Mitomycin C

334.33

334.33

200-008-6

50SG953SK6

26980

2811|3077

DTXSID2020898

C1820

BLUE-VIOLET CRYSTALS

L - Antineoplastic and immunomodulating agents

29419090

147

-0.4

blue-gray powder

1.2238 (rough estimate)

>360 °C

534 °C

305.6ºC

1.68

H2O: 4 mL/vial Stock solutions should be filter sterilized and stored at 2-8 °C in the dark., clear to slightly hazy, blue to purple

2-8°C

Oral-rat LD50: 30 mg/kg; Oral-Mouse LD50: 23 mg/kg

Flammable; burning produces toxic nitrogen oxide fumes

10.9None

LogP = -0.38; Henry's Law constant = 2.5X10-10 atm-cu m/mol

10.9

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

Water soluble.

Amides and Imides

MITOMYCIN C is sensitive to prolonged exposure to light. It may be sensitive to prolonged exposure to air. This chemical is incompatible with strong oxidizing agents, strong acids and strong bases. Calcium salts may cause decomposition. (NTP, 1992)

II

6.1(a)

UN 3462 6.1/PG 2

3

25-40-22-45-26/27/28

36/37-45-28A-28-53-22

CN0700000

T,Xn,T+

Warehouse ventilated, low temperature and dry

Stable. Incompatible with strong acids, strong bases, strong oxidizing agents.

P201, P202, P264, P270, P281, P301+P310, P308+P313, P321, P330, P405, P501

H300

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U010, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.|A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.|PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/|For more Disposal Methods (Complete) data for MITOMYCIN C (14 total), please visit the HSDB record page.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Weisburger EK; Bioassay Program for Carcinogenic Hazards of Cancer Chemotherapeutic Agents; Cancer 40: 1935-49 (1977). Route: intraperitoneal injection; Species: rats and mice.|Beijnen JH et al; Mitomycin Antitumor Agents: a Review of their Physico-Chemical and Analytical Properties and Stability; J Pharm Biomed Anal 4 (3): 275-295 (1986).|Sinha BK, Mimnaugh EG; Free Radicals and Anticancer Drug Resistance: Oxygen Free Radicals in the Mechanisms of Drug Cytotoxicity and Resistance by Certain Tumors Free Radic Biol Med 8 (6): 567-81 (1990).

Flash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)

|Danger|H300 (92.59%): Fatal 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 54 companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (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)

Avoid inhalation and skin contact. (EPA, 1998)

