1). A 2.3 ug/L increase (from 6.3 to 8.9 ug/L) of chloral hydrate was observed following ozonation as a method to control trihalomethanes and other disinfection by-products at a conventional drinking water treatment plant(2). A second plant experienced a doubling of chloral hydrate concentration, from 19 to 28 ug/L following treatment with ozone(2).
(1) Stevens AA et al; J Amer Water Works Assoc 81: 54-60 (1989)
(2) Jacangelo JG et al; J Amer Water Works Assoc 81: 74-84 (1989)

12.2.15 Milk Concentrations

Chloral hydrate has been detected in /human/ ... milk ... .
Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 836
Chloral hydrate and its metabolite, trichloroethanol reached 50-100% /in breast milk/ of maternal blood levels in most of 50 women given 1.3 g rectally. Drug and metabolites were detectable for up to 24 hr; the maximum dose that an infant could have received approximates a sedative dose. In another study, drowsiness was noted in 1 infant the morning after a bedtime hypnotic dose of a chloral hydrate derivative in the mother.
Knoben, J.E. and P.O. Anderson (eds.) Handbook of Clinical Drug Data. 6th ed. Bethesda, MD: Drug Intelligence Publications, Inc. 1988., p. 174
Following therapeutic doses of chloral hydrate, only small, clinically insignificant amt of the active metabolite are distributed into milk.
American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008, p. 2610

12.2.16 Other Environmental Concentrations

Chloral hydrate, along with trihalogenated methanes, halogenated acetic acids, 2,2-dichloropropionic acid, and dihalogenated acetonitriles, with a total concentration maximum of 538 ug/L, was detected in swimming pool waters following CL2 disinfection(1). Sampling of 109 swimming pools in Germany listed chloral hydrate as one of the main halogenated compounds detected(2).
(1) Clemens M, Schoeler HF; Zentralbl Hyg Umweltmed 193: 91-8 (1992)
(2) Mannshott P et al; Zentralbl Hyg Umweltmed 197: 516- 33(1995)
Chloral hydrate is a degradation by-product of trichloroethylene oxidation by methanothrophic Methylosinus sp.(1).
(1) Newman LM, Wackett LP; Appl Environ Microbiol 57: 2399-402 (1991)

12.2.17 Probable Routes of Human Exposure

NIOSH (NOES Survey 1981-1983) has statistically estimated that 11,278 workers (8,131 of these were female) were potentially exposed to chloral hydrate in the US(1). Occupational exposure to chloral hydrate may occur through inhalation and dermal contact with this compound at workplaces where chloral hydrate is produced or used. Monitoring data indicate that the general population may be exposed to chloral hydrate via ingestion of chlorinated drinking water, and dermal contact with this compound when swimming in chlorinated pools; limited exposure is expected from its use as a sedative(SRC).
(1) NIOSH; NOES. National Occupational Exposure Survey conducted from 1981-1983. Estimated numbers of employees potentially exposed to specific agents by 2-digit standard industrial classification (SIC). Available at https://www.cdc.gov/noes/ as of May 21, 2008.

12.2.18 Body Burden

Chloral hydrate has been detected in /human/ ... milk ... .
Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 836
Chloral hydrate and its metabolite, trichloroethanol reached 50-100% /in breast milk/ of maternal blood levels in most of 50 women given 1.3 g rectally.
Knoben, J.E. and P.O. Anderson (eds.) Handbook of Clinical Drug Data. 6th ed. Bethesda, MD: Drug Intelligence Publications, Inc. 1988., p. 174

13 Associated Disorders and Diseases

Associated Occupational Diseases with Exposure to the Compound
Solvents, acute toxic effect [Category: Acute Poisoning]

14 Literature

14.1 Consolidated References

14.2 NLM Curated PubMed Citations

14.3 Springer Nature References

14.4 Thieme References

14.5 Wiley References

14.6 Chemical Co-Occurrences in Literature

14.7 Chemical-Gene Co-Occurrences in Literature

14.8 Chemical-Disease Co-Occurrences in Literature

15 Patents

15.1 Depositor-Supplied Patent Identifiers

15.2 WIPO PATENTSCOPE

15.3 Chemical Co-Occurrences in Patents

15.4 Chemical-Disease Co-Occurrences in Patents

15.5 Chemical-Gene Co-Occurrences in Patents

16 Interactions and Pathways

16.1 Chemical-Target Interactions

16.2 Drug-Drug Interactions

16.3 Drug-Food Interactions

  • Avoid alcohol. Ingesting alcohol may cause a disulfiram-like-reaction (flushing, dizziness, tachycardia).
  • Take after a meal. If chloral hydrate is being used for sedation, it should be taken after meals. Otherwise, it can be taken with or without food.

