In vivo, urethane is a good clastogen in mammalian somatic cells, however in vitro, it has inconsistent effects on cells. In many different types of cells, urethane is an efficient inducer of sister chromatid exchange [2].

Tumor models and animal modeling both benefit from the usage of polyurethane.

Absorption, Distribution and Excretion
This study used whole-body autoradiography to compare the distribution of radiolabeled ethyl carbamate administered in aqueous or ethanol solutions in mice. Two fasted male A/JAX mice were orally administered 6 μCi of (ethyl-1-(14)C) ethyl carbamate. One mouse received 1 mL of aqueous ethyl carbamate solution, and the other received a 12% ethanol solution. One hour after administration, the mice were frozen and subjected to whole-body autoradiography. When ethyl carbamate was dissolved in water, radioactivity was mainly distributed in the salivary glands, serous mucous glands, Haver's glands, bone marrow, liver, bile, and gastrointestinal epithelium. Lower levels of radioactivity were observed in brown adipose tissue, thymus, and esophagus. When ethyl carbamate was dissolved in ethanol, radioactivity in the above sites was almost completely suppressed; high concentrations were still detected in the stomach and intestinal lumen. No evidence of transesterification was found in a 12% ethanol solution at pH 1.5. To understand the dependence on the route of administration, we administered (3)H-benzo[a]pyrene, (14)C-carbamate, and (14)C-acrylamide to male Sencar mice via single oral or topical administration. The distribution of these compounds in the skin, stomach, liver, and lungs was determined over a 48-hour observation period. The binding of these compounds to DNA, RNA, and proteins in these tissues was also measured at 6 and 48 hours post-administration. For all three compounds, high concentrations were detected in the skin after topical administration, but very little reached the target organs after oral administration. The levels in visceral organs were generally higher after oral administration compared to topical administration, while the opposite was true for the skin. The difference in drug distribution in the skin and binding to macromolecules after oral or topical administration does not explain the stronger tumorigenicity of ethyl carbamate and acrylamide after oral administration in Sencar mice. In mice, ethyl carbamate exerts its effects via the placental route and is passed to offspring via breast milk.
After oral administration, ethyl carbamate is completely absorbed from the gastrointestinal tract and rapidly distributed throughout the body. Mice excrete ethyl carbamate as carbon dioxide faster than rats.
For more complete data on the absorption, distribution, and excretion of ethyl carbamates (6 in total), please visit the HSDB records page.

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Metabolites
In rats, rabbits, and humans (multiple myeloma patients treated with ethyl carbamate in combination with alkylating agents), urinary metabolites include: ethyl carbamate (0.5–1.7% of the administered dose), N-hydroxycarbamate (0.02–0.15%), acetyl-N-hydroxycarbamate (0.1–0.6%), ethyl mercaptourate (0.1–0.2%), and N-acetyl-S-ethoxycarbonylcysteine (0.9–2.1%).
The in vitro and in vivo reactivity of N-hydroxycarbamate makes it a matter of consideration. As a proximal carcinogenic metabolite of ethyl carbamate…
It is metabolized to ethanol and carbamic acid, the latter being a weak diuretic.
Ethyl carbamate undergoes biotransformation in rats, rabbits, and humans, with urinary metabolites being N-hydroxycarbamate, N-acetyl-S-carboxyethylcysteine, and ethyl mercaptouric acid. Therefore, ethyl carbamate is converted to an alkylating agent via N-hydroxylation.
For more complete metabolite/metabolite data on ethyl carbamate (10 metabolites in total), please visit the HSDB record page.
Known human metabolites of ethyl carbamate include vinyl carbamate.
Ethyl carbamate is rapidly metabolized in the body, with 95% excreted as carbon dioxide. It is readily absorbed by the gastrointestinal tract and skin. The metabolism of ethyl carbamate is mediated by cytochrome P450 2E1. Its metabolites include N-hydroxyethyl carbamate, α-hydroxyethyl carbamate, and vinyl carbamate. N-hydroxyethylcarbamate is excreted in urine after binding, α-hydroxyethylcarbamate is metabolized into ammonia and carbon dioxide, and vinylcarbamate is converted into vinylcarbamate epoxide. Vinylcarbamate epoxide is considered a carcinogenic metabolite of ethylcarbamate because it can form vinyl-DNA adducts (A15086).