For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)|PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Protective apparel: Disposable closed-front gown or coveralls, disposable utility gloves over disposable latex gloves, NIOSH-approved air-purifying half-mask respirator equipped with a high efficiency filter, and eye protection should be worn. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Class 100 clean-air work stations, both horizontal and vertical airflow (with no containment characteristics), are inappropriate engineering controls for handling hazardous drugs because they provide no personnel protection and permit environmental contamination. Although there are no engineering controls designed specifically for the safe handling of hazardous chemicals as sterile products, Class II contained vertical-flow biological safety cabinets (biohazard cabinets) have been adopted for this use. Biohazard cabinetry is, however, designed for the handling of infectious agents, not hazardous chemicals. ... Based on design, ease of use, and cost considerations, Class II contained-vertical-flow biohazard cabinetry is currently recommended for use in preparing sterile doses of hazardous drugs. Class II cabinetry design and performance specifications are defined in NSF Standard 49. Biological safety cabinets selected for use with hazardous drugs should meet NSF Standard 49 specifications to ensure the maximum protection from these engineering controls. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers should wear powder free, disposable surgical latex gloves of good quality when preparing hazardous drugs. Selection criteria for gloves should include thickness (especially at the fingertips where stress is the greatest), fit, length, and tactile sensation. ... The practice of double gloving is supported by research that indicates that many glove materials vary in drug permeability even within lots; therefore, double gloving is recommended. ... In general, surgical latex gloves fit better, have appropriate elasticity for double gloving and maintaining the integrity of the glove-gown interface, and have sufficient tactile sensation (even during double gloving) for stringent aseptic procedures. ... Powdered gloves should be avoided. /Antineoplastic agents/|For more Personal Protective Equipment (PPE) (Complete) data for MITOMYCIN C (6 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Spill kits containing all materials needed to clean up spills of hazardous drugs should be assembled or purchased. These kits should be readily available in all areas where hazardous drugs are routinely handled. If hazardous drugs are being prepared or administered in a nonroutine area (home setting or unusual patient-care area), a spill kit should be obtained by the drug handler. The kit should include two pairs of disposable gloves (one outer pair of utility gloves and one inner latex pair); low-permeability, disposable protective garments (coveralls or gown and shoe covers); safety glasses or splash goggles; respirator; absorbent, plastic-backed sheets or spill pads; disposable toweling; at least 2 sealable thick plastic hazardous waste disposal bags (prelabeled with an appropriate warning label); a disposable scoop for collecting glass fragments; and a puncture-resistant container for glass fragments. All individuals who routinely handle hazardous drugs must be trained in proper spill management and cleanup procedures. Spills and breakages must be cleaned up immediately according to the following procedures. If the spill is not located in a confined space, the spill area should be identified and other people should be prevented from approaching and spreading the contamination. Wearing protective apparel from the spill kit, workers should remove any broken glass fragments and place them in the puncture-resistant container. Liquids should be absorbed with a spill pad; powder should be removed with damp disposable gauze pads or soft toweling. The hazardous material should be completely removed and the area rinsed with water and then cleaned with detergent. The spill cleanup should proceed progressively from areas of lesser to greater contamination. The detergent should be thoroughly rinsed and removed. All contaminated materials should be placed in the disposal bags provided and sealed and transported to a designated containment receptacle. Spills occurring in the biohazard cabinet should be cleaned up immediately; a spill kit should be used if the volume exceeds 150 ml or the contents of one drug vial or ampule. If there is broken glass, utility gloves should be worn to remove it and place it in the puncture-resistant container located in the biohazard cabinet. The biological safety cabinet, including the drain spillage trough, should be thoroughly cleaned. If the spill is not easily and thoroughly contained, the biological safety cabinet should be decontaminated after cleanup. If the spill contaminates the high efficiency particulate air filter, use of the biological safety cabinet should be suspended until the cabinet has been decontaminated and the high efficiency particulate air filter replaced. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ If hazardous drugs are routinely prepared or administered in carpeted areas, special equipment is necessary to remove the spill. Absorbent powder should be substituted for pads or sheets and left in place on the spill for the time recommended by the manufacturer. The powder should then be picked up with a small vacuum unit reserved for hazardous drug cleanup. The carpet should then be cleaned according to usual procedures. The vacuum bag should be removed and discarded or cleaned, and the exterior of the vacuum cleaner should be washed with detergent and rinsed before being covered and stored. The contaminated powder should be discarded into a sealable plastic bag and segregated with other contaminated waste materials. Alternatively, inexpensive wet or dry vacuum units may be purchased for this express use and used with appropriate cleaners. All such units are contaminated, once used, and must be cleaned, stored, and ultimately discarded /properly/ ... The circumstances and handling of spills should be documented. Health-care personnel exposed during spill management should also complete an incident report or exposure form. /Antineoplastic agents/

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/|For more Preventive Measures (Complete) data for MITOMYCIN C (28 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

U010; A toxic waste when, a discarded commercial chemical product or manufacturing chemical intermediate or, an off-specification commercial chemical product or manufacturing chemical intermediate.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 10 lb or 4.54 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).|Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Mitomycin C is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500/10,000 lbs.

U010; As stipulated in 40 CFR 261.33, when mitomycin C, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

most toxic

Oral, mouse: LD50 = 23 mg/kg; Oral, rat: LD50 = 30 mg/kg. Symptoms of overdose include nausea and vomiting.

Chemotherapy with mitomycin in combination with other agents is associated with serum enzyme elevations in a proportion of patients, depending upon the dose and other agents used. ALT elevations during mitomycin therapy are usually asymptomatic and transient and may resolve without dose modification. In many instances, it is difficult to attribute the liver test abnormalities to mitomycin, because of the exposure to other potentially hepatotoxic agents. High doses of mitomycin have been linked to cases of sinusoidal obstruction syndrome, typically presenting with right upper quadrant pain 10 to 30 days after the infusion, followed by weight gain, ascites and liver test abnormalities. Fatalities due to hepatic failure have occurred, but most patients recover within 1 to 3 months of onset. The frequency of sinusoidal obstruction syndrome limits the dosage of mitomycin that can be used in cancer chemotherapy and in myeloablation in preparation for bone marrow transplantation. There have been no convincing instances of acute, clinically apparent idiosyncratic liver injury with jaundice associated with mitomycin therapy.

