Cyclophosphamide monohydrate

279.1

278.035370

8167897

200-015-4

2811

DTXSID6024888

2934999090

42.6

2.14850

White to almost white Crystals or Crystalline Powder

41-45 °C

336.1ºC at 760 mmHg

>230 °F

H2O: 40 g/L

2-8°C

146.5 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Water soluble. Sensitive to moisture and light. Aqueous solutions may be kept for a few hours above room temperature, but hydrolysis occurs at temperatures above 86°F. It undergoes both specific acid and specific base catalysis at extreme pHs. Spontaneous hydrolysis in aqueous solutions.

Amines, Phosphines, and Pyridines

Polymerization can occur at temperatures > 120° F. CYCLOPHOSPHAMIDE MONOHYDRATE reacts with strong oxidizing agents, strong acids and strong bases. Benzyl alcohol increases rate of hydrolysis. (NTP, 1992)

Ⅲ

6.1

UN 3464 6.1/PG 3

3

45-25-61-46-36/37/38-23/24/25

53-45-37/39-26

RP6157750

T

Constitute solns should be used within 24 hr if stored at room temp or within 6 days if stored under refrigeration. When constituted with sterile water for injection or paraben-preserved bacteriostatic water for injection to a concn of 21 mg/ml, <1.5% cyclophosphamide decomposition will occur within 8 hr at 24-27 deg C & within 6 days at 5 deg C.

P201-P301 + P310 + P330-P308 + P313

H301-H350

This chemical is probably combustible. (NTP, 1992)

|Danger|H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P264, P270, P281, P301+P310, P308+P313, P321, P330, P405, and P501|Aggregated GHS information provided by 103 companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P264, P270, P273, P280, P281, P301+P312, P305+P351+P338, P308+P313, P310, P314, P330, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.|H301: Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P260, P263, P264, P270, P281, P301+P310, P307+P311, P308+P313, P314, P321, P330, P405, and P501

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be use. (NTP, 1992)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should protect this material from exposure to light and moisture. Keep it away from oxidizing materials and store it under refrigerated temperatures. If possible, it would be prudent to store this compound under inert atmosphere. (NTP, 1992)

MINIMUM PROTECTIVE CLOTHING: If Tyvek-type disposable protective clothing is not worn during handling of this chemical, wear disposable Tyvek-type sleeves taped to your gloves. RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

Mild and transient elevations in serum aminotransferase levels are found in up to 43% of patients with cancer who are treated with cyclophosphamide. The abnormalities are generally asymptomatic and transient and do not require dose modification. Enzyme elevations are more common with higher doses and with intravenous therapy. In some instances, marked elevations arise warranting dose modification or discontinuation of cyclophosphamide (Case 3).

Cyclophosphamide is an alkylating agent used in the treatment of several forms of cancer including leukemias, lymphomas and breast cancer. Cyclophosphamide therapy is associated with minor transient serum enzyme elevations and has been linked to rare cases of acute liver injury. In addition, when given in high doses as a part of a myeloablative therapy, cyclophosphamide can cause acute sinusoidal obstruction syndrome.

Antineoplastic Agents, Alkylating Agents

A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026) (See all compounds classified as Antineoplastic Agents, Alkylating.)|Drugs that are used to treat RHEUMATOID ARTHRITIS. (See all compounds classified as Antirheumatic Agents.)|Agents that destroy bone marrow activity. They are used to prepare patients for BONE MARROW TRANSPLANTATION or STEM CELL TRANSPLANTATION. (See all compounds classified as Myeloablative Agonists.)|Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. (See all compounds classified as Mutagens.)|Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. (See all compounds classified as Immunosuppressive Agents.)

SYMPTOMS: Symptoms of exposure to this compound may include sterility, testicular atrophy, hematuria, nausea, anorexia, abdominal discomfort or pain, diarrhea, hemorrhagic colitis, oral mucosal ulceration, jaundice, pigmentation of the skin and changes in nails, neutropenia, thrombocytopenia, anemia, urinary bladder fibrosis, hemorrhagic ureteritis, interstitial pulmonary fibrosis, anaphylactic reaction, death, suppression of immune system, interference with normal wound healing, amenorrhea associated with decreased estrogen and increased gonadotropin secretion, ovarian fibrosis with apparently complete loss of germ cells. When administered to pregnant women it may cause the fetus to have ectrodactylia. It may cause transient blurring of vision and blepharoconjunctivitus. It may also cause blood, bladder, lung and cardiac changes, gonadal suppression, skin rash and conjunctivitis. Other symptoms of exposure may include leukopenia, lymphocytopenia, reversible alopecia, hemorrhagic cystitis, vomiting, acute and fatal myopericarditis, necrosis of the renal tubular epithelium, hemorrhagic pancreatitis, reduced sperm count, occasional pneumonitis and adverse effects on the thyroid. It may cause myocardial damage. It may also cause chromosomal aberrations and sister chromatid exchanges. ACUTE/CHRONIC HAZARDS: This compound may be harmful if swallowed, inhaled or absorbed through the skin. It may cause irritation. When heated to decomposition it emits toxic fumes of carbon monoxide, carbon dioxide, nitrogen oxides, phosphorus oxides, phosphine and hydrogen chloride gas. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. IMMEDIATELY call a hospital or poison control center even if no symptoms (such as redness or irritation) develop. IMMEDIATELY transport the victim to a hospital for treatment after washing the affected areas. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Generally, the induction of vomiting is NOT recommended outside of a physician's care due to the risk of aspirating the chemical into the victim's lungs. However, if the victim is conscious and not convulsing and if medical help is not readily available, consider the risk of inducing vomiting because of the high toxicity of the chemical ingested. Ipecac syrup or salt water may be used in such an emergency. IMMEDIATELY transport the victim to a hospital. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992)

(+,-)-2-(bis(2-Chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-Oxide Monohydrate

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients