Carbamic acid, ethyl ester

-0.15

log Kow = -0.15

-0.15

-0.15

0.9862 at 70 °F (NTP, 1992) - Less dense than water; will float

0.9813

Relative density (water = 1): 0.98

1.107 @25 °C

Colorless, columnar crystals or white, granular powder

Prisms from benzene and toluene

greater than or equal to 100 mg/mL at 72 °F (NTP, 1992)

480000

Soluble in benzene

1g dissolves in 0.8 mL alcohol; 1.5 mL ether; 0.9 mL chloroform; 2.5 mL glycerol; 32 mL olive oil

In water, 4.8X10+5 mg/L at 15 °C

480 mg/mL at 15 °C

198 °F (NTP, 1992)

92 °C c.c.

360 to 363 °F at 760 mmHg (NTP, 1992)

185

185 °C

185.00 °C. @ 760.00 mm Hg

185 °C

118 to 122 °F (NTP, 1992)

49

49 °C

48.5 - 50 °C

49 °C

49 °C

Danger

H350: May cause cancer [Danger Carcinogenicity]

P203, P280, P318, P405, and P501 (click each P-code to see the statement)

Danger

Chemical: Carbamic acid, ethyl ester

Hazard Traits - Carcinogenicity; Developmental Toxicity; Hepatotoxicity and Digestive System Toxicity; Nephrotoxicity and Other Toxicity to the Urinary System; Neurotoxicity; Respiratory Toxicity；Authoritative List - CA TACs; EC Annex VI CMRs - Cat. 1B; IARC Carcinogens - 2A; NTP RoC - reasonable; Prop 65；Report - regardless of intended function of ingredient in the product

Regulation (EC) No 178/2002 (amended)

S - indicates a substance that is identified in a final Significant New Use Rule.

Carbamic acid, ethyl ester: Does not have an individual approval but may be used under an appropriate group standard

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.)

This chemical is combustible. (NTP, 1992)

Combustible. Gives off irritating or toxic fumes (or gases) in a fire.

SYMPTOMS: Symptoms of exposure to this compound include burning in the throat, watery to bloody diarrhea, abdominal pain, oliguria, fall in blood pressure, anuria, cardiovascular collapse, delirium, convulsions, muscular weakness with respiratory failure, coma, hemorrhages and kidney and liver injury. It may cause nausea, vomiting and bone marrow depression. Other symptoms may include central nervous system depression and focal degeneration in the brain. Exposure may lead to gastroenteric hemorrhages and drowsiness. It may also cause irritation. Anorexia and dizziness have been reported. Large doses make debilitated persons more prone to hepatitis or fatal hepatic necrosis.；ACUTE/CHRONIC HAZARDS: This compound is toxic by ingestion. It is harmful by inhalation or skin absorption. It may cause irritation. When heated to decomposition it emits toxic fumes of carbon monoxide, carbon dioxide and nitrogen oxides. (NTP, 1992)

Ethyl carbamate is used as an intermediate in the synthesis of a number of chemicals. Acute (short-term) exposure of humans to high levels of ethyl carbamate may result in injury to the kidneys and liver and induce vomiting, coma, or hemorrhages. No information is available on the chronic (long-term), reproductive, or developmental effects of ethyl carbamate in humans. An increased incidence of lung tumors has been observed in rodents exposed to ethyl carbamate by oral or inhalation exposure. The International Agency for Research on Cancer (IARC) has classifed ethyl carbamate as a Group 2B, possibly carcinogenic to humans.

Harmful by inhalation or skin absorption and toxic by ingestion; Toxic to the liver; May cause CNS depression; [CAMEO] Inhalation can cause unconsciousness; [ICSC] Induces genetic damage in germ cells of humans or animals (3A); [MAK]

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. Urethane (51-79-6) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s184uret.pdf]

U238; As stipulated in 40 CFR 261.33, when ethyl carbamate, 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).

URETHANE is incompatible with alkalis, acids, chloral hydrate, camphor, menthol and thymol. Also incompatible with antipyrine and salol. May react with strong oxidizing agents. Liquefies with benzoic acid, resorcinol and salicylic acid. Reacts with phosphorus pentachloride to form an explosive product (NTP, 1992).

