improve upon the accuracy of measurements and reduce or eliminate
sources of variability have the potential for reducing the number
of animals required in a given protocol." Brockway B, Hassler C and Hicks
"The standards ... shall, with respect to animals in research
facilities, include requirements-- (A) for animal care, treatment,
and practices in experimental procedures to ensure that animal
pain and distress are minimized, including adequate veterinary
care with the appropriate use of anesthetic, analgesic or tranquilizing
drugs, or euthanasia." AWA Section 13 (a)(3).
- "Advancing refinement of
laboratory animal use."
Smaje LH. 1998. Laboratory Animals 32 (2), 137-142.
- Various aspects of refinement
are described and a series of practical recommendations for advancing
refinement of laboratory animal use are given.
- Altweb special section on Refinement. 2009
- This refinement section begins
with introductory text explaining the topic in non-technical
language, accompanied by a set of links to relevant databases,
web sites, books, articles, abstracts, and so on. The section
addresses the following topics: What is pain and distress? Definitions,
biology and physiology; Recognition and assessment of pain and
distress; Alleviation and prevention of pain in animals; Humane
endpoints; Euthanasia; Enrichment.
- "Animal definition: a necessity
for the validity of animal experiments?" Öbrink KJ and Rehbinder C. 1999.
Laboratory Animals 22, 121-130.
- "In most scientific journals,
experimental animals are described poorly... The animal definition
should not only include species, sex and age but also ... the
environmental conditions to which the animals are exposed. ...
The prerequisites for the use of fewer animals per project, while
still retaining a sufficiently high degree of accuracy are high
levels of reproducibility and precision in the experimental results.
Factors that may affect these will be discussed in this paper.
If a researcher, through carelessness or ignorance, should use
more animals for a project than is necessary, it must be considered
- "Ethology recommendations
for a standardized minimum description of animal treatment." Davis DE, Bennett CL, Berkson G, Lang
CM, Snyder RL and Pick JR, ILAR Committee on Laboratory Animals.
1973. ILAR [Institute for Laboratory Animal Research] News/Journal
- "It is clear [from this
survey] that many investigators do not realize the influence
of ... environmental variables [e.g., housing, handling, temperature,
light] on experimental results or at least do not adequately
describe the environmental history of the animals used for experimentation."
of non-statistical design in refining animal experiments."
Morton D. 1998. Australian and New Zealand Council for the
Care of Animals in Research and Teaching (ANZCCART) News
11(2), insert: 1-12. An ANZCCART News Fact Sheet.
- Detailed discussion of approaches
to refinement, including good animal care, use of anaesthetics
and analgesics, humane end points; suggestions of strategies
that can contribute markedly to minimising pain and suffering
in an experiment and reduce animal numbers; extensive bibliography.
Refinement can be defined as: "Those methods which avoid,
alleviate or minimise the potential pain, distress or other adverse
effects suffered by the animals involved, or which enhance animal
wellbeing If scientists wish to claim they practise humane science
then they have to pay as much attention to avoiding unnecessary
pain and distress to their animals as they do to their scientific
objectives. Factors leading to good animal welfare will usually
also lead to reliable, accurate and economic science."
- "The influences of standard laboratory cages on rodents
and the validity of research data." Sherwin CM. 2004. Science
in the Service of Animal Welfare. Kirkwood JK, Roberts EA
and Vickery S, eds. Proceedings of the UFAW International Symposium,
Edinburgh, 2-4 April 2003. Animal Welfare 13: S9-15.
- This paper reviews various influences
of standard laboratory cage design and husbandry... These studies
show that the development and responses of animals from standard
laboratory housing and husbandry conditions are often unrepresentative
and idiosyncratic, indicating that data are likely to have reduced
external validity. .. Standard laboratory housing may sometimes
be associated both with reduced welfare and with reduced benefits
gained from research.
- "Minimizing stress during
physiological monitoring." Brockway BP, Hassler CR and Hicks
N. 1993. Refinement and Reduction in Animal Testing. Niemi
SM and Willson JE , eds, 56-69. Proceedings of a conference held
by the Scientists Center for Animal Welfare.
- "Minimizing or eliminating
extraneous stress factors from the experimental design is crucial
to a true understanding of the compound, device or technique
being evaluated for its effects. Furthermore, it follows that
the elimination of sources of variability (stress, for example)
may allow the use of fewer animals giving equally valid results."
Alternatives to traditional methods of monitoring laboratory
animals are suggested.
and reduction through the control of variation."
Festing MFW. 2004. In: The Three
Rs at the Beginning of the 21st Century: Proceedings of the Fourth
World Congress on Alternatives and Animal Use in the Life Sciences,
11-15 August 2002, New Orleans, LA, USA. Balls M, Firmani D and
Rowan A, eds. 2004. ATLA 32, Supplement 1, 259-263.
- "The key to doing animal
experiments efficiently, while using the minimum number of animals
without loss of scientific information, lies in good control
of random variation, and recognition and control of fixed
effect variation, such as the sex or strain of the animals."
and other abnormal repetitive behaviors: Potential impact on
validity, reliability, and replicability of scientific outcomes."
Garner JP. 2005. ILAR Journal Vol 46(2).
- "Captive environments may
affect the following aspects of an experiment: validity, by introducing
abnormal animals into experiments; reliability, by increasing
interindividual variation through the introduction of such individuals;
and replicability, by altering the number and type of such individuals
between laboratories. Thus, far from increasing variability,
enrichment may actually improve validity, reliability, and replicability
by reducing the number of abnormal animals introduced into experiments.
In this article, the specific example of abnormal repetitive
behaviors (ARBs) is explored... ARBs in laboratory animals may
compromise validity, reliability, and replicability, especially
in behavioral experiments; and enrichments that prevent ARB may
enhance validity, reliability, and replicability."
Fewer Research Animals." Chamove AS. 2003. Laboratory
Primate Newsletter 42(1), 1-2.
- Sequential sampling and power
analysis are more ethical alternatives to reduce animal numbers
to the lowest number possible, especially when test procedures
in animal based research: Part 2. Variability associated with
experimental conditions and techniques." Reilly J 1998.
Australian and New Zealand Council for the Care of Animals
in Research and Teaching (ANZCCART) News 11(1), insert: 1-12.
An ANZCCART News Fact Sheet.
- This Facts Sheet addresses the
issues of variability associated with experimental conditions
and techniques and includes the effects of stress, sampling techniques,
anaesthesia and euthanasia, and how these may affect research
data. "These variables should be defined, standardised,
and minimised in order to obtain results which are meaningful,
repeatable, and comparable with others... Refinement of research
techniques using animals will lead to less animal distress and
at the same time will usually lead to higher quality and more
- Variables, Refinement and Environmental Enrichment
for Rodents and Rabbits kept in Research Institutions. Making
Life Easier for Animals in Laboratories. Reinhardt
V and Reinhardt A. 2006. Animal Welfare Institute. Washington,
DC. Available from Animal Welfare Institute, PO Box 3650, Washington,
- This book summarizes and discusses
refinement and environmental improvement techniques for rodents
and rabbits kept in research facilities. The review of the literature
focuses on data-supported published material and mentions descriptive
and theoretical articles only if they have practical relevance.
A total of 260 relevant articles published in 85 different journals
have been reviewed.
to Table of Contents
and Alleviation of Pain
Guidelines on Euthanasia." 2007.
- Useful reference to insure that
appropriate methods of euthanasia are being used for different
laboratory animal species.
- "Adverse effects in animals
and their relevance to refining scientific procedures."
Morton DB. 1990. ATLA (Alternatives to Laboratory Animals)
- The author highlights areas in
which suffering can be prevented, alleviated and avoided. The
terms "pain, stress, eustress, distress and fear" are
clearly defined to help determine animal suffering. "One
has to recognize suffering by non-verbal means, i.e., through
observing changes in behavior patterns and in physiology."
and alleviation of post-operative pain." Flecknell P.
1997/98. Animal Welfare Information Center Newsletter
- The author addresses a few common
concerns about the use of analgesics to relieve post-operative
pain, describes various methods of pain assessment such as scoring
systems, gives suggestions on the clinical use of analgesics
and offers recommendations on the relief of post-operative distress.
Tables with recommended dosages of analgesics are given. "Providing
effective post-operative pain relief can have a dramatic effect
on the speed with which animals return to normality following
surgical procedures. The provision of good post-operative care
should be considered essential both because of a concern for
the animal's welfare and also because it is good scientific practice."
the Health and Welfare of Laboratory Animals. Web site. University of Newcastle. 2008.
Supported by the 3R Research Foundation Switzerland.
- Tutorials and resources for guidance
in recognizing signs of health and good welfare and identifying
signs of pain, distress and poor welfare in laboratory animals.
- Guidance Document on the Recognition, Assessment,
and Use of Clinical Signs as Humane Endpoints for Experimental
Animals Used in Safety Evaluation. 2000. Organisation for Economic Cooperation
and Development (OECD). Paris, France.
- The purpose of the document is to apply the principles
of the Three Rs to the use of animals in regulatory toxicity
tests. It specifically addresses refinement and describes approaches
to detecting clinical signs of pain and distress and procedures
that can be put in place to minimise test animal pain, distress,
and suffering during testing.
- "Guidelines on the recognition
of pain, distress and discomfort in experimental animals and
an hypothesis for assessment." Morton DB and Griffiths PHM.
1985. Veterinary Record 116, 431-436.
- The article helps not only newcomers
inexperienced in the recognition of pain, but also experienced
workers who may be called upon to evaluate the pain involved
in a new model or an individual animal. Specific signs of behavior
and common clinical signs indicating pain, distress or discomfort
in laboratory animals are listed and discussed.
