Limitations On Tumor Size
Approved June 15, 2000 (Download)
Background: Tumors may occur spontaneously in research animals or as a result of transplantation, induction from administration of carcinogens, or the breeding of tumor prone strains. The disposition of cases involving spontaneously occurring tumors that are determined to be painful or to seriously threaten the health and well-being of research animals has been made in most cases by the veterinarian concerned. Cases involving tumorigenesis as part of a specific research project may be more complex. For example, in treatment studies where euthanizing animals that were likely to be experiencing pain and distress conflicts with experimental design.
Increasing sensitivity to this problem has resulted in efforts to adopt more humane alternative endpoints and to consider during the protocol review process what these endpoints will be and how tumor growth will be monitored. Tumor growth in excess of 10% of body weight and a number of other measurements and signs of clinical deterioration have been used as alternatives to using death as an endpoint.
Policy: Investigators proposing projects involving tumorigenesis must specify in their protocol submissions the criteria that establish when the endpoint has been reached and animals, or studies, terminated. The preferred type of study is one that is terminated when animals begin to exhibit clinical signs of disease including, the presence of ulceration, necrosis, or infection or where animals are found to be moribund, cachectic, or unable to obtain food or water. Compelling scientific reasons must be cited to justify allowing tumor growth to proceed beyond:
- 10% of body weight
- a mean tumor diameter exceeding 20 mm in an adult mouse
- a mean tumor diameter exceeding 40 mm in an adult rat
In studies involving tumors, a plan for monitoring study animals and providing for their care, if appropriate, must be provided. At a minimum, such a plan should provide for monitoring health, including direct observation every 2 to 3 days by investigative personnel trained and experienced in recognizing clinical disease in the species being studied before clinical signs occur, daily observation after clinical signs occur, and care and treatment to be given. A record system must also be described for animal weights, clinical observations, and treatment or animal disposition. These records must be available for veterinary or IACUC review.
Protocols in which justification has been provided for using death or moribundity as an endpoint must also address the following issues: a) pain relief measures to be used, b) scientific justification for withholding analgesics if they are not to be administered, c) the criteria for determining that animals are moribund and when, or if, euthanasia can be administered; and d) reasons why euthanasia cannot be administered. Monitoring and record keeping procedures must be described. Animals should be moved to individual cages when their condition deteriorates to avoid injury from other animals and dead animals must be promptly removed.