Guidelines for Choosing Appropriate Intervention and Endpoints

Approved September 19, 2008

A guiding principle of the Canadian Council on Animal Care (CCAC) is that, “animals must not be subjected to unnecessary pain or distress”. The experimental design must offer them every practicable safeguard, whether in research, in teaching, or in testing procedures” (CCAC 1989) An endpoint is defined by the CCAC as the point at which an animal's pain and/or distress is terminated, minimized or reduced, by taking actions such as killing the animal humanely, terminating a painful procedure, or giving treatment to relieve pain and/or distress.”

Whether using animals for teaching or research, any actual or potential pain, distress, or discomfort should be minimized or alleviated by choosing the earliest endpoint that is compatible with achieving the scientific objectives of the research, or educational objective for teaching. The majority of early endpoints rely on regular observations of animal behaviour to find the earliest clues of distress. Waiting until stressors are manifested in illness or death is not satisfactory unless it can be rigorously defended under the scientific objectives of the study design (CCAC 1998) e.g. by a proportionate benefit.

The Vancouver Island University (VIU) Animal Care Committee (ACC) suggests the following list as elements of observations that investigators or instructors monitor on a daily basis (minimum) as part of their animal use protocol:

1. Feeding activity or feed consumption
   1. Animals are eating an appropriate amount at an appropriate interval for their age, physiological needs and environment.
      1. Water intake is an essential component to monitor for mammals and birds as well.
   2. Feeding activity is a more sensitive measure for fish than is feed consumption. In addition, given that some fish are slow growing, lack of gain is better than weight loss.
2. Physical appearance and posture
   1. Fish: eye, fin and skin condition, colour, mucus production.
   2. Reptiles: skin and eye condition, fecal output and consistency, shedding ability/regularity, discharges from body openings (nasal, oral, cloacal).
   3. Mammals: fur condition, fecal output and consistency, discharges from body openings (nasal, oral, cloacal), body condition score, abnormal posture e.g. hunched, recumbent.
   4. Birds: plumage condition, fecal output and consistency, discharges from body openings (nasal, oral, anal, urogenital).
3. Observable clinical signs
   1. Respiratory rate
   2. Abnormal position indicating that they are seeking specific areas in their environment (near water inflow, near warm areas of the cage, away from cage or tank mates etc.).
   3. Production of abnormal excretions or discharge.
4. Unprovoked behaviour
   1. Ability of the animal to carry out normal behaviours for that species in that environment e.g. rearing, running away searching for escape routes (escape attempts), utilizing enrichment devices e.g. running wheels, climbing, spending time in a nest.
   2. Ability to move normally and at the normal rate.
   3. Normal behaviours
      1. Social interactions, hyperactivity, hypoactivity.
   4. Any change in the known normal behaviour of an individual animal e.g. as observed by its caretaker (especially true of larger animals, and by strain with small rodents).
5. 5. Provoked behaviour
   1. Change in their response to handlers (more or less aggressive).
   2. Flight reaction change in the presence of staff, light or other disturbances.
   3. Changes in response to a known stimulus e.g. red light response in rats, a noise or “tch” sound.

The VIU ACC requires that the details of how these observations will be accomplished be incorporated into any relevant Animal Use Protocols (AUP) and Standard Operating Procedures (SOP).  In an effort for these procedures to be as effective as possible it is important that researchers also identify which aspects of regular observations are most likely to be most sensitive to the stressors that are likely to arise during a given experiment, procedure or teaching exercise and how these will be monitored to minimize animal stress in light of the experimental or teaching objectives.  Including the time at which these abnormal observations may be critical e.g. at feeding time, or at night or during the day.

Consider using Table 1 below as part of your animal welfare monitoring procedure when you describe it in your AUP.

Endpoints: Clearly stipulate which particular changes will signal when action is required to reduce or relieve animal distress. Please add any additional activity categories as they apply to your experimental species or procedure.

Table 1 - Table is to assist animal care personnel with monitoring observable changes in animal behaviour in an effort to maintain clear points of intervention in order to adhere to the pre-established endpoints for terminating a treatment or experiment.

(CCAC 2005)

Please see the bibliography list for further information pertaining to the importance and application of humane endpoints and intervention points in research, teaching and testing using animals. In addition, the CCAC guidelines to choosing an appropriate endpoint have a list of useful references in addition to the ones listed below.

References

CCAC (2005) Guidelines on: the care and use of fish in research, teaching and testing. Ottawa ON: CCAC, 86 pp.

CCAC (1998) Guidelines on: choosing an appropriate endpoint in experiments using animals for research, teaching and testing. Ottawa ON: CCAC, 30 pp.

CCAC (1989) Policy Statement: Ethics of Animal Investigation. Ottawa ON: CCAC.

Bibliography

Flecknell, PA (1994).  Refinement of animal use – assessment and alleviation of pain and distress. Laboratory Animals 28(3): 222-231.

ILAR Journal V41(2) 2000

Humane Endpoints for Animals Used in Biomedical Research and Testing

Introduction: Reducing Unrelieved Pain and Distress in Laboratory Animals Using Humane Endpoints
William S. Stokes

Recognizing Pain and Distress in Laboratory Animals
E. Carstens and Gary P. Moberg

Defining the Moribund Condition as an Experimental Endpoint for Animal Research
Linda A. Toth

A Systematic Approach for Establishing Humane Endpoints
David B. Morton

Humane Endpoints and Cancer Research
James Wallace

Humane Endpoints for Genetically Engineered Animal Models
Melvin B. Dennis, Jr.

Humane Endpoints for Infectious Disease Animal Models
Ernest D. Olfert and Dale L. Godson

Refinement of Vaccine Potency Testing with the Use of Humane Endpoints
Coenraad F. M. Hendriksen and Bjorn Steen

Humane Endpoints and Acute Toxicity Testing
Neil Sass

Book Review
Charles R. McCarthy

Special Thanks to Institutional Members

Morton, DB (1999) Humane endpoints in animal experimentation for biomedical research: ethical, legal and practical aspects. In: Humane Endpoints in Animal Experiments for Biomedical Research, eds Hendriksen and Morton, London: Royal Society of Medicine Press, pp. 5 -12

Morton, DB (1998) The importance of non-statistical design in refining animal experiments.  ANZCCART Facts Sheet.  ANACCART News 11, No. 2, June 1998 Insert, ANZCCART, PO Box 19, Glen Osmond, SA 5064, Australia, p 12.

Morton, DB and Griffiths, PHM (1985) Guidelines on the recognition of pain and discomfort in experimental animals and a hypothesis for assessment. Veterinary Record 116: 431-436.

Olfert, ED (1995) Defining an acceptable endpoint in invasive experiments.  Animal Welfare Information Center Newsletter 6(1): 3 - 7.