1-Methyl-1-nitrosourea

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

The Uses of 1-Methyl-1-nitrosourea

Precursor of Diazomethane. It has a cytotoxicity effect. This product contains an undetermined amount of water

The Uses of 1-Methyl-1-nitrosourea

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.