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2H-1,3,2-Oxazaphosphorin-2-amine,N,N-bis(2-chloroethyl)tetrahydro-, 2-oxide cas no:50-18-0

Synonyms: 2H-1,3,2-Oxazaphosphorine,2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide (6CI,8CI);(RS)-Cyclophosphamide;2-[Bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorin 2-oxide;Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester;CB 4564;CY;Clafen;Claphene;Cycloblastin;Cyclophosphamid;Cyclophosphan;Cyclophosphane;Cyclostin;Cytophosphan;Cytoxan;Endoxan;Endoxan R;Endoxan-Asta;Endoxana;Endoxanal;Endoxane;Enduxan;Genoxal;Mitoxan;N,N-Bis(b-chloroethyl)-N',O-trimethylenephosphoricacid ester diamide;Neosar;Neosar (antineoplastic);Procytox;Revimmune;SK 20501;Semdoxan;Sendoxan;Senduxan;Zyklophosphamid;

Identification
Name2H-1,3,2-Oxazaphosphorin-2-amine,N,N-bis(2-chloroethyl)tetrahydro-, 2-oxide
CAS50-18-0
Synonyms2H-1,3,2-Oxazaphosphorine,2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide (6CI,8CI);(RS)-Cyclophosphamide;2-[Bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorin 2-oxide;Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester;CB 4564;CY;Clafen;Claphene;Cycloblastin;Cyclophosphamid;Cyclophosphan;Cyclophosphane;Cyclostin;Cytophosphan;Cytoxan;Endoxan;Endoxan R;Endoxan-Asta;Endoxana;Endoxanal;Endoxane;Enduxan;Genoxal;Mitoxan;N,N-Bis(b-chloroethyl)-N',O-trimethylenephosphoricacid ester diamide;Neosar;Neosar (antineoplastic);Procytox;Revimmune;SK 20501;Semdoxan;Sendoxan;Senduxan;Zyklophosphamid;
EINECS(EC#)200-015-4
Molecular FormulaC7H15Cl2N2O2P
Molecular Weight261.09
Chemical Properties
Appearancewhite crystalline powder
Globally Harmonized System of Classification adn Labelling of Chemicals(GHS)
Hazardclass6.1(b)
Safety Data

Hazard An experimental carcinogen by injection.
Safety

Confirmed human carcinogen producing leukemia, Hodgkin's disease, gastrointestinal and bladder tumors. Experimental carcinogenic, neoplastigenic, and teratogenic data. A human poison by ingestion and many other routes. Human systemic effects: kidney changes (hepatic dysfunction), leukopenia (reduced white blood cell count), nausea and alopecia (loss of hair), liver changes, agranulocytosis. Human reproductive and teratogenic effects by multiple routes: spermatogenesis, testicular changes, epididymis and sperm duct changes, menstrual cycle changes, fetal developmental abnormalities of the craniofacial area, musculoskeletal and cardiovascular systems. Experimental reproductive effects. Human mutation data reported. A powerful skin irritant. Used as an immunosuppressive agent in nonmalignant diseases. When heated to decomposition it emits highly toxic fumes of POx, NOx, and Cl?.
Safety Statements: 22-24/25
S22: Do not breathe dust.?
S24/25: Avoid contact with skin and eyes.
RIDADR: UN 1851
HazardClass: 6.1(b)
PackingGroup: III


Toxicity

Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
cat LDLo intraperitoneal 50mg/kg (50mg/kg) BEHAVIORAL: ATAXIA

LUNGS, THORAX, OR RESPIRATION: DYSPNEA
Kiso to Rinsho. Clinical Report. Vol. 16, Pg. 431, 1982.
child TDLo oral 2500ug/kg (2.5mg/kg) BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD American Journal of Diseases of Children. Vol. 140, Pg. 1094, 1986.
dog LDLo intraperitoneal 50mg/kg (50mg/kg) BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION
Kiso to Rinsho. Clinical Report. Vol. 16, Pg. 431, 1982.
dog LDLo intravenous 11mg/kg (11mg/kg) BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

BLOOD: CHANGES IN BONE MARROW NOT INCLUDED ABOVE
Cancer Chemotherapy Reports, Part 2. Vol. 2, Pg. 191, 1965.
domestic animals - goat/sheep LD50 intravenous 45100ug/kg (45.1mg/kg) CARDIAC: OTHER CHANGES

KIDNEY, URETER, AND BLADDER: OTHER CHANGES

LIVER: OTHER CHANGES
Dongbei Nongxueyuan Xuebao. Journal of Northeast Agricultural College. Vol. 34, Pg. 56, 1980.
guinea pig LDLo intraperitoneal 200mg/kg (200mg/kg) SENSE ORGANS AND SPECIAL SENSES: PTOSIS: EYE

BEHAVIORAL: ATAXIA

BEHAVIORAL: MUSCLE WEAKNESS
Kiso to Rinsho. Clinical Report. Vol. 16, Pg. 431, 1982.
hamster LD10 parenteral 110mg/kg (110mg/kg) ? Journal of Surgical Oncology. Vol. 15, Pg. 355, 1980.
hamster LD50 intraperitoneal 429mg/kg (429mg/kg) ? Cancer Letters Vol. 2, Pg. 267, 1977.
hamster LD50 oral 763mg/kg (763mg/kg) BEHAVIORAL: CHANGES IN MOTOR ACTIVITY (SPECIFIC ASSAY)