IN RATS GIVEN SINGLE DOSES OF 3 MG METHYLCHOLANTHRENE BY SC INJECTION INCIDENCE OF LOCAL SARCOMAS AFTER 120 DAYS WAS REDUCED WHEN WEEKLY IP INJECTIONS OF MITOMYCIN C WERE ALSO GIVEN.|IN MICE ... ADMIN 0.2 ML OF 1% SOLN OF METHYLCHOLANTHRENE IN BENZENE ON SKIN DAILY FOR 5-10 DAYS, INCIDENCE OF SKIN PAPILLOMAS WAS GREATLY INCR WHEN MITOMYCIN C WAS GIVEN DAILY BY 20 IP INJECTIONS ... .|IN RATS GIVEN 40 UG/KG BODY WT MITOMYCIN C IP & ORAL DOSE DMBA, INCIDENCE OF MAMMARY TUMORS AFTER 120 DAYS WAS SIMILAR TO THAT IN RATS GIVEN DMBA ALONE.|Absorption of cephalexin, sulfanilamide, salicylic acid, and D- and L-tryptophan was significantly decreased by the pretreatment with /iv/ mitomycin C /in rats/. Absorption of 6-carboxyfluorescein and fluorescein isothiocyanate conjugated dextran was not significantly affected by mitomycin C pretreatment. Maximal effects, using sulfanilamide as a model, were noted 48 hours after mitomycin C pretreatment. The dosage of mitomycin C ... did not affect the percentage of sulfanilamide absorbed.|For more Interactions (Complete) data for MITOMYCIN C (25 total), please visit the HSDB record page.

LD50 Mouse iv 5 mg/kg|LD50 cat iv 1-2.5 mg/kg|LD50 dog iv 1-2.5 mg/kg|LD50 monkey iv 1-2.5 mg/kg

Produced by Streptomyces caespitosus, an organism from Japanese soil.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The danger to health-care personnel from handling a hazardous drug stems from a combination of its inherent toxicity and the extent to which workers are exposed to the drug in the course of carrying out their duties. This exposure may be through inadvertent ingestion of the drug on foodstuffs (eg, workers' lunches), inhalation of drug dusts or droplets or direct skin contact. /Antineoplastic agents/

For treatment of malignant neoplasm of lip, oral cavity, pharynx, digestive organs, peritoneum, female breast, and urinary bladder. Also used as an adjunct to ab externo glaucoma surgery. Mitomycin is also indicated as a pyelocalyceal solution for the treatment of adults with low-grade upper tract urothelial cancer (LG-UTUC).|FDA Label|Drug: Mitomycin

Mitomycin is a cytotoxic antibiotic which is used as anticancer therapy of advanced cancers of the stomach and pancreas. Mitomycin in combination with other anticancer agents frequently causes mild-to-moderate serum enzyme elevations during therapy and is capable of causing sinusoidal obstruction syndrome, but mitomycin by itself has not been specifically linked to instances of clinically apparent liver injury with jaundice.

Antineoplastic Agents

Antibiotics, Antineoplastic; Nucleic Acid Synthesis Inhibitors|Mitomycin is useful for the palliative treatment of gastric adenocarcinoma, in conjunction with fluorouracil and doxorubicin. It has produced temporary beneficial effects in carcinomas of the cervix, colon, rectum, pancreas, breast, bladder, head and neck, and lung, and in melanoma. It has also shown activity against lymphomas and leukemia, particularly chronic granulocytic leukemia, but not in myeloma.|Thirty patients with advanced colorectal adenocarcinoma were treated by chemotherapy with an alternating regimen consisting of 5-fluorouracil mitomycin C and 5-fluorouracil dacarbazine at 3 wk intervals. ... The toxicity of this regimen was essentially digestive with 30% of grade 3 or 4 nausea and vomiting. In spite of the reported active and synergistic action of drug association in colorectal carcinoma, this treatment schedule is not better than 5-fluorouracil alone. Gastrointestinal toxicity was incr.|Forty-two patients with metastatic breast cancer refractory to first line therapies were treated with combination chemotherapy with mitomycin-C and vinblastine. ... The toxicity was acceptable with 20 episodes of moderate myelosuppression (58.8%) and 2 cases with congestive heart failure that responded to medical treatment.|For more Therapeutic Uses (Complete) data for MITOMYCIN C (19 total), please visit the HSDB record page.

