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N-Ethyl-N-nitrosourea

HCID 12967
NotesReactions
Basic informationOverviewNames & identifiersPropertiesSafety & regulationChemistry & industryRelated reactionsCompound notes
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Basic information

CAS
759-73-9
Standard SMILES
CCN(N=O)C(N)=O
InChIKey
FUSGACRLAFQQRL-UHFFFAOYSA-N
Molecular formula
C3H7N3O2
Average molar mass
117.11 g/mol
Monoisotopic mass
117.05382648

Overview

N-Nitroso-N-ethylurea can cause cancer according to an independent committee of scientific and health experts.

Names & identifiers

Preferred name
N-Ethyl-N-nitrosourea
IUPAC
1-ethyl-1-nitrosourea
English name
N-Nitroso-N-ethylurea
Molecular formula
C3H7N3O2
Molecular weight
117.11

Names & synonyms

1-Ethyl-1-nitrosourea759-73-9N-Ethyl-N-nitrosoureaN-NITROSO-N-ETHYLUREAEthyl nitrosoureaEthylnitrosoureaN-EthylnitrosoureaNitrosoethylureaN-Ethyl-N-nitroso-ureaAethylnitroso-harnstoffAenhNE-Urea
Show more names
anhENUNANHNGLNEUTKR1MLN19SIAL1
NSC 45403Urea, 1-ethyl-1-nitroso-N-Ethyl-N-nitroso carbamideN-Nitrosoethylurea1-Ethyl-1-nitrosomocovinaN-Ethyl-N-nitosoureaCarbamide, N-ethyl-N-nitroso-DTXSID8020593

Database identifiers

CAS
759-73-9
PubChem CID
12967
DTXSID
DTXSID8020593
ChEMBL
CHEMBL167667
ChEBI
CHEBI:23995
UNII
P8M1T4190R
EC Number
212-072-2
Nikkaji
J3.321I

Properties

Computed structural properties

XLogP
0.2
Topological polar surface area
75.8 Ų
Hydrogen bond donors
1
Hydrogen bond acceptors
3
Rotatable bonds
1
Heavy atoms
8
Formal charge
0
Complexity
103

Experimental & physicochemical properties

Chemical Classes · 2 items

Nitrogen Compounds -> Other Nitrogen Compounds

Carcinogens

LogP · 2 items

log Kow = 0.23

-0.15

Color/Form · 3 items

Very pale pink crystalline solid

Pale yellow, crystalline

Pale buff-yellow hexagonal plates

Solubility · 3 items

10 to 50 mg/mL at 70 °F (NTP, 1992)

In water, 1.283X10+4 mg/L at room temperature

Soluble in polar organic solvents

Decomposition · 2 items

Hazardous decomposition products formed under fire conditions - Carbon oxides, nitrogen oxides (NOx).

When heated to decomposition it emits toxic fumes of /nitrogen oxides/.

Melting Point · 2 items

217 to 219 °F (decomposes) (NTP, 1992)

100 °C; decomposes

Vapor Pressure0.01 [mmHg]
Physical Description · 2 items

Safety & regulation

Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.

GHS classification

GHS Classification · 6 items

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P261, P264, P270, P271, P280, P301+P316, P302+P352, P304+P340, P317, P318, P321, P330, P362+P364, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 43 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]

Hazard information

Regulatory Information · 2 items

Hazard Traits - Carcinogenicity

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

DOT LabelPoison
Fire HazardsFlash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)
Health Hazards · 1 item

ACUTE/CHRONIC HAZARDS: This compound is extremely unstable at high pH. It will decompose to extremely unstable decomposition products if acidic conditions are not maintained. When heated to decomposition it emits toxic fumes of nitrogen oxides. Decomposition products may be explosive. (NTP, 1992)

Hazards Summary · 1 item

Mutagenic and to human cells; Evidence of carcinogenicity in experimental animals and their offspring; Teratogenic and embryotoxic; [HSDB] Causes adverse effects in pregnancy in animal experiments, but no human data; [REPROTOX] Sensitive to light and reacts with water; [CAMEO] May cause irritation; [Aldrich MSDS]

Chemistry & industry

Pharmacology

Mechanism of Action · 5 items

Thirty-day-old Sprague--Dawley rats were used to study the persistence of DNA lesions (e.g., O6-alkylguanine) induced by various doses of ethylnitrosourea (ENU). Cellular proliferation was measured as an increment of DNA content per organ at 7 days post-treatment. We observed that the persistence of O6-EtGua was not affected by the various dose levels. Comparing the 3 organs, the persistence of O6-EtGua ranked in the order of brain greater than kidney greater than liver, while the percent increase in DNA content was measured as liver greater than kidney greater than brain. When the target specificity of ENU carcinogenesis in 30-day-old rats was compared to that following transplacental exposure in terms of its relationship to the persistence of DNA lesions and the rate of target cellular proliferation, it permitted the conclusion that induction of neoplasia in target cells is not only determined by persistent DNA lesions but also by the rate of proliferation of target cells at the time of exposure.