BEHAVIORAL: MUSCLE WEAKNESS

BEHAVIORAL: ATAXIA
Experientia. Vol. 37, Pg. 401, 1981.
human TDLo oral 20mg/kg (20mg/kg) GASTROINTESTINAL: OTHER CHANGES

SKIN AND APPENDAGES (SKIN): HAIR: OTHER

KIDNEY, URETER, AND BLADDER: OTHER CHANGES
Arthritis and Rheumatism. Vol. 12, Pg. 663, 1969.
man LDLo multiple routes 45mg/kg/26W-I (45mg/kg) BLOOD: OTHER CHANGES American Journal of the Medical Sciences. Vol. 254, Pg. 48, 1967.
man TDLo oral 56mg/kg/26D-I (56mg/kg) BLOOD: AGRANULOCYTOSIS American Journal of Medicine. Vol. 81, Pg. 1059, 1986.
man TDLo oral 56mg/kg/4W-I (56mg/kg) LIVER: OTHER CHANGES Southern Medical Journal. Vol. 78, Pg. 222, 1985.
man TDLo oral 579mg/kg/2Y-I (579mg/kg) LIVER: "JAUNDICE, OTHER OR UNCLASSIFIED"

LIVER: LIVER FUNCTION TESTS IMPAIRED

LIVER: OTHER CHANGES
American Journal of Gastroenterology. Vol. 95, Pg. 845, 2000.
monkey LDLo intravenous 45mg/kg (45mg/kg) BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

BLOOD: CHANGES IN BONE MARROW NOT INCLUDED ABOVE
Cancer Chemotherapy Reports, Part 2. Vol. 2, Pg. 191, 1965.
mouse LD50 intraperitoneal 110mg/kg (110mg/kg) ? Farmakologiya i Toksikologiya Vol. 41, Pg. 90, 1978.
mouse LD50 intravenous 140mg/kg (140mg/kg) ? "Radiation-Induced Cancer, Proceedings of a Symposium, Athens, 1969," Lanham, MD, Bernan-UNIPUB, 1969Vol. -, Pg. 97, 1969.
mouse LD50 oral 137mg/kg (137mg/kg) ? Russian Pharmacology and Toxicology Vol. 36, Pg. 240, 1973.
mouse LD50 parenteral 315mg/kg (315mg/kg) ? Transplantation. Vol. 13, Pg. 316, 1972.
mouse LD50 subcutaneous 200mg/kg (200mg/kg) ? Advances in the Study of Birth Defects. Vol. 2, Pg. 95, 1979.
mouse LD50 unreported 480mg/kg (480mg/kg) ? Nippon Yakurigaku Zasshi. Japanese Journal of Pharmacology. Vol. 64(4), Pg. 157S, 1968.
mouse LDLo intratracheal 200mg/kg (200mg/kg) ? Toxicology Letters. Vol. 30, Pg. 63, 1986.
rabbit LDLo intraperitoneal 200mg/kg (200mg/kg) SENSE ORGANS AND SPECIAL SENSES: MIOSIS (PUPILLARY CONSTRICTION): EYE

BEHAVIORAL: MUSCLE WEAKNESS

LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION
Kiso to Rinsho. Clinical Report. Vol. 16, Pg. 431, 1982.
rabbit LDLo intravenous 300mg/kg (300mg/kg) ? Journal of Toxicological Sciences. Vol. 34, Pg. 308, 1999.
rat LD50 intracrebral > 400ug/kg (0.4mg/kg) ? Journal of Pharmacy and Pharmacology. Vol. 18, Pg. 760, 1966.
rat LD50 intraperitoneal 40mg/kg (40mg/kg) ? Clinical Proceedings of the Children's Hospital of the District of Columbia. Vol. 18, Pg. 307, 1962.
rat LD50 intravenous 148mg/kg (148mg/kg) BLOOD: NORMOCYTIC ANEMIA Kiso to Rinsho. Clinical Report. Vol. 16, Pg. 431, 1982.
rat LD50 oral 100mg/kg (100mg/kg) ? Drugs in Japan Vol. -, Pg. 516, 1995.
rat LD50 subcutaneous 144mg/kg (144mg/kg) BLOOD: NORMOCYTIC ANEMIA Kiso to Rinsho. Clinical Report. Vol. 16, Pg. 431, 1982.
rat LD50 unreported 190mg/kg (190mg/kg) ? Nippon Yakurigaku Zasshi. Japanese Journal of Pharmacology. Vol. 64(4), Pg. 157S, 1968.
women LDLo oral 16mg/kg/4D-I (16mg/kg) BLOOD: OTHER CHANGES American Journal of the Medical Sciences. Vol. 254, Pg. 48, 1967.
women TDLo intravenous 13500ug/kg (13.5mg/kg) SENSE ORGANS AND SPECIAL SENSES: VISUAL FIELD CHANGES: EYE Annals of Internal Medicine. Vol. 116, Pg. 92, 1992.
women TDLo intravenous 60mg/kg/9W-I (60mg/kg) ? Archives of Internal Medicine. Vol. 145, Pg. 548, 1985.
women TDLo oral 45mg/kg (45mg/kg) KIDNEY, URETER, AND BLADDER: OTHER CHANGES Arthritis and Rheumatism. Vol. 15, Pg. 530, 1972.

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