Semustine

247.72

247.72

2281H4FBL9|EGU4CMI14D

758471|135091|95441

3249

DTXSID8031603

C827

Crystals

L - Antineoplastic and immunomodulating agents

2924299090

61.8

3.30

Light yellow powder

1.31 g/cm3

64 deg C (decomposes)

1.51

Chloroform 667.00 (mg/mL)

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.

5.61X10-6 mm Hg at 25 deg C (est)

Oral-mouse LD50: 49.9 mg/kg; peritoneal-mouse LD10: 37 mg/kg

Flammable, releases toxic chloride and nitrogen oxide fumes

Henry's Law constant = 2.5X10-10 atm-cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 2.4X10-11 cu cm/molecule-sec at 25 °C (est)

Insoluble in water.

Amides and Imides

A halogenated and nitrated amide. Organic amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx).

II

6.1(a)

3249

3

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

53-22-26-36/37/39-45

YS5000000

T

The warehouse is low-temperature, ventilated and dry; stored separately from food materials

Bulk: A sample stored at room temperature for 30 days showed 4% decomposition (UV). Solution: A refrigerated solution in 10% EtOH decomposed 2% in 6 hours while a solution at room temperature showed 25% decomposition in 6 hours (UV). Solutions in methanol were also found to be unstable by UV analysis.

P201-P261-P264-P280-P301 + P310-P305 + P351 + P338

H300-H311-H315-H319-H331-H335-H350-H360

SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.|Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Observe all federal, state, and local environmental regulations. Contact a licensed professional waste disposal service to dispose of this material.|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 Semustine (7 total), please visit the HSDB record page.

Materials to avoid: Strong oxidizing agents, strong bases.|It is incompatible with strong oxidizing agents and strong bases.

National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (13909-09-6) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of September 29, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s036mecc.pdf]

Flash point data for this compound are not available. It is probably combustible. (NTP, 1992)

|Danger|H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P280, P281, P301+P310, P302+P352, P304+P340, P305+P351+P338, P308+P313, P311, P312, P321, P322, P330, P332+P313, P337+P313, P361, P362, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 38 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity]|P201, P202, P260, P264, P270, P281, P307+P311, P308+P313, P309+P311, P314, P321, P405, and P501

Excerpt from ERG Guide 151 [Substances - Toxic (Non-combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol 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. STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

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)|Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N99 (US) or type P2 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).|Hand protection: The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and the standard EN 374 derived from it. Handle with gloves.|Eye protection: Safety glasses.|Skin and body protection: Choose body protection according to the amount and concentration of the dangerous substance at the work place.|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/

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.|Special protective equipment for fire-fighters: Wear self contained breathing apparatus for fire fighting if necessary.

Personal precautions: Wear respiratory protection. Avoid dust formation. Avoid breathing dust. Ensure adequate ventilation. Evacuate personnel to safe areas.|Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.|Methods for cleaning up: Pick up and arrange disposal without creating dust. Keep in suitable, closed containers for disposal.|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/

In case of skin contact: Wash off with soap and plenty of water. Take victim immediately to hospital. Consult a physician.|In case of eye contact Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.|Hygiene measures: Avoid contact with skin, eyes and clothing.|Handling: Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.|For more Preventive Measures (Complete) data for Semustine (14 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/

most toxic

LD50 Mouse oral 49,900 ug/kg

Semustine's production and use as an antineoplastic agent(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 330(SRC), determined from a structure estimation method(2), indicates that semustine is expected to have moderate mobility in soil(SRC). However, by analogy to N-nitroso-N-ethylurea which exhibited a hydrolysis half-life of 47 minutes at pH 9(3), adsorption may be precluded by hydrolysis(SRC). Volatilization of semustine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.5X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Semustine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.6X10-6 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2009).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 330(SRC), determined from a structure estimation method(2), indicates that semustine is expected to adsorb to suspended solids and sediment(SRC). However, by analogy to N-nitroso-N-ethylurea which exhibited a hydrolysis half-life of 47 minutes at pH 9(3), adsorption may be precluded by hydrolysis(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 2.5X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(6), an estimated BCF of 70(SRC), from its log Kow of 3.30(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Semustine is an alkylating agent that may hydrolyze under environmental conditions(4). Biodegradation data were not available(SRC, 2009).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), semustine, which has an estimated vapor pressure of 5.6X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase semustine 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 16 hours(SRC), calculated from its rate constant of 2.4X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase semustine may be removed from the air by wet or dry deposition(SRC). Semustine contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of semustine with photochemically-produced hydroxyl radicals has been estimated as 2.4X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 16 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Semustine is an alkylating agent that may hydrolyze under environmental conditions(2). The analogous compound N-nitroso-N-ethylurea exhibited a half-life of 47 minutes at pH 9(3). Semustine contains chromophores that absorb at wavelengths >290 nm(2) and therefore may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 70 was calculated in fish for semustine(SRC), using a log Kow of 3.30(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of semustine can be estimated to be 330(SRC). According to a classification scheme(2), this estimated Koc value suggests that semustine is expected to have moderate mobility in soil. However, by analogy to N-nitroso-N-ethylurea which exhibited a hydrolysis half-life of 47 minutes at pH 9(3), adsorption may be precluded by hydrolysis(SRC).

The Henry's Law constant for semustine is estimated as 2.5X10-10 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that semustine is expected to be essentially nonvolatile from water surfaces(2). Semustine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.6X10-6 mm Hg(SRC), determined from a fragment constant method(3).

While data specific to semustine were not located(SRC, 2009), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 229 workers (82 of these were female) were potentially exposed to semustine in the US(1). Occupational exposure to semustine dermal contact with this compound at workplaces where semustine is produced or used(SRC). The general population may only be exposed to semustine via its use as drug, an antineoplastic agent(SRC).

