Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

IFOSFAMIDE

NFPA

PRODUCT USE

Antineoplastic agent which is converted in the body to an active alkylating metabolite
with properties similar to mustine. Structurally related to cyclophosphamide. Also
possesses marked immunosuppressant properties. Has also been used in the treatment of
solid tumours such as carcinomas of the breast, cervix, lung and ovary. Given by
intravenous injection or infusion.

SYNONYMS

C7-H15-Cl2-N2-O2-P, "1, 3, 2-oxazaphosphorine, ", "1, 3, 2-oxazaphosphorine, ", "3-(2-
chloroethyl)-2-[(2-chloroethyl)amino]tetrahydro-, 2-oxide", "3-(2-chloroethyl)-2-[(2-
chloroethyl)amino]tetrahydro-, 2-oxide", "N, N-bis(beta-chloroethyl)-amino-N', O-
propylenephosphoric acid ester diamide", "N, N-bis(beta-chloroethyl)-amino-N', O-
propylenephosphoric acid ester diamide", "2, 3-[N, N(sup 1)-bis(2-chloroethyl)diamido]-1,
3, 2-oxazaphosphoridinoxyd", "2, 3-[N, N(sup 1)-bis(2-chloroethyl)diamido]-1, 3, 2-
oxazaphosphoridinoxyd", "N, 3-bis(2-chloroethyl)tetrahydro-2H-1, 3, 2-oxazaphosphorin-2-
amine 2-oxide", "N, 3-bis(2-chloroethyl)tetrahydro-2H-1, 3, 2-oxazaphosphorin-2-amine 2-
oxide", "3-(2-chloroethyl)-2[(2-chloroethyl)amino]perhydro-2H-1, 3, 2-oxazaphosphorine",
"3-(2-chloroethyl)-2[(2-chloroethyl)amino]perhydro-2H-1, 3, 2-oxazaphosphorine", oxide, 3-
(2-chloroethyl)-2-[(2-chloroethyl)amino]-, 3-(2-chloroethyl)-2-[(2-chloroethyl)amino]-,
"tetrahydro-2H-1, 3, 2-oxazaphosphorine 2-oxide", "tetrahydro-2H-1, 3, 2-oxazaphosphorine
2-oxide", "N-(2-chloroethyl)-N'-(2-chloroethyl)-N', O-propylenephosphoric acid diamide",
"N-(2-chloroethyl)-N'-(2-chloroethyl)-N', O-propylenephosphoric acid diamide", "N-(2-
chloroethyl)-N'-(2-chloroethyl)-N', O-propylenephosphoric acid ester", "N-(2-chloroethyl)-
N'-(2-chloroethyl)-N', O-propylenephosphoric acid ester", diamide, "2H-1, 3, 2-
oxazaphosphorin-2-amine, N, 3-bis(chloroethyl)tetrahydro-, 2-oxide", "2H-1, 3, 2-
oxazaphosphorin-2-amine, N, 3-bis(chloroethyl)tetrahydro-, 2-oxide", A-4942, "ASTA Z-
4942", "ASTA Z-4942", Cyfos, "Holoxan 1000", Ifosfamid, Iphosphamide, Isoendoxan,
Isofosfamide, Isophosphamide, Mitoxana, "MJF 9325", Naxamide, NCI-CO1638, NSC-109724, Z-
4942, Z-4942, "antineoplastic/ cytotoxic"

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

EMERGENCY OVERVIEW

RISK

Toxic if swallowed.
Irritating to eyes.
May cause CANCER.
May cause heritable genetic damage.
Toxic: danger of serious damage to health by prolonged exposure through
inhalation, in contact with skin and if swallowed.

POTENTIAL HEALTH EFFECTS

ACUTE HEALTH EFFECTS

SWALLOWED

  The material can produce chemical burns within the oral cavity and gastrointestinal tract following ingestion.  The killing action of antineoplastic drugs used for cancer chemotherapy is not selective for cancerous cells alone but affect all dividing cells. Acute side effects include loss of appetite, nausea and vomiting, allergic reaction (skin rash, itch, redness, low blood pressure, unwellness and anaphylactic shock) and local irritation. Gout and renal failure can occur.  Toxic effects may result from the accidental ingestion of the material; animal experiments indicate that ingestion of less than 40 gram may be fatal or may produce serious damage to the health of the individual.  Absorption of nitrogen mustards from the gastrointestinal tract may produce systemic poisoning. The effects may include prolonged tremor, inco-ordination, and convulsions.  

