THE UNIVERSITY OF WESTERN AUSTRALIA
ANIMAL ETHICS COMMITTEE
GUIDELINES ON THE INDUCTION OF TUMOURS
AND MONITORING OF ANIMAL WELFARE
September 2013
Purpose
The purpose of this document is to provide guidelines for the induction of tumours in animals
used for scientific purposes at The University of Western Australia. They are designed to
assist researchers, animal care technicians and the Animal Ethics Committee (AEC) to
ensure that the scientific aims of a proposal to induce tumours are achieved with minimal
discomfort for the animals involved.
Definition of ‘Tumour’
By ‘tumour’ these guidelines mean one or more solid neoplasms or metastases induced in a
laboratory animal by transplantation of tumour cells, exposure to carcinogenic agents,
including viruses, or arising in animal strains selected or engineered for spontaneous tumour
development.
Policy
All scientific procedures carried out on animals must comply with the Australian Code for
the Care and Use of Animals for Scientific Purposes (NHMRC, 2013), which states:
3.3.23 For animals in studies that involve the induction of tumours, methods used and
endpoints chosen must ensure that valid results are obtained with minimal harm,
including pain and distress, to the animal. Animal wellbeing must be supported and
safeguarded by:
(i) considering potential adverse impacts associated with the development and
biology of the tumour (including growth rate, invasiveness, potential for
ulceration, development of metastases and cachectic effects), effects of therapeutic
agents, side effects of immunotherapy including irradiation, and consequences of
surgery involved in transplantation of tumours;
(ii) choosing an appropriate implantation site or method of induction of the tumour
that causes the least harm, including pain and distress, to the animal. The footpad,
tail, brain or eye must not be used unless there is no valid alternative;
(iii) monitoring the growth or impact of the tumour and efficacy of therapy, and using
early experimental endpoints, to obtain valid results as early as possible. Death
from the tumour must not be an endpoint
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(iv) establishing and implementing early intervention points and humane endpoints;
(v) wherever possible, using techniques that facilitate measurement of tumour growth
and determination of early endpoints;
(vi) monitoring and assessing animals for signs of pain and distress, including changes
in body condition and body weight; ulceration; adverse effects of procedures used
for induction of the tumour; signs of growth, invasion and metastases of the
tumour; and toxic effects of therapeutic agents.
Guidelines
General
When inducing tumours in animals, the overriding consideration must be to minimise the
pain and distress experienced by the animals. It is expected that researchers will follow the
Guidelines to Promote the Wellbeing of Animal Used for Scientific Purposes: The Assessment
and Alleviation of Pain and Distress in Research Animals (NHMRC, 2008), where Appendix
M relates specifically to Tumour Induction.
Training
Researchers involved in tumour induction must have appropriate training in all the techniques
they are required to perform.
Site of Injection
The site of injection, where applicable, must be selected with the aim of causing the least
pain and distress for the animal compatible with the production of valid and useful scientific
data [see 3.3.23(ii) of the NHMRC Code, 2013].
Assessment of Animal Wellbeing
The use of a scoring system to assess the wellbeing of animals used in tumour induction
experiments is strongly encouraged. Preference is given to a scoring system in which an
increasingly positive score indicates deterioration in the animal’s wellbeing based on indicators
such as normal active behaviour, physiological responses, food and water intake and physical
body condition. All animals should have an initial body weight measured and recorded at the
beginning of the experiment. Any use of weight to justify wellbeing must take account of
tumour size and expected weight changes with age. Assessments of wellbeing may also take
into account marked difference between individual animals where there is no obvious, simple
explanation for variation to occur.
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Tumour Size Limits
The standards used to set maximum limits for the size of induced tumours in laboratory
animals, or the sum of all detected tumours or extent of metastases, are not based on fixed
limits that are applied invariably to all study protocols. Rather, the cost to the animals of
tumour induction and growth is balanced against the scientific benefit of the research on a case
by case basis placed within a general framework.
Preference is given to the use of two thresholds for intervention to prevent undue suffering.
When the first threshold is reached, the animal enters a regime of more intensive monitoring
and provision of palliative care, based on appropriate indicators of animal wellbeing, with a
prospect for euthanasia before reaching the second threshold, whenever those indicators show
that undue suffering is taking place. The second threshold is a limit of tumour size that is
applied as an absolute criterion for euthanasia of the animal regardless of other observations.
Researchers should justify the selection of both threshold points through the use of published
guidelines specific to the tumour and species (eg, British Journal of Cancer 2012; 102: 15551577), published research articles or empirical data from past work. This should include a
description of size taking account of volume or mass, especially if size is operationally defined
only by measures of length and breadth.
Unacceptable Tumour Features Regardless of Size
Depending on site and biological characteristics, induced tumours may develop features that
are an unacceptable impost even in smaller tumours. Euthanasia must also be performed, for
example, if a tumour located on the animal’s belly or its inner leg is causing it to be abraded or
to interfere with locomotion or if a tumour shows signs of ulceration.
Monitoring of Induced Tumours and Animal Wellbeing
Preference is given to the following guidelines:
1. Inspection and palpation initially to locate the sites of tumour growth and then to detect
distension, ulceration and compromised mobility should be performed and documented on
a regular basis and at least three times per week from the time of carcinogen or tumour
exposure or inoculation. Wellness scores should also be recorded at least three times per
week from that time.
2. The size of induced tumours should be measured with increasing frequency and should be
measured at least three times per week from the time of first detection and at least daily as
the first threshold is approached and thereafter, including on weekends. Development and
use of a measure of tumour growth rate is strongly encouraged, especially for rapidly
growing tumours, to assist in the timing of intervention decisions [see 3.3.23(v) of the
NHMRC Code, 2013]. Wellness scores should also be recorded at least daily as the first
threshold is approached and thereafter, including on weekends.
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3. The method of measurement of tumours must be clearly specified in the study protocol.
4. If an induced tumour, or the sum of all detected tumours or extent of metastases, in any
animal reaches the approved first threshold, the Animal Welfare Officer (AWO) or other
approved reviewer should be notified. Depending on the wellness score and other signs
present, the reviewer may then choose to monitor the situation for a period of time or
require treatment, palliative care, euthanasia or temporary cessation of the experimental
program pending further deliberation by the AEC.
Before a decision is taken to euthanise an animal prior to reaching the second approved
threshold, the reviewer should consider the impact of potentially wasted animal lives on the
production of valid and useful scientific data.
This must be balanced against the
prevention of undue animal suffering.
5. If an induced tumour burden in any animal reaches the approved second threshold or there
is an unacceptable tumour feature, euthanasia must be performed. Euthanasia may also be
mandatory if a wellness score limit has been stipulated.
References
National Health and Medical Research Council. Australian Code for the Care and Use of
Animals for Scientific Purposes, 8th Edition. Canberra: NHMRC, 2013.
National Health and Medical Research Council. Guidelines to Promote the Wellbeing of
Animals Used for Scientific Purposes. Canberra: NHMRC, 2008.
UK Co-ordinating Committee on Cancer Research. Guidelines for the Welfare of Animal in
Experimental Neoplasia. London: UKCCCR, 1997.
Workman p, Aboagye EO, Balkwill F, et al. Guidelines for the welfare and use of animals
in cancer research. British Journal of Cancer 2012: 102: 1555-1577.
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