/EXPERIMENTAL THERAPY:/ Methyl-CCNU is an investigational drug used in chemotherapy to treat several types of cancers, including some brain cancers ... It also has been used to treat cancers of the lung and digestive tract.|/EXPERIMENTAL THERAPY/ The National Surgical Adjuvant Breast and Bowel Project C-01 trial reported in 1988 that, for patients with adenocarcinoma of the colon, compared with surgery alone, 1) postoperative chemotherapy with 1-(2-chloroethyl)-3-(4-trans-methylcyclohexyl)-1-nitrosourea (i.e., MeCCNU or semustine), vincristine, and 5-fluorouracil was associated with better 5-year disease-free and overall survival and 2) postoperative immunotherapy with bacillus Calmette-Guerin was associated with better 5-year overall, but not disease-free, survival. /This report is/ a 10-year update of this trial. Between November 11, 1977, and February 28, 1983, 1166 patients with resected Dukes' stage B and C adenocarcinoma of the colon were stratified by Dukes' stage, sex, and age (<65 years or > or =65 years) and then randomly assigned to receive no further treatment (surgery alone; 394 patients), adjuvant chemotherapy (379 patients), or adjuvant immunotherapy (393 patients). Those eligible for follow-up included 375 (95.2%) patients in the surgery-alone group, 349 (92.1%) patients in the adjuvant-chemotherapy group, and 372 (94.7%) patients in the adjuvant-immunotherapy group. All statistical tests were two-sided. No difference was observed between patients in the chemotherapy group and those in the surgery-alone group in 10-year disease-free survival (hazard ratio [HR] = 1.14, 95% confidence interval [CI] = 0.94 to 1.39; P =.17) or overall survival (HR = 1.12, 95% CI = 0.91 to 1.38; P=.27). Immunotherapy did not appear to prevent tumor relapse after 10 years (for surgery alone versus immunotherapy, relative risk [RR] = 0.99, 95% CI = 0.78 to 1.25; P =.93) but had a beneficial effect on 10-year overall survival (for surgery alone versus immunotherapy, RR = 1.27, 95% CI = 1.03 to 1.56; P =.02) that apparently results from a reduction in deaths associated with comorbidities in the immunotherapy group. The disease-free and overall survival benefit associated with chemotherapy in this patient population is of limited duration, disappearing after 10 years.

The risk of developing leukemia or preleukemia following adjuvant treatment with methyl- CCNU during clinical trials was evaluated in 3,633 patients with gastrointestinal cancer. Fourteen cases of leukemic disorders were reported out of 2,067 patients given methyl-CCNU compared to only one case of acute nonlymphocytic leukemia out of 1,566 patients given other therapies (relative risk of over 12 fold). A strong dose-response relationship was shown in a later report; a relative risk of about 40 fold, adjusted for survival time, was found for patients treated with the highest dose of methyl-CCNU.|Dose-related nephrotoxicity subsequent to administration of certain chloroethylnitrosourea compounds (carmustine, semustine and streptozocin) is commonly heralded by increased serum creatinine levels, uremia and proteinuria .....

A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026) (See all compounds classified as Antineoplastic Agents, Alkylating.)

SYMPTOMS: Symptoms of exposure to this compound may include delayed bone marrow depression, nausea and vomiting. ACUTE/CHRONIC HAZARDS: When heated to decomposition this compound emits toxic fumes. (NTP, 1992)

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

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ Human systemic effects by ingestion: nausea or vomiting, damage to kidney tubules and glomeruli, and hematuria (blood in the urine).|/SIGNS AND SYMPTOMS/ May be fatal if inhaled. Causes respiratory tract irritation. Toxic if absorbed through skin. Causes skin irritation. Causes eye irritation.|/CASE REPORTS/ The nephrotoxicity of semustine (methyl-CCNU) has been studied in 45 adult patients with surgically resected Stage I or II malignant melanoma who received this drug as adjuvant chemotherapy. Abnormalities of renal function (including three cases of renal failure) were noted in seven of 45 patients (16 percent); all these patients received more than 1,400 mg/sq m. This represents an incidence of 26 percent in patients receiving more than 1,400 mg/sq m of semustine. Two distinct patterns emerged. Abnormal serum creatinine levels developed in two patients while receiving semustine and later progressed to renal failure. Five patients had normal serum creatinine levels throughout their treatment courses but had abnormal creatinine values one month to two years following the completion of drug therapy. Renal failure developed in one of these patients, but the remaining four have had stable renal function for one to two years of additional follow-up. No clinical signs of renal insufficiency were detected in any patients receiving less than 1,400 mg/sq m of semustine. No changes unequivocally attributable to semustine were seen in eight patients at autopsy despite the fact that three had received greater than 1,900 mg/sq m of nitrosourea. This incidence of nephrotoxicity appears to be significantly lower than that previously reported in children.|/CASE REPORTS/ Pulmonary fibrosis is a serious side effect of nitrosourea therapy, occurring most frequently in patients treated with BCNU. Pulmonary fibrosis developed in a 63 year-old male patient while being treated with adjuvant methyl-CCNU for rectal carcinoma. This toxicity is rare with methyl-CCNU, having only been reported once previously. The case of methyl-CCNU-induced pulmonary fibrosis reported here occurred at a much lower total dose than the first reported case (604 mg/sq m vs. 2,733 mg/sq m). ...|For more Human Toxicity Excerpts (Complete) data for Semustine (7 total), please visit the HSDB record page.

Me CCNU

Withdrawn as Investigational New Drug Application|Methyl derivative of lomustine|A methylated derivative of carmustine with antineoplastic activity.