Chloral hydrate

RTECS #
FM8750000
CAS #
302-17-0
See: NMAM or OSHA Methods
Updated
March 2018
Molecular Weight
165.40
Molecular Formula
C2H3Cl3O2
Synonyms
1,1,1-Trichloro-2,2-dihydroxyethane
1,1,1-Trichloro-2,2-ethanediol
1,1-Ethanediol, 2,2,2-trichloro- (9CI)
2,2,2-Trichloro-1,1-ethanediol
Aquachloral
Bi 3411
Chloraldurat
Dormal
Felsules
Hydral
Hydrate de chloral
Kessodrate
Lorinal
Noctec
Nycoton
Nycton
Phaldrone
Rectules
SK-Chloral hydrate
Somni SED
Somnos
Sontec
Tosyl
Trawotox
Trichloracetaldehyd-hydrat (German)
Trichloroacetaldehyde hydrate
Trichloroacetaldehyde monohydrate

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
Cytogenetic Analysisother cell types/non-mammalian species100 mmol/LCHROAU 45,215,1974
Cytogenetic Analysislymphocyte/mouse1250 mg/LMUREAV 413,265,1998
DNA adductintraperitoneal/mouse2000 nmol/L/1W- intermittentCALEDQ 185,13,2002
DNA Damageovary/hamster5000 mg/L/3HMUREAV 537,151,2003
DNA Damageliver/human3 mmol/L/48HFCTOD7 41,621,2003
DNA Damagelymphocyte/human0.5 mmol/L/48HFCTOD7 41,621,2003
DNA Damagelymphocyte/human5.67 mg/L/48HMUREAV 607,160,2006
gene conversion and mitotic recombination/Saccharomyes cerevisiae15 mmol/LMUREAV 141,19,1984
host-mediated assaySaccharomyes cerevisiae/mouse500 mg/kgMUREAV 141,19,1984
micronucleus testlung/hamster80 mg/LMUREAV 287,71,1993
micronucleus testmultiple/non-mammalian species200 ppmMUREAV 292,83,1993
micronucleus testintraperitoneal/mouse41 mg/kgMUREAV 323,81,1994
micronucleus testlymphocyte/human500 µmol/LCRNGDP 18,1687,1997
micronucleus testother cell types/mouse500 mg/L/24H (-enzymatic activation step)MUTAEX 14,403,1999
micronucleus testoral/human50 mg/kgMUREAV 564,159,2004
morphological transformembryo/hamster5 mg/L/7DMUREAV 654,108,2008
morphological transformembryo/hamster1 mg/LMUREAV 343,7,1995
mutation in mammalian somatic cellslymphocyte/mouse1 gm/LMUREAV 413,265,1998
mutation in microorganisms/Aspergillus nidulans5 mg/plate (-enzymatic activation step)CBINA8 30,9,1980
mutation in microorganisms/Salmonella typhimurium1 mg/plate (+/-enzymatic activation step)ENMUDM 5(Suppl 1),3,1983
mutation in microorganisms/Other microorganisms2 mg/plate (-enzymatic activation step)CBINA8 30,9,1980
other mutation test systemslymphocyte/human100 mg/LMUREAV 334,1,1995
other mutation test systemsembryo/hamster165 mg/LMUREAV 287,47,1993
other mutation test systemsother cell types/non-mammalian species100 mmol/LCHROAU 45,215,1974
sex chromosome loss and nondisjunctionlymphocyte/human50 mg/LMUREAV 287,57,1993
sex chromosome loss and nondisjunctionembryo/hamster100 mg/LMUREAV 287,47,1993
sex chromosome loss and nondisjunctionlung/hamster500 mg/LMUREAV 287,29,1993
sex chromosome loss and nondisjunction/Aspergillus nidulans5 mmol/LMUREAV 155,105,1985
sex chromosome loss and nondisjunctionintraperitoneal/mouse82700 µg/kgENMUDM 6,695,1984
sister chromatid exchangeoral/human50 mg/kgMUREAV 564,159,2004
sister chromatid exchangelymphocyte/human54 mg/LAGTQAH 24,105,1981
specific locus testoral/Drosophila melanogaster5 mmol/LMUREAV 322,111,1994
specific locus testother cell types/mouse3400 µmol/l/24H (-enzymatic activation step)MUTAEX 26,771,2011