- Guidelines on Choosing an Appropriate Endpoint
in Experiments Using Animals for Research, Education, and Testing.
1999. Canadian Council on Animal Care. Ottawa, Ontario.
- Guidelines are presented for
selecting an endpoint that reduces animal pain and/or distress.
"For the purposes of these guidelines, the term 'Endpoint'
is defined as the point at which an experimental 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."
- Humane Endpoints in Animal
Experiments for Biomedical Research.
Hendriksen FM, Morton DB, eds. 1998. Proceedings of the International
Conference, 22-25 November 1998, Zeist, The Netherlands. Laboratory
Animals Ltd. London, England.
- The papers presented address
issues relating to the recognition and assessment of adverse
effects in animals, and the determination, validation, implementation
and acceptance of humane endpoints.
assessment techniques for pain management and humane endpoints."
Morton DB. 1998. Pain Management and Humane Endpoints.
Proceedings of a workshop. Johns Hopkins Center for Alternatives
to Animal Testing (CAAT).
- Score sheets are drawn up for
each scientific procedure, and for each species, listing cardinal
clinical signs that are observable and measurable, developed
through the experience of a team of observers. The score sheet
system helps focus attention on an animal's condition throughout
the procedure. It also helps determine the effectiveness of any
therapy intended to relieve adverse effects, and which experimental
models cause the least pain and distress, thus helping to refine
scientific procedures. This technique is especially useful with
new procedures, or when users are not sure of what effects a
procedure will have.
- "Invasiveness scales for
animal pain and distress." Orlans FB. 1996. Lab Animal
- Recommends the use of well-defined
invasiveness scales to improve animal welfare standards. By using
such scales "laboratory workers would acquire greater sensitivity
to animal pain and distress, improving ethical decision making."
alleviation and avoidance in laboratory animals." Flecknell
P. 1999. An ANZCCART factsheet. Australian and New Zealand
Council for the Care of Animals in Research and Teaching (ANZCCART)
News 12 (4), insert 1-10.
- Valuable suggestions are given
for the recognition of pain in laboratory animals and facilitation
of its assessment. Available methods of pain control and their
implementation are outlined. Control of acute pain can be achieved
relatively easily in most mammalian species by use of analgesics
agents. It is important to consider not only measures directed
towards alleviating or preventing pain, but also the overall
care of the animal and the prevention of distress. Tables with
analgesic dosages for ferrets, guinea pigs, mice, rats, rabbits,
cats, dogs, pigs, sheep and non-human primates are included.
- "Pain and distress: what
really matters?" Koch
VW 2006. Lab Animal 35(5) 27-32.
- "The author argues that
IACUCs and investigators should shift their focus from the word
'pain' to the more inclusive word 'distress' referring to any
mentally unpleasant level of stress in an animal, including slight
discomfort. She discusses criteria for defining 'significant'
distress, and offers suggestions for the conduct of studies to
determine levels of distress."
- Pain Management and Humane Endpoints. Johns
Hopkins Center for Alternatives to Animal Testing. 1998. Proceedings
of a workshop.
- Excellent papers on assessment
and alleviation of pain and distress, policy, implementation
and humane endpoints. Useful information for IACUCs on how to
review protocols and potentially painful procedures, and on their
responsibilities in the implementation of policy leading to avoidance
and minimization of pain in animals.
- "Physiological and ethological
aspects of the assessment of pain, distress and suffering."
Scharmann W. 1998. Humane Endpoints in Animal Experiments
for Biomedical Research. Hendriksen FM, Morton DB, eds. Proceedings
of the International Conference, 22-25 November 1998, Zeist,
The Netherlands. 33-39. Laboratory Animals Ltd. London, England.
- Practical approaches to the recognition
of pain and grading of pain intensity are described.
- "Practical applications
of animal harm scales: international perspectives." Orlans,
FB. 2000. In Progress
in the Reduction, Refinement and Replacement of Animal Experimentation.
Balls E, van Zeller
AM and Halder ME, eds. 1049-1056. Elsevier. Amsterdam, Netherlands.
- Harm scales have been introduced
in several countries to categorise degrees of animal pain or
distress resulting from experimental procedures. These scales
serve three purposes: 1. They promote an understanding of fundamental
concepts of humane animal experimentation, the three Rs, and
sensitise investigators and reviewers to the ethical significance
of animal harm. 2. Harm scales are useful in framing policies
on the use of animals in education. 3. In the reporting of national
statistics on laboratory animal use, increased public accountability
occurs if data are reported according to level of harm.
- Recognition and Alleviation of Pain and Distress
in Laboratory Animals. Committee on Pain and Distress in Laboratory
Animals, Institute for Laboratory Animals Research, National
Research Council. 2008. National Academy Press. Washington, DC.