16.4 Pathways

17 Biological Test Results

17.1 BioAssay Results

18 Taxonomy

19 Classification

19.1 MeSH Tree

19.2 NCI Thesaurus Tree

19.3 ChEBI Ontology

19.4 KEGG: Drug

19.5 KEGG: ATC

19.6 KEGG: JP15

19.7 WHO ATC Classification System

19.8 ChemIDplus

19.9 CAMEO Chemicals

19.10 ChEMBL Target Tree

19.11 UN GHS Classification

19.12 Drug Enforcement Administration (DEA) Classification

19.13 NORMAN Suspect List Exchange Classification

19.14 EPA DSSTox Classification

19.15 International Agency for Research on Cancer (IARC) Classification

19.16 EPA TSCA and CDR Classification

19.17 EPA Substance Registry Services Tree

19.18 MolGenie Organic Chemistry Ontology

20 Information Sources

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    https://cameochemicals.noaa.gov/browse/react
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    https://www.epa.gov/tsca-inventory
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  32. Drugs and Lactation Database (LactMed)
  33. EPA Regional Screening Levels for Chemical Contaminants at Superfund Sites
  34. Hazardous Chemical Information System (HCIS), Safe Work Australia
  35. NITE-CMC
    Chloral hydrate - FY2010 (New/original classication)
    https://www.chem-info.nite.go.jp/chem/english/ghs/10-mhlw-0067e.html
    Chloral hydrate - FY2018 (Revised classification)
    https://www.chem-info.nite.go.jp/chem/english/ghs/18-mhlw-2051e.html
  36. Regulation (EC) No 1272/2008 of the European Parliament and of the Council
    LICENSE
    The copyright for the editorial content of this source, the summaries of EU legislation and the consolidated texts, which is owned by the EU, is licensed under the Creative Commons Attribution 4.0 International licence.
    https://eur-lex.europa.eu/content/legal-notice/legal-notice.html
    chloral hydrate; 2,2,2-trichloroethane-1,1-diol
    https://eur-lex.europa.eu/eli/reg/2008/1272/oj
  37. FDA Approved Animal Drug Products (Green Book)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  38. NMRShiftDB
  39. Human Metabolome Database (HMDB)
    LICENSE
    HMDB 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 (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications.
    http://www.hmdb.ca/citing
  40. International Agency for Research on Cancer (IARC)
    LICENSE
    Materials made available by IARC/WHO enjoy copyright protection under the Berne Convention for the Protection of Literature and Artistic Works, under other international conventions, and under national laws on copyright and neighbouring rights. IARC exercises copyright over its Materials to make sure that they are used in accordance with the Agency's principles. All rights are reserved.
    https://publications.iarc.fr/Terms-Of-Use
    IARC Classification
    https://www.iarc.fr/
  41. Japan Chemical Substance Dictionary (Nikkaji)
  42. 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
    Therapeutic category of drugs in Japan
    http://www.genome.jp/kegg-bin/get_htext?br08301.keg
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Drugs listed in the Japanese Pharmacopoeia
    http://www.genome.jp/kegg-bin/get_htext?br08311.keg
  43. Metabolomics Workbench
  44. Natural Product Activity and Species Source (NPASS)
  45. 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
  46. SpectraBase
    2,2,2-TRICHLORO-1,1-ETHANEDIOL
    https://spectrabase.com/spectrum/BTckaWW89Tk
    1,1-Ethanediol, 2,2,2-trichloro-
    https://spectrabase.com/spectrum/L3CIe20UZh0
    2,2,2-trichloro-1,1-ethanediol
    https://spectrabase.com/spectrum/IIctEAScCT6
  47. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  48. Springer Nature
  49. SpringerMaterials
  50. 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/
  51. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
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    https://www.whocc.no/copyright_disclaimer/
  52. Wikidata
  53. Wikipedia
  54. Wiley
  55. Medical Subject Headings (MeSH)
    LICENSE
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    https://www.nlm.nih.gov/copyright.html
  56. PubChem
  57. GHS Classification (UNECE)
  58. EPA Substance Registry Services
  59. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  60. PATENTSCOPE (WIPO)
  61. NCBI
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