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
oral/mouse 13 gm/kg (3W pre-3W after birth)Reproductive: Effects on newborn: BehavioralNTOTDY 6,137,1984

Tumorigenic Data and References

Route/OrganismDoseEffectReference
oral/mouse lowest published toxic dose: 10 mg/kgTumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors
CDPRD4 9,279,1986
skin/mouse lowest published toxic dose: 960 mg/kg/1W- intermittentTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Skin and Appendages: Tumors
BJCAAI 9,177,1955

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
In Vitro/Human, kidney tumor Inhibitor Concentration (50 percent kill): 1380 mg/LIn Vitro Toxicity Studies: Cell viability (dye exclusion): trypan blue assay etc.TIVIEQ 27,1347,2013
In Vitro/Human, liver tumor Inhibitor Concentration (50 percent kill): 3610 mg/LIn Vitro Toxicity Studies: Cell viability (dye exclusion): trypan blue assay etc.TIVIEQ 27,1347,2013
In Vitro/Human, liver tumor Inhibitor Concentration (50 percent kill): 1340 mg/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 27,1347,2013
In Vitro/Human, liver tumor Inhibitor Concentration (50 percent kill): 7.9 mmol/L/24HIn Vitro Toxicity Studies: Cell protein synthesisTIVIEQ 3,189,1989
In Vitro/Human, neuroblastoma Inhibitor Concentration Low: 140 µmol/L/4MIn Vitro Toxicity Studies: Membrane currentsTXAPA9 245,191,2010
In Vitro/Human, neuroblastoma Inhibitor Concentration (50 percent kill): 2500 mg/LIn Vitro Toxicity Studies: Cell viability (dye exclusion): trypan blue assay etc.TIVIEQ 27,1347,2013
In Vitro/Human, skin Inhibitor Concentration (50 percent kill): 132 mg/L/48HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 27,1347,2013
In Vitro/Mouse, fibroblast Inhibitor Concentration (50 percent kill): 171 mg/L/48HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 27,1347,2013
In Vitro/Mouse, fibroblast Inhibitor Concentration (50 percent kill): 179 mg/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 27,1347,2013
In Vitro/paaInhibitor Concentration Low: 371 µmol/L/44HIn Vitro Toxicity Studies: Other assaysTIVIEQ 27,1416,2013
In Vitro/Rat, liver Inhibitor Concentration (50 percent kill): 176 mg/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 27,1347,2013
intraarterial/guinea pig lowest published lethal dose: 400 mg/kgAEPPAE 131,171,1928
intraperitoneal/mouse lethal dose (50 percent kill): 580 mg/kgBehavioral: Somnolence (general depressed activity)ARZNAD 10,665,1960
intraperitoneal/rat lethal dose (50 percent kill): 472 mg/kgBehavioral: Somnolence (general depressed activity)

Lung, Thorax, or Respiration: Other changes
JAPMA8 41,100,1952
intraperitoneal/rat lowest published toxic dose: 400 mg/kgNutritional and Gross Metabolic: Body temperature decreaseFATOAO 47,21,1984
intraperitoneal/rat lowest published toxic dose: 100 mg/kgBiochemical: Metabolism (intermediary): Lipids including transportFCTOD7 41,621,2003
intraperitoneal/rat lowest published toxic dose: 350 mg/kgBehavioral: General anestheticACPSI* 25,1267,2004
intravenous/cattle lowest published lethal dose: 10 mg/kgHBAMAK 4,1289,1935
intravenous/child lowest published toxic dose: 39 mg/kgBehavioral: Somnolence (general depressed activity)

Skin: After systemic exposure: Dermatitis, other
JTCTDW 34,101,1996
intravenous/child lowest published toxic dose: 88 mg/kgBehavioral: Somnolence (general depressed activity)