O6-Alkylguanine-DNA alkyltransferase (AGT) is responsible for repairing the O6-alkylguanine lesion in DNA. There is wide variation in the levels of alkylguanine-DNA alkyltransferase between organ and cell types, which appears to correlate with cell and tissue type sensitivity to the mutagenic and carcinogenic effects of alkylating agents. ... to investigate the role of alkylguanine-DNA alkyltransferase in modulating the frequency and types of mutations induced in one type of normal human parenchymal cells, we examined the types and frequency of mutations in the hypoxanthine (guanine) phosphoribosyltransferase (hprt gene in 116 mutants derived from two N-ethyl-N-nitrosourea (ENU)-treated normal human skin keratinocyte cell lines. O6-Benzylguanine (O6-BZ; 5 um x 2 hr) was used to specifically inhibit alkylguanine-DNA alkyltransferase activity before N-ethyl-N-nitrosourea treatment (0 to 5 mM x 1 hr). O6-Benzylguanine increased both the cytotoxic and mutagenic effects of N-ethyl-N-nitrosourea by 1.8- and 3- to 5-fold, respectively. In both treatment groups, most of the mutations were base substitutions (72%). The proportion of GC to AT transitions in the O6-Benzylguanine group (14/31) was twice that in the group treated with N-ethyl-N-nitrosourea alone, consistent with the loss of alkylguanine-DNA alkyltransferase activity in these cells. There was no strand specificity of GC to AT and AT to GC transitions in both groups. Base transversions accounted for 28% of total base substitutions. A lower than expected proportion of AT to TA transversions were observed in both cell lines, which decreased in the O6-Benzylguanine pretreated group. A strand bias was observed for GC to TA and AT to TA transversions. Most of the G to A and G to T base substitutions had one or more purines flanking 3' to the mutated deoxyguanosines. There were more deletion mutants with the deletion of exon 1,4,6, and 8 in the BZ group than in the control group. These data, characterizing the mutational spectra of N-ethyl-N-nitrosourea in normal human keratinocytes treated in vitro, indicate that GC to AT and AT to GC transition mutations predominate in these cells depleted or not depleted of alkylguanine-DNA alkyltransferase.

Related reactions

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Compound notes

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On this pageBasic informationOverviewNames & identifiersPropertiesSafety & regulationChemistry & industryRelated reactionsCompound notes

N-nitroso-n-ethylurea appears as yellow-pink crystals or off-white powder. Sensitive to light.

Pale buff-yellow solid; [Merck Index] Yellowish-pink or off-white solid; [CAMEO]

Stability/Shelf Life · 2 items

Stable under recommended storage conditions.

Decomposes to diazoethane in alkaline solutions; stability in aqueous solutions is pH-dependent (20 °C) ... . Sensitive to humidity and light and should be refrigerated for storage.

Other Experimental Properties · 1 item

Decomposes to diazoethane in alkaline solutions; stability in aqueous solutions is pH dependent: pH 4.0, half-life 190 hours; pH 6.0, half-life 31 hours; pH 7.0, half-life 1.5 hours; pH 8.0, half-life 0.1 hours; pH 9.0, half-life 0.05 hours (at 20 °C).

Physicochemical properties

Melting point
103 · 103-1040C (dec)
Boiling point
182 ℃ · 182℃
Density
1.35 · 1.35
refractive index
1.49 · 1.4900 (estimate)
Flash point
64 ℃ · 64℃
storage temp.
-20 °C · -20°C
solubility
DMSO (Soluble), Methanol (Sparingly)
form
Semi-Solid to Low-Melting Solid
pka
12.32 · 12.32±0.50(Predicted)
color
Off-White to Red
Water Solubility
12.83 g/L · 12.83g/L(room temperature)
Specific Activity
9 · 9-13nmol/min·mg
Stability
40 % · Unstable at RT, Contains approximately 40% Water, 2.0% Acetic Acid to stabilize
InChI
1S/C3H7N3O2/c1-2-6(5-8)3(4)7/h2H2,1H3,(H2,4,7)
InChIKey
FUSGACRLAFQQRL-UHFFFAOYSA-N
SMILES
CCN(N=O)C(N)=O
CAS DataBase Reference
759 · 759-73-9(CAS DataBase Reference)
EWG's Food Scores
2 · 2
FDA UNII
8 M1T4190R · P8M1T4190R
Proposition 65 List
N-Nitroso-N-ethylurea
IARC
2 A · 2A (Vol. 17, Sup 7) 1987
EPA Substance Registry System
N-Nitroso-N-ethylurea (759-73-9)
UNSPSC Code
51111800 · 51111800
NACRES
32 · NA.32
Symbol(GHS)
6 · GHS06,GHS08
Signal word
Danger
Hazard statements
301 · H301-H312+H332-H350-H360
Precautionary statements
201 · P201-P202-P280-P301+P310-P302+P352+P312-P304+P340+P312
PPE
3 · Eyeshields, Faceshields, Gloves, type P3 (EN 143) respirator cartridges
Hazard Codes
T
Risk Statements
45 · 45-46-61-20/21/22
Safety Statements
53 · 53-22-36/37/39-45
RIDADR
2811 · UN 2811 6.1/PG 3
WGK Germany
3 · 3
RTECS
3150000 · YT3150000
TSCA
TSCA listed
HazardClass
6.1 · 6.1(b)
PackingGroup
III
Storage Class
6.1 C · 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
Hazard Classifications
3 OralCarc · Acute Tox. 3 OralCarc. 1BRepr. 1B
Hazardous Substances Data
759 · 759-73-9(Hazardous Substances Data)
Toxicity
50 i.v · LD50 i.v. in rats: 240 mg/kg (Druckrey)
Reactive Group
Amides and Imides
Special Reports · 1 item