Mitomycin is contraindicated in patients with pre-existing myelosupression & anemia.|Because normal defense mechanisms may be suppressed by mitomycin therapy, the patient's antibody response to the vaccine may be decreased. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year.|cBecause normal defense mechanisms may be suppressed by mitomycin therapy, concurrent use with a live virus vaccine may potentiate the replication of the vaccine virus, may increase the side/adverse effects of the vaccine virus, and/or may decrease the patient's antibody response to the vaccine; immunization of these patients should be undertaken only with extreme caution after careful review of the patient's hematologic status and only with the knowledge and consent of the physician managing the cytarabine therapy. The interval between discontinuation of medication that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medications used, the underlying disease, and other factors; estimates vary from 3 months to 1 year. Patients with leukemia in remission should not receive live virus vaccine until at least 3 months after their last chemotherapy. In addition, immunization with oral polio-virus vaccine should be postponed in persons in close contact with the patient, especially family members.|Gonadal suppression, resulting in amenorrhea or azoospermia, may occur in patients taking antineoplastic therapy, especially with the alkylating agents. In general, these effects appear to be related to dose and length of therapy and may be irreversible. Prediction of the degree of testicular or ovarian function impairment is complicated by the common use of combinations of several antineoplastics, which makes it difficult to assess the effects of individual agents.|For more Drug Warnings (Complete) data for MITOMYCIN C (6 total), please visit the HSDB record page.

Mitomycin is one of the older chemotherapy drugs, which has been around and in use for decades. It is an antibiotic which has been shown to have antitumor activity. Mitomycin selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. Mitomycin has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2.

Compounds that inhibit cell production of DNA or RNA. (See all compounds classified as Nucleic Acid Synthesis Inhibitors.)|Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other. (See all compounds classified as Cross-Linking Reagents.)|Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. (See all compounds classified as Alkylating Agents.)|Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms. (See all compounds classified as Antibiotics, Antineoplastic.)

Erratic.|Approximately 10% of a dose of mitomycin is excreted unchanged in the urine.|FOLLOWING IV INJECTION OF 2 MG/KG BODY WT ... WISTAR RATS, 18% WAS RECOVERED UNCHANGED IN URINE WITHIN 24 HR AT ... 8 MG/KG ... 35% WAS RECOVERED IN URINE, BUT NONE IN FECES OR TISSUES.|THIRTY MIN AFTER IV INJECTION OF 8 MG/KG BODY WT TO MICE TRACES REMAINED IN BLOOD. IN GUINEA PIGS DRUG WAS CONCN IN KIDNEYS & NOT IN LIVER, SPLEEN OR BRAIN & WAS EXCRETED IN URINE.|Mitomycin is absorbed inconsistently from the gastrointestinal tract, and it is therefore administered intravenously. It disappears rapidly from the blood after injection. Peak concentrations in plasma are 0.4 ug/ml after doses of 20 mg/m sq ... The drug is widely distributed throughout the body but is not detected in the brain.|In animals, highest mitomycin concentrations are found in the kidneys, followed by muscles, eyes, lung, intestines, and stomach. The drug is not detectable in the liver, spleen, or brain which rapidly inactivate mitomycin. Higher concentrations of the drug are generally present in cancer tissues than in normal tissues.|For more Absorption, Distribution and Excretion (Complete) data for MITOMYCIN C (9 total), please visit the HSDB record page.

Primarily hepatic, some in various other tissues.|SUGGESTED ALKYLATING METABOLITES OF CARCINOGENS: MITOMYCIN C: REDUCTION PRODUCTS. /FROM TABLE/|Inactivation occurs by metabolism, but the products have not been identified. It is metabolized primarily in the liver, and less than 10% of the active drug is excreted in the urine or the bile.|The drug is eliminated primarily by hepatic metabolism with about 20% hepatic extraction and 10-30% recovery of intact drug in the urine. Clearance is 0.3-0.4 l/hr/kg.|Mitomycin disappears rapidly from the blood after intravenous injection. It is widely distributed but does not appear to cross the blood-brain barrier. Mitomycin is metabolized mainly in the liver; up to 10% of a dose is excreted unchanged in the urine.|MITOMYCIN C WAS PREFERENTIALLY ACTIVATED & METABOLIZED BY SONICATED CELL PREPARATIONS. BIOACTIVATION OF MITOMYCIN TO ALKYLATING AGENT BY EMT6 & SARCOMA 180 CELL SONICATES REQUIRED HYPOXIC CONDITIONS & NADPH-GENERATING SYSTEM.

