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Refinement Alternatives
Humane Endpoints
What is a humane endpoint?
The term "humane endpoint" refers to the point at which an experimental animal's pain and/or
distress is terminated, minimized or decreased by taking actions such as killing the animal
humanely, terminating a painful procedure or giving treatment to relieve pain and/or distress.
Therefore, using humane endpoints in animal experiments or testing provides an alternative to
the use of more severe signs of animal pain and distress, including death, and contributes
to refinement.
Implementation of a humane endpoint in a scientific study should ensure that the scientific
goal of the study is reached while minimizing the impact for the animal. While humane endpoints
should be considered for all experiments involving animals, they are essential in those
situations with a strong potential for pain and distress (e.g., acute toxicology, or animal
models of infection, cancer or inflammatory disease).
Humane endpoints are best established prior to the commencement of a study; they should not
be negotiated during a study either to meet "new" scientific aims or to address welfare
concerns as they arise.
Selecting a humane endpoint
A moribund animal is one that is close to death and may be unresponsive to stimuli, exhibit
dyspnea (breathlessness), hypothermia, prostration, etc. However, before the animal gets to
the point of being moribund, detailed observations of the animal can help to set an earlier
experimental endpoint, and thereby decrease the pain and/or distress to the animal. In
designing an experiment and considering humane endpoints, investigators should:
- consider the experimental result they wish to achieve and what might be the earliest
observable indicators of that effect prior to observable signs of animal pain and/or
distress, keeping in mind that a moribund state will also invariably affect
scientific results;
- consider that it may not be necessary to reproduce a condition or effect in every
detail (and potential severity) as may be seen in humans (for example, using animals
to study arthritis may not actually require chronic painful joint disease to be
manifested, just an increase or decrease in urinary excretion of cartilage breakdown
products to be measured);
- develop specific endpoints for each experiment after consulting references on humane
endpoints and a clinical veterinarian, to ascertain likely adverse effects and
clinical signs;
- make appropriate observations of the animals (behaviour, physiology, etc.) to determine
which are the most significant indicators of pain and/or distress in the specific
circumstances of the research;
- determine which observations are the most significant predictors of further deterioration
in the animal's condition, and identify the earliest point at which those signs appear
more frequent observations may be necessary at first to determine a definitive schedule;
- apply, monitor and record the use of humane endpoints during the experiment these should
be reviewed and changed in consultation with the veterinarian and ACC;
- use pilot studies using small numbers of animals when necessary to determine the onset
and progress of adverse effects and identify early scientific and humane endpoints;
- include all information about humane endpoints used when publishing the results of
the study; and
- ensure appropriate training and competencies for all those engaged in monitoring
animals for signs of adverse effects.
Humane endpoint score sheets
The use of observational checklists or score sheets for scoring the animal's condition
in a study provides an objective basis on which decisions about endpoints can be made.
The advantages of score sheets are that specific observations are not overlooked or taken
for granted. In addition, such score sheets help improve observational skills, particularly
with the smaller laboratory animals where some of the conventional clinical observations
made on larger animals are not readily determined (e.g., temperature, heart rate and
respiratory rate). However, score sheets do not cover all abnormalities or observations,
and thus are only a useful way to record certain findings. They cannot replace a thorough
examination of the animal.
(This section has been adapted from the NC3Rs website and CCAC guidelines)
For more information on humane endpoints, the following resources may be useful:
CCAC resources
Online resources
- Altweb. Humane Endpoints Database.
- This database covers the period 1981-2003 and uses references
drawn from the laboratory animal science peer reviewed literature
and full-text books, and also includes searches undertaken on
Medline, Embase, Biosis, ISI World of Science, and Agricola.
Search terms included (but were not limited to): humane endpoint,
early endpoint, early indicator, predictive of, telemetry,
telemetric, noninvasive, biomarker, marker, animal welfare, and
laboratory animal welfare.
- Institute for Laboratory Animal Research (ILAR) (2000) Humane Endpoints for
Animals Used in Biomedical Research and Testing, theme issue. ILAR 41(2).
- See in particular
Morton D.B. A systematic approach for establishing humane endpoints.
- Netherlands Centre Alternatives to Animal Use (NCA) Humane endpoints in laboratory
animal experimentation.
- This is a CD-ROM to educate and train investigators,
veterinarians, animal care staff and animal care committee members
about implementation of humane endpoints.
- Netherlands Centre Alternatives to Animal Use (NCA) (2008) Humane endpoints.
- Organisation for Economic Cooperation and Development (OECD) (2000) OECD Guidance
document on the recognition, assessment, and use of clinical signs as humane
endpoints for experimental animals used in safety evaluation. OECD Environmental
Health and Safety Publications, Series on Testing and Assessment. No. 19.
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