DHHS/National Toxicology Program; Report on Carcinogens, Fourteenth Edition: Chloramphenico (November 2016). 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. N-Nitroso-N-ethylurea (759-73-9) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of December 10, 2018: http://ntp.niehs.nih.gov/pubhealth/roc/index-1.html]

RCRA Requirements · 1 item

U176; As stipulated in 40 CFR 261.33, when N-nitroso-N-ethylurea, 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).

Reactivity AlertsWater-Reactive
Reactivity Profile · 1 item

N-NITROSO-N-ETHYLUREA is highly reactive. Sensitive to moisture and light. Its stability in aqueous solutions is pH-dependent. Incompatible with water and nucleophilic reagents. Alkaline hydrolysis produces a highly explosive gas. (NTP, 1992).

Air and Water ReactionsWater soluble. Sensitive to moisture--stability in aqueous alkaline solutions depends on pH.
EPA Hazardous Waste NumberU176; A toxic waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or manufacturing chemical intermediate.

Safety & protection

Fire FightingFires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)
First Aid · 1 item

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.

Fire Fighting Procedures · 3 items

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Use dry chemical, carbon dioxide, water spray, or foam extinguishers. ... If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors, or shows any signs of deforming), withdraw immediately to a secure position. ... The only respirators recommended for firefighting are self-contained breathing apparatuses that have full face-pieces and are operated in a pressure-demand or other positive-pressure mode.

Storage Conditions · 4 items

Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature -20 °C. Storage class (TRGS 510): 6.1D: Non-combustible, acute toxic Cat.3 / toxic hazardous materials or hazardous materials causing chronic effects.

... Should be refrigerated for storage.

General storage may be used. Prior to working with this chemical you should be trained on its proper handling and storage. Store in tightly closed containers in a cool, well-ventilated area. Where possible, automatically transfer this material from storage containers to process containers. Sources of ignition, such as smoking and open flames, are prohibited where this chemical is handled, used, or stored. Metal containers involving the transfer of this chemical should be grounded and bonded. Use only nonsparking tools and equipment, especially when opening and closing containers of this chemical. Wherever this chemical is used, handled, manufactured, or stored, use explosion-proof electrical equipment and fittings. A regulated, marked area should be established where this chemical is handled, used, or stored in compliance with OSHA Standard 1910.1045.

PRECAUTIONS FOR "CARCINOGENS": 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. /Chemical Carcinogens/

Cleanup Methods · 3 items

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Evacuate persons not wearing protective equipment from area of spill or leak until cleanup is complete. Remove all ignition sources. Use HEPA vacuum or wet method to reduce dust during cleanup. Do not dry sweep. Collect powdered material in the most convenient and safe manner and deposit in sealed containers. Ventilate area after cleanup is complete. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters.

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/

Nonfire Spill Response · 1 item

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with 5% acetic acid, then transfer the dampened material to a suitable container. Use absorbent paper dampened with 5% acetic acid to pick up any remaining material. Your contaminated clothing and the absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with 5% acetic acid 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.

Disposal Methods · 5 items

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U176, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product.

A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.

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/

For more Disposal Methods (Complete) data for N-Nitroso-N-ethylurea (9 total), please visit the HSDB record page.

Preventive Measures · 5 items

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.

Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

For more Preventive Measures (Complete) data for N-Nitroso-N-ethylurea (15 total), please visit the HSDB record page.

Isolation and EvacuationExcerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]:
Personal Protective Equipment (PPE) · 6 items

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)

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (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).

For more Personal Protective Equipment (PPE) (Complete) data for N-Nitroso-N-ethylurea (6 total), please visit the HSDB record page.