8-48 min|After doses of 20 mg/m sq ... Mitomycin is cleared from plasma with a half-time of approximately 1 hour.|/Mitomycin/ has an alpha half-life of 5-10 min after IV injection and beta half-life of 46 min.

Mitomycin is activated in vivo to a bifunctional and trifunctional alkylating agent. Binding to DNA leads to cross-linking and inhibition of DNA synthesis and function. Mitomycin is cell cycle phase-nonspecific.|... REACTS WITH BACTERIAL DNA BUT NOT WITH ISOLATED DNA, UNLESS ... REDUCING SYSTEM IS ADDED. CROSS LINKING EFFICIENCY ... INCR IN ISOLATED BACTERIAL DNA CONTAINING INCR AMT OF CYTOSINE & GUANOSINE.|ITS REDUCED FORM CONTAINS INDOLE GROUP EMBODYING ALLYLIC CARBAMATE RESIDUE. ANTIBIOTIC IS CYTOTOXIC & CARCINOGENIC BUT IS INACTIVE AS CYTOTOXIC AGENT UNLESS REDUCED ... IT ACTS AS DIFUNCTIONAL AGENT IN CROSS LINKING DNA.|The drug inhibits DNA synthesis and cross-links DNA at the N6 position of adenine and at the O6 and N2 positions of guanine. In addition, single-strand breakage of DNA is caused by reduced mitomycin; this can be prevented by free radical scavengers. Its action is most prominent during the late G1 and early S phases of the cell cycle.|In high concentrations ... /mitomycin/ may ... inhibit RNA and protein synthesis.|For more Mechanism of Action (Complete) data for MITOMYCIN C (11 total), please visit the HSDB record page.

Toxic doses as low as 750 mg/kg have been reported in humans. The major toxic effect is myelosuppression, characterized by marked leukopenia and thrombocytopenia; this may be delayed and cumulative. Interstitial pneumonia and glomerular damage resulting in kidney failure are unusual but well documented complications. Lung conditions -- administration of mitomycin has been recognized as causing pneumonitis, alveolitis and pulmonary fibrosis. Kidney conditions -- administration of mitomycin can cause kidney damage. Kidney toxicity was observed in 1-5 percent of patients. Depressed immune conditions. (EPA, 1998)|Carcinogens

Warning: Mitomycin C may produce delayed secondary malignancies. Caution is advised. Signs and Symptoms of Mitomycin C Exposure: Signs and symptoms of acute exposure to mitomycin c may include headache, blurred vision, anorexia (loss of appetite), nausea, vomiting, diarrhea, ileus (obstruction of the intestines), and inflammation of the lungs and mucous membrances. Confusion, drowsiness, fatique, lethargy, and weakness may also be seen. Renal toxicity, bladder contraction, hemolytic anemia, and thrombosis (blood clots) may also occur. Emergency Life-Support Procedures: Acute exposure to mitomycin c exposure may require decontamination and life support for the victims. Emergency personnel should wear protective clothing appropriate to the type and degree of contamination. Air-purifying or supplied-air respiratory equipment should also be worn, as necessary. Rescue vehicles should carry supplies such as plastic sheeting and disposable plastic bags to assist in preventing spread of contamination. Inhalation Exposure: 1. Remove victims fresh air. Emergency personnel should avoid self-exposure to mitomycin c. 2. Evaluate vital signs including pulse and respiratory rate and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer 100% humidified oxygen or other respiratory support. 3. Transport to a health care facility. 4. Obtain authorization and/or further instructions from the local hospital for performance of other invasive procedures. Dermal/Eye Exposure: 1. Remove victims from exposure. Emergency personnel should avoid self-exposure to mitomycin c. 2. Evaluate vital signs including pulse and respiratory rate and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer 100% humidified oxygen or other respiratory support. 3. Remove and isolate contaminated clothing as soon as possible. 4. If eye exposure has occurred, eyes must be flushed with lukewarm water for at least 15 minutes. 5. Wash exposed skin areas three times with soap and water. 6. Obtain authorization and/or further instructions from the local hospital for performance of other invasive procedures. 7. Transport to a health care facility. Ingestion Exposure: 1. Evaluate vital signs including pulse and respiratory rate and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer 100% humidified oxygen or other respiratory support. 2. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 3. Vomiting may be induced with syrup of Ipecac. If elapsed time since ingestion of mitomycin is unknown or suspected to be greater than 30 minutes, do not induce vomiting and proceed to Step 4. Ipecac should not be administered to children under 6 months of age.Warning: Ingestion of mitomycin may result in sudden onset of seizures or loss of consciousness. Syrup of Ipecac should be administered only if victims are alert, have an active gag-reflex, and show no signs of impending seizure or coma. If ANY uncertainty exists, proceed to Step 4.The following dosages of Ipecac are recommended: children up to 1 year old, 10 mL (1/3 oz); children 1 to 12 years old, 15 mL (1/2 oz); adults, 30 mL (1 oz). Ambulate (walk) the victims and give large quantities of water. If vomiting has not occurred after 15 minutes, Ipecac may be readministered. Continue to ambulate and give water to the victims. If vomiting has not occurred within 15 minutes after second administration of Ipecac, administer activated charcoal. 4. Activated charcoal may be administered if victims are conscious and alert. Use 15 to 30 g (1/2 to 1 oz) for children, 50 to 100 g (1-3/4 to 3-1/2 oz) for adults, with 125 to 250 mL (1/2 to 1 cup) of water. 5. Promote excretion by administering a saline cathartic or sorbitol to conscious and alert victims. Children require 15 to 30 g (1/2 to 1 oz) of cathartic; 50 to 100 g (1-3/4 to 3-1/2 oz) is recommended for adults. 6. Transport to a health care facility. (EPA, 1998)