- An introduction to the basis,
recognition and assessment of pain, stress and distress. Discusses
the pharmacology of general anesthesia; describes major classes
of drugs used to achieve the clinical goals of analgesia, sedation
and immobilization and lists doses per animal species; summarizes
and supplements the Report of the American Veterinary Medical
Association Panel on Euthanasia with emphasis on animals used
in research, testing and teaching.
- "Recognizing animal suffering
and pain." Mroczek NS. 1994. Lab Animal 23(1), 27-31.
- "Recognizing pain in animals
requires empathic observation, which in turn engenders identification
and often sympathy. Scientists have undertaken voluminous research
which is based on the assumption that animals do feel pain. Pain
inherent in animal research, however, is often ignored as subjective
experience of the animal's reality in a simplistic attempt to
objectify animal life and hence reduce it to measurable data."
care and analgesia of farm animals used in biomedical research.[scroll down]"
Randolph MM. 1994. Animal Welfare Information Center 5(1),
- Excellent guidance for the post-operative
care and analgesia of farm animals used in research. "An
astute caretaker's knowledge of the normal behavior for that
particular age, sex, species, and individual is crucial in determining
when animals are experiencing unacceptable levels of pain. ...
The recovery period should be viewed as the final stage in the
surgical procedure. Some investigators and their staff have underestimated
the importance of this stage of the surgical endeavor. There
can be no successful surgery with an unsuccessful recovery."
This article includes a clear table with practical, post-operative
analgesics for ruminants and pigs.
- Research Animal Anesthesia,
Analgesia and Surgery. Smith
AC and Swindle MM , eds. 1994. Scientists Center for Animal Welfare.
- A conference report with excellent
contributions on "Intraoperative monitoring and equipment"
Hoyt RF, 137-146; "Cardiopulmonary complications and
emergencies in surgery" Swearengen JR, 159-166; "Rabbits
and rodents: Anesthesia and analgesia" Wixson SK, 59-92;
"Dogs and cats: Anesthesia and analgesia" Daunt
DA, 93-105; "Miscellaneous species: Anesthesia and analgesia"
Schaeffer DO, 129-136.
and distress." Roberts
SA et al. 2006. Animal Technology and Welfare, 5, 99-102
- Definitions and practical hints
on how to recognize stress and distress.
to Table of Contents
of Handling and Housing Conditions (Enrichment)
and management of animal facilities are essential to animal well-being,
to the quality of research data and teaching or testing programs
in which animals are used, and to the health and safety of personnel.
A good management program provides the environment, housing, and
care that permit animals to grow, mature, reproduce, and maintain
good health; provides for their well-being; and minimizes variations
that can affect research results."
Guide for the Care and Use of Laboratory
- "Behavioral indexes of poor
welfare in laboratory rats." Patterson-Kane EG, Hunt M and
Harper DN. 1999. Journal of Applied Animal Welfare 2,
- Fearfulness associated with single-housing
was alleviated by pair-housing, and even further alleviated by
group-housing in enriched cages. Problem solving ability
was improved when rats were kept in groups in enriched cages
rather than in barren single cages.
- "Cage enrichment for hamsters
housed in suspended wire cages." McClure DE and Thomson
JI. 1992. Contemporary Topics in Laboratory Animal Science
- "When these hamsters were
provided with nesting material their well-being was improved
as indicated by resolution of inappetence and depression. Providing
the PVC apparently resolved the aggressive behavior problem by
providing a means for seclusion in addition to functioning as
a burrow and as a toy."
- "Catching individual rhesus
monkeys living in captive groups." Reinhardt V. 1990. Available
from Wisconsin Regional Primate Research Center, 1220 Capitol
Court, Madison, WI 53715.
- This 17-minute videotape demonstrates
how rhesus macaques living in a breeding troop can readily be
trained to enter a chute voluntarily or on vocal command and
exit one-by-one into a transport box to allow capture. The procedure
avoids undue stress; it is carried out by a single person.
- Comfortable Quarters for Laboratory Animals. Reinhardt
V and Reinhardt A. eds. 2002. 9th edition, Animal Welfare Institute.
Washington, DC. Available from Animal Welfare Institute, PO Box
3650, Washington, DC 20007.
- A collection of 16 articles outlining
refined, i.e., species-appropriate housing conditions and handling
techniques for mice, gerbils, rats, hamsters, guinea pigs, rabbits,
cats, dogs, primates, pigs, sheep, cattle, horses, chickens,
amphibians and reptiles. Suggestions and recommendations are
made which minimize or eliminate variables such as distress,
fear, anxiety, discomfort, depression and boredom "thereby
maximizing the research animals' well-being and reducing the
number of subjects required to achieve statistical significance
of the research data."
