Isophosphamide cas no:3778-73-2

NameIsophosphamide
CAS3778-73-2
Synonyms2H-1,3,2-Oxazaphosphorine,3-(2-chloroethyl)-2-[(2-chloroethyl)amino]tetrahydro-, 2-oxide (8CI);3-(2-Chloroethyl)-2-(2-chloroethylamino)tetrahydro-2H-1,3,2-oxaazaphosphorin2-oxide;A 4942;Asta Z 4942;Cyfos;Holoxan;Holoxan 1000;Ifex;Ifomide;Ifosfamid;Ifosfamide;MJF 9325;Mitoxana;NSC 109724;Naxamide;Z 4942;Ifosfamide;
EINECS(EC#)223-237-3
Molecular FormulaC₇H₁₅Cl₂N₂O₂P
Molecular Weight261.09

AppearanceCrystalline Solid
storage temp2-8°C

Hazardclass6.1(b)

Hazard T: Toxic;
Risk R25

CHEMICAL IDENTIFICATION

RTECS NUMBER :

RP6050000

CHEMICAL NAME :

1,3,2-Oxazaphosphorine, 3-(2-chloroethyl)-2-((2-chloroethyl)amino)tetrahydro- , 2-oxide

CAS REGISTRY NUMBER :

3778-73-2

LAST UPDATED :

199612

DATA ITEMS CITED :

73

MOLECULAR FORMULA :

C7-H15-Cl2-N2-O2-P

MOLECULAR WEIGHT :

261.11

WISWESSER LINE NOTATION :

T6NPOTJ AM2G BO B2G

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

150 mg/kg

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting Kidney, Ureter, Bladder - proteinuria Skin and Appendages - hair

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Blood - leukopenia Blood - thrombocytopenia

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human

DOSE/DURATION :

2298 mg/kg/3D-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - hematuria Blood - leukopenia

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human

DOSE/DURATION :

1915 mg/kg/2W-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - hematuria Kidney, Ureter, Bladder - inflammation, necrosis, or scarring of bladder

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human

DOSE/DURATION :

130 mg/kg/13D-I

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting Kidney, Ureter, Bladder - hematuria Kidney, Ureter, Bladder - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

218 mg/kg

TOXIC EFFECTS :

Brain and Coverings - demyelination Brain and Coverings - changes in surface EEG

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

143 mg/kg

TOXIC EFFECTS :

Blood - normocytic anemia Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

140 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

160 mg/kg

TOXIC EFFECTS :

Blood - normocytic anemia Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

190 mg/kg

TOXIC EFFECTS :

Blood - normocytic anemia Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

325 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1005 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

397 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

656 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

338 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human

DOSE/DURATION :

2873 mg/kg/5D-C

TOXIC EFFECTS :

Behavioral - hallucinations, distorted perceptions Kidney, Ureter, Bladder - hematuria Tumorigenic - active as anti-cancer agent

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

50 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - body temperature decrease

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

200 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - miosis (pupillary constriction) Behavioral - muscle weakness Lungs, Thorax, or Respiration - respiratory depression

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

400 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Behavioral - muscle weakness Behavioral - ataxia

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

480 mg/kg/10W-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - other changes in urine composition Nutritional and Gross Metabolic - changes in phosphorus Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

432 mg/kg/6W-I

TOXIC EFFECTS :

Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

300 mg/kg/30D-C

TOXIC EFFECTS :

Endocrine - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

360 mg/kg/6W-I

TOXIC EFFECTS :

Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

540 mg/kg/9W-I

TOXIC EFFECTS :

Blood - changes in leukocyte (WBC) count

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

5220 mg/kg/87W-I

TOXIC EFFECTS :

Blood - changes in leukocyte (WBC) count

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

140 mg/kg/35D-I

TOXIC EFFECTS :

Blood - normocytic anemia Blood - changes in leukocyte (WBC) count Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

940 mg/kg/1Y-I

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Skin and Appendages - tumors Reproductive - Tumorigenic effects - uterine tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

450 mg/kg/8W-I

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2600 mg/kg/65W-I

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Tumorigenic - tumors at site of application

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1872 mg/kg/1Y-I

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Skin and Appendages - tumors Reproductive - Tumorigenic effects - uterine tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

3120 mg/kg/1Y-I

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

90 mg/kg

SEX/DURATION :

male 30 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

300 mg/kg

SEX/DURATION :

male 30 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

300 mg/kg

SEX/DURATION :

female 30 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - ovaries, fallopian tubes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

810 mg/kg

SEX/DURATION :

female 27 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - uterus, cervix, vagina

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

10 mg/kg

SEX/DURATION :

female 10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

260 mg/kg

SEX/DURATION :

female 17-21 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - urogenital system Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

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 - respiratory system Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

13750 ug/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

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) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

13750 ug/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

20 mg/kg

SEX/DURATION :

female 11 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

20 mg/kg

SEX/DURATION :

female 11 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

10 mg/kg

SEX/DURATION :

female 11 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

260 mg/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

65 mg/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

Sex chromosome loss and nondisjunction

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Sperm Morphology

TYPE OF TEST :

Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :

Sister chromatid exchange

TEST SYSTEM :

Bird - chicken Cells - not otherwise specified

DOSE/DURATION :

1250 ug/kg

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 268,115,1992 *** REVIEWS *** IARC Cancer Review:Animal 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: 26,237,1981 IARC Cancer Review:Human No Adequate Data 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: 26,237,1981 IARC Cancer Review:Group 3 IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,56,1987 TOXICOLOGY REVIEW ZKKOBW Zeitschrift fuer Krebsforschung und Klinische Onkologie. (Berlin, Fed. Rep. Ger.) V.76-92, 1971-78. For publisher information, see JCROD7. Volume(issue)/page/year: 88,185,1977 TOXICOLOGY REVIEW KDYIA5 Kidney International. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus Secaucus, NJ 07094) V.1- 1972- Volume(issue)/page/year: 10,82,1976 TOXICOLOGY REVIEW SOLGAV Seminars in Oncology. (Grune & Stratton Inc., Journal Subscription Dept., POB 6280, Duluth, MN 55806) V.1- 1974- Volume(issue)/page/year: 9(Suppl 1),8,1982