Description
Methylnitrosourea (MNU) is a methylated nitrosourea compound
with alkylating,mutagenic, teratogenic, carcinogenic, and
cytotoxic properties. The toxic effects of MNU are caused by the
transfer of its methyl group to nucleobases in nucleic acids.
Chemical Properties
Off-White to Pale Yellow Solid
Uses
Precursor of Diazomethane. It has a cytotoxicity effect.
This product contains an undetermined amount of water
Uses
MNU is the starting material for diazomethane generation.
Diazomethane provides methyl derivatives with carboxylic
acids and phenols in a very smooth and gentle reaction.
Phenols are slower in their reactivity compared to carboxylic
acids and should be converted at temperatures greater than
0 C. However, since MNU is unstable at temperatures greater
than 20 C and is shock sensitive to a degree, other (N-methyl)
nitrosamides have replaced MNU for use in diazomethane
generation, and most chemical supply houses no longer carry
MNU. MNU has been studied as a chemotherapeutic agent as
it is an effective therapy for mice that are intraperitoneally or
intracerebrally implanted with L1210 leukemia cells. MNU is
currently used as a research chemical to develop animal models
for human diseases.
Definition
ChEBI: N-methyl-N-nitrosourea is a member of the class of N-nitrosoureas that is urea in which one of the nitrogens is substituted by methyl and nitroso groups. It has a role as a carcinogenic agent, a mutagen, a teratogenic agent and an alkylating agent.
General Description
Pale yellow crystals or light yellow moist powder.
Air & Water Reactions
Sensitive to humidity and light when pure. Insoluble in water. Slowly decomposes in water. Alkaline hydrolysis produces a highly toxic, irritating and explosive gas.
Reactivity Profile
1-Methyl-1-nitrosourea is incompatible with strong acids and bases. Also incompatible with water and nucleophilic reagents. Alkaline hydrolysis produces a highly toxic, irritating and explosive gas. Can detonate with (potassium hydroxide + methylene chloride) .
Fire Hazard
Flash point data for 1-Methyl-1-nitrosourea are not available; however, 1-Methyl-1-nitrosourea is probably combustible.
Safety Profile
Confirmed carcinogen
with experimental carcinogenic,
neoplastigenic, tumorigenic, and teratogenic
data. Poison by ingestion and intravenous
routes. Experimental reproductive effects.
Human mutation data reported. Explodes at
room temperature. Can detonate with
(KOH + CHzCh). When heated to
decomposition it emits toxic fumes of NOx.
Carcinogenicity
N-Nitroso-N-methylurea is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.
Environmental Fate
There is no evidence that MNU has ever been produced or used
commercially; therefore, no data from human case reports or
epidemiological studies are available. MNU is available in small
quantities for research purposes and may be released into the
environment with laboratory waste. In air, MNU is expected
to exist solely as a vapor with an estimated vapor pressure of
2.9×10
-2 mmHg at 25℃. Vapor-phase MNU is expected to
degrade in the atmosphere by reaction with photochemically
produced hydroxyl radicals with an estimated half-life of 10 days.
MNU is expected to hydrolyze in moist soils; therefore, MNU
adsorption and volatilization from soil are not expected to be
prevalent. In water,MNUis expected to hydrolyze and has a halflife
of 1.2 h at pH 7 and 20℃; therefore, volatilization,
adsorption into suspended solids and sediments, biodegradation,
and bioconcentration are not expected to be important
processes in aquatic systems. Occupational exposure to MNU
may occur through oral contact, inhalation, and/or dermal
contact at workplaces where it is used as a research chemical.
Potential exposure may occur during the preparation and
administration ofMNUor during clean up. To avoid spills,MNU
should be transported in securely sealed glass bottles or ampules,
which should themselves be placed inside strong screw-cap or
snap-top containers that will not open when dropped. Both
bottle and the outside container should be appropriately labeled.
Toxicity evaluation
MNU is a direct-acting alkylating agent that interacts with DNA
to yield a variety of reaction products. The predominant adduct
(70–90%) is at the nucleophilic position 7 of guanine, yielding
7-methyldeoxyguanosine (7-medGua). While 7-medGua does
not appear to be directly mutagenic, the presence of 7-medGua
in susceptible tissues and cells can be used as a marker of recent
exposure to methylating agents such as MNU, because it is
more stable than mutagenic O6-medGua. Alterations in DNA
structure that are left unrepaired may lead to an accumulation
of mutations and eventually enhance cancer risk. When the
DNA damage is very severe, MNU may act as a cytotoxic agent
and cause cell death.