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. Ethyl carbamate is included on this list.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)

Use powder, alcohol-resistant foam, water spray, carbon dioxide.

Fresh air, rest. Refer for medical attention.

Rinse skin with plenty of water or shower.

Rinse with plenty of water (remove contact lenses if easily possible).

Rinse mouth.

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: DO NOT INDUCE VOMITING. 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. Be prepared to transport the victim to a hospital if advised by a physician. 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)

... Should be stored in cool, well ventilated place, out of direct rays of sun, away from areas of high fire hazard, & should be periodically inspected & monitored. Incompatible materials should be isolated from each other.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practicable 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/

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces 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 under ambient temperatures. (NTP, 1992)

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U238, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

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/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for ETHYL CARBAMATE (9 total), please visit the HSDB record page.

Personal protection: chemical protection suit including self-contained breathing apparatus. Sweep spilled substance into sealable containers. If appropriate, moisten first to prevent dusting. Carefully collect remainder. Then store and dispose of according to local regulations.

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. 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. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for ETHYL CARBAMATE (11 total), please visit the HSDB record page.

EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration.

It was ... shown to enhance leukemogenic effects of x-irradiation.

The antipellagratic vitamin, nicotinamide, significantly suppressed urethane induced malformations, when it was given intraperitoneally to pregnant JCL:ICR mice immediately after a single subcutaneous injection of urethane (1.0 mg/g) on the 9th day of gestation. The level of inhibition increased with the doses of nicotinamide: 33.0, 55.8, and 70.0% at doses of 0.2, 0.3, and 0.5 mg/g, respectively. Polydactyly and tail anomalies were markedly suppressed by the post treatment with nicotinamide, while cleft palates were less effectively suppressed. Nicotinamide was still effective, when it was given during the period of 24-48 hr after urethane treatment. The level of inhibition was 39.4 and 61.1% at 0.5 and 1.0% of nicotinamide in the diet, respectively. Higher doses of nicotinamide (3 and 5% in diet) also inhibited urethane induced malformations, but not so effectively as lower doses. The inhibiting effects of nicotinamide on the spontaneous incidence of cleft lips and palates in CL/Fr mice were significant at a low dose (0.5% in diet), but not at a higher dose (1.0%).

The progression of papillomas to squamous cell carcinomas (malignant conversion) was studied in the skin of Sencar and Charles River CD-1 mice, using a three stage treatment protocol. After initiation with 7,12-dimethylbenz(a)anthracene (stage 1) and limited promotion by 12-O-tetradecanoylphorbol-13-acetate (stage II), papilloma bearing mice were treated (stage III) with either tumor initiators, such as urethane, N-methyl-N'-nitro-N-nitrosoguanidine or 4-nitroquinoline-n-oxide; the promoter 12-O-tetradecanoylphorbol-13-acetate, or solvent (acetone). Treatment with tumor initiators in stage III increased both the rate of appearance and the final yield of carcinomas. Similar results were obtained in both Sencar and CD-1 mice. A papilloma stage appears to be necessary for carcinoma development since elimination of 12-O-tetradecanoylphorbol-13-acetate treatment in stage II greatly reduced the incidence of both papillomas and carcinomas in both stocks of mice. The carcinomas that develop using the three stage regimen vary in metastatic potential. In CD-1 mice, the frequency of metastases to lymph nodes were similar in groups treated in stage III with N-methyl-N'-nitro-N-nitrosoguanidine, urethane, 4-nitroquinoline-n-oxide, 12-O-tetradecanoylphorbol-13-guanidine or acetone, but treatment with urethane substantially increased metastases to the lung.

