*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : RP6157750
CHEMICAL NAME : 2H-1,3,2-Oxazaphosphorine,
tetrahydro-2-(bis(2-chloroethyl)amino)-, 2-oxide,
monohydrate
CAS REGISTRY NUMBER : 6055-19-2
LAST UPDATED : 199710
DATA ITEMS CITED : 36
MOLECULAR FORMULA : C7-H15-Cl2-N2-O2-P.H2-O
MOLECULAR WEIGHT : 279.13
COMPOUND DESCRIPTOR : Tumorigen
Mutagen
Reproductive Effector
SYNONYMS/TRADE NAMES :
* N,N-Bis(beta-cloraethyl) N'-O-propylenphosphorildiamid monohydratum
* 2-(Bis(2-chloroethyl)amino)-1-oxa-3-aza-2-phosphocyclohexane 2-oxide
monohydrate
* 1-Bis(2-chloroethyl)amino-1-oxo-2-aza-5-oxaphosphoridine monohydrate
* (Bis(chloro-2-ethyl)amino)-2-tetrahydro-3,4,5,6-oxazaphosphorine-1,3,2-o
xide-2 monohydrate
* Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester monohydrate
* N,N-Bis(beta-chloroethyl)-N',O-propylenephosphoric acid ester amide
monohydrate
* N,N-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxaphosphorin-2-amine, 2-oxide
monohydrate
* N,N-Bis(beta-chloroethyl)-N',O-trimethylenephosphoric acid ester diamide
monohydrate
* Cyclic N',O-propylene ester of N,N-bis(2-chloroethyl)phosphorodiamidic
acid monohydrate
* Cyclophosphamide hydrate
* Cyclophosphamide monohydrate
* 2-(Di(2-chloroethyl)amino)-1-oxa-3-aza-2-phosphacyclohexane-2-oxide
monohydrate
* N,N-Di(2-chloroethyl)amino-N,O-propylene phosphoric acid ester diamide
monohydrate
* Endoxan monohydrate
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 94 mg/kg
TOXIC EFFECTS :
Behavioral - ataxia
Kidney, Ureter, Bladder - urine volume increased
Blood - hemorrhage
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
4,324,1962
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 121 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
FRMBAZ Farmacia (Bucharest). (Rompresfilatelia, POB 12-201, Bucharest,
Romania) V.1- 1953- Volume(issue)/page/year: 18,409,1970
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 350 mg/kg
TOXIC EFFECTS :
Behavioral - ataxia
Kidney, Ureter, Bladder - urine volume increased
Blood - hemorrhage
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
4,324,1962
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 275 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
4,324,1962
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 44 mg/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Behavioral - ataxia
Gastrointestinal - nausea or vomiting
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
4,324,1962
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 40 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
DMWOAX Deutsche Medizinische Wochenschrift. (Stuttgart, Fed. Rep. Ger.)
V.1-104, 1875-1979. Volume(issue)/page/year: 83,453,1958
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rabbit
DOSE/DURATION : 130 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
DMWOAX Deutsche Medizinische Wochenschrift. (Stuttgart, Fed. Rep. Ger.)
V.1-104, 1875-1979. Volume(issue)/page/year: 83,453,1958
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - guinea pig
DOSE/DURATION : 400 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
DMWOAX Deutsche Medizinische Wochenschrift. (Stuttgart, Fed. Rep. Ger.)
V.1-104, 1875-1979. Volume(issue)/page/year: 83,453,1958
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 240 mg/kg/4W-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - hematuria
Blood - changes in leukocyte (WBC) count
Related to Chronic Data - death
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
4,324,1962
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 480 mg/kg/8W-I
TOXIC EFFECTS :
Blood - changes in erythrocyte (RBC) count
Blood - changes in leukocyte (WBC) count
Related to Chronic Data - death
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
4,324,1962
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 480 mg/kg/24D-C
TOXIC EFFECTS :
Liver - changes in liver weight
Blood - changes in leukocyte (WBC) count
Immunological Including Allergic - decrease in humoral immune response
REFERENCE :
TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85,
Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 30,103,1984
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 150 mg/kg/9W-I
TOXIC EFFECTS :
Blood - changes in leukocyte (WBC) count
Related to Chronic Data - death
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
4,324,1962
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 150 mg/kg/4W-I
TOXIC EFFECTS :
Blood - changes in leukocyte (WBC) count
Related to Chronic Data - death
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
4,324,1962
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Bird - domestic
DOSE/DURATION : 60 mg/kg/3D-I
TOXIC EFFECTS :
Endocrine - changes in spleen weight
Blood - changes in leukocyte (WBC) count
Immunological Including Allergic - decrease in humoral immune response
REFERENCE :
JWIDAW Journal of Wildlife Diseases. (Wildlife Disease Assoc., POB 886,
Ames, IA 50010) V.6- 1970- Volume(issue)/page/year: 30,328,1994
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE : 40 mg/kg
SEX/DURATION : female 14 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - blood and lymphatic
systems (including spleen and marrow)
Reproductive - Specific Developmental Abnormalities - hepatobiliary system
REFERENCE :
EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E.
11th St., New York, NY 10003) V.10- 1987- Volume(issue)/page/year:
18,1,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 321 mg/kg
SEX/DURATION : male 9 week(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - pre-implantation mortality (e.g. reduction in
number of implants per female; total number of implants per corpora lutea)
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 229,129,1990
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 88 mg/kg
SEX/DURATION : male 9 week(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 229,129,1990
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE : 27500 ug/kg
SEX/DURATION : female 7-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - ovaries, fallopian tubes
Reproductive - Effects on Embryo or Fetus - extra-embryonic structures
(e.g., placenta, umbilical cord)
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 16,517,1982
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE : 27500 ug/kg
SEX/DURATION : female 7-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - Central Nervous System
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
Reproductive - Specific Developmental Abnormalities - cardiovascular
(circulatory) system
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 16,517,1982
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE : 27500 ug/kg
SEX/DURATION : female 7-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight
gain)
Reproductive - Effects on Newborn - behavioral
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 16,517,1982
** MUTATION DATA **
TYPE OF TEST : Sex chromosome loss and nondisjunction
TEST SYSTEM : Yeast - Saccharomyces cerevisiae
DOSE/DURATION : 42 mg/L
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 242,231,1990
TYPE OF TEST : Micronucleus test
ROUTE OF EXPOSURE : Multiple routes
TEST SYSTEM : Non-mammalian species
DOSE/DURATION : 500 ppb
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 292,83,1993
TYPE OF TEST : Micronucleus test
ROUTE OF EXPOSURE : Multiple routes
TEST SYSTEM : Non-mammalian species
DOSE/DURATION : 5 ppm
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 292,83,1993
TYPE OF TEST : Unscheduled DNA synthesis
ROUTE OF EXPOSURE : Intraperitoneal
TEST SYSTEM : Rodent - rat
DOSE/DURATION : 200 mg/kg
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 203,135,1988
TYPE OF TEST : Micronucleus test
ROUTE OF EXPOSURE : Oral
TEST SYSTEM : Rodent - mouse
DOSE/DURATION : 15 mg/kg
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 234,169,1990
TYPE OF TEST : Micronucleus test
ROUTE OF EXPOSURE : Intraperitoneal
TEST SYSTEM : Rodent - mouse
DOSE/DURATION : 12500 ug/kg
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 278,99,1992
TYPE OF TEST : Mutation test systems - not otherwise specified
ROUTE OF EXPOSURE : Intraperitoneal
TEST SYSTEM : Rodent - mouse
DOSE/DURATION : 25 mg/kg
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 299,19,1993
TYPE OF TEST : Cytogenetic analysis
ROUTE OF EXPOSURE : Intraperitoneal
TEST SYSTEM : Rodent - mouse
DOSE/DURATION : 25 mg/kg
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 299,19,1993
TYPE OF TEST : Sister chromatid exchange
ROUTE OF EXPOSURE : Intraperitoneal
TEST SYSTEM : Rodent - mouse
DOSE/DURATION : 50 umol/kg
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 222,271,1989
TYPE OF TEST : Sperm Morphology
ROUTE OF EXPOSURE : Intraperitoneal
TEST SYSTEM : Rodent - mouse
DOSE/DURATION : 100 mg/kg/5D (Continuous)
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 69,149,1980
*** REVIEWS ***
IARC Cancer Review:Human Limited Evidence
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- Volume(issue)/page/year: 9,135,1975
IARC Cancer Review:Animal Sufficient Evidence
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- Volume(issue)/page/year: 9,135,1975
IARC Cancer Review:Animal Sufficient Evidence
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- Volume(issue)/page/year: 26,165,1981
IARC Cancer Review:Human Sufficient Evidence
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- Volume(issue)/page/year: 26,165,1981
*** STATUS IN U.S. ***
EPA GENETOX PROGRAM 1988, Positive: Sperm morphology-mouse
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JUNE 1998
*** END OF RECORD ***