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Registry of Toxic Effects of Chemical Substances (RTECS)

Morpholine

RTECS #

QD6475000

CAS #

110-91-8

Updated

September 201

Molecular Weight

87.14

Molecular Formula

C4H9NO

Synonyms

1-Oxa-4-azacyclohexane
2H-1,4-Oxazine, tetrahydro-
4H-1,4-Oxazine, tetrahydro-
BASF 238
Diethylene imidoxide
Diethylene oximide
Diethyleneimide oxide
Diethylenimide oxide
Drewamine
Morpholine (ACGIH:OSHA)
p-Isoxazine, tetrahydro-
Tetrahydro-1,4-isoxazine
Tetrahydro-1,4-oxazine
Tetrahydro-2H-1,4-oxazine

Skin and Eye Irritation and References

Route/OrganismDoseEffectReference
eye /rabbit 2 mg severeAJOPAA 29,1363,1946
skin /rabbit 500 mg open irritation test moderateUCDS** 4/21/1967

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
Cytogenetic Analysisinhalation/rat0.07 mg/L/122D- intermittentTPKVAL 13,92,1973
morphological transformfibroblast/mouse125 mg/LEPASR* 8EHQ-0779-0294
morphological transformlymphocyte/mouse1 µL/LENMUDM 4,390,1982
mutation in mammalian somatic cellslymphocyte/mouse1 gm/LEPASR* 8EHQ-0779-0294
sister chromatid exchangeovary/hamster160 mg/LEPASR* 8EHQ-0779-0294

Tumorigenic Data and References

Route/OrganismDoseEffectReference
oral/mouse lowest published toxic dose: 2560 mg/kg/1Y- continuousTumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Bronchogenic carcinoma

Liver: Tumors		GISAAA 44(8),15,1979

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
inhalation/mammal (species unspecified) lethal concentration (50 percent kill): 12000 mg/m3TPKVAL 14,90,1975
inhalation/mouse lowest published toxic concentration: 0.1 gm/m3/2HLung, Thorax, or Respiration: Other changesTPKVAL 10,25,1968
inhalation/mouse lethal concentration (50 percent kill): 1320 mg/m3/2HEye: Lacrimation

Behavioral: Ataxia

Lung, Thorax, or Respiration: Cyanosis		TPKVAL 8,60,1966
inhalation/mouse lethal concentration (50 percent kill): 12000 mg/m3Behavioral: Alteration of classical conditioningTPKVAL 15,116,1979
inhalation/mouse lethal concentration (50 percent kill): 1.35 gm/m3TPKVAL 8,70,1966
inhalation/mouse Lowest published lethal concentration: 1.98 gm/m3/2HTPKVAL 8,60,1966
inhalation/mouse Lowest published lethal concentration: 1.67 gm/m3/2HBlood: Hemorrhage

Nutritional and Gross Metabolic: Weight loss or decreased weight gain		TPKVAL 8,60,1966
inhalation/mouse Lowest published lethal concentration: 0.45 gm/m3/2HBehavioral: Irritability

Lung, Thorax, or Respiration: Dyspnea

Gastrointestinal: Nausea or vomiting		TPKVAL 8,60,1966
inhalation/rat lethal concentration (50 percent kill): 8000 ppm/8HNPIRI* 1,85,1974
intraperitoneal/mouse lethal dose (50 percent kill): 413 mg/kgReproductive: Paternal effects: Testes, epididymis, sperm ductCANCAR 2,1055,1949
ocular/rabbit lowest published toxic dose: 100 pphEye: Conjunctiva irritation

Eye: Corneal damage

Eye: Other eye effects		TPKVAL 8,60,1966
oral/guinea pig lowest published lethal dose: 100 mg/kgOlfaction: Other olfaction effects

Gastrointestinal: Ulceration or bleeding from stomach

Gastrointestinal: Ulceration or bleeding from small intestine		JIHTAB 21,236,1939
oral/mammal (species unspecified) lethal dose (50 percent kill): 1220 mg/kgTPKVAL 14,90,1975
oral/mouse lethal dose (50 percent kill): 1200 mg/kgTPKVAL 15,116,1979
oral/mouse lowest published lethal dose: 1200 mg/kgMUREAV 539,65,2003
oral/mouse lethal dose (50 percent kill): 525 mg/kgBehavioral: Sleep

Behavioral: Somnolence (general depressed activity)		BBIADT 44,795,1985
oral/rat lowest published toxic dose: 500 mg/kgTPKVAL 8,60,1966
oral/rat lethal dose (16 percent kill): 700 mg/kgReproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)TPKVAL 8,60,1966
oral/rat lethal dose (50 percent kill): 1738 mg/kgKidney, Ureter, and Bladder: Changes in blood vessels or in circulation of kidneyTPKVAL 8,60,1966
oral/rat lowest published lethal dose: 1500 mg/kgTPKVAL 8,60,1966
oral/rat lowest published lethal dose: 2300 mg/kgBrain and Coverings: Changes in circulation

