Date: October 1998
Reference:   Administrative Panel on Laboratory Animal Care

DIRECTIONS: Review the following material. Keep copies of guidelines with applicable protocols. You may find it helpful to post a copy of these guidelines in your laboratory. Questions should be forwarded to the A-PLAC office, 723-4550.

TRAINING: Training in these techniques and the humane treatment of laboratory animals during the procedures is taught by the Veterinary Service Center (VSC) staff. All new personnel who will be performing these techniques should contact VSC staff for training (723-6735).

In order to comply with guidelines governing the use of animals in experimentation, the use of death as an endpoint to experimental manipulation, rather than performing euthanasia to humanely terminate an animal, is discouraged. Directors must perform euthanasia on all moribund experimental animals unless there is scientific justification that euthanasia would invalidate experimental data collection.

Moribund is defined as "in a dying state." Animals are considered to be moribund if they manifest any of the following clinical signs:

1. Inability to ambulate that prevents the animal's easy access to food and/or water.
2. Inability to maintain itself in an upright position.
3. Prolonged (greater than 48 hours) inappetence and/or clinical dehydration.
4. Agonal breathing and cyanosis; chronic diarrhea or constipation.
5. Hematologic or biochemical parameters that indicate organ failure incompatible with life.
6. Unconsciousness with no response to external stimuli such as a toe-pinch withdrawal test.

If killing a moribund animal would invalidate the study, the scientific justification for using death as an endpoint must be provided in writing as part of the animal care protocol and must be approved by the Administrative Panel on Laboratory Animal Care (A-PLAC) prior to initiating this procedure. Directors who receive approval from the A-PLAC to use death as an experimental endpoint must also agree to the following:

1. To use the minimum number of animals necessary to achieve statistical significance and to use alternative endpoints other than death whenever possible.
   
   
2. Animals must be monitored twice daily (in the early morning and late afternoon including weekends and holidays) and any animals evidencing clinically abnormal behavior must be removed from group housing situations and housed individually with easy access to food and water.
   
   
3. Written records of all monitoring sessions, indicating the time of the observations, the person observing the animals, and any observations such as the number of animals evidencing clinically abnormal behavior and the number of animals found dead, must be maintained and made available to VSC or A-PLAC staff on request.
   

DIRECTORS SHOULD NOTE THAT ANY APPROVED USE OF DEATH AS AN EXPERIMENTAL ENDPOINT WILL BE NOTED ON ALL PROTOCOL FORMS AND REGULATORY PAPERS AS BEING IN THE HIGHEST PAIN LEVEL CATEGORY, "E," UNLESS ANALGESICS OR ANESTHETICS ARE PROVIDED TO ALLEVIATE PAIN OR DISTRESS IN THE EXPERIMENTAL ANIMALS.