Toxicology

Interactions · 3 items

Rats were pretreated for a number of weeks with ... N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea ... . A subsequent challenge with a single, low-dose of radioactivity labeled dimethylnitrosamine was given to assay the capacity of the liver for O6-methlyguanine repair. ... Pretreatment for 2 weeks with N-ethyl-N-nitrosourea resulted in strongly enhanced O6-methylguanine repair, as did a similar pretreatment with diethylnitrosamine, which was included as a positive control. The same pretreatment scheme which was highly effective in the case of N-ethyl-N-nitrosourea, was found to be totally ineffective in the case of N-methyl-N-nitrosourea. When N-methyl-N-nitrosourea was admin for 8 wk instead of 2, a small but statistical incr in O6-methylguanine repair was observed. ... Two factors are responsible for the low effectivity of N-methyl-N-nitrosourea. The first is the relatively low extent of liver DNA methylation by this cmpd when compared with dimethylnitrosoamine. The second is the low efficiency of methylating agents to induce 06-methylguanine repair in rat liver when compared with ethylating agents. ... It is concluded that the capacity of an agent to enhance O6-methylguanine repair in rat liver reflects the hepato(co)carcinogenic capacity of that agent.

BD rats were given simultaneous s.c. administrations of 10 mg/kg bw NEU and 1 mg/kg bw anhydrous cobalt chloride or anhydrous cupric sulfate once weekly; all of 24 rats treated with cobalt and NEU developed local sarcomas at the injection site, and, in addition, 2 malignant neurinomas were seen. Of those treated with copper and NEU, 4 animals developed local sarcomas. A single i.p. injection of 25-90 mg/kg bw NEU with 5-10 mg/kg bw anhydrous cupric sulfate or anhydrous cobalt chloride caused local sarcomas in the abdominal cavity in 6/20 animals. Rats treated with NEU or with cobalt or copper salts alone did not develop local sarcomas.

Ethylnitrosourea /was administered/ intraperitoneally in doses of 0, 5, or 20 mg/kg bw to 15-day-old outbred CD-1 Swiss mice. At weaning, at 5 weeks of age, 23 to 29 mice at each dose level were given drinking water containing 1,800 ppm concentrations of chloroform. Other groups of 25 to 36 of the ENU-treated mice were given sodium phenobarbital in water at concentrations of 500 ppm. After 46 weeks of exposure, that is, at 51 weeks of age, the mice were killed for necropsy. There was dose-related development of liver adenomas and hepatocellular carcinomas in males and of lung tumors (mostly adenomas) in both sexes that were attributable to ethylnitrosourea alone. The administration of chloroform seemed to inhibit tumor development in male mice that had received ethylnitrosourea. Phenobarbital seems to have increased the incidence of liver tumors among ethylnitrosourea treated mice. A significant effect of chloroform or phenobarbital on lung-tumor incidence was not evident.

Ecotoxicity Values · 2 items

LC50; Species: Oryzias latipes (Japanese medaka) embryo, 66 hr post-fertilization; Conditions: freshwater, static; Concentration: 597.24825 mg/L for 2 hr (95% confidence interval: 526.98375-679.2235 mg/L)

EC50; Species: Oryzias latipes (Japanese medaka) embryo, 66 hr post-fertilization; Conditions: freshwater, static; Concentration: 339.61175 mg/L for 2 hr (95% confidence interval: 269.34725-421.587 mg/L); Effect: abnormal growth

Environmental Fate · 3 items

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a log Kow of 0.23(2) and a regression-derived equation(3), indicates that N-nitroso-N-ethylurea is expected to have very high mobility in soil(SRC). Volatilization of N-nitroso-N-ethylurea from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.3X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). N-Nitroso-N-ethylurea is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.0X10-2 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). Biodegradation data in soil were not available(SRC, 2018).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a log Kow of 0.23(2) and a regression-derived equation(3), indicates that N-nitroso-N-ethylurea is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 1.3X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2018).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), N-nitroso-N-ethylurea, which has an estimated vapor pressure of 2.0X10-2 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase N-nitroso-N-ethylurea 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 3 days(SRC), calculated from its rate constant of 5.0X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). N-Nitroso compounds, like N-nitroso-N-ethylurea , commonly absorb at wavelengths of approximately 330 nm(3) and, therefore, N-nitroso-N-ethylurea may be susceptible to direct photolysis by sunlight since sunlight consists of wavelengths above 290 nm(SRC).

Adverse Effects · 1 item

Reproductive Toxin - A chemical that is toxic to the reproductive system, including defects in the progeny and injury to male or female reproductive function. Reproductive toxicity includes developmental effects. See Guidelines for Reproductive Toxicity Risk Assessment.