Lung, Thorax, or Respiration: Cyanosis

Lung, Thorax, or Respiration: Respiratory depression
JTCTDW 34,101,1996
intravenous/Dog lowest published lethal dose: 180 mg/kgBehavioral: General anestheticBDHU** -,-,1936
intravenous/guinea pig lowest published lethal dose: 400 mg/kgAEPPAE 131,171,1928
intravenous/mouse lethal dose (50 percent kill): 530 mg/kgAPFRAD 38,65,1980
intravenous/rabbit lowest published lethal dose: 400 mg/kgJPETAB 63,453,1938
oral/cat lowest published lethal dose: 400 mg/kgBehavioral: SleepJPETAB 78,340,1943
oral/cattle lowest published lethal dose: 30 mg/kgHBAMAK 4,1289,1935
oral/child lowest published toxic dose: 70 mg/kgEye: Miosis (pupilliary constriction)

Behavioral: Convulsions or effect on seizure threshold

Cardiac: Pulse rate increased without fall in BP
JOPDAB 131,787,1997
oral/child lowest published toxic dose: 219 mg/kgCardiac: Arrythmias (indlucing changes in conduction)JTCTDW 34,101,1996
oral/Dog lowest published lethal dose: 1 gm/kgBehavioral: SleepJPETAB 78,340,1943
oral/frog lowest published lethal dose: 938 mg/kgAIPTAK 8,77,1901
oral/human lowest published lethal dose: 4 mg/kgEye: Miosis (pupilliary constriction)

Gastrointestinal: Nausea or vomiting
PHBTH* 3,132,1967
oral/human lowest published toxic dose: 300 mg/kgBehavioral: General anesthetic

Cardiac: Arrythmias (indlucing changes in conduction)

Vascular: BP lowering not characterized in autonomic section
BMJOAE 2,994,1977
oral/man lowest published toxic dose: 1 gm/kgBehavioral: Coma

Cardiac: Pulse rate increased without fall in BP

Lung, Thorax, or Respiration: Cyanosis
JTCTDW 34,97,1996
oral/man lowest published lethal dose: 143 mg/kgEye: Miosis (pupilliary constriction)

Behavioral: Coma

Gastrointestinal: Hypermotility, diarrhea
JFSCAS 46,1507,2001
oral/mouse lowest published toxic dose: 5 mg/kgLiver: TumorsEVHPAZ 108,241,2000
oral/mouse lethal dose (50 percent kill): 1100 mg/kgJPETAB 106,444,1952
oral/pigeon lowest published lethal dose: 300 mg/kgHBAMAK 4,1289,1935
oral/rabbit lowest published lethal dose: 1200 mg/kgBehavioral: General anestheticAEPPAE 132,214,1928
oral/rat lethal dose (50 percent kill): 479 mg/kgTXAPA9 18,185,1971
oral/woman lowest published toxic dose: 960 mg/kgBehavioral: Somnolence (general depressed activity)

Behavioral: Hallucinations, distorted perceptions

Cardiac: Pulse rate increased without fall in BP
JTCTDW 34,101,1996
oral/woman lowest published toxic dose: 465 mg/kgEye: Other eye effects

Behavioral: Coma

Vascular: BP lowering not characterized in autonomic section
AMSVAZ 223,269,1988
parenteral/frog lowest published lethal dose: 900 mg/kgAEPPAE 166,437,1932
parenteral/rat lethal dose (50 percent kill): 710 mg/kgNIIRDN 6,784,1982
rectal/cattle lowest published lethal dose: 30 mg/kgHBAMAK 4,1289,1935
rectal/child lowest published toxic dose: 75 mg/kgBehavioral: Somnolence (general depressed activity)

Vascular: BP lowering not characterized in autonomic section

Lung, Thorax, or Respiration: Respiratory depression
FCLPH* 18,347,2004
rectal/child lowest published toxic dose: 97 mg/kgCardiac: Pulse rate increased without fall in BPAACRAT 65,691,1986
rectal/rabbit lowest published lethal dose: 1 gm/kgBehavioral: General anesthetic

Lung, Thorax, or Respiration: Other changes
AEPPAE 132,214,1928
rectal/rat lethal dose (50 percent kill): 710 mg/kgNIIRDN -,1114,1990
skin/rat lethal dose (50 percent kill): 3030 mg/kg85JFAN A065,1984
subcutaneous/mouse lowest published lethal dose: 800 mg/kgBehavioral: General anesthetic

Behavioral: Excitement

Lung, Thorax, or Respiration: Other changes
AEPPAE 166,437,1932
subcutaneous/rabbit lowest published lethal dose: 1 gm/kgBehavioral: General anesthetic