- "The effect of feeding and
housing on the behaviour of the laboratory rabbit." Krohn
TC, Ritskes-Hoitinga J and Svendsen P. 1999. Laboratory Animals
- "While the [individually
housed] rabbits in cages spent 2-5% of the time performing abnormal
behaviour like biting the bars or scratching the bottom of the
cage, these activities were virtually absent in group-housed
rabbits in floor pens."
- "Effects of environmental
enrichment on behaviour and reproductivity of growing pigs."
Beattie VW, Walker N and Sneddon IA. 1995. Animal Welfare
- "Enriching the environment
[extra area with peat and a straw hopper; four times as much
floor space] reduced both the amount of time pigs spent inactive
and the time involved in harmful social and aggressive behaviour.
Tail biting was absent from the enriched environment but four
pigs were removed from barren pens with severe tail damage."
- "An enrichment object that
reduces aggressiveness and mortality in caged laying hens."
Gvaryahu G, Ararat E, Asaf E, Lev M, Weller JI, Robinzon B and
Snapir N. 1994. Psychology and Behavior 55, 313-316.
- "The enrichment devices
(colored key rings) significantly reduced aggressive head-pecking
behavior and significantly decreased the mortality rate."
- Enrichment Strategies for Laboratory Animals. (whole issue). 2005. ILAR Journal Volume
- "Currently, it is recognized
that science also has an ethical responsibility to house animals
according to their species-specific needs, and that responsibility
invokes the concept of behavioral and environmental enrichment....
To develop enrichment programs and to assess the effectiveness
of such programs, it is critically important for all staff members
involved in the care and use of the animals to understand the
behaviors of the individual species that are housed."
- "Environmental enrichment
of laboratory animals used in regulatory toxicology studies."
Dean SW. 1999. Laboratory Animals 33, 309-327.
- "A creative approach to
environmental enrichment is indeed compatible with regulatory
toxicology. It is hoped that this will encourage those responsible
for the care and welfare of animals in such a laboratory to challenge
historical practices and include environmental enrichment as
a fundamental necessity of study design... The assumption that
certain regulatory authorities 'prefer' single-housing should
be challenged... Group housing should become the norm whenever
animals are compatible, and anything less should be justified
on the basis of sound science."
- Guide to the Care and Use of Experimental
2, Gilman J , ed. 1984.
Canadian Council on Animal Care. Ottawa, Ontario.
- Excellent guidelines for the species-appropriate keeping
of amphibians, reptiles, and pigeons in the research laboratory
setting; in the process of being updated. Chapters can still
be accessed individually: amphibians;
& doves; etc.
on: the care and use of farm animals in research, teaching and
testing. Tennessen T. et al. 2009. Canadian Council on
Animal Care. Ottawa, Ontario.
- Provides information for investigators, animal care committees,
facility managers and animal care staff that will assist in improving
both the care given to farm animals and the manner in which experimental
procedures are carried out. The refinement of animal care and
use guidelines is a continuous process. These guidelines are
intended primarily to provide assistance in the implementation
of best practices. They apply to farm animals used by institutions
for scientific purposes. under which animals should be cared
for and maintained.
on: The Care and Use of Fish in Research, Teaching and Testing.
Chris Harvey-Clark et al. 2005. Canadian Council on Animal
Care. Ottawa, Ontario.
- These guidelines aim to provide
information for investigators, animal care committees, facility
managers and animal care staff that will assist in improving
both the care given to fishes and the manner in which experimental
procedures are carried out.
Lives Easier for Animals in Research Labs: Discussions by the
Laboratory Animal Refinement & Enrichment Forum.
Baumans V et al. (eds) 2007. Animal Welfare Institute.
Washington, DC. Available from Animal Welfare Institute, PO Box
3650, Washington, DC 20007.
- This book is a collection of electronic discussions that
took place on the Laboratory Animal Refinement & Enrichment
Forum (LAREF) between October 2002 and May 2007. The forum serves
the international animal care and animal research community to
promote animal welfare and improve scientific methodology by
avoiding or minimizing stress and distress resulting from husbandry
and handling practices.
Of more than 5,000 comments posted, approximately 3,000 were
selected for this book because they have practical animal welfare
relevance and are based on first-hand experiences about ways
to improve the conditions under which animals are housed and
handled in research facilities.
The following main topics are discussed: Basic Issues; Maladaptive
Behaviors; Environmental Enrichment; Social Housing; Working
With Animals; Extraneous Variables.
overcomes self-biting behavior in macaques." Reinhardt
V. 1999. Laboratory Primate Newsletter 38(1), 4.
- "The transfer to a compatible
social-housing arrangement [isosexual pair-housing] effectively
cured the [seven] rhesus subjects from the behavioral pathology
of habitual self-biting."
methods of laboratory nonhuman primates: A critical review."
Reinhardt V, Liss C and Stevens C. 1995. Animal Welfare
- Nonhuman primates can readily
be trained to co-operate rather than resist during common handling
procedures, thereby avoiding data-biasing distress responses
associated with traditional involuntary restraint techniques.
