Purpose

To provide guidance in identifying humane endpoint related to experimental investigations. Investigators should consult with the Attending Veterinarian (530-752-0514) for additional information, questions, or unique circumstances that may require deviation from these guidelines.

Background

Although it is crucial to minimize the level of pain and distress experienced by laboratory animals, it is imperative that the scientific objectives of the study are achieved. The criteria that can serve as the basis for ending a test procedure sooner, to terminate or avoid pain and distress while still attaining study objectives, are referred to as humane endpoints.¹ The ILAR Journal, volume 41, is devoted to this topic. Ideal humane endpoints are those that can be identified before the onset of pain and distress.

Guidelines

A.  General Humane Endpoints

The following are general humane endpoints that require euthanasia.

1. The inability to reach food or water for more than 24 hours.
2. A 20% decrease in normal body weight.
3. Development of conditions that result in untreatable pain.
   

General observations for assessing pain and distress include change in body weight, external physical appearance, clinical signs (inability to reach food and water, lethargy or decreased mental alertness, labored breathing, inability to remain upright), changes in behavior, and responses to external stimuli. Moribund animals, those that are considered to be in a dying state, must be identified early in the experiment. This requires that laboratory personnel carefully observe the animals for changes in health status, appearance, and behavior, and have knowledge of the treatment and procedures that the animals have undergone.

During periods in which morbidity and mortality are expected to increase, animals must be evaluated a minimum of three times daily (every 8 hours). Those animals that are not expected to survive until the next scheduled evaluation should be humanely euthanized.

Humane endpoints will vary depending on the nature of the study and must be discussed with the Attending Veterinarian. Identifying the initial signs that occur prior to a moribund state so that additional pain and suffering may be prevented should be developed in consultation with the Attending Veterinarian. Score sheets are an excellent resource to identify humane endpoint and can be developed in consultation with the Attending Veterinarian specifically for each project. This would include a Body Condition Score.²

Pilot studies will provide an opportunity to evaluate humane endpoints and assure the scientific objectives are met, before proceeding to large scale studies.

B.  Death as an Endpoint

Death as an endpoint requires scientific justification and documentation that humane endpoints cannot be used. This includes the requirements of regulatory agencies (i.e. EPA, FDA, etc).

C.  Tumor burden

General guidelines regarding tumor burden can be followed. Euthanasia is indicated if the tumor burden is greater than or equal to 10% of the animal's normal body weight, exceeds 1.5 cm in size in any direction, a diminished body condition score, the tumor prevents ambulation or ability to reach food and water, the tumor is ulcerated or abscessed, or the tumor is causing significant pain and distress.

Premature euthanasia may result in the loss of valuable information regarding the success of novel therapies. Pilot studies may be used to establish individual humane endpoints for therapeutic cancer research.

D.  Euthanasia

If the veterinary staff has examined an animal and determined that it will not survive until the next scheduled examination, every attempt will be made to contact the principle investigator to obtain permission to euthanize the animal. If the veterinary staff is unable to contact the PI, the Attending Veterinarian (or delegate) will be contacted to obtain permission to euthanize the animal.

References

1. ILAR Journal V41(2) 2000.
2. Ullman-Cullere MH, Foltz CJ. Body condition scoring: a rapid and accurate method for assessing health status in mice. Lab Anim Sci. 1999 Jun;49(3):319-23.

IACUC approved: 9/14/04