Toxicity Summary · 1 item

IDENTIFICATION AND USE: N-Nitroso-N-ethylurea (NEU) is a solid. It is used experimentally as mutagen, and as ethylating agent in the laboratory synthesis of diazoethane. Mutagenic effect has been studied for promoting growth of various plants. HUMAN STUDIES: Treatment of cultured human fibroblasts with NEU induced both chromatid and chromosome aberrations. The effect of NEU on human chromosomes from cultured blood lymphocytes was studied. The incidence of single chromatid and isochromatid breaks, exchanges and multiple breaks in human lymphocytes in vitro was dose-dependent, at doses ranging 25-200 ug/mL. Both O6-alkylguanine-DNA alkyltransferase and nucleotide excision repair play an important role in protecting human cells from the toxic and mutagenic effects of NEU. ANIMAL STUDIES: Rats were given single oral doses of 10, 20, 40 or 80 mg/kg bw NEU, and malignant neurogenic tumors were induced in the brain, spinal cord and peripheral nervous system in 75/80 animals. Even at the lowest dose, 23/26 animals died with neurogenic tumors (21 with brain tumors). At the highest dose, 9/16 rats had nephroblastomas. Among 39 rats given 60 mg NEU/L of drinking-water on 5 days/week for 52 weeks, the following tumors were observed: 7 tumors of the stomach (3 papillomas, 1 squamous-cell carcinoma and 3 sarcomas, all in males), 9 tumors of the large intestine (6 adenocarcinomas and 3 sarcomas, all in males), 9 adenocarcinomas of the mammary gland (8 in females and 1 in a male) and 12 myelocytic leukemias were observed. A variety of epithelial and mesenchymal embryonal neoplasms of the eye, liver, brain, kidney, muscle and jaw (including neuroectodermal tumors of the eye and nephroblastomas), closely analogous to tumors of human infancy, were found in opossums (Didelphis virginiana Kerr) treated orally from birth to 16 weeks of age with 100 mg/kg bw NEU in either single or split doses. One-day-old mice given single s.c. injections of NEU at dose levels ranging from 10-160 mg/kg bw developed a high incidence of tumors. Monthly i.p. injections of 10 mg/animal NEU for 3 months caused thymic lymphomas in 3/10 adult rats. Monthly treatment with 10 mg/animal for 5 months produced thymic lymphomas in 9/20 treated rats and myeloid leukemias in 5 others. When 30 mg/kg bw NEU were given by i.v. injection to Syrian golden hamsters on day 15 of pregnancy, 14/22 offspring developed tumors, mainly of the nervous system (5 tumors the trigeminal nerve and 11 tumors of the peripheral nerves). No tumors of the brain or spinal cord were observed. Teratogenic effects of NEU on craniofacial development were investigated in rat embryos in vivo, and in vitro using a whole-embryo culture technique. A single intraperitoneal injection of NEU into the pregnant rat on day 9.5 of gestation induced several types of craniofacial malformations. A functional defect (respiratory distress), in addition to morphological defects, was induced in the offspring of male mice treated with NEU before mating. NEU Induces mutations in Salmonella typhimurium, Escherichia coli, lower and higher plants, in Drosophila melanogaster and in other organisms. A mutation yield of 85% X-linked recessive lethal and visible mutations was seen in Drosophila exposed to 4-5 mg NEU.

Ecotoxicity Excerpts · 1 item

/PLANTS/ Three-year long investigations were conducted for the purpose of assessing the effect of N-nitroso-N-ethylurea treatment applied single or in combination with gamma irradiation (4 krad) on the variability of some quantitative characteristics in beans cv. No. 564. It was found that in the two generations investigated (M1 and M2) th effect of the factors year (A) and treatment (B) and of their interaction (A treatment with 0.0031 M N-nitroso-N-ethylurea, as compared to the control, had a stimulating effect on the quantitative characteristics studied in M1 generation. Combined treatment (4 krad gamma rays + 0.0031 M N-nitroso-N-ethylurea), as compared to the control, produced as stimulating effect in M1 generation on the characteristic plant height, number of fruit bearing branches and number of pods per plant. No significant differences were found between treated and non-treated plants in M2 for the quantitative characters investigated.

Ongoing Test Status · 2 items

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for N-nitroso-N-ethylurea is available.[Available from, as of February 1, 2019: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of February 4, 2019: http://actor.epa.gov/dashboard/]

Medical Surveillance · 1 item

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/

Soil Adsorption/Mobility · 1 item

The Koc of N-nitroso-N-ethylurea is estimated as 10(SRC), using a log Kow of 0.23(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that N-nitroso-N-ethylurea is expected to have very high mobility in soil(SRC).

Human Toxicity Excerpts · 5 items

/GENOTOXICITY/ Treatment of cultured human fibroblasts with NEU induced both chromatid and chromosome aberrations. The effect of NEU on human chromosomes from cultured blood lymphocytes ... was studied. The incidence of single chromatid and isochromatid breaks, exchanges and multiple breaks in human lymphocytes in vitro was dose-dependent, at doses ranging 25-200 ug/mL.