- "The role of husbandry in
promoting the welfare of laboratory animals." Reese EP.
1991. Animals in Biomedical Research, Hendriksen CFM and
Koëter HBWM , eds, 155-192. Elsevier. Amsterdam, Netherlands.
- A very well written outline of
refinement options to promote the welfare of laboratory animals.
"It appears that many of our laboratory findings are based
upon data from distressed animals."
housing ameliorates behavioral pathology in Cebus apella."
Bayne K, Dexter SL and Suomi SJ. 1991. Laboratory Primate
Newsletter 30(2), 9-12.
- Change from single- to group-housing
"effectively reduced stereotypic behavior s; however, it
also was associated with more passive behaviors being exhibited
by the subjects. The concurrent shifts in these components of
the behavioral repertoire suggests that the animals were in a
calmer state when housed socially."
Better Care of Monkeys and Apes: : Refinement of Housing and
Handling Practices for Caged Nonhuman Primates. Reinhardt V. 2008.
- Reviews the literature on the
refinement of traditional housing and handling practices for
nonhuman primates who live in cages alone, in pairs or trios.
housing and handling practices of caged nonhuman primates can
be refined, without undue labor and expenses, in such a way that
distress responses are minimized or avoided if basic ethological
principles are applied: (1) address the animals need to
be with and interact with at least one compatible conspecific;
(2) structure their living quarters in species-appropriate ways;
(3) address their biologically strong motivation to forage; (4)
train them to cooperate during procedures.
- "Use of cornhusk nesting
material to reduce aggression in caged mice." Armstrong
KR, Clark TR and Peterson MR. 1998. Contemporary Topics in
Laboratory Animal Science 37(4), 64-66.
- The provision of cornhusk reduced
aggressive interactions by offering subordinate animals cover
and escape routes.
databases and bibliographies section below.
to Table of Contents
Requirements for Enrichment
must develop, document, and follow an appropriate plan to provide
dogs with the opportunity for exercise85 The plan must include
written standard procedures to be followed in providing the opportunity
Part 3. Standards. A73.8 Exercise for dogs.
Enhancement for Primates
quarters for dogs in research institutions." Hubrecht
RC. 2002. In Comfortable Quarters for Laboratory Animals,
9th Edition. Reinhardt V and Reinhardt A, eds. Animal Welfare
Institute. Washington, DC.
- Well-tested refinement options
for the housing and handling of laboratory dogs are outlined.
The following issues are addressed in detail: Space considerations
and minimum space allowances, social housing, exercise, structures
and enrichment within the dog enclosure, social interaction of
dogs with animal care staff, minimization of stress during interactions
between people and dogs, noise in kennels, and dog supply and
- "Correlates of pen size
and housing conditions on the behaviour of kennelled dogs."
Hubrecht RC, Serpell JA and Poole TB.1992. Applied Animal
Behaviour Science 34:365-383.
- Behavioral data were collected
from solitary and group-housed dogs [of different breeds] from
animal shelters and laboratories. "Solitary dogs were more
inactive and spent more time in non-social repetitive locomotory
behaviour categories." Dogs housed in pens with spacious,
complex outdoor runs were more active and engaged in more species-typical
locomotory behaviors than dogs kept in small and barren standard
- Guidelines for the Care and Housing of Dogs
in Scientific Institutions.
1999. NSW Agriculture. Orange, NSW, Australia.
- Guidelines on exercise pen design;
exercising and contact with humans apart from normal husbandry
procedures are spelled out. "Regular exercise allows for
dogs to increase their range of behaviours... The ideal time
for social interaction [with humans] is during the exercise period....The
minimum exercise period should be 30 minutes for healthy dogs...Group-housed
dogs should be exercised as a group..."
- "A Novel approach for addressing
enrichment and exercise for dogs in a teaching institution."
Hammer JG. 2001, Lab
Animal 30(7), 26-29.
- An IACUC approved, successfully
tested [with four beagle dogs] program to foster positive human-animal
interactions [a retirement home was visited on a regular basis]
and exercise [via preparatory training program] is described.
must develop, document, and follow an appropriate plan for environmental
enhancement adequate to promote the psychological well-being of
nonhuman primates". The physical environment in the primary
enclosures must be enriched by providing means of expressing noninjurious
Regulations. Part 3. Standards. A73.81 Environmental enhancement
to promote psychological well-being.
- * Environmental
Enrichment and Refinement for Nonhuman Primates Kept in Research
Laboratories: A Photographic Documentation and Literature Review. Reinhardt V and Reinhardt A. 3rd edition.
2008. Animal Welfare Institute. Washington, DC . Available free
from Animal Welfare Institute, PO Box 3650, Washington, DC 20007.