N-homocysteine thiolactonyl retinamide was synthesized from trans-retinoic acid and the free base of homocysteine thiolactone. In doses of 90-1800 mg/kg given ip in mixed lipid vehicle over nine weeks, the compound decreased to 60% of controls the number of lung tumors which was induced in A/J mice by 20 mg of ethyl carbamate. The highest dose also decreased the mean volume of lung tumors to 505 of controls, resulting in a total tumor volume of 30% of controls. Retinoic acid itself of 450 mg/kg was toxic, and no chemopreventive activity was observed. The free base and the lipophilic perchlorate salt of homocysteine thiolactone both increased the number of lung tumors to 114-117% of controls, indicating a co-carcinogenic effect. In C57BL/6N mice with transplanted MUO4 rhabdomyosarcoma, N-homocysteine thiolactonyl retinamide in a dose of 1000 mg/kg given over 11-21 days decreased the weight of the tumors to 30-70% of controls. Therefore, N-homocysteine thiolactonyl retinamide has chemopreventive activity against chemical carcinogenesis and antineoplastic activity against a transplanted neoplasm.

For more Interactions (Complete) data for ETHYL CARBAMATE (23 total), please visit the HSDB record page.

Ethyl carbamate can cause cancer. Acute exposure can cause severe eye irritation and skin irritation. Urethane is toxic to kidneys, the nervous system, liver, gastrointestinal tract. Repeated or prolonged exposure to urethane can produce organ damage.

LC50 Xenopus laevis 5,580 mg/L /Conditions of bioassay not specified in source examined/

LC50 Oryzias latipes (Medaka) 1 g/L/24, 48 hr; static

LC50 Pimephales promelas (Fathead minnow, mean length 17.8 mm, mean weight 0.073 g) 5.24 g/L/96 hr (95% confidence interval: 4.96-5.54 g/L); flow-through, 25.1 °C, dissolved oxygen 7.2 mg/L, hardness 45.9 mg/L CaCO3, alkalinity 40.0 mg/L CaCO3, pH 7.8

EC50 Pimephales promelas (Fathead minnow, mean length 17.8 mm, mean weight 0.073 g; affected fish lost schooling behavior, were hypoactive and underreactive to external stimuli and were darkly colored) 3.77 g/L/96 hr (95% confidence interval: 3.57-3.99 g/L); flow-through, 25.1 °C, dissolved oxygen 7.2 mg/L, hardness 45.9 mg/L CaCO3, alkalinity 40.0 mg/L CaCO3, pH 7.8

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 20(SRC), determined from a log Kow of -0.15(2) and a regression-derived equation(3), indicates that ethyl carbamate is expected to have very high mobility in soil(SRC). Volatilization of ethyl carbamate from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 6.4X10-8 atm-cu m/mole(SRC), derived from its extrapolated vapor pressure, 0.262 mm Hg(4), and water solubility, 4.8X10+5 mg/L(5). Ethyl carbamate is not expected to volatilize from dry soil surfaces(SRC) based upon the extrapolated vapor pressure(4). Ethyl carbamate is converted to nitrate in fresh soils after a lengthy lag period(6). The initial step in this process is the hydrolysis of the ethyl carbamate to ethanol, ammonia, and CO2 by soil microorganisms(6).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 20(SRC), determined from a log Kow of -0.15(2) and a regression-derived equation(3), indicates that ethyl carbamate is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 6.4X10-8 atm-cu m/mole(SRC), derived from its vapor pressure, 0.262 mm Hg(4), and water solubility, 4.8X10+5 mg/L(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). A base-catalyzed second-order hydrolysis rate constant of 2.6X10-4 L/mole-sec(SRC) was estimated using a structure estimation method(8); this corresponds to half-lives of 3,300 and 330 years at pH values of 7 and 8, respectively(8). Ethyl carbamate was classified as easy to biodegrade using river die-away tests(9). However at high concentrations biodegradation proceeds slowly using activated sludge inocula since ethyl carbamate may be toxic to the microbes at high levels and require an adaptation period(10,11).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ethyl carbamate, which has a vapor pressure of 0.262 mm Hg at 25 °C(2) is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase ethyl carbamate 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 17 hours(SRC), calculated from its rate constant of 7.4X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Ethyl carbamate does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Monitoring data have revealed ethyl carbamate in beverages with pH's lower than 4.0 at 10 ug/L and in diethylpyrocarbonate-treated wines at up to 50 ug/L(1). It has been demonstrated that ethyl carbamate is formed in acid beverages as a result of the reaction of ammonia and diethylpyrocarbonate(1). However the use of the fermentation inhibitor, diethylpyrocarbonate, in food products is no longer allowed by the U.S. FDA(2).