Cardiac: Cardiomyopathy including infarction

Cardiac: Other changes		TPKVAL 8,60,1966
skin/rabbit lethal dose (50 percent kill): 500 µL/kgAMIHBC 10,61,1954
subcutaneous/mouse lethal dose (50 percent kill): 458 mg/kgUSXXAM #4576951
unreported route/rat lowest published lethal dose: 1600 mg/kg34ZIAG -,662,1969

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
inhalation/guinea pig lowest published toxic concentration: 70 mg/m3/4H/17W- intermittentLiver: Liver function tests impaired

Kidney, Ureter, and Bladder: Other changes in urine composition		TNICS* 13,87,1973
inhalation/guinea pig lowest published toxic concentration: 0.07 gm/m3/2W- intermittentPeripheral Nerve and Sensation: Recording from peripheral motor nerveTPKVAL 13,92,1973
inhalation/guinea pig lowest published toxic concentration: 0.07 gm/m3/30D- intermittentBlood: Other changes

Blood: Changes in leukocyte (WBC) count		TPKVAL 13,92,1973
inhalation/guinea pig lowest published toxic concentration: 0.008 gm/m3/61D- intermittentLiver: Liver function tests impaired

Kidney, Ureter, and Bladder: Other changes in urine composition		TPKVAL 13,92,1973
inhalation/rat lowest published toxic concentration: 70 mg/m3/4H/17W- intermittentVascular: BP lowering not characterized in autonomic section

Blood: Changes in leukocyte (WBC) count		TNICS* 13,87,1973
inhalation/rat lowest published toxic dose: 250 ppm/6H/13W- intermittentLung, Thorax, or Respiration: Fibrosis, focal (pneumoconiosis)FAATDF 4,465,1984
inhalation/rat lowest published toxic concentration: 0.07 gm/m3/2W- intermittentPeripheral Nerve and Sensation: Recording from peripheral motor nerve

Vascular: BP elevation not characterized in autonomic section

Blood: Other changes		TPKVAL 13,92,1973
inhalation/rat lowest published toxic concentration: 0.07 gm/m3/30D- intermittentBlood: Changes in other cell count (unspecified)TPKVAL 13,92,1973
inhalation/rat lowest published toxic concentration: 0.008 gm/m3/61D- intermittentVascular: BP lowering not characterized in autonomic section

Blood: Changes in other cell count (unspecified)		TPKVAL 13,92,1973
inhalation/rat lowest published toxic concentration: 0.07 gm/m3/122D- intermittentLiver: Other changes

Kidney, Ureter, and Bladder: Other changes

Blood: Changes in leukocyte (WBC) count		TPKVAL 13,92,1973
inhalation/rat lowest published toxic concentration: 0.008 gm/m3/122D- intermittentBlood: Changes in spleen

Immunological Including Allergic: Decrease in cellular immune response		TPKVAL 13,92,1973
oral/guinea pig lowest published toxic dose: 13500 mg/kg/30D- intermittentGastrointestinal: Necrotic changes

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field		JIHTAB 21,236,1939
oral/rat lowest published toxic dose: 24 gm/kg/30D- intermittentGastrointestinal: Necrotic changes

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field		JIHTAB 21,236,1939
skin/guinea pig lowest published toxic dose: 27 gm/kg/30D- intermittentKidney, Ureter, and Bladder: Changes in both tubules and glomeruli

Skin: After topical application: Primary irritation

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field		JIHTAB 21,236,1939
skin/rabbit lowest published toxic dose: 9 gm/kg/10D- intermittentLiver: Fatty liver degeneration

Skin: After topical application: Primary irritation

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field		JIHTAB 21,236,1939

Reviews

OrganizationStandardReference
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-time-weighted average 20 ppm (skin)DTLVS* TLV/BEI,2013
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-Not classifiable as a human carcinogenDTLVS* TLV/BEI,2013
International Agency for Research on Cancer (IARC)Cancer Review:Animal Inadequate EvidenceIMEMDT 47,199,1989
International Agency for Research on Cancer (IARC)Cancer Review:Animal Inadequate EvidenceIMEMDT 71,1511,1999
International Agency for Research on Cancer (IARC)Cancer Review:Human No Adequate DataIMEMDT 71,1511,1999
International Agency for Research on Cancer (IARC)Cancer Review:Group 3IMEMDT 71,1511,1999
TOXICOLOGY REVIEWJACTDZ 8,707,1989
TOXICOLOGY REVIEWCHHSA* 9,6,2002