- A collection of annotated photos
dealing with all aspects of environmental enrichment including
refinement of housing and handling conditions for all nonhuman
primate species. "Sharing the same roots makes it easy for
any compassionate human primate to make life easier for a nonhuman
primate subjected to biomedical research." A comprehensive
bibliography is appended to this document.
- The Psychological Well-Being of Nonhuman
Primates. Committee on Well-Being of Nonhuman Primates.
1998. Institute for Laboratory Animal Research Commission on
Life Sciences National Research Council. National Academy Press.
- Concise guidelines for the adequate
housing and handling of captive nonhuman primates. Criteria of
psychological well-being are: 20 "Appropriate social companionship; opportunities
to engage in behavior related to foraging, exploration, and other
activities appropriate to the species, age, sex, and condition
of the animal; housing that permits suitable postural and locomotor
expression; interactions with personnel that are generally positive
and not a source of unnecessary stress."
- "Social enhancement for
adult nonhuman primates in research laboratories: A review."
Reinhardt V and Reinhardt A. 2000. Lab Animal 29(1), 34-41.
- Comprehensive review of safe,
effective and inexpensive options (pair-housing, human interaction,
training to cooperate during procedures) to address the social
needs of adult nonhuman primates in accordance with the stipulations
set forth in the Animal Welfare Act.
of previously single-caged macaques: What are the options and
the risks?" Reinhardt V, Liss C and Stevens C. 1995.
Animal Welfare 4, 307-328.
- "The published data show
that previously single-caged macaques can be transferred to social
housing adequate for the species ... without undue risk to individual
animals" and without interfering with husbandry and common
databases and bibliographies section below.
to Table of Contents
- "Alternatives to the use
of animals in higher education." van der Valk J et al. 1999. ATLA
(Alternatives to Laboratory Animals) 27(1), 39-52.
- The issues reviewed and discussed
include the current use of animals in higher education, the range
of alternatives currently available, the advantages and disadvantages
of using alternatives in education, methods of disseminating
information about alternatives to those involved in education
systems, and strategies for evaluating the educational effectiveness
(Association of Veterinarians for Animal Rights) Alternatives
in Education Database. 1990-2000. 2009*. Association of
Veterinarians for Animal Rights. Davis, CA.
- Searchable database containing
audiovisual and textual materials, computer programs, simulations,
models and other resources that can be used as alternatives to
animals at all levels of education from primary school to the
training of medical and veterinary professionals.
Guinea Pig to Computer Mouse: Alternative methods for a progressive,
humane education. Jukes N and Chiuia M.
2nd edition 2003. International Network for Humane Education.
- The book investigates state-of-the-art alternative tools
and approaches to support ethical and effective knowledge and
skills acquisition within biological science, medical and veterinary
for humane education: Alternatives to the use of animals in teaching
and training." Smith A and Smith K. 2004. The Three
Rs at the Beginning of the 21st Century: Proceedings of the
Fourth World Congress on Alternatives and Animal Use in the Life
Sciences. Balls M, Firmani D and Rowan A, eds, 29-39. ATLA
32, Supplement 1 & 2.
- "This paper attempts to clarify the issues raised, presents
an overview of the alternatives available with their strengths
and weaknesses, and finally offers guidelines for humane education
that take into consideration both the practical issues and the
feelings of all those involved."
The International Website for Humane Education.
- Interniche supports progressive science teaching and the
replacement of animal experiments by working with teachers to
introduce alternatives and with students to support freedom of
conscience. The web site is aimed at teachers and students of
biological science, veterinary and human medicine, as well as
university ethics committee or animal care and use committee
members, legislators, and animal welfare advocates. It offers
a Alternatives Loan System, a library of products available for
free loan anywhere in the world, as well as literature, support
and advice for teachers and students.
European Resource Centre for Alternatives in Higher Education.
- Actively promotes the use of
alternatives to using animals in higher education (HE). Aims
to provide a mechanism for effective dissemination of information
about alternatives to using animals in HE. Is compiling
an Alternatives Database that include full description of the
alternatives, reviews, user comments and additional educational
- The NORINA (A Norwegian Inventory of Alternatives)
Alternatives to Laboratory Animals in Teaching. Smith K and Smith A , eds. 2007*. Norwegian
School of Veterinary Medicine. Oslo, Norway.
- English-language database of
audiovisuals for the use of teachers and instructors in the biological
sciences. Its primary purpose is to provide an overview of possible
alternatives at all educational levels, from elementary school
to university. The database consists of more than 3700 entries
including computer programs, interactive videos, films, and traditional
teaching aids such as slide sets, 3-D models, and classroom charts.
- "The PVC-Rat and Other Alternatives
in Microsurgical Training."
Remie R. 2001. Lab
- "The number of animals used in educational training
programs in experimental microsurgery can be reduced by using
artificial devices such as the anastomoses device and the MD
PVC-Rat. Such in vitro methods allow development of technical
skills, making the transition to in vivo models much easier....
