6-Amino-8-(((aminocarbonyl)oxy)-methyl)-1,1a,2,8,8a,8b-hexahydro-8a-methoxy-5-methylazirino-(2',3': 3,4)pyrrolo(1,2-a)indol-4,7-dion,(1aS-(1a alpha, 8 beta, 8a alpha,8b alpha))-

Mitomycin powder for injection should be protected from light and preferably stored at 15-30 °C: temperature greater than 40 °C should be avoided.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

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/

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.

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.

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/

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.

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.

IARC Carcinogen - Class 3: Chemicals are not classifiable by the International Agency for Research on Cancer.

Bone marrow toxicity is the most commonly reported adverse effect, occurring in most patients treated with mitomycin in one study. It produces cumulative myelosuppression. Thrombocytopenia and possibly leukopenia may occur anytime within the first two months after beginning therapy, with an average duration of one month. The recovery time after the termination of therapy was about ten weeks. About 25% of the leukopenic or thrombocytopenic episodes were permanent and did not return to baseline levels. As these patients are already immunocompromised, extreme caution is necessary to ensure further bone marrow suppression does not contribute to overwhelming subsequent infections.

Pulmonary toxicity is a rare but well-documented adverse effect of mitomycin C. In one trial at the Mayo Clinic, despite pre-medication with the use of corticosteroids, pulmonary toxicity occurred, with changes in diffusing lung capacity of 9 and PaO2 of 49 mm Hg. A significant number of patients who had bronchoscopies had changes noted on pulmonary histology consistent with lung injury.

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.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=50-07-7]

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ There is no method available for routine monitoring of personnel for evidence of hazardous drug exposure. Tests for the presence of mutagens or chromosomal damage are not drug specific and are of value only in controlled studies. Chemical analysis of urine for the presence of hazardous drugs at the sensitivity level needed to detect occupational exposure is limited to a few drugs and is not yet commercially available. /Antineoplastic agents/

Mitomycin C (CAS # 50-07-7) was evaluated for primary dermal irritation. The test substance was applied undiluted to the clipped intact skin of 6 New Zealand white rabbits under an occlusive dressing at a level of 0.5 ml for 4-hours. No deaths or clinical signs were observed during the study. Irritation consisted of erythema (moderate to severe till Day 14) and edema (decreasing severity, but still present by Day 21). Significant lesions were present on Day 21. The test substance was determined to be corrosive to skin.

Mitomycin C (CAS # 50-07-7) was evaluated for its potential to induce chromosome aberrations in cultured Chinese hamster ovary cells with and without metabolic activation. Testing was conducted using concentrations of test substance at 125, 63, 31, 16, 7.8, and 3.9 ug/ml (without activation) and 500, 450, 400, 350, 300, 250, 200, 100, and 50 ug/ml (with activation). There were statistically significant increases in the number of aberrants cells at 125 ug/ml (10-17%) without activation and at 75 ug/ml (10-11%) and 100 ug/ml (38-49%) with activation.

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.

Mitomycin C

Group 2B: Possibly carcinogenic to humans

Volume 10: (1976) Some Naturally Occurring Substances

1987

1987

2B, possibly carcinogenic to humans. (L135)

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).

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).

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.

Used as an alkylating agent in cancer chemotherapy; [HSDB]

MEDICATION

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.

PRODUCED BY STREPTOMYCES CAESPITOSUS (GRISEOVINACESEUS).

Yamamoto, Kenkyusho, Japan pat. 2898 (1956); Kenkyusho, Brit. pat. 830,874 (1960 to Kyowa); Gourevitch et al, U.S. pat. 3,042583 (1962 to Bristol-Myers) /production of the complex/

...derived from Streptomyces

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.