Animal Health & Welfare

Defining Humane Experimental Endpoints

Animals used in biomedical research sometimes display signs of pain or distress related to the experimental procedures they are subjected to. Experimental endpoints are a set of predetermined physiological or behavioral signs that define the point at which an animal will be removed from an experimental study. The establishment of appropriate endpoints prior to the start of an experiment allows the researcher to prevent unnecessary animal pain and distress while ensuring accurate and timely data collection.

To be effective, experimental endpoints must be clearly defined and based on objective criteria . Familiarity with the animal model in use is necessary to select relevant endpoints. As experience with and data collected from a specific animal model accrue, endpoints may be refined or modified. Examples of humane experimental endpoints include:

Deteriorating body condition score

• Very useful and easy to use for assessing the condition of animals used in research, especially studies where animals may experience some degree of debilitation as the study progresses.
• Scoring methods have been developed for many species including mice (Ullman-Cullere, M. Body condition scoring: a rapid and accurate method for assessing health status of mice. Laboratory Animal Science 1999, 49(3):319-323.)

Weight loss

• Rapid weight loss of 15-20 percent within a few days. This requires frequent monitoring of body weight.
• Gradual weight loss - over an extended period of time leading to emaciation. The degree of weight loss should be specified in terms of % or quantity (grams, pounds, kg).
• Note: Certain debilitating conditions such as tumor growth and ascites may mask true weight loss.

The inability to rise or ambulate

• Correlates with inability to access food or water.
• Visually obvious, objective and easy to assess.

Tumor size

• Usually measured as diameter of the mass or percentage of body weight (i.e. greater than 1.5 cm diameter in mice or greater than 10% of body weight)

The presence of labored respiration

• The animal shows increased respiratory rate and/or effort. Labored respiration is often accompanied by a strong abdominal component to breathing.

Dehydration

• The skin looses its elasticity. Skin pinched over the back should return to its normal position after it is released. In a dehydrated animal the skin will remain tented.

Ulcerated, necrotic or infected tumors.

• The presence of large open wounds.

Suggestions for the use of humane endpoints in selected

studies:

Chronic studies where some degree of debilitation is expected.

• Body Condition Scoring
• Weight Loss
• Loss of ability to ambulate (inability to access food or water).
• Labored respiration may be associated with lung pathology or abdominal enlargement placing pressure on the diaphragm.

Experimental Neoplasia

• Tumor size - should not exceed 10% of body weight (approximately 1.5 cm diameter for a mouse, up to 3.0 cm diameter for a rat).
• Tumor ulceration, infection, or necrosis.
• For internal tumors Body Condition Scoring may be more useful.
• Loss of ability to ambulate (inability to access food or water).
• Labored respiration may be associated with lung pathology or abdominal enlargement placing pressure on the diaphragm.

Acute Studies

• Body condition scoring
• Weight loss of greater than 20%
• Dehydration
• Loss of ability to ambulate (inability to access food or water).
• Labored respiration may be associated with lung pathology or abdominal enlargement placing pressure on the diaphragm.

Experimental Surgery

Many of the same signs as listed above in addition to conditions specific to post-surgical infections or other complications including:

• Pain, swelling, redness or discharge from surgical incisions.
• Dehiscense (splitting apart) of surgical incisions.

These signs may not by themselves be endpoints but are medical issues that suggest there are deficiencies in surgical techniques or care that require attention.

Non-specific signs of illness such as inactivity, hunched posture or a rough coat are an indication that an animal should be examined more closely. By themselves these signs do not often constitute an endpoint.

Moribund animals - Stating that animals will be euthanized when they become moribund is not an appropriate experimental endpoint as this term is poorly defined and subject to varying interpretations. In addition, it can be assumed that the moribund animal has experienced significant (and in many cases, unnecessary) distress in the period leading up to the moribund condition. The purpose of identifying endpoints is to prevent or minimize animal suffering.

Death as an Endpoint - The continuation of a study until an animal dies is almost never acceptable. Strong scientific justification would be required for such a study.

Further information on humane endpoints may be found at http://www.vetmed.ucdavis.edu/Animal_Alternatives/endpoints.htm.