The use of the PVC-Rat model reduces the number of animals used
during training of scientists and animal technicians by roughly
to Table of Contents
RESOURCES FOR THE LITERATURE SEARCH (USDA
Engines, Search Guidelines
- Alternatives to the Use of Live Vertebrates
in Biomedical Research and Testing. A Bibliography with Abstracts. Hudson VW and Nguyen Q. 2002. National Library
of Medicine. Bethesda, MD.
- A quarterly publication citing
techniques that replace or may replace intact vertebrates in
biomedical testing to evaluate the toxicological potential of
various substances. Very comprehensive. A search engine now enables
users to search all issues and/or to limit the search by field,
year, and category, and browse the index.
- Altweb Pain Management Database. Allen
T. 2007*. Altweb Web Site.
- "This database includes
information about anesthesia and analgesia for most commonly
used laboratory animals, including: rats, mice, primates, dogs,
cats, rabbits, pigs, guinea pigs, birds, sheep, fish, and exotic
species. It provides information about available drugs and the
side effects of commonly used drugs. Citations are from publications
that have published laboratory animal studies or human clinical
studies with relevance to animal research." Contains approximately
10,000 records, most of them with abstracts. It covers the period
1990 to the present, and is updated quarterly. Almost all of
the records--98%--have abstracts. Records have been drawn from
three major databases: MEDLINE (with records from TOXLINE as
well), AGRICOLA, and AGRIS.
- AnimalAlt-ZEBET Database. Spielmann
H, Grune B, Dorendahl A and Skolik S. 1989, 2006. Zentralstelle
zur Erfassung und Bewertung von Ersatz und Erganzungsmethoden
zum Tierversuch (ZEBET) [Center for Documentation and Evaluation
of Alternative Methods to Animal Experiments]. Berlin, Germany.
- Invaluable resource for the literature
search. ZEBET is a database of alternative methods (replacement,
refinement and reduction) to animal experiments in the English
language. It contains over 4300 bibliographical references on
more than 125 methods covering the field of biomedicine and related
fields. Each record contains a short description of a method
in its most important details, i.e. aim, principle, and the stage
of development or validation of the method and bibliographical
references. An evaluation by ZEBET staff indicates whether the
method results in the replacement, reduction or refinement of
animal use according to the "3R's." Fields are searchable.
The database is hosted by DIMDI where it may be searched free
Bibliography on Refinement and Environmental Enrichment for Primates
kept in Laboratories. Reinhardt
V and Reinhardt A. 2008. 12th Edition. Animal Welfare Institute.
- This bibliography offers practical
information on techniques that promote the expression of species-appropriate
behavioral and mental activities in captive nonhuman primates.
Specifically geared towards animal caregivers, animal technicians,
zoo keepers, students and veterinarians. All entries are annotated.
on Refinement of Housing and Handling Conditions and Environmental
Enrichment for Laboratory Animals: Rodents,
Rabbits, Cats, Dogs, Ferrets, Farm Animals, Horses, Birds, Fishes,
Amphibians and Reptiles. Reinhardt V and Reinhardt A. 2009*. Animal
Welfare Institute. Washington, DC.
- More than a thousand annotated
entries, 13% full-text, on all aspects of environmental enrichment
and refinement of housing and handling conditions of laboratory
animals and farm animals used in research. Access to the database
is free. It is searchable by citation and keywords and updated
at least once every two months.
Databases." FRAME Web Page. 2006*.
- Excellent, comprehensive annotated
list of databases with links. Includes 3 Rs databases; alternatives
in education; cell-line databases; current research; general
scientific; normal, transgenic and knockout strains.
- Environmental Enrichment Information Resources
for Laboratory Animals: Birds, Cats, Dogs, Farm Animals, Ferrets,
Rabbits, And Rodents: 1965-1995. Smith
CP and Taylor V. 1995. (AWIC Resource Series no. 2). U.S. Department
of Agriculture, National Agricultural Library, Animal Welfare
Information Center. Beltsville, MD.
- Articles and bibliographies covering
environmental enrichment techniques for birds, cats, dogs, farm
animals, ferrets, rabbits and rodents.
- Environmental Enrichment for Primates: Annotated
Database on Environmental Enrichment and Refinement of Husbandry
for Nonhuman Primates. Reinhardt V and Reinhardt A. 2009*. Animal
Welfare Institute. Washington, DC.
- More than 1500 annotated entries
22% full-text on all aspects of environmental enhancement, including
social housing, feeding enrichment, inanimate enrichment and
training to cooperate during procedures. Access to the database
is free. It is searchable by citation and keywords including
species names and is updated at least once every two months.
- Environmental Enrichment for Nonhuman Primates
Adams K. 2009.
National Agricultural Library, Animal Welfare Information
Center, Beltsville, MD.
- "This publication updates
and expands AWIC's