Toxicity Summary
Ethyl carbamate is genotoxic and a potent carcinogen. It exerts its effects by forming DNA adducts (via its vinyl carbamate epoxide metabolite), which can induce chromosomal aberrations, micronuclei, and sister chromatid exchanges. It also tends to induce specific mutations in codon 61 of exon 2 of the Kras oncogene, including A:T transversion and A→G transition at the second base, and A→T transversion at the third base. Interactions Studies have shown that it can enhance the leukemic effects of X-rays. Anti-pellagra Vitamin Nicotinamide significantly inhibited ethyl carbamate-induced malformations. The inhibition rate was significantly increased when pregnant JCL:ICR mice received a single subcutaneous injection of ethyl carbamate (1.0 mg/g) followed immediately by intraperitoneal injection of nicotinamide on day 9 of gestation. The inhibition rate increased with increasing nicotinamide dosage: at doses of 0.2, 0.3, and 0.5 mg/g, the inhibition rates were 33.0%, 55.8%, and 70.0%, respectively. Polydactyly and tail deformities were significantly inhibited after nicotinamide treatment, while the inhibition of cleft palate was poor. Nicotinamide remained effective when administered within 24–48 hours after urethane treatment. When the dietary nicotinamide concentration was 0.5% and 1.0%, the inhibition rates were 39.4% and 61.1%, respectively. Higher doses of nicotinamide (3% and 5% in the diet) also inhibited urethane-induced deformities, but the effect was not as good as at lower doses. The inhibitory effect of nicotinamide on spontaneous cleft lip and palate in CL/Fr mice was significant at low doses (0.5% added to the diet), but not significant at higher doses (1.0%). This study employed a three-stage treatment regimen to investigate the progression of papilloma to squamous cell carcinoma (malignant transformation) in the skin of Sencar and Charles River CD-1 mice. Tumorigenesis was first induced with 7,12-dimethylbenzanthracene (stage one), followed by limited promotion with 12-O-tetradecanoylphorbol-13-acetate (stage two). Subsequently, in stage three, mice carrying papillomas were treated with: tumor inducers such as urethane, N-methyl-N'-nitro-N-nitrosoguanidine, or 4-nitroquinoline-N-oxide; the promoter 12-O-tetradecanoylphorbol-13-acetate; or a solvent (acetone). Treatment with the tumor initiator in stage three increased both the incidence and the final incidence of cancer. Similar results were observed in both Sencar and CD-1 mice. The papillary stage appears to be a necessary condition for carcinogenesis, as discontinuation of 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment in the second stage significantly reduced the incidence of papillomas and carcinomas in both mouse strains. The metastatic potential of carcinomas induced by the three-stage treatment regimen differed. In CD1 mice, lymph node metastasis frequencies were similar across groups treated in stage III with N-methyl-N'-nitro-N-nitrosoguanidine, ethyl carbamate, 4-nitroquinoline-N-oxide, 12-O-tetradecanoylphorbol-13-guanidine, or acetone, but ethyl carbamate treatment significantly increased lung metastasis. N-homocysteine thiolactone retinamide is synthesized from trans-retinoic acid and the free base of homocysteine thiolactone. Over 9 weeks, intraperitoneal injection of this compound in a mixed lipid carrier at doses of 90–1800 mg/kg reduced the number of lung tumors in A/J mice (induced by 20 mg urethane) to 60% of the control group. The highest dose also reduced the mean volume of lung tumors to 50% of the control group, ultimately reducing the total tumor volume to 30% of the control group. Retinoic acid at 450 mg/kg is toxic, and no chemopreventive activity was observed. Both the free base of homocysteine thiolactone and its lipophilic perchlorate increased the number of lung tumors to 114–117% of the control group, indicating a synergistic carcinogenic effect. In C57BL/6N mice transplanted with MUO4 rhabdomyosarcoma, continuous administration of 1000 mg/kg of N-homocysteine thiolactone acyl retinamide for 11–21 days reduced tumor weight to 30–70% of the control group. Therefore, N-homocysteine thiolactone retinamide possesses chemopreventive activity, counteracting chemical carcinogenicity and exhibiting anti-transplanted tumor activity. For more complete data on interactions of ethyl carbamates (23 in total), please visit the HSDB record page. Non-human toxicity values: Rat oral LD50: 1809 mg/kg; Rat intraperitoneal LD50: 1500 mg/kg; Rat intramuscular LD50: 1400 mg/kg; Mouse oral LD50: 2500 mg/kg. For more complete data on non-human toxicity values of ethyl carbamates (7 in total), please visit the HSDB record page.

