Policy for Tumor Models *)

Table of Contents

Overview

The importance of limiting the discomfort, pain and distress animals may experience during the conduct of biomedical research is well recognized and the primary force behind the animal welfare regulations governing the use of animals in research. Outcomes of tumor studies, including death as an endpoint, vary depending on the species and strain of animals, the route of injection for transplantable tumors and the subsequent chemotherapy or other modality in cancer treatment studies.

It is up to the investigator, who should be the most knowledgeable of the available models, to decide which alternatives using live animals are necessary for a study and present these to Animal Care Committee (ACC) for approval. Only when alternatives have been fully considered and found unacceptable for scientific reasons, will death of an animal as a study endpoint be allowed by the ACC.  At all times during this process, the well being of the research animals must be balanced against requirements of the study (1).

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Cancer Biology and Therapy

Cancer studies can broadly be divided into two categories, biology and treatment. Cancer biology is the study of how tumors grow and behave. The guidelines presented here are intended to limit the tumor burden an animal experiences to that which does not cause excessive pain or distress.

Cancer treatment is the study of the response of tumors to chemical, radiologic or immunologic therapy. In this class of study, not only must the tumor burden be considered, but the effect of the treatment modality must also be evaluated. The purpose of all cancer treatments, whether radiologic, immunologic or chemical is to destroy or disable the cancer cells while minimizing damage to healthy tissues. The success of a treatment becomes a balance between cancer destruction and reduction of side effects. Table 1 for alternative endpoints for studies with potential lethality.

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Table 1

Example Alternative Endpoints for Studies with Potential Lethality

Experimental Endpoint Example Clinical Assessment
Tumor Size Not to exceed 10% of normal body weight (2),(3) Frequent weighing (3-5 times/week)
Estimated tumor mass not to exceed 10% of body weight (2),(3) Frequent measurements of solitary tumor (1 cm3 = 1 gm)
Physical Characteristics of Tumor(s) Evidence of necrosis
Evidence of sepsis
Evidence of metastasis		 Physical examination: scabbing, ulceration, exudate, anorexia, hypothermia, etc.
Evidence of local invasiveness Restricted ambulation, inability to access food or water
Neurologic impairment (2),(3) Circling, blindness, dementia, convulsions
Tumor Location Head/neck and extremities  Inability to access or ingest food and water, inability to ambulate and keep clean
Moribund or Pre-moribund State Define with specific clinical tests or signs  
Cachexia, Chronic Wasting Weight loss >20% of normal body weight (3),(4) Frequent weighing
Signs of Organ or System Failure Respiratory Dyspnea, rapid or labored breathing, coughing, rales
Cardiovascular Shock, hemorrhage, anaphylaxis
Gastrointestinal Diarrhea (>2 days' duration), vomiting
CNS Circling, blindness, dementia, convulsions, unresponsiveness
Integument Extensive hair loss, inflammation, self-trauma

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References

  1. Office for Protection from Research Risks (NIH) and Applied Research Ethics National Association. 1992. Institutional Animal Care and Use Committee Guidebook. NIH Publication No. 92-3415. B15-B17.
     
  2. Tomasovic SP, LG Coghlan, KN Gray et al. 1988. IACUC Evaluation of Experiments Requiring Death as an End Point: A Cancer Center's Recommendations. Lab Animal 17(1) : 31-34.
     
  3. Workman P, A Balmain, JA Hickman et al. 1988. UKCCCR guidelines for the welfare of animals in experimental neoplasia. Laboratory Animals 22:195-201.
     
  4. Montgomery CA. 1990. Oncologic and Toxicologic Research: Alleviation and Control of Pain and Distress in Laboratory Animals. The Cancer Bulletin 42(4):230-237.

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Suggested Reading

  1. Browder EJ. 1995. Death as an Endpoint. In Current Issues and New Frontiers in Animal research. Greenbelt, MD: Scientists Center for Animal Welfare. pp 25-29.
     
  2. Olfert ED. 1995. Defining and Acceptable Endpoint in Invasive Experiments. AWIC Newsletter 6 (1) :3-7.
     
  3. Rygaard J. 1994 Animal Models in Cancer Research. In Handbook of Laboratory Animal Science, Vol. II. Boca Raton, FL: CRC Press, Inc. pp 199-205.

*) These guidelines are primarily derived from those introduced in the Institutional Animal Care and Use Committee Guidebook, a joint publication of the Office for Protection from Research Risks and the Applied Research Ethics National Association.(1) They have been modified from those of the National Cancer Institute Animal Care and Use Committee (NCI ACUC) to fit the special conditions involving cancer and other research at UConn Health Center. Adapted from NCI Animal Care and Use Committee's Humane Concerns Guidelines, April 1995, by Patricia Brown, DVM.

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 Web page compiled by Dr. Peter Autenried with from UCI permission
Revised: 11/15/2005