/GENOTOXICITY/ The concentration dependent mutagenic, clastogenic and cytocidal activities of Mitomycin C, methylnitrosourea, and ethylnitosourea were measured in the human lymphoblast cell line TK6. For treatments resulting in fewer than 2 lethal hits methylnitrosourea, ethylnitrosourea and Mitomycin C gave rise to apparently linear dose-response curves for gene mutations (hgprt and tk genes) as well as for chromosomal aberrations. The numbers of induced mutants at the tk and hgprt loci were similar between the two loci for each compound. However, the ratio of mutagenic activity relative to the clastogenic activity (aberrations/cell) was lowest for Mitomycin C, intermediate for methylnitrosourea, and highest for ethylnitrosourea. These results confirm in human cells the general observation that the processes of mutagenesis and clastogenesis are nonidentical: compounds vary independently in their mutagenic and clastogenic potentials.

/GENOTOXICITY/ We have developed a recombinant DNA shuttle vector that permits the molecular analysis of mutations induced in human cells by chemical or physical mutagens. The vector is able to replicate as a plasmid in Escherichia coli and in Epstein-Barr virus (EBV)-transformed human lymphoblastoid cell lines and contains the herpes simplex virus type 1 thymidine kinase gene (HSV tk) as the target for mutagenesis studies. After introduction of the vector into an EBV-transformed lymphoblastoid cell line (LCL-721) by electroporation, approximately equal to 2% of the transfected cells expressed the vector-encoded gene for hygromycin resistance. Plasmid DNA isolated from cells immediately after selection for hygromycin resistance (10 population doublings posttransfection) contained mutations in the HSV tk gene at a frequency of 6 x 10(-5). Treatment of plasmid-bearing LCL-721 cells with N-ethyl-N-nitrosourea resulted in a dose-dependent increase of up to 15-fold in the frequency of mutations in the HSV tk gene. The dose-response for the induction of mutations in the plasmid-encoded gene closely paralleled that for the induction of mutations in the cellular gene for hypoxanthine (guanine) phosphoribosyltransferase.

/GENOTOXICITY/ ... The toxicity, mutagenicity, and mutational spectra of N-ethyl-N-nitrosourea in three Epstein-Barr virus-transformed human lymphoblastoid cell lines, each with a different DNA repair phenotype /were examined/. One cell line lacks O6-alkylguanine-DNA alkyltransferase activity; another, derived from a patient with xeroderma pigmentosum, complementation group A, lacks nucleotide excision repair capability, and the third is competent in both repair functions. N-Ethyl-N-nitrosourea induced toxicity and mutagenicity at the hypoxanthine-guanine phosphoribosyltransferase locus were increased to a similar degree relative to the repair-competent cells in both O6-alkylguanine-DNA alkyltransferase deficient and nucleotide excision repair-deficient cells. We determine the mutational spectra for N-ethyl-N-nitrosourea by identifying DNA sequence changes at the hypoxanthine-guanine phosphoribosyltransferase locus in at least 26 clones resistant to 6-thioguanine from each cell line. Of the characterized mutations, 89% were single-base pair substitutions. Transitions and transversions were found at AT and GC base pairs in all three cell lines. The biggest difference within the spectra was in the rate of transitions at GC base pairs. Compared to the repair-competent cell line, this mutation was elevated about 8-fold in the O6-alkylguanine-DNA alkyltransferase deficient cells and about 3-fold in the nucleotide excision repair-deficient cells. We conclude that both O6-alkylguanine-DNA alkyltransferase and nucleotide excision repair play an important role in protecting human cells from the toxic and mutagenic effects of N-ethyl-N-nitrosourea. Furthermore, the mutational spectra suggest that both of these repair systems participate in the repair of O6-ethylguanine adducts.

Artificial Pollution Sources · 1 item

N-Nitroso-N-ethylurea's production and use in laboratory synthesis for research purposes(1,2) may result in its release to the environment through laboratory waste streams. No evidence was found that N-nitroso-N-ethylurea is produced or used commercially(SRC).

Carcinogen Classification · 6 items

N-Ethyl-N-nitrosourea

Group 2A: Probably carcinogenic to humans

Volume 17: (1978) Some N-Nitroso Compounds

1987

1987

NB Overall evaluation upgraded to Group 2A with supporting evidence from other relevant data

Regulatory information

RCRA Requirements · 1 item

U176; As stipulated in 40 CFR 261.33, when N-nitroso-N-ethylurea, 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).

CERCLA Reportable Quantities · 1 item

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 1 lb or 0.454 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV.D.3.b).

Safety data

PPE
Eyeshields, Faceshields, Gloves, type P3 (EN 143) respirator cartridges
wgk
3
tsca
TSCA listed
rtecs
YT3150000
ridadr
UN 2811 6.1/PG 3
Toxicity
LD50 i.v. in rats: 240 mg/kg (Druckrey)
risk_code
45-46-61-20/21/22
Signal word
Danger
Symbol(GHS)
GHS06,GHS08
hazard_code
T
safety_code
53-22-36/37/39-45
hazard_class
6.1(b)
Storage Class
6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
packing_group
III
Hazard statements
H301-H312+H332-H350-H360
Hazard Classifications
Acute Tox. 3 OralCarc. 1BRepr. 1B
Precautionary statements
P201-P202-P280-P301+P310-P302+P352+P312-P304+P340+P312
Hazardous Substances Data
759-73-9(Hazardous Substances Data)

The experiments investigated the induction of ethylations to DNA in yeast cells exposed to the chemical mutagen ethylnitrosourea. A similar level of alkylation was seen at the N7 and O6 of guanine and at the N3 of adenine in either log phase cells or in temperature sensitive cdc4 and cdc7 cells growth arrested at their specific G1 positions. Hence, the changes in chromosome structure associated with the above cdc phenotypes do not modify the amount of DNA damage induced by ethylnitrosourea.

