General Description
Orange-yellow solid.
Reactivity Profile
1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA(154-93-8) decomposes rapidly in acid and in solutions above pH 7; most stable in petroleum ether or aqueous solution at pH 4.
Air & Water Reactions
Insoluble in water.
Hazard
Extremely toxic, central nervous system
depression, pulmonary fibrosis, renal and hepatic
damage, cytotoxic, immunosuppressive, carcino-
gen.
Potential Exposure
BCNU has been used since 1971 as an
antineoplastic agent in the treatment of Hodgkin’slymphoma; multiple meyloma; and primary or metastatic
brain tumors. It also has been reported to have antiviral,
antibacterial, and antifungal activity, but no evidence was
found that it is used in these ways. BCNU is not known to
be naturally occurring. Health professionals who handle
this drug (for example, pharmacists, nurses, and physicians)
may possibly be exposed to BCNU during drug preparation, administration, or cleanup; however, the risks can be
avoided through use of containment equipment and proper
work practices
Fire Hazard
Flash point data for this chemical are not available. 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA is probably combustible.
First aid
Skin Contact: Flood all areas of body that have
contacted the substance with water. Don’t wait to remove
contaminated clothing; do it under the water stream. Use
soap to help assure removal. Isolate contaminated clothing when removed to prevent contact by others. Eye
Contact: Remove any contact lenses at once. Immediately
flush eyes well with copious quantities of water or normal
saline for at least 2030 minutes. Seek medical attention.
Inhalation: Leave contaminated area immediately;
breathe fresh air. Proper respiratory protection must be
supplied to any rescuers. If coughing, difficult breathing,
or any other symptoms develop, seek medical attention at
once, even if symptoms develop many hours after exposure. Ingestion: Contact a physician, hospital, or poison
center at once. If the victim is unconscious or convulsing,
do not induce vomiting or give anything by mouth.
Assure that the patient’s airway is open and lay him on
his side with his head lower than his body and transport
immediately to a medical facility. If conscious and not
convulsing, give a glass of water to dilute the substance.Vomiting should not be induced without a physician’s
advice.
Shipping
UN3249 Medicine, solid, toxic, n.o.s., Hazard
Class: 6.1; Labels: 6.1-Poisonous materials. UN2811 Toxic
solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-
Poisonous materials, Technical Name Required.
Incompatibilities
Acids and acid solutions above pH 7
cause rapid decomposition. Most stable at pH 4 in aqueous
solution or petroleum ether.
Description
Bischloroethyl nitrosourea (BCNU) is a mustard-gas-derived
alkylating agent that underwent clinical trials for use as an
antineoplastic agent in the mid-1960s. Intravenous BCNU
received US Food and Drug Administration (FDA) approval for
brain tumor treatments in 1977. Further development and
trials led to the FDA approval of a BCNU-impregnated polymer
wafer for use as an intracavity surgical adjunct for recurrent
glioblastoma moltiforme in 1996. These wafers were again
reapproved in 2003 for use in high-grade malignant glioma as
an adjunct to surgery and radiation.
Waste Disposal
It is inappropriate and possibly dangerous to the environment to dispose of expired or
waste pharmaceuticals by flushing them down the toilet or
discarding them to the trash. Household quantities of
expired or waste pharmaceuticals may be mixed with wet
cat litter or coffee grounds, double-bagged in plastic, discard in trash. Larger quantities shall carefully take into consideration applicable DEA, EPA, and FDA regulations. If
possible return the pharmaceutical to the manufacturer for
proper disposal being careful to properly label and securely
package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a
state licensed medical waste contractor to dispose by burial
in a licensed hazardous or toxic waste landfill or
incinerator.
Originator
BCNU,Gencorp Aerojet,US
Definition
ChEBI: A member of the class of N-nitrosoureas that is 1,3-bis(2-chloroethyl)urea in which one of the nitrogens is substituted by a nitroso group.
Manufacturing Process
A solution of sodium nitrite (6.9 g, 0.10 mole) in water (60 ml) was added
dropwise to a cold (0-5°C), stirred solution of 1,3-bis(2-chloroethyl)urea (8.0
g, 0.044 mole) in formic acid (50 ml). The reaction mixture was stirred further
at 0°C until the pale yellow oil that had formed solidified. The nitrosourea was
collected and washed quickly with cold water (2 x 10 ml), and dried in
vacuum; yield 6.7 g. (71%).
Brand name
Bicnu (Bristol-Myers Squibb); Gliadel
(Millot Laboratories, France).
Therapeutic Function
Antitumor
Biochem/physiol Actions
Carmustine is a DNA alkylating agent causing DNA interstrand crosslinks. Effective against glioma and other solid tumors.
Clinical Use
Alkylating agent:
Myeloma, lymphoma and brain tumours
Safety Profile
Confirmed carcinogen withexperimental carcinogenic and tumorigenic data. A humanpoison by parenteral route. An experimental poison byingestion, intravenous, intraperitoneal, parenteral, andsubcutaneous routes. Human systemic effects byparenteral, int
Synthesis
Carmustin, 1,3-bis-(2-chloroethyl)-1-nitrosourea (30.2.4.4), is made by
nitrating 1,3-bis(2-chloroethyl)urea with nitrogen trioxide.
Drug interactions
Potentially hazardous interactions with other drugs
Antipsychotics: avoid with clozapine (increased risk
of agranulocytosis).
Carcinogenicity
Bis(chloroethyl) nitrosourea (BCNU) is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.
Environmental Fate
It is generally assumed that BCNU exerts its cytotoxicity
through the liberation of alkylating and carbamoylating
moieties. An alkylating entity, particularly chloroethyl carbonium
ion, is strongly electrophilic and can alkylate a variety
of biomolecules, including the purine and pyrimidine bases of
DNA. BCNU causes DNA interstrand cross-linking, which is
associated with cytotoxicity. The carbamoylation of lysine
residues of protein can inactivate certain enzymes, thus interfering
with DNA and RNA synthesis and repair processes. The
inhibition of glutathione reductase by this carbamoylation
further contributes to cytotoxicity.
Metabolism
Intravenous carmustine is rapidly metabolised, and no
intact drug is detectable after 15 minutes. It is partially
metabolised to active metabolites by liver microsomal
enzymes, which have a long half-life. It is thought that the
antineoplastic activity may be due to metabolites.
Approximately 30% of a dose is excreted in the urine after
24 hours, and 60-70% of the total dose after 96 hours.
About 10% is excreted as respiratory CO2
. Terminal halflife of the metabolites is about 1 hour.
storage
-20°C, protect from light
Toxicity evaluation
There is no information available on the environmental fate of
BCNU. However, it is predicted that BCNU spontaneously decomposes due to its high reactivity. Estimates indicate that
the half-life of BCNU particulates and vapor in air is 4.4 days.
Though expected to be highly mobile when adsorbed to soil
and suspended solids, it is likely that this adsorption may be
precluded by hydrolysis. Volatilization from soil or water is not
expected, and the potential for bioaccumulation is low. BCNU
degrades into 2-chloroethylamine, which is not considered
hazardous to the environment.