EYE

  This material can cause eye irritation and damage in some persons.  The material can produce chemical burns to the eye following direct contact. Vapors or mists may be extremely irritating.  If applied to the eyes, this material causes severe eye damage.  Nitrogen mustards are severely irritating to the eyes and may produce corneal damage and injury to the iris and lens.  

SKIN

  The material can produce chemical burns following direct contactwith the skin.  Skin contact is not thought to produce harmful health effects (as classified using animal models). Systemic harm, however, has been identified following exposure of animals by at least one other route and the material may still produce health damage following entry through wounds, lesions or abrasions. Good hygiene practice requires that exposure be kept to a minimum and that suitable gloves be used in an occupational setting.  Open cuts, abraded or irritated skin should not be exposed to this material.  Entry into the blood-stream, through, for example, cuts, abrasions or lesions, may produce systemic injury with harmful effects. Examine the skin prior to the use of the material and ensure that any external damage is suitably protected.  Nitrogen mustards can cause serious blisters and burns of the skin, causing deep, slow-  healing ulcers. High quantities can also cause internal toxic effects.  

INHALED

  The material is not thought to produce adverse health effects following inhalation (as classified using animal models). Nevertheless, adverse effects have been produced following exposure of animals by at least one other route and good hygiene practice requires that exposure be kept to a minimum and that suitable control measures be used in an occupational setting.  Persons with impaired respiratory function, airway diseases and conditions such as emphysema or chronic bronchitis, may incur further disability if excessive concentrations of particulate are inhaled.  Inhalation of dusts, generated by the material during the course of normal handling, may be damaging to the health of the individual.  If nitrogen mustard vapors or aerosols are inhaled, there may be irritation of mucous membranes and swelling of the lungs may occur later. They may be absorbed into the body from the lungs, causing effects such as stomach upset, nausea, vomiting and diarrhea, headache, hair loss, bone marrow impairment, damage to the lymph nodes, loss of white blood cells, period irregularities and reduced male fertility. High concentrations can cause damage to the nervous system.  Limited evidence exists that the substance may cause irreversible but non-lethal mutagenic effects following a single exposure.  

CHRONIC HEALTH EFFECTS

  Toxic: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed.  This material can cause serious damage if one is exposed to it for long periods. It can be assumed that it contains a substance which can produce severe defects. This has been demonstrated via both short- and long-term experimentation.  Ample evidence exists, from results in experimentation, that developmental disorders are directly caused by human exposure to the material.  Limited evidence suggests that repeated or long-term occupational exposure may produce cumulative health effects involving organs or biochemical systems.  Exposure to the material may result in a possible risk of irreversible effects. The material may produce mutagenic effects in man. This concern is raised, generally, on the basis ofappropriate studies with similar materials using mammalian somatic cells in vivo. Such findings are often supported by positive results from in vitro mutagenicity studies.  Anti-cancer drugs used for chemotherapy can depress the bone marrow with reduction in the number of white blood cells and platelets and bleeding. Susceptibility to infections and bleeding is increased, which can be life- threatening. Digestive system effects may include inflammation of the mouth cavity, mouth ulcers, esophagus inflammation, abdominal pain and bleeds, diarrhea, bowel ulcers and perforation. Reversible hair loss can result and wound healing may be delayed. Long-term effects on the gonads may cause periods to stop and inhibit sperm production. Most anti-cancer drugs can potentially cause mutations and birth defects, and coupled with the effects of the suppression of the immune system, may also cause cancer.  Studies in mice, rats, and rabbits show that ifosfamide is teratogenic when given in doses 0.05 to 0.75 times greater than the therapeutic dose. Ifosfamide induces mammary tumours, uterine cancer and malignant lymphomas in female rats and mice.  The congener substance, cyclophosphamide, represents a gonadal hazard when given to children with idiopathic nephrotic syndrome. Spermatogenesis in adults is affected. Ovarian tissue appears to be less sensitive to cyclophosphamide than testicular germinal epithelium. Occasional reports  have appeared which describe the development of pneumonitis and pulmonary fibrosis. When administered in the drinking water of rats cyclophosphamide induced transitional cell carcinomas and papillomas of the urinary bladder and neurogenic sarcomas arising from the peripheral nerves. Subcutaneous injection of cyclophosphamide in mice induced mammary carcinomas, lymphomas  and lympho-reticular neoplasms, pulmonary adenomas and sarcomas, squamous cell carcinomas (at the site of injection) and ovarian carcinomas.  Five epidemiological studies consistently demonstrate an excess of various neoplasms in patients undergoing treatment with cyclophosphamide. Bladder cancer and leukaemia are prominent.