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Morpholine

RTECS #: QD6475000

CAS #: 110-91-8


UPDATE: May 2009 MW: 87.14 MF: C4H9NO


NOTE:

TABLE OF CONTENTS:
  1. SYNONYMS:
  2. SKIN AND EYE IRRITATION DATA:
  3. MUTATION DATA:
  4. TUMORIGENIC DATA:
  5. ACUTE TOXICITY DATA:
  6. OTHER MULTIPLE DOSE DATA:
  7. REVIEWS:
  8. STANDARDS AND REGULATIONS:
  9. NIOSH DOCUMENTATION AND SURVEILLANCE:
  10. STATUS IN FEDERAL AGENCIES:
  11. REFERENCES:

SYNONYMS:

  1. 1 - Oxa - 4 - azacyclohexane
  2. 2H - 1,4 - Oxazine, tetrahydro -
  3. 4H - 1,4 - Oxazine, tetrahydro -
  4. BASF 238
  5. Diethyleneimide oxide
  6. Diethylene imidoxide
  7. Diethylene oximide
  1. Diethylenimide oxide
  2. Drewamine
  3. Morpholine (ACGIH:OSHA)
  4. Tetrahydro - 1,4 - isoxazine
  5. Tetrahydro - 1,4 - oxazine
  6. Tetrahydro - 2H - 1,4 - oxazine
  7. p - Isoxazine, tetrahydro -


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM
DOSE
EFFECT

REFERENCE
eye
rabbit
2 mg severe AJOPAA 29,1363,1946
skin
rabbit
500 mg open irritation test moderate UCDS** 4/21/1967


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE
DOSE REFERENCE
cytogenetic analysis inhalation
rat
0.7 mg/L/122 day- intermittent TPKVAL 13,92,1973
mutation in mammalian somatic cells mouse lymphocyte 1 gm/L EPASR* 8EHQ-0779-0294
morphological transform mouse fibroblast 125 mg/L EPASR* 8EHQ-0779-0294
morphological transform mouse lymphocyte 1 ÁL/L ENMUDM 4,390,1982
sister chromatid exchange hamster ovary 160 mg/L EPASR* 8EHQ-0779-0294


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM
DOSE
EFFECT

REFERENCE
N/R
N/R N/R N/R


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM
DOSE
EFFECT

REFERENCE
oral
mouse
lowest published toxic dose: 2,560 mg/kg/1 year- continuous Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Bronchogenic carcinoma

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


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM
DOSE
EFFECT

REFERENCE
inhalation
mammal (species unspecified)
lethal concentration (50 percent kill): 12,000 mg/m3 N/R TPKVAL 14,90,1975
inhalation
mouse
lethal concentration (50 percent kill): 1,320 mg/m3/2 hour Eye: Lacrimation

Behavioral: Ataxia

Lung, Thorax, or Respiration: Cyanosis
TPKVAL 8,60,1966
inhalation
mouse
lowest published toxic concentration: 0.1 gm/m3/2 hour Lung, Thorax, or Respiration: Other changes TPKVAL 10,25,1968
inhalation
mouse
lethal concentration (50 percent kill): 12,000 mg/m3 Behavioral: Alteration of classical conditioning TPKVAL 15,116,1979
inhalation
mouse
lethal concentration : 0.45 gm/m3/2 hour Behavioral: Irritability

Lung, Thorax, or Respiration: Dyspnea

Gastrointestinal: Nausea or vomiting
TPKVAL 8,60,1966
inhalation
mouse
lethal concentration : 1.67 gm/m3/2 hour Blood: Hemorrhage

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
TPKVAL 8,60,1966
inhalation
mouse
lethal concentration : 1.98 gm/m3/2 hour N/R TPKVAL 8,60,1966
inhalation
mouse
lethal concentration (50 percent kill): 1.35 gm/m3 N/R TPKVAL 8,70,1966
inhalation
rat
lethal concentration (50 percent kill): 8,000 ppm/8 hour N/R NPIRI* 1,85,1974
intraperitoneal
mouse
lethal dose (50 percent kill): 413 mg/kg Reproductive: Paternal effects: Testes, epididymis, sperm duct CANCAR 2,1055,1949
ocular
rabbit
lowest published toxic dose: 100 pph Eye: Conjunctiva irritation

