5-(Bis(2-chlorethyl)amino)-2,4-(1H,3H)-pyrimidin-dion

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.

Uracil mustard is unstable in the presence of water. Uracil mustard capsules should be stored in tight containers at a temperature less than 40 °C, preferably between 15-30 °C.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practicable 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/

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing 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.

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U237, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

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/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for URACIL MUSTARD (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 URACIL MUSTARD (29 total), please visit the HSDB record page.

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)

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/

URACIL MUSTARD NONCOMPETITIVELY BLOCKED THE ACTIVATION OF RAT HEPATIC GUANYLATE CYCLASE BY N'-NITRO-N-NITROSO-N-PROPYLGUANIDINE & HYDRAZINE. ANTICANCER CHEMOTHERAPEUTIC AGENTS MAY EXERT THEIR EFFECTS BY INHIBITING TUMOR GUANYLATE CYCLASE ACTIVITY.

Uracil mustard may raise the concentration of blood uric acid; dosage adjustment of antigout agents /allopurinol or colchicine or probenecid or sulfinpyrazone/ may be necessary to control hyperuricemia and gout; allopurinol may be preferred to prevent or reverse uracil mustard-induced hyperuricemia because of risk of uric acid nephropathy with uricosuric antigout agents.

Leukopenic and/or thrombocytopenic effects of uracil mustard may be increased with concurrent use or recent therapy if these medications /blood dyscrasia-causing medications/ cause the same effects; dosage adjustment of uracil mustard, if necessary, should be based on blood counts.

Additive bone marrow depression may occur; dosage reduction may be required when two or more bone marrow depressants, including radiation, are use concurrently or consecutively /with uracil mustard/.

TERRESTRIAL FATE: Based on a recommended classification scheme(1), an estimated Koc value of 138(SRC), determined from a structure estimation method(2), indicates that uracil mustard should have high mobility in soil(SRC). Volatilization of uracil mustard should not be important from moist soil surfaces(SRC) given an estimated Henry's Law constant of 3.9X10-13 atm-cu m/mole(3,SRC), or from dry soil surfaces(SRC), based on an estimated vapor pressure of 7.5X10-10 mm Hg(4,SRC). Insufficient data are available to determine the rate or importance of biodegradation of uracil mustard in soil(SRC). Uracil mustard is unstable in water(5) suggesting that the compound will hydrolyze in moist soil(SRC). Uracil mustard has experimental neutral and base-catalyzed hydrolysis rates in water at 25 °C of 0.57/hour and 2.05/hour, respectively, which correspond to a calculated half-life of 1.2 hours at a pH of 7(6).

AQUATIC FATE: Based on a recommended classification scheme(1), an estimated Koc value of 138(SRC), determined from a structure estimation method(2), indicates that uracil mustard would not adsorb to suspended solids and sediment(SRC) in water. Uracil mustard will be essentially non-volatile from water surfaces based on an estimated Henry's Law constant of 3.9X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). An estimated BCF value of 1.8(1,SRC), from an estimated log Kow(4,SRC), suggests that uracil mustard will not bioconcentrate in aquatic organisms(SRC), according to a recommended classification scheme(5). Insufficient data are available to determine the rate or importance of biodegradation of uracil mustard in water(SRC). Uracil mustard has experimental neutral and base-catalyzed hydrolysis rates in water at 25 °C of 0.57/hour and 2.05/hour, respectively, which correspond to a calculated half-life of 1.2 hours at a pH of 7(6).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), uracil mustard, which has an estimated vapor pressure of 7.5X10-10 mm Hg at 25 °C(2,SRC), will exist almost entirely in the particulate phase in the ambient atmosphere. Vapor-phase uracil mustard is degraded in the atmosphere by reaction with photochemically produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be about 19 hours(3,SRC). Vapor-phase uracil mustard is also degraded in the atmosphere by reaction with atmospheric ozone(SRC); the half-life for this reaction in air is estimated to be about 6.5 days(3,SRC). Particulate-phase uracil mustard may be physically removed from the air by wet deposition(SRC).

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=66-75-1]

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/

Using a structure estimation method based on molecular connectivity indices(1), the Koc for uracil mustard can be estimated to be about 138(SRC). According to a recommended classification scheme(2), this estimated Koc value suggests that uracil mustard should have high mobility in soil(SRC).

The Carcinogen Assessment Group in EPA's Research and Development Office has evaluated uracil mustard for carcinogenicity. According to their analysis, the weight of evidence for uracil mustard is group B2, which is based on no evidence in humans and sufficient evidence in animals. As a group B2 chemical, uracil mustard is considered a possible human carcinogen.

Secondary malignancies are potential delayed effects of many antineoplastic agents, although it is not clear whether the effect is related to their mutagenic or immunosuppressive action. The effect of dose and duration of therapy is also unknown, although risk seems to increase with long-term use. Although information is limited, available data seem to indicate that the carcinogenic risk is greatest with the alkylating agents. /Antineoplastic agents/

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. /Antineoplastic agents/

The major adverse effect uracil mustard is hematologic toxicity. Leukopenia and thrombocytopenia occur frequently at therapeutic dosage, and anemia has also been reported. Depression of platelet counts appears to be more pronounced and to occur more frequently than depression of leukocyte counts. Although the manufacturer states that most patients have recovered from toxic reactions to uracil mustard within 2-3 weeks after discontinuance of the drug, hematopoietic toxicity of uracil mustard is cumulative and, as the total dose hematopoietic toxicity of uracil mustard is cumulative and, as the total dose approaches 1 mg/kg, irreversible damage to the bone marrow may occur.

For more Human Toxicity Excerpts (Complete) data for URACIL MUSTARD (7 total), please visit the HSDB record page.

Uracil mustard's production and use as an antineoplastic agent(1) may result in its release to the environment through various waste streams(SRC). Small quantities of the drug(2) may be released to the environment in waste emissions from facilities which formulate the compound into a finished product; however, no monitoring data are available(SRC).

Uracil mustard

Group 2B: Possibly carcinogenic to humans

Volume 9: (1975) Some Aziridines, N-, S- and O-Mustards and Selenium

1987

1987

2B, possibly carcinogenic to humans. (L135)

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

uracil mustard

DILI Positive

DOI:10.1016/j.drudis.2019.09.022

An estimated BCF value of 1.8 was calculated for uracil mustard(SRC), using an estimated log Kow of 0.64(1,SRC) and a recommended regression-derived equation(2). According to a recommended classification scheme(3), this BCF value suggests that bioconcentration in aquatic organisms will not be an important fate process(SRC).

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).

U237: As stipulated in 40 CFR 261.33, when uracil mustard, 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).

MEDICATION

Used for its antineoplastic properties.