Ethyl carbamate was detected in (concentration range in ppb): whiskey (60.0 to 389), sherry (32 to 242), port (13.6 to 60), and wine(3 to 9)(1). Ethyl carbamate was detected in a variety of fermented foods and beverages (concentration range in ppb): 15 cheeses (0 to 3); 6 teas (0 to 3); 12 yogurts (0 to 3); 8 ciders (0 to 3); 30 breads (0 to 13); 69 malt beverages (0 to 13); and in 12 soy sauces (0 to 84)(2). Ethyl carbamate was detected in 56 out of 19,851 domestic and imported food and feed samples between Oct 1981 and Sept 1986; 39 of the positive detections were between 0 and 0.05 ppm, 8 were between 0.06 and 0.1 ppm, and 9 were between 0.20 and 0.50 ppm(3). Ethyl carbamate was detected in alcoholic beverages from various countries(number of samples; concn range, ug/kg): white wines(15; 0 to 24); red wines (7; 1.8 to 14); Sake (2; 3 to 29); sherry (4; 28 to 58); whiskey (6; 26 to 247); rye (1; 8); bourbon (4; 44 to 208); gin (1; 0.5); rum (1; 19) fruit brandy (3; 104 to 2,344); apricot brandy (1; 11); Armagnac (2; 410 to 432); other brandies (3; 25 to 28)(4). Various breads and toasts were found to contain ethyl carbamate: 10 bread varieties had an average ethyl carbamate concn of 3.1 ug/kg; light toast and dark toast made from these breads contained ethyl carbamate at mean concns of 4.3 and 15.7 ug/kg, respectively(4). Soy sauce contained ethyl carbamate at concns ranging from 0 to 59 ug/kg(4). Plain natural yogurt contained ethyl carbamate at concns ranging from 0.1 to 0.4 ug/kg(4).

Neurotoxin - Acute solvent syndrome；Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.；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.；IARC Carcinogen - Class 2: International Agency for Research on Cancer classifies chemicals as probable (2a), or possible (2b) human carcinogens.；NTP Carcinogen - Reasonably anticipated to be a human carcinogen.

The substance can be absorbed into the body by ingestion.

Ingestion; Inhalation; Injection

Ethyl carbamate is genotoxic and a potent carcinogen. It exerts its effects through the formation of DNA adducts (via its vinyl carbamate epoxide metabolite) that induce choromosomal aberrations, micronuclei and sister chromatid exchange. It also tends to induce specific mutations in the Kras oncogene in codon 61 of exon 2 including A:T transversions and A-->G transitions in the second base and A-->T transversions in the third base.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=51-79-6]

Raw wastewater from two kraft paper mills in Georgia sampled in March 1972 were found to contain an average of 0.018 and 0.037 mg/L ethyl carbamate(1). The wastewater treatment in the first kraft mill consisted of a trickling biofilter and aerated lagoon, while that in the second consisted of lime treatment and holding in a storage basin(1). Ethyl carbamate was identified, but not quantified, in groundwater samples from the saturated zone of a landfill well, near Norman, OK(2).

Chemical: Carbamic acid, ethyl ester

Hazard Traits - Carcinogenicity; Developmental Toxicity; Hepatotoxicity and Digestive System Toxicity; Nephrotoxicity and Other Toxicity to the Urinary System; Neurotoxicity; Respiratory Toxicity；Authoritative List - CA TACs; EC Annex VI CMRs - Cat. 1B; IARC Carcinogens - 2A; NTP RoC - reasonable; Prop 65；Report - regardless of intended function of ingredient in the product

Regulation (EC) No 178/2002 (amended)

S - indicates a substance that is identified in a final Significant New Use Rule.

Carbamic acid, ethyl ester: Does not have an individual approval but may be used under an appropriate group standard

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.)

U238; As stipulated in 40 CFR 261.33, when ethyl carbamate, 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).

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. Ethyl carbamate is included on this list.

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 100 lb or 45.4 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

The clonal origin of pulmonary tumors by treatment with the chemical carcinogens, urethane and 4-nitroquinoline-1-oxide, were verified by PGK-isozyme mosaicism in DS strain mice. Six pulmonary tumors (12.5%) in 48 mice treated with urethane, and one (3.4%) in 23 mice treated with 4-nitroquinoline 1-oxide, were observed respectively. A single band, either PGK-la or PGK-lb occurred in two out of 7 tumors; and 5 remaining tumors showed either band la and lb associated with a trace band of the other isozyme. Though traces of stromal element and/or blood cells seem to be mixed among the neoplastic tissue, the pulmonary tumor could have originated from a single cell, when one takes into account the significantly higher expression in one band.

The suitability of urethane anesthesia for physiopharmacological investigations is reviewed. Total dose administered and route of administration are recognized as factors having a great influence on both resting parameters and biological responses to drugs. A peculiar characteristic of urethane is represented by its ability to induce a surgical plane of anesthesia without affecting neurotransmission in various subcortical areas and the peripheral nervous system. This makes urethane a suitable general anesthetic nervous systems and accounts for the preservation of a number of reflex responses in urethane anesthetized animals.

The carbamates alone weakly activated estrogen- or progesterone-responsive reporter genes in breast and endometrial cancer cells. All of the carbamates decreased estradiol- or progesterone-induced reporter gene activity in the breast and endometrial cancer cells. In whole cell competition binding assays, the carbamates demonstrated a limited capacity to displace radiolabeled estrogen or progesterone from /estrogen receptor/ or /progesterone receptor/. /Carbamates/

... Urethane potentiated the functions of neuronal nicotinic acetylcholine, gamma-aminobutyric acid(A), and glycine receptors, and it inhibited N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors in a concentration-dependent manner. At concentrations close to anesthetic 50% effective concentration, urethane had modest effects on all channels tested. ... A large concentration of urethane exerts marked effects on all channels.

For more Mechanism of Action (Complete) data for ETHYL CARBAMATE (7 total), please visit the HSDB record page.

In rats, rabbits & humans (patients with multiple myeloma treated with urethane in conjunction with alkylating agent), urinary metabolites are: urethane (0.5-1.7% of admin dose), n-hydroxy urethane (0.02-0.15%), acetyl-n-hydroxy urethane (0.1-0.6%), ethyl mercapturic acid (0.1-0.2%) & N-acetyl-s-ethoxy carbonylcysteine (0.9-2.1%).

Reactivity of ... /n-hydroxyurethane/ in vitro and in vivo favors its consideration as being a proximal carcinogenic metabolite of ... /urethane/ ...

It is metabolized to ethyl alcohol and carbamic acid, and the latter acts as a weak diuretic.

Biotransformation of urethane in rats and rabbits and in man affords n-hydroxyurethane, N-acetyl-s-carboxyethylcysteine, and ethylmercapturic acid as urinary metabolites, and thus urethane is converted into an alkylating agent through n-hydroxylation.

For more Metabolism/Metabolites (Complete) data for ETHYL CARBAMATE (10 total), please visit the HSDB record page.

Urethane has known human metabolites that include Vinyl carbamate.

Substances that inhibit or prevent the proliferation of NEOPLASMS.

Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.

Ultrashort-acting anesthetics that are used for induction. Loss of consciousness is rapid and induction is pleasant, but there is no muscle relaxation and reflexes frequently are not reduced adequately. Repeated administration results in accumulation and prolongs the recovery time. Since these agents have little if any analgesic activity, they are seldom used alone except in brief minor procedures. (From AMA Drug Evaluations Annual, 1994, p174)

The distribution of radiolabelled urethane administered in water or ethanolic solution, was compared in mice by whole-body autoradiography. Two fasted male A/JAX mice were administered 6 uCi (ethyl-1-(14)C)urethane by oral intubation. One mouse received urethane in 1 mL of an aqueous solution, the other in a 12% ethanol solution. One hour after treatment, the mice were frozen and processed for whole body autoradiography. When urethane was administered in water, the radioactivity localized in the salivary, seromucous, and Harderian glands, medullary bone, liver, bile, and epithelia of the stomach and intestine. Lower levels were seen in brown fat, and in the thymus and esophagus. When urethane was administered in ethanol, localization of urethane at each of these sites was almost completely inhibited; high concentrations were still found in the lumen of the stomach and intestine. No evidence was found of transesterification at pH 1.5 in 12% ethanol.

In an attempt to understand route of administration dependency, (3)H-benzo(a)pyrene, (14)C-urethane and (14)C-acrylamide were administered as single doses orally or topically to male Sencar mice. Distribution in skin, stomach, liver, and lung was determined for time periods up to 48 hr. The binding of these compounds to DNA, RNA, and protein in these tissues was determined 6 and 48 hr after administration. For all three compounds, high concentrations were found in the skin following topical application, but very little material reached this target organ following oral administration. The internal organs generally contained more material after oral administration compared to topical application, whereas the opposite was true for the skin. Differences in distribution to the skin and binding to macromolecules following oral or topical administration cannot explain the greater tumorigenicity of urethane and acrylamide after oral administration in the Sencar mouse.

In mice, urethane is active by transplacental route & is passed to offspring in milk.

After oral administration to rats and mice, /carbamic acid, ethyl ester/ is completely absorbed from the GI tract and rapidly distributed throughout the body. ...Mice eliminated /carbamic acid, ethyl ester/ as /carbon dioxide/ more rapidly than rats.

For more Absorption, Distribution and Excretion (Complete) data for ETHYL CARBAMATE (6 total), please visit the HSDB record page.

Ethyl carbamate is used as an intermediate in the synthesis of a variety of products (e.g., pharmaceuticals) and as a solubilizer and cosolvent for pesticides and fumigants. Ethyl carbamate has also been used as an anti-neoplastic agent.

Used as an antineoplastic agent, veterinary anesthetic, and chemical intermediate; [ChemIDplus] Used as an intermediate, amino resin modifier, solvent, and animal anesthetic; Occurs naturally in fermented wines and foods; [Merck Index]

Molten urethan as solvent for various organic materials. Intermediate in organic synthesis. In the preparation and modification of amino resins. As solubilizer and cosolvent for pesticides, fumigants.

SOLUBILIZER & CO-SOLVENT FOR COSMETICS.

AS CHEMICAL INTERMEDIATE, PRIMARILY FOR REACTION WITH FORMALDEHYDE TO PRODUCE N-HYDROXYMETHYL DERIVATIVES, WHICH ARE USEFUL AS CROSS LINKING AGENTS IN TEXTILE TREATMENTS DESIGNED TO IMPART WASH AND WEAR PROPERTIES TO FABRICS.

THERAP CAT: Antineoplastic

By heating ethanol & urea nitrate at 120-130 °C; by action of ammonia on ethyl carbonate or ethyl chloroformate.

Prepared by the reaction of carbamic acid with ethyl alcohol.

... Commercial production is probably the reaction of ethyl chlorocarbonate (made from ethanol and phosgene) with ammonia.

Carbamic acid, ethyl ester: ACTIVE

URETHANE HAS BEEN REPORTED TO OCCUR AS RESULT OF REACTION OF AMMONIA & DIETHYLPYROCARBONATE ADDED AT LEVELS OF 10 UG/L IN CERTAIN BEVERAGES AT PH BELOW 4.0 ... ALSO ... IN DIETHYLPYROCARBONATE TREATED WINES AT LEVELS UP TO 50 UG/L; IT WAS CONSIDERED POSSIBLE THAT SOME OF THIS WAS OF NATURAL ORIGIN ... .

... Urethane can occur as a contaminant in two anticonvulsant drugs (trimethadione and paramethadione), with an allowable limit of 1 ppm; these anticonvulsant drugs may be used only to treat epilepsy. ...

Ethyl carbamate was in use in Japan from 1950 to 1975 as a cosolvent for dissolving water insoluble analgesic drugs, but this practice was stopped after 1975.