NEU is a direct alkylating agent and has been shown to ethylate nucleic acids both in vitro and in vivo. 7-Ethylguanine, 06-ethylguanine, 3-ethyladenine and 7-ethyladenine and ethylphosphate triesters have been detected in rat tissues after administration of NEU in vivo. 06-Ethylguanine was lost from DNA of brain (a target organ) much more slowly than from liver DNA, whereas no such difference was observed for the rate of loss of the other ethylated products.

For more Mechanism of Action (Complete) data for N-Nitroso-N-ethylurea (7 total), please visit the HSDB record page.

Biological Half-LifeNEU was rapidly lost from the blood after its i.v. injection, with a half-life of 5-6 minutes.
Metabolism/Metabolites · 2 items

In the ethylation of tRNA from calf liver with (14)C-labeled ENU in vitro, 1,7-diethylguanine was obtained as the main product. ... After in vivo ethylation, the main reaction product isolated from rat liver tRNA was 7-ethylguanine and a pyrimidine nucleotide-like fraction containing a 1,7-diethylguanine derivative with an opened imidazole ring.

NEU is a direct alkylating agent and has been shown to ethylate nucleic acids both in vitro and in vivo. 7-Ethylguanine, 06-ethylguanine, 3-ethyladenine and 7-ethyladenine and ethylphosphate triesters have been detected in rat tissues after administration of NEU in vivo. 06-Ethylguanine was lost from DNA of brain (a target organ) much more slowly than from liver DNA, whereas no such difference was observed for the rate of loss of the other ethylated products.

MeSH Pharmacological Classification · 1 item

Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases.

Absorption, Distribution and Excretion · 2 items

NEU was rapidly lost from the blood after its i.v. injection, with a half-life of 5-6 minutes. The high chemical reactivity of NEU renders it unlikely that enzymic catalysis is involved in its decomposition.

The tissue-disposition and fate of N-[(14)C]ethyl-N-nitrosourea has been studied in mice. A large part of the injected N-[(14)C]ethyl-N-nitrosourea radioactivity was found to be exhaled as (14)CO2. Whole-body autoradiography showed evenly distributed radioactivity in most tissues shortly after the administration of N-[(14)C]ethyl-N-nitrosourea which probably is due to the homogeneously distributed substance and the non-enzymatically formed ethyl-carbonium ions which have reacted with the tissues. The blood-brain barrier seemed to have a capacity to partially prevent the uptake of the substance in the central nervous system. A high radioactivity was observed in the liver, which may imply that N-[(14)C]ethyl-N-nitrosourea is enzymatically decomposed in this tissue. An observed labelling of kidneys may be connected with urinary excretion of radioactivity. The radioactivity in the liver and kidney decreased at later survival intervals and a distribution pattern appeared, which was characterized by a labelling of tissues with a high protein or steroid synthesis and of fat containing tissues. The distribution pattern corresponded to the one seen after the administration of [(14)C]acetaldehyde and is probably due to normal biosynthetic incorporation of radioactivity in the 2-carbon pool. Pretreatments with pyrazole, nialamide and diethyldithiocarbamate caused a marked inhibition of the exhalation of (14)CO2 and of the incorporation of radioactivity in the liver. This effect may be directed towards the decomposition of N-[(14)C]ethyl-N-nitrosourea itself, but an effect on the metabolism of formed 2-carbon fragments is also possible. The incorporation of radioactivity in other tissues was not influenced by the pretreatments.

Uses & manufacturing

Uses · 3 items

Used as experimental mutagen, ethylating agent, and to synthesize diazoethane in the laboratory; No evidence of commercial production; [HSDB]

Experimentally as mutagen; ethylating agent.

In the laboratory synthesis of diazoethane. Mutagenic effect has been studied for promoting growth of various plants. No evidence was found that N-nitroso-N-ethylurea has been produced commercially for these purposes.

U.S. Imports(1986) 2.31X10+10 g /Ethylureas, Methylureas, NSPF/
U.S. Production · 3 items

(1977) NOT PRODUCED COMMERCIALLY IN USA

(1982) NOT PRODUCED COMMERCIALLY IN USA

500 lb (1979)

Methods of ManufacturingThe reaction of N-ethylurea with nitrous acid.
General Manufacturing Information · 3 items

Urea, N-ethyl-N-nitroso-: ACTIVE

There is no information that ENU /N-nitroso-N-ethylurea/ was manufactured commercially, but it has been used in laboratories to prepare the ethylating agent, diazoethane.