Eye: Corneal damage

Eye: Other eye effects
TPKVAL 8,60,1966
oral
guinea pig
lowest published lethal dose: 100 mg/kg Olfaction: 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): 1,220 mg/kg N/R TPKVAL 14,90,1975
oral
mouse
lethal dose (50 percent kill): 525 mg/kg Behavioral: Sleep

Behavioral: Somnolence (general depressed activity)
BBIADT 44,795,1985
oral
mouse
lowest published lethal dose: 1,200 mg/kg N/R MUREAV 539,65,2003
oral
mouse
lethal dose (50 percent kill): 1,200 mg/kg N/R TPKVAL 15,116,1979
oral
rat
lowest published toxic dose: 500 mg/kg N/R TPKVAL 8,60,1966
oral
rat
lethal dose (16 percent kill): 700 mg/kg Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) TPKVAL 8,60,1966
oral
rat
lethal dose : 1,500 mg/kg N/R TPKVAL 8,60,1966
oral
rat
lethal dose : 2,300 mg/kg Brain and Coverings: Changes in circulation

Cardiac: Cardiomyopathy including infarction

Cardiac: Other changes
TPKVAL 8,60,1966
oral
rat
lethal dose (50 percent kill): 1,738 mg/kg Kidney, Ureter, and Bladder: Changes in blood vessels or in circulation of kidney TPKVAL 8,60,1966
subcutaneous
mouse
lethal dose (50 percent kill): 458 mg/kg N/R USXXAM #4576951
skin
mouse
lowest published toxic dose: 100 pph/15 minute Skin: After topical application: Corrosive TPKVAL 8,60,1966
skin
rabbit
lethal dose (50 percent kill): 500 ÁL/kg N/R AMIHBC 10,61,1954
unreported route
rat
lowest published lethal dose: 1,600 mg/kg N/R 34ZIAG -,662,1969


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM
DOSE
EFFECT

REFERENCE
inhalation
guinea pig
lowest published toxic concentration: 70 mg/m3/4 hour/17 week- intermittent Liver: Liver function tests impaired

Kidney, Ureter, and Bladder: Other changes in urine composition
TNICS* 13,87,1973
inhalation
guinea pig
lowest published toxic concentration: 0.7 gm/m3/2 week- intermittent Peripheral Nerve and Sensation: Recording from peripheral motor nerve TPKVAL 13,92,1973
inhalation
guinea pig
lowest published toxic concentration: 0.7 gm/m3/30 day- intermittent Blood: Other changes

Blood: Changes in leukocyte (WBC) count
TPKVAL 13,92,1973
inhalation
guinea pig
lowest published toxic concentration: 0.8 gm/m3/61 day- intermittent Liver: 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/m3/4 hour/17 week- intermittent Vascular: 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/6 hour/13 week- intermittent Lung, Thorax, or Respiration: Fibrosis, focal (pneumoconiosis) FAATDF 4,465,1984
inhalation
rat
lowest published toxic concentration: 0.7 gm/m3/2 week- intermittent Peripheral 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: 0.7 gm/m3/30 day- intermittent Blood: Changes in other cell count (unspecified) TPKVAL 13,92,1973
inhalation
rat
lowest published toxic concentration: 0.8 gm/m3/61 day- intermittent Vascular: BP lowering not characterized in autonomic section

Blood: Changes in other cell count (unspecified)
TPKVAL 13,92,1973
inhalation
rat
lowest published toxic concentration: 0.7 gm/m3/122 day- intermittent Liver: Other changes

Kidney, Ureter, and Bladder: Other changes

Blood: Changes in leukocyte (WBC) count
TPKVAL 13,92,1973
inhalation
rat
lowest published toxic concentration: 0.8 gm/m3/122 day- intermittent Blood: Changes in spleen

Immunological Including Allergic: Decrease in cellular immune response
TPKVAL 13,92,1973
oral
guinea pig
lowest published toxic dose: 13,500 mg/kg/30 day- intermittent Gastrointestinal: 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/30 day- intermittent Gastrointestinal: 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/30 day- intermittent Kidney, 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/10 day- intermittent Liver: 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:

ORGANIZATION STANDARD
REFERENCE

American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value time-weighted average 20 ppm (skin) DTLVS* TLV/BEI,2007
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value Not classifiable as human carcinogen DTLVS* TLV/BEI,2007
International Agency for Research on Cancer (IARC) Cancer Review Animal Inadequate Evidence IMEMDT 47,199,1989
International Agency for Research on Cancer (IARC) Cancer Review Animal Inadequate Evidence IMEMDT 71,1511,1999
International Agency for Research on Cancer (IARC) Cancer Review Human No Adequate Data IMEMDT 71,1511,1999
International Agency for Research on Cancer (IARC) Cancer Review Group 3 IMEMDT 71,1511,1999
TOXICOLOGY REVIEW
JACTDZ 8,707,1989
TOXICOLOGY REVIEW
CHHSA* 9,6,2002


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE

Mine Safety and Health Administration (MSHA) STANDARD - air time-weighted average 20 ppm (70 mg/m3) (skin) DTLVS* 3,175,1971
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (General Industry) 8 hour time-weighted average 20 ppm (70 mg/m3) (skin) CFRGBR 29,1910.1000,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Construction) 8 hour time-weighted average 20 ppm (70 mg/m3) (skin) CFRGBR 29,1926.55,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Shipyards) 8 hour time-weighted average 20 ppm (70 mg/m3) (skin) CFRGBR 29,1915.1000,1993
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Federal Contractors) 8 hour time-weighted average 20 ppm (70 mg/m3) (skin) CFRGBR 41,50-204.50,1994
Occupational Exposure Limit - AUSTRALIA time-weighted average 20 ppm (71 mg/m3), JUL2008
Occupational Exposure Limit - BELGIUM time-weighted average 10 ppm (36 mg/m3), MAR2002
Occupational Exposure Limit - BELGIUM short term exposure limit 20 ppm (72 mg/m3), Skin, MAR2002
Occupational Exposure Limit - DENMARK time-weighted average 20 ppm (70 mg/m3), OCT 2002
Occupational Exposure Limit - EC time-weighted average 36 mg/m3 (10 ppm);
short term exposure limit 72 mg/m3 (20 ppm), FEB 2006
Occupational Exposure Limit - FINLAND time-weighted average 20 ppm (70 mg/m3), short term exposure limit 30 ppm (105 mg/m3), Skin, JAN1999
Occupational Exposure Limit - FRANCE VME 20 ppm (70 mg/m3), VLE 30 ppm (105 mg/m3), FEB2006
Occupational Exposure Limit - GERMANY MAK 36 mg/m3 (10 mL/m3), 2005
Occupational Exposure Limit - HUNGARY time-weighted average 70 mg/m3, short term exposure limit 70 mg/m3, Skin, SEP2000
Occupational Exposure Limit - KOREA time-weighted average 20 ppm (70 mg/m3), short term exposure limit 30 ppm (105 mg/m3), skin, 2006
Occupational Exposure Limit - MEXICO time-weighted average 20 ppm (70 mg/m3);
short term exposure limit 30 ppm (skin), 2004
Occupational Exposure Limit - THE NETHERLANDS MAC-TGG 36 mg/m3, Skin, 2003
Occupational Exposure Limit - NEW ZEALAND time-weighted average 20 ppm (71 mg/m3), skin, JAN2002
Occupational Exposure Limit - NORWAY time-weighted average 20ppm (70 mg/m3), JAN1999
Occupational Exposure Limit - THE PHILIPPINES time-weighted average 20 ppm (70 mg/m3), Skin, JAN1993
Occupational Exposure Limit - POLAND MAC(time-weighted average) 70 mg/m3, MAC(short term exposure limit) 100 mg/m3, JAN1999
Occupational Exposure Limit - RUSSIA time-weighted average 0.5 mg/m3, short term exposure limit 1.5 mg/m3, Skin, JUN2003
Occupational Exposure Limit - SWEDEN time-weighted average 10 ppm (35 mg/m3);
short term exposure limit 15 ppm (50 mg/m3), Skin, JUN2005
Occupational Exposure Limit - SWITZERLAND MAK- week 10 ppm (36 mg/m3),KZG- week 20 ppm (72 mg/m3), Skin, DEC2006
Occupational Exposure Limit - UNITED KINGDOM time-weighted average 20 ppm (72 mg/m3);
short term exposure limit 30 ppm (skin), 2005
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value;

Not classifiable as human carcinogen
Occupational Exposure Limit IN SINGAPORE, VIETNAM American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value
Not classifiable as human carcinogen


