Urethane (ethyl carbamate)

Guidelines from the U of Minn.:   "Urethane- is a long-acting (8-10h) anesthetic with minimal cardiopulmonary depression. The drug is used for long procedures in rodents. However, it is carcinogenic and is only allowed to be used with special justification and only for terminal (acute) procedures."

Urethane is used alone or in combination with other drugs to produce anesthesia in laboratory animals. It is known to provide long periods of anesthesia with minimal physiological changes. However, due to the potential health risks of urethane, it should be used with care.

Urethane has demonstrated carcinogenic properties when administered to rats and mice as well as mutagenic properties in mice, when administered at anesthetic dosages.

Urethane is well absorbed across the skin, shows multiple organ effects, suppresses the bone marrow, readily crosses the placenta, induces tumor formation in fetuses exposed in utero, and initiates preneoplastic changes in the skin.

It is therefore important that when using urethane, certain precautions be taken to promote safe handling and use of the compound. The following are procedures on should follow to minimize the risk of exposure.

1. When handling urethane in the crystalline or powdered form and when mixing urethane into aqueous solutions, always wear a face mask, protective eye-wear, and chemical resistant gloves.
2. In order to prevent inhaling the volatized drug, mix urethane in a fume hood. Urethane should only be heated if mixing takes place in a fume hood.
3. Gloves should be worn if the user is to come in contact with blood or serum from an animal anesthetized with urethane.
4. Open containers of urethane should never be permitted.  Once mixed into an aqueous solution, urethane should then be transferred into a sealed bottle. This will prevent volatilization, spillage, and accidental contamination of the environment.
5. If accidental contact of the skin., eyes, or other mucous membranes occurs, the area of contamination should be washed thoroughly with water. Repeated transdermal exposure could result in bone marrow suppression.
6. Pregnant women should avoid working with urethane.
7. Due to its long term carcinogenic effects in laboratory animals, urethane should be limited in use to non-recovery procedures.

Comments below are taken from internet discussions among researchers and veterinarians regarding Urethane usage.  These are not articles, but personal comments regarding the use of urethane in research settings.

Comment:  Urethane alone is the anesthetic of choice for many rodent respiratory physiologists due to its minimal effect on respiratory frequency. Might expect a similar effect on cardiac dynamics. Only potential problem is that it is a carcinogen.

Comment:  Urethane is a convenient one shot method of providing surgical anaesthesia in a range of species, for non-recovery studies , but its a carcinogen - there are a number of reviews dealing with this aspect, so I won't dwell on it. The point worth noting is that urethane appears to maintain its CV stability by a continued stimulation of the sympathetic system - catecholamine levels rise steadily throughout the period of anaesthesia. We could , therefore, suggest that an alternative is isolfurane coupled with
an adrenalin infusion.

Comment:  Urethane is a carcinogen AND it is volatile. While there are times and places when it's an appropriate research anesthetic,in my opinion it would NEVER be appropriate for use in a class.  You are just putting too much reliance on the students to recognize the hazard, make certain they don't let the animal's blood get on their skin, and make certain that all the workstations in the class are well enough ventilated.

Picture your OSHA inspector, walking into your class, and then going down the rows and asking each student if they had seen the MSDS for methyl-carbamate. How do you think they'd do?

Urethane in rabbits  Back to Top

Question:  I need your help and/or advice on the use of urethane anesthesia in Dutch-belted rabbits. I have a researcher who needs to keep the animal completely still for at least two hours. He has found two published papers that used 1 to 2 mg/kg acepromazine administered subcutaneously in a baseline procedure followed by 2 mg/kg xylazine administered intramuscularly to relax the rabbit prior to intraperitoneally administered urethane.

Response:  Since urethane admin IV is considered to have a long duration of action (5-6hr or longer) & perivascular injection is reported to cause tissue necrosis, what's the rationale for IP administration? One of the refs cited in the ACLAM anes book  reported postop death following IP urethane anesthesia. I haven't read the article, but you might want to look at it.

Response:  The ACLAM information doesn't mention the use of alpha2 agonists with  urethane. The statement regarding urethane 1.5 g/kg says that it's administered "slowly IV to effect" and no other drugs were included in the description of Bree & Cohen's work. You might want to read Bree & Cohen's paper for details.

Urethane in Mice  Back to Top

Question:  I was wondering about the following anesthesia protocol for the mouse.

urethane 750-1000mg/kg
etomidate 20-25 mg/kg
morphine 1-2 mg/kg

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Response:  An interesting mix!  Should work, but remember that one reason that the blood pressure and heart rate are up with urethane is that it stimulates endogenous catecholamine release, so this background activity may not be ideal - nevertheless, if I were doing Cardiovascular work I'd prefer this to anything with xylazine. An etomidate/fentanyl or metomidate/fentanyl mix might be even better - see Colin Green's paper.

Urethane in Rats  Back to Top

Comment:  Having done some investigating into this subject, with regard to pulmonary function, it seems that the general feeling about urethane is that it produces far fewer respiratory effects than either gas or barbiturate anesthesia. A number of pulmonary pharmacologists I am in contact with have suggested that, in the rat for pulmonary assessments, this is the only really useful anesthetic.

References:

• Field and Lang, Laboratory Animals (1988), 22, 255-262
• Buelke-Sam et al., Laboratory Animal Science (1978), 28, 157-162
• Field et al., Laboratory Animals (1993), 27, 258-269