Lung, Thorax, or Respiration: Other changes
ZEPTAT 18,61,1916
unreported route/child lowest published toxic dose: 48 mg/kg/6H- intermittentCardiac: Pulse rate increased without fall in BPAACRAT 65,691,1986
unreported route/guinea pig lethal dose (50 percent kill): 940 mg/kgBehavioral: Somnolence (general depressed activity)

Behavioral: Excitement

Behavioral: Ataxia
GISAAA 35(3),14,1970
unreported route/infant lowest published toxic dose: 160 mg/kg/3D- intermittentCardiac: Arrythmias (indlucing changes in conduction)AACRAT 65,691,1986
unreported route/man lowest published lethal dose: 103 mg/kg85DCAI 2,73,1970
unreported route/mouse lethal dose (50 percent kill): 850 mg/kgBehavioral: Somnolence (general depressed activity)

Behavioral: Excitement

Behavioral: Ataxia
GISAAA 35(3),14,1970
unreported route/rabbit lethal dose (50 percent kill): 1400 mg/kgBehavioral: Somnolence (general depressed activity)

Behavioral: Excitement

Behavioral: Ataxia
GISAAA 35(3),14,1970
unreported route/rat lethal dose (50 percent kill): 725 mg/kgBehavioral: Somnolence (general depressed activity)

Behavioral: Excitement

Behavioral: Ataxia
GISAAA 35(3),14,1970

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
oral/mouse lowest published toxic dose: 2016 mg/kg/14D- intermittentLiver: Changes in liver weight

Endocrine: Changes in spleen weight

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)
EVHPAZ 44,137,1982
oral/mouse lowest published toxic dose: 1440 mg/kg/90D- continuousLiver: Changes in liver weight

Nutritional and Gross Metabolic: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.)
EVHPAZ 44,137,1982
oral/mouse lowest published toxic dose: 4800 mg/kg/16D- intermittentLiver: Changes in liver weightNTPTR* NIH-99-3944
oral/mouse lowest published toxic dose: 120.85 gm/kg/104W- continuousLiver: Tumors

Tumorigenic: Tumor types after systemic administration not seen spontaneously
EVHPAZ 108,241,2000
oral/mouse lowest published toxic dose: 2016 mg/kg/14D- intermittentLiver: Changes in liver weightEVHPAZ 108,241,2000
oral/rat lowest published toxic dose: 3983 mg/kg/13W- continuousLiver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
JJATDK 22,227,2002
oral/rat lowest published toxic dose: 1.82 mg/kg/13W- continuousLiver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases
JAPTO* 22,227,2002
oral/rat lowest published toxic dose: 17.29 mg/kg/13W- continuousLiver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Catalases
JAPTO* 22,227,2002
oral/rat lowest published toxic dose: 1798 mg/kg/13W- continuousEye: Optic nerve neuropathy

Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
JAPTO* 22,227,2002
oral/rat lowest published toxic dose: 2144.87 mg/kg/13W- continuousLiver: Other changes

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Catalases
JAPTO* 22,227,2002
oral/rat lowest published toxic dose: 230.23 mg/kg/13W- continuousLiver: Other changes

Biochemical: Metabolism (intermediary): Other
JAPTO* 22,227,2002
oral/rat lowest published toxic dose: 17.5 mg/kg/7D- continuousLiver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases
JJATDK 20,455,2000
oral/rat lowest published toxic dose: 1750 mg/kg/7D- continuousLiver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other transferases
JJATDK 20,455,2000
oral/rat lowest published toxic dose: 10800 mg/kg/90D- continuousLiver: Hepatitis (hepatocellular necrosis), diffuseEVHPAZ 108,241,2000
oral/rat lowest published toxic dose: 15120 mg/kg/90D- continuousLiver: Hepatitis (hepatocellular necrosis), zonal

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
DCTODJ 15,217,1992
oral/rat lowest published toxic dose: 210 mg/kg/30W- intermittentBlood: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: True cholinesterase
GISAAA 35(3),14,1970
oral/rat lowest published toxic dose: 1413 mg/kg/90D- continuousNutritional and Gross Metabolic: Body temperature decreaseNTOTDY 6,137,1984
oral/rat lowest published toxic dose: 4800 mg/kg/17D- intermittentBehavioral: Somnolence (general depressed activity)

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
NTPTR* NIH-99-3944

Reviews

OrganizationStandardReference
International Agency for Research on Cancer (IARC)Cancer Review:Animal Limited EvidenceIMEMDT 63,245,1995
International Agency for Research on Cancer (IARC)Cancer Review:Animal Sufficient EvidenceIMEMDT 106,467,2014
International Agency for Research on Cancer (IARC)Cancer Review:Human Inadequate EvidenceIMEMDT 63,245,1995
International Agency for Research on Cancer (IARC)Cancer Review: Group 3IMEMDT 84,349,2004
International Agency for Research on Cancer (IARC)Cancer Review:Human Inadequate EvidenceIMEMDT 106,467,2014
International Agency for Research on Cancer (IARC)Cancer Review:Group 3IMEMDT 63,245,1995
International Agency for Research on Cancer (IARC)Cancer Review:Group 2AIMEMDT 106,467,2014
TOXICOLOGY REVIEWNEJMAG 342,186,2000
TOXICOLOGY REVIEWIMEMDT 84,317,2004
TOXICOLOGY REVIEWMUREAV 628,31,2007
TOXICOLOGY REVIEWENTOX* -,535,2005
TOXICOLOGY REVIEWENTOX* -,546,2005
TOXICOLOGY REVIEWMUREAV 627,10,2007
TOXICOLOGY REVIEWMUREAV 584,1,2005
TOXICOLOGY REVIEWBCLPT* 96,131,2005
TOXICOLOGY REVIEWMUREAV 636,178,2007
TOXICOLOGY REVIEWREPTED 22,557,2006
TOXICOLOGY REVIEWMUREAV 659,248,2008
TOXICOLOGY REVIEWPSBUL* 36,91,2002
TOXICOLOGY REVIEWHUTOX* -,281,1996
TOXICOLOGY REVIEWIMEMDT 84,317,
TOXICOLOGY REVIEWMUTAEX 23,271,2008
TOXICOLOGY REVIEWMUREAV 705,20,2010
TOXICOLOGY REVIEWNCLNA* 16,503,1998
TOXICOLOGY REVIEWNBREV* 5,1,1981
TOXICOLOGY REVIEWTXCYAC 286,1,2011
TOXICOLOGY REVIEWMUREAV 750,1,2012
TOXICOLOGY REVIEWTXAPA9 254,100,2011
TOXICOLOGY REVIEWMUREAV 769,34,2014
TOXICOLOGY REVIEWMUREAV 762,22,2014
TOXICOLOGY REVIEWMUREAV 763,181,2015
TOXICOLOGY REVIEWMUREAV 783,66,2015
TOXICOLOGY REVIEWMUREAV 802,1,2016
TOXICOLOGY REVIEWMUTAEX 31,347,2016

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Occupational Exposure Survey 1983Hazard Code 84490; Number of Industries 4; Total Number of Facilities 264; Number of Occupations 11; Total Number of Employees Exposed 11278; Total Number of Female Employees Exposed 8131
National Occupational Hazard Survey 1974Hazard Code 84490; Number of Industries 3; Total Number of Facilities 1191; Number of Occupations 10; Total Number of Employees Exposed 10916

Status in Federal Agencies

OrganizationReference
EPA GENETOX PROGRAM 1988, Inconclusive: Carcinogenicity-mouse/rat; Mammalian micronucleus
EPA GENETOX PROGRAM 1988, Negative: Aspergillus-recombination; N crassa-aneuploidy
EPA GENETOX PROGRAM 1988, Negative: Sperm morphology-mouse
EPA GENETOX PROGRAM 1988, Positive: Aspergillus-aneuploidy; Histidine reversion-Ames test
EPA TSCA Section 8(b) CHEMICAL INVENTORY
NCI Carcinogenesis Studies (gavage);equivocal evidence:mouse,rat
NTP Carcinogenesis studies; test completed (post peer review), October 2000
NTP Toxicity studies, RPT# TOX-59, October 2000
On EPA IRIS database
Page last reviewed: November 16, 2018