Standard on Preparation, Storage, and Use of Tribromoethanol (Avertin)

Title

University of North Carolina at Chapel Hill Standard on Preparation, Storage, and Use of Tribromoethanol (Avertin)

Introduction

Purpose

To provide uniform guidance to researchers in the preparation, storage and use of Tribromoethanol (Avertin).

Scope

All laboratory personnel engaged in the preparation, storage and use of Tribromoethanol (Avertin).

The University of North Carolina at Chapel Hill ("UNC-Chapel Hill" or "University") Institutional Animal Care and Use Committee (IACUC) expects that anyone involved in animal work at the University will comply with this Standard. Requests for exceptions to this Standard must be reviewed and approved by the IACUC.

Standard

In compliance with regulatory and oversight bodies, the IACUC expects that investigators use pharmaceutical grade agents whenever they are available, even in acute-terminal procedures. Non-pharmaceutical grade compounds should only be used after specific review and approval by the IACUC for reasons such as scientific necessity, or non-availability of an acceptable veterinary or human pharmaceutical-grade product. Cost savings is not adequate justification for using non-pharmaceutical grade compounds in research animals.

Tribromoethanol, previously referred to by the brand name Avertin, is an injectable anesthetic that is only available as a non-pharmaceutical grade agent, It has been successfully used as an anesthetic for mice because it provides rapid induction and recovery for single use, short duration (approximately 15-20 minutes) surgical procedures. Some investigators choose Avertin over other anesthetics because it is readily available, easy to use, effective, and not a controlled substance. However, there are conflicting reports in the literature regarding variable effectiveness and adverse effects due to Tribromoethanol (Avertin) degrading in the presence of heat or light to produce the toxic byproducts, dibromoacetaldehyde and hydrobromic acid, which are nephrotoxic and hepatotoxic. Regulatory and accrediting agencies have recommended that alternative options for Tribromoethanol (Avertin) be considered for anesthesia in mice whenever possible. These alternatives would include pharmaceutical grade injectable and/or inhalation options described in UNC-Chapel Hill’s mouse formulary. Options can also be discussed with the Division of Comparative Medicine (DCM) veterinary staff.

For detailed instructions on preparing and storing Tribromoethanol (Avertin), please refer to the Standard Operating Procedures (SOP) for Preparation and Storage of Tribromoethanol (Avertin).

Dosages

• 125-250 mg/kg IP
• 0.02 ml per gram body weight (1.25% solution)
  • Example: 25g mouse gets 0.5 ml, 30g mouse gets 0.6 ml
• For survival procedures, Tribromoethanol (Avertin) may only be administered IP once.
• NOTE: 1.25% Tribromoethanol (Avertin) working solution is usually sufficient for most surgical procedures.  However, as with all anesthetics, sex and strain may alter efficacy.
• Higher concentrations (2-2.5%) and/or dosages (up to 300 mg/kg) have been used for non-survival, or more invasive procedures, but carry a higher risk of adverse reactions.

Animal Use Protocol

• Scientific justification should be described in the protocol.
• The animal use protocol may reference this Standard and SOP or alternatively must provide details regarding the preparation of the working solution and proper storage of the stock solution in the animal use protocol.
• Tribromoethanol (Avertin) is only available as a non-pharmaceutical grade compound so its use requires completing Section 11.3 in the IACUC application.

References

1. Weiss, J. and Zimmermann, F., Tibromoethanol (Avertin) as an anesthetic in mice. Lab. Animal, 1999. 33(2): 192-3.
2. Gopala, C., et al., Tribromoethanol-medetomidine combination provides a safe and reversible anesthetic effect in Sprague-Dawley rats. Contemp. Top. Lab. Animal Science, 2005. 44(1): 7-10.
3. Zeller, WM; Burki, G; and Panoussis, B. Adverse Effects of Tribromoethanol as Used in the Production of Transgenic Mice. Laboratory Animal Science, 1998. October, 32(4): 407-413
4. Lieggi, C.C., et al., An evaluation of preparation methods and storage conditions of tribromoethanol. Contemp Top Lab Anim Sci, 2005. 44(1): 11-6
5. Lieggi, C.C., et al., Efficacy and safety of stored and newly prepared tribromoethanol in ICR mice. Contemp Top Lab Anim Sci, 2005. 44(1): 17-22.
6. Meyer, R.E. and R.E. Fish, A review of tribromoethanol anesthesia for production of genetically engineered mice and rats. Lab Anim (NY), 2005. 34(10): 47-52.
7. Papaioannou, VE and Gox, JG. Efficacy of Tribromoethanol Anesthesia in Mice. Laboratory Animal Science, 1993. April, 43(2): 189-192.
8. Kohn, DF; Wixson, SK; White,WJ; and Benson, GJ. Anesthesia and Analgesia in Laboratory Animals, 1997.
9. PHS Policy on the Human Care and Use of Laboratory Animals, Frequently Asked Questions
10. Koizumi, T., H. Maeda, and K. Hioki, Sleep-time variation for ethanol and the hypnotic drugs tribromoethanol, urethane, pentobarbital, and propofol within outbred ICR mice. Exp Anim, 2002. 51(2): p119-24. National Human Genome Research Institute Guideline 03.2, http://www.theodora.com/rodent_laboratory/guideline_03_2.html

Exceptions:

Requests for exceptions to this Standard must be reviewed and approved by the IACUC.

Contact Information

Policy Contact

• Name: Michael Chi
• Title: Associate Director, Office of Animal Care and Use
• Email: mchi@unc.edu

Subject: Use or Alternative Uses for Tribromoethanol (Avertin)

• Contact: Department of Comparative Medicine
• Telephone: 919-843-3407

Subject: Amendments or Exceptions

• Telephone: 919-966-5569
• Email: iacuc@med.unc.edu

Important Dates

• Effective Date and title of Approver 8/4/2017; UNC IACUC
• Revision and Review Dates, Change notes, title of Reviewer or Approver: 08/04/2017; UNC IACUC

Approved by: UNC IACUC