Standards and Regulations

OrganizationStandardReference
Mine Safety and Health Administration (MSHA) STANDARD-airtime-weighted average 20 ppm (70 mg/m3) (skin)DTLVS* 3,175,1971
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN check ACGIH TLV;
Occupational Exposure Limit IN SINGAPORE, VIETNAM check ACGIH TLV
Occupational Exposure Limit-AUSTRALIAtime-weighted average 20 ppm (71 mg/m3), JUL2008
Occupational Exposure Limit-AUSTRIAMAK-TMW 10 ppm (36 mg/m3);KZW 10 ppm (36 mg/m3), skin, 2007
Occupational Exposure Limit-BELGIUMtime-weighted average 10 ppm (36 mg/m3), MAR2002
Occupational Exposure Limit-BELGIUMshort term exposure limit 20 ppm (72 mg/m3), Skin, MAR2002
Occupational Exposure Limit-DENMARKtime-weighted average 10 ppm (36 mg/m3), skin, MAY2011
Occupational Exposure Limit-ECtime-weighted average 36 mg/m3 (10 ppm);short term exposure limit 72 mg/m3 (20 ppm), FEB2006
Occupational Exposure Limit-FINLANDtime-weighted average 10 ppm (36 mg/m3), short term exposure limit 20 ppm (72 mg/m3), skin, NOV2011
Occupational Exposure Limit-FRANCEVME 20 ppm (70 mg/m3), VLE 30 ppm (105 mg/m3), FEB2006
Occupational Exposure Limit-GERMANYMAK 10 ppm (36 mg/m3), 2011
Occupational Exposure Limit-HUNGARYtime-weighted average 70 mg/m3, short term exposure limit 70 mg/m3, Skin, SEP2000
Occupational Exposure Limit-ICELANDtime-weighted average 10 ppm (36 mg/m3), short term exposure limit 20 ppm (72 mg/m3), skin, NOV2011
Occupational Exposure Limit-KOREAtime-weighted average 20 ppm (70 mg/m3), short term exposure limit 30 ppm (105 mg/m3), skin, 2006
Occupational Exposure Limit-MEXICOtime-weighted average 20 ppm (70 mg/m3);short term exposure limit 30 ppm (skin), 2004
Occupational Exposure Limit-NEW ZEALANDtime-weighted average 20 ppm (71 mg/m3), skin, JAN2002
Occupational Exposure Limit-NORWAYtime-weighted average 20ppm (70 mg/m3), JAN1999
Occupational Exposure Limit-PERUtime-weighted average 20 ppm (71 mg/m3), JUL2005
Occupational Exposure Limit-POLANDMAC(time-weighted average) 70 mg/m3, MAC(short term exposure limit) 100 mg/m3, JAN1999
Occupational Exposure Limit-RUSSIAtime-weighted average 0.5 mg/m3, short term exposure limit 1.5 mg/m3, Skin, JUN2003
Occupational Exposure Limit-SWEDENtime-weighted average 10 ppm (35 mg/m3);short term exposure limit 15 ppm (50 mg/m3), Skin, JUN2005
Occupational Exposure Limit-SWITZERLANDMAK-week 10 ppm (36 mg/m3), KZG-week 20 ppm (72 mg/m3), skin, JAN2011
Occupational Exposure Limit-THE NETHERLANDSMAC-TGG 36 mg/m3, Skin, 2003
Occupational Exposure Limit-THE PHILIPPINEStime-weighted average 20 ppm (70 mg/m3), Skin, JAN1993
Occupational Exposure Limit-UNITED KINGDOMtime-weighted average 10 ppm (36 mg/m3);short term exposure limit 20 ppm (72 mg/m3), skin, OCT2007
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Construction)8H time-weighted average 20 ppm (70 mg/m3) (skin)CFRGBR 29,1926.55,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Federal Contractors)8H time-weighted average 20 ppm (70 mg/m3) (skin)CFRGBR 41,50-204.50,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (General Industry)8H time-weighted average 20 ppm (70 mg/m3) (skin)CFRGBR 29,1910.1000,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Shipyards)8H time-weighted average 20 ppm (70 mg/m3) (skin)CFRGBR 29,1915.1000,1993

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO MORPHOLINE-air10H time-weighted average 20 ppm (Sk);short term exposure limit 30 ppm (Sk)NIOSH* DHHS #92-100,1992
National Occupational Exposure Survey 1983Hazard Code 48910; Number of Industries 133; Total Number of Facilities 13767; Number of Occupations 105; Total Number of Employees Exposed 214367; Total Number of Female Employees Exposed 65146
National Occupational Hazard Survey 1974Hazard Code 48910; Number of Industries 132; Total Number of Facilities 20431; Number of Occupations 82; Total Number of Employees Exposed 122734

Status in Federal Agencies

OrganizationReference
EPA GENETOX PROGRAM 1988, Positive: Host-mediated assay
EPA TSCA Section 8(b) CHEMICAL INVENTORY
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001

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