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE

National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO MORPHOLINE-air 10 hour time-weighted average 20 ppm (Sk);
short term exposure limit 30 ppm (Sk)
NIOSH* DHHS #92-100,1992
National Occupational Hazard Survey 1974 National Occupational Hazard Survey 1974: Hazard Code: 48910;
Number of Industries 132;
Total Number of Facilities 20,431;
Number of Occupations 82;
Total Number of Employees Exposed 122,734
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: 48910;
Number of Industries 133;
Total Number of Facilities 13,767;
Number of Occupations 105;
Total Number of Employees Exposed 214,367;
Total Number of Female Employees Exposed 65,146


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE

EPA GENETOX PROGRAM 1988, Positive: Host-mediated assay
EPA TSCA Section 8(b) CHEMICAL INVENTORY
Used as a separating agent for volatile amines, intermediate for textile lubricants
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001


REFERENCES:

CODEN
REFERENCE

34ZIAG "Toxicology of Drugs and Chemicals," Deichmann, W.B., New York, Academic Press, Inc., 1969
AJOPAA American Journal of Ophthalmology. (Ophthalmic Pub. Co., 435 N. Michigan Ave., Suite 1415, Chicago, IL 60611) Series 3: V.1- 1918-
AMIHBC AMA Archives of Industrial Hygiene and Occupational Medicine. (Chicago, IL) V.2-10, 1950-54. For publisher information, see AEHLAU.
BBIADT Biomedica Biochimica Acta. (Akademie-Verlag GmbH, Postfach 1233, Berlin DDR-1086, Ger. Dem. Rep.) V.42- 1983-
CANCAR Cancer (Philadelphia). (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1948-
CFRGBR Code of Federal Regulations. (U.S. Government Printing Office, Supt. of Documents, Washington, DC 20402)
CHHSA* Chemical Health & Safety (Orlando, FL : Published by Elsevier Inc. for the ACS Division of Chemical Health and Safety) V.1- 1994-
DTLVS* The Threshold Limit Values (TLVs) and Biological Exposure Indices (BEIs) booklet issues by American Conference of Governmental Industrial Hygienists (ACGIH), Cincinnati, OH, 1996
ENMUDM Environmental Mutagenesis. (New York, NY) V.1-9, 1979-87. For publisher information, see EMMUEG.
EPASR* United States Environmental Protection Agency, Office of Pesticides and Toxic Substances. (U.S. Environmental Protection Agency, 401 M St., SW, Washington, DC 20460) History unknown.
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1-40, 1981-97. For publisher information, see TOSCF2
GISAAA Gigiena i Sanitariya. For English translation, see HYSAAV. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.1- 1936-
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972-
JACTDZ Journal of the American College of Toxicology. (Mary Ann Liebert, Inc., 1651 Third Ave., New York, NY 10128) V.1-12, 1982-1993. Discontinued.
JIHTAB Journal of Industrial Hygiene and Toxicology. (Cambridge, MA) V.18-31, 1936-49. For publisher information, see AEHLAU.
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
NIOSH* National Institute of Occupational Safety and Health, U.S. Dept. of Health, Education, and Welfare, Reports and Memoranda.
NPIRI* Raw Material Data Handbook, Vol.1: Organic Solvents, 1974. (National Assoc. of Printing Ink Research Institute, Francis McDonald Sinclair Memorial Laboratory, Lehigh Univ., Bethlehem, PA 18015)
TNICS* Toxicology of New Industrial Chemical Substances. English translation of TPKVAL. (USSR Academy of Medical Sciences, Meditsina, Moscow, USSR)
TPKVAL Toksikologiya Novykh Promyshlennykh Khimicheskikh Veshchestv. Toxicology of New Industrial Chemical Substances. For English translation, see TNICS*. (Izdatel'stvo Meditsina, Moscow, USSR) No.1- 1961-
UCDS** Union Carbide Data Sheet. (Union Carbide Corp., 39 Old Ridgebury Rd., Danbury, CT 06817)
USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231)

Used as a separating agent for volatile amines, intermediate for textile lubricants

NIOSH PROFILE (TIRE MANUFACTURING), SRI, 2/77

NIOSH PROFILE (TIRE MANUFACTURING), FIRL, 4/78

RTECS Compound Description:
   Tumorigen
   Drug
   Mutagen
   Primary Irritant

Click Here for Additional Information about RTECS

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