Although N-nitroso-N-ethylurea is available in small quantities for research purposes, no evidence was found that it has been produced commercially.

Applications · 4 items

UsesN-Nitroso-N-ethylurea has been used as a mutation-inducing agent.

UsesExperimentally as mutagen; ethylating agent.

UsesA precursor of Diazoethane

General DescriptionYellow-pink crystals or off-white powder. Sensitive to light.

Suppliers59 total

苏州道澜生物医药科技有限公司15952404857 · [email protected]
上海阿拉丁生化科技股份有限公司400-6206333 13167063860 · [email protected]
艾吉析科技(上海)有限公司17717235263 · [email protected]
绍兴恒创合益生物科技有限公司15158234258 · [email protected]
上海毕得医药科技股份有限公司400-1647117 13681763483 · [email protected]
湖北云镁科技有限公司027-59206672 18327059871 · [email protected]
Dayang Chem (Hangzhou) Co.,Ltd.+86-0571-88938639 17705817739 · [email protected]
广州隽唐科技有限公司020-36607679 13502246435 · [email protected]
Syntechem Co.,Ltd[email protected]
湖南瑞威尔生物科技有限公司18627957289 18173226957 · [email protected]
武汉易泰科技有限公司上海分公司18930552037 · [email protected]
上海颖心实验室设备有限公司021-59178156 17002132182 · [email protected]
安耐吉化学&3A(安徽泽升科技有限公司)021-58432009 400-005-6266 · [email protected]
希瓦生物科技(广州)有限公司13268215580 · [email protected]
山东西亚化学有限公司13355009207 13355009207 · [email protected]
天津希恩思生化科技有限公司400 638 7771 · [email protected]
上海珂华生物科技有限公司021-60455363 18019463053 · [email protected]
斯百全化学(上海)有限公司021-021-021-67601398-809-809-809 15221380277 · [email protected]
TargetMol 中国(陶术生物)400-821-0310 15002144251 · [email protected]
上海毕得医药科技股份有限公司400-164-7117 18317119277 · [email protected]
上海鑫圭生物科技有限公司15121041756 · [email protected]
上海麦克林生化科技股份有限公司15221275939 15221275939 · [email protected]
凯试(上海)科技有限公司021-50135380 · [email protected]
Sigma-Aldrich西格玛奥德里奇(上海)贸易有限公司021-61415566 800-8193336 · [email protected]
Henan Alfa Chemical Co., Ltd+8618339805032 · [email protected]
浙江珲达生物科技有限公司0571-89903022 18679456698 · [email protected]
上海双锕化学科技有限公司15010167677 · [email protected]
陕西缔都医药化工有限公司029-029-81120477 17792793610 · [email protected]
上海源叶生物科技有限公司18916372613 · [email protected]
上海颖心实验室设备有限公司021-021-59178156 15300768757 · [email protected]
成都华纯科技有限公司400-1166-196 15982826727 · [email protected]
安徽酷尔生物工程有限公司0551-65171243 13856024262 · [email protected]
深圳纽柯尔化学技术有限公司13612807752 · [email protected]
上海贤鼎生物科技有限公司021-021-52271985 17721149837 · [email protected]
上海康满林生物医药有限公司68080707 15021879576 · [email protected]
Shaanxi Dideu New Materials Co. Ltd18192503167 · [email protected]
Shanghai Acmec Biochemical Technology Co., Ltd.+86-18621343501 · [email protected]
Shaanxi Didu New Materials Co. Ltd+86-86-17392712779 +86-13289823923 · [email protected]
上海臻励生物科技有限公司021-16621358918; 18516310516;16621358918;13045646768 · [email protected]
江苏艾康生物医药研发有限公司025-58859352 15955137747 · [email protected]
厦门盈融达化工有限公司+86-0592-6210733 · [email protected]
天津希恩思生化科技有限公司400-6387771-6039 18920764717 · [email protected]
上海吉至生化科技有限公司021-4009004166/18616739031 18616739031 · [email protected]
深圳聚合生化科技有限公司+86-400-002-6226 13028896684 · [email protected]
上海铂科医药科技有限公司18367689840 · [email protected]
Aladdin Scientific[email protected]
长沙福臻生物科技有限公司15111215862 18229892877 · [email protected]
河南拉瓦锡化工产品有限公司0371-63682289 18625781376 · [email protected]
湖北玖天生物医药科技有限公司027-88013699 17354350817 · [email protected]
安徽敬同药业股份有限公司13675155016 · [email protected]

Additional notes

DefinitionChEBI: A member of the class of N-nitrosoureas that is urea in which one of the nitrogens is substituted by ethyl and nitroso groups.

For more Human Toxicity Excerpts (Complete) data for N-Nitroso-N-ethylurea (6 total), please visit the HSDB record page.