Two cases are presented which suggest that pyridoxine injected into a Mitomycin-C extravasation site may slow or prevent necrosis, and may decrease the pain associated with the chronic ulceration of extravasation.

APHTHOUS STOMATITIS, ALOPECIA, DESQUAMATION. INDURATION, PRURITUS, PAIN ON INJECTION, PARESTHESIA, & NECROSIS OCCUR IN APPROX 4% OF PATIENTS. CELLULITIS, ULCERATION, & SLOUGH @ INJECTION SITE ... IF EXTRAVASATION OF DRUG OCCURS. /IV ADMIN/|... INCIDENCE OF BONE MARROW DEPRESSION (PARTICULARLY THROMBOCYTOPENIA & LEUKOPENIA) IS HIGH (65%) ... . /IV ADMIN/|PULMONARY TOXICITY, CONSISTING OF HEMOPTYSIS, DYSPNEA, COUGH, & PNEUMONIA, IS OBSERVED IN APPROX 1-1.5% OF PATIENTS. RENAL TOXICITY HAS BEEN DEMONSTRATED IN COMPARABLE PERCENTAGE OF PATIENTS & USUALLY IS MANIFESTED BY INCR BUN LEVELS. FEVER, ANOREXIA, NAUSEA, & VOMITING HAVE BEEN REPORTED IN ABOUT 15% OF PATIENTS. /IV ADMIN/|HEADACHES, BLURRED VISION, CONFUSION, DROWSINESS, SYNCOPE, FATIGUE, DIARRHEA, & PAIN HAVE BEEN NOTED OCCASIONALLY. THESE DO NOT APPEAR TO BE DOSE RELATED. /IV ADMIN/|For more Human Toxicity Excerpts (Complete) data for MITOMYCIN C (25 total), please visit the HSDB record page.

Ametycine

MUTAMYCIN ... INJECTION: POWDER 5 MG.|Mitomycin ... available as deep blue-violet crystals in vials containing 5, 20, or 40 mg ... administered by intravenous infusion.|Mitomycin for injection is a dry mixture of Mitomycin and Mannitol. It contains not less than 90.0% and not more than 120.0% of the labeled amount of mitomycin C.|Mitomycin has a potency of not less than 900 ug of mitomycin C per mg.

Azirino[2',3':3,4]pyrrolo[1,2-a]indole-4,7-dione, 6-amino-8-[[(aminocarbonyl)oxy]methyl]-1,1a,2,8,8a,8b-hexahydro-8a-methoxy-5-methyl-, (1aS,8S,8aR,8bS)-: ACTIVE|S - indicates a substance that is identified in a final Significant New Use Rule.