[1]. K J Field, et al. Hazards of urethane (ethyl carbamate): a review of the literature. Lab Anim. 1988 Jul;22(3):255-62.
[2]. R E Sotomayor, et al. Mutagenicity, metabolism, and DNA interactions of urethane. Toxicol Ind Health. 1990 Jan;6(1):71-108.

Therapeutic Uses
Intravenous anesthetic; antitumor drug; carcinogen
According to a 1968 report, ethyl carbamate has been used in human medicine as an antitumor drug, previously as a hypnotic, adjunct to sulfonamides, a component of sclerotherapy (mixed with quinine), and a topical bactericide.
Updated data show that high doses of ethyl carbamate can cause bone marrow suppression and it was once used to treat chronic leukemia and multiple myeloma. There is currently no evidence of ethyl carbamate being used in human medicine in the United States.
Veterinary Use: Reports indicate that exposure to ethyl carbamate includes limited use as a hypnotic and more common use as an anesthetic in laboratory animals.
For more complete data on the therapeutic uses of ethyl carbamate (7 in total), please visit the HSDB records page.

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Drug Warnings
Overdose of any anticancer drug (including ethyl carbamate) can cause leukopenia, granulocytopenia, thrombocytopenia, dysplasia of all components of bone marrow, nausea… and anorexia. (Excerpt from table)
Drug (Veterinary):…Hepatotoxicity. Contraindicated in patients with nephritis or hepatitis. Hematopoietic suppressant. May be teratogenic in hamsters and carcinogenic in rats and mice. Continued use may decrease white blood cell count. May increase blood sugar levels. …Usually used only for terminal experiments because pulmonary edema may occur during prolonged anesthesia and recovery.
While not all anticancer drugs have conclusive evidence of teratogenicity in humans, it is recommended that pregnant women, especially in the first trimester, avoid their use, and breastfeeding women should also avoid them. /Anticancer Drugs/
…Ethyl carbamate may be present as a contaminant in two anticonvulsant drugs (metformin and para-metformin), with an allowable limit of 1 ppm; these anticonvulsant drugs are only for the treatment of epilepsy…

C3H7NO2

89.0932

89.047

51-79-6

Urethane-d5;73962-07-9

5641

Colorless, columnar crystals or white, granular powder
Prisms from benzene and toluene

1.1±0.1 g/cm3

105.7±23.0 °C at 760 mmHg

48-50 °C(lit.)

17.7±22.6 °C

15.9±0.4 mmHg at 25°C

1.423

0.07

1

2

2

6

52.8

0

O(C(N([H])[H])=O)C([H])([H])C([H])([H])[H]

JOYRKODLDBILNP-UHFFFAOYSA-N

InChI=1S/C3H7NO2/c1-2-6-3(4)5/h2H2,1H3,(H2,4,5)

ethyl carbamate

NSC-746; NSC 746; Urethane

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~1122.46 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (23.35 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (23.35 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: 2.08 mg/mL (23.35 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 50 mg/mL (561.23 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)