MITOMYCIN C WAS SEPARATED BY HIGH-PRESSURE LIQUID CHROMATOGRAPHY.|A packed-column supercritical-fluid chromatograph was interfaced with a mass spectrometer via a modification of a thermospray probe. This modification allowed a capillary restrictor for the suprecritical-fluid carbon dioxide and reagent gas for chemical ionization to be introduced directly into a thermospray source. Chemical ionization conditions were observed when either the filament or discharge electrode was used and the source pressure was above 0.5 torr. The discharge electrode produced more efficient ionization, resulting in approx a ten-fold larger signal than that observed in the filament mode. The usefulness of this instrumentation was demonstrated on several anticancer drugs. Methanol posositive ion chemical ionization (PICI) spectra were recorded for cyclophosphamide, diaziquone, mitomycin C, and thiotepa.|Electrochemical detection at constant potential in online combination with HPLC was a sensitive detection method for the title drugs. For improved collection and handling of detection signals, 4 modes of software filtering are studied and compared with hardware filtering. In the investigated chromatography-electrochemical system, off-line parabolic filtering after online averaging of 16 measurements proved to be the system of first choice, with respect to execution time, noise level, signal to noise ratio, peak height and resolution.|An automatic, reliable, scanning reductive electrochemical detection system is described for online qualitative and semiquantitative determination and characterization of electroactive cmpd in effluents from HLPC system. Applying a static mercury drop electrode, detection can be performed at constant potential for quantitative analysis (current range: 50 nA F.S) at a routine base. Applying potential scans, qualitative analysis can be performed (current range: 0.5 mu A F.S.). The system was evaluated through analysis of mitomycin C, porfiromycin and the degradation products of mitomycin C from alkaline and acid hydrolysis.

An HPLC method for the detection of mitomycin C in blood plasma and urine of rats and humans is reported. Samples of urine and rat plasma with the internal standard porfiromycin were extracted by ethyl acetate-chloroform-isopropanol (70:15:15), human blood was extracted with ethyl acetate. Dry residues of the organic phase were dissolved in methanol and analyzed on a reversed-phase Pecosphere C18 column using a mobile phase of acetonitrile-2.5 mM phosphate buffer pH 6.9 (12.5:87.5) and UV-detection at 35 nm. The calibration was linear at 0.1-10 ug/ml, coefficients of variation 1.3-7.5%, and detection limit 0.5 ng/ml.|A sensitive HPLC method with a dual-electrode coulometric detection system for the determination of mitomycin C (I) in human blood serum is presented. The method is based on a Develosil 5-um column, methyl cyanide-0.05M sodium hypochlorite (15:85) as the mobile phase, a flow-rate of 1.0 ml/min, and porfiromycin as an internal standard. The standard response curves were linear over the concentration range 10-100 ng/ml of mitomycin C. The recovery rates of mitomycin C were 100.5-110.0%. The detection limit was 1 ng (single-to-noise ratio= 5). The sensitivity was ten times better than that with UV detection.|Mitomycin C reacted with components of culture medium containing antibiotics with and without fetal calf serum within 30 min incubation at 38 degree. The amount of mitomycin C in medium with fetal calf serum was reduced by 29% after 30 min and by 53% after 60 min incubation. Many changes in species composition were apparent after 60 min incubation, with the greater change in composition occuring in culture medium containing fetal calf serum. The purity of several commercial preparation of mitomycin-C varied considerably; 1 preparation contained a contaminant of greater concentration than mitomycin C, if one assumes the same relative response of the mass spectrometer.|A fully automated liquid chromatography system for the bioanalysis of mitomycin C has been described. The isolation of the analyte from the biological matrix (plasma, ascites and urine) is performed using a continuous-flow system equipped with a dialysis membrane in order to remove proteins. The drug is detected by absorbance measurements at 360 nm. Using the described system up to 100 samples a day can be analyzed with detection limits in the order of 1 ng/ml.|An HPLC method for the determination of mitomycin C in human blood is described. The method has the advantage of reduced sample handlings and direct injection of plasma samples into a loop-column and a low detection limit of approximately 1.0 ng/ml plasma. Detection was photometric at 65 nm the calibration curve was linear over the range 1-600 ng/ml. Recovery was 100% for standard solutions. Quantitation was performed by running a 4-point calibration curve (1, 50, 100, and 250 ng/ml) for 9 plasma samples. The day-to-day coefficient of variation was 1.6% and the within-day coefficient of variation was 1.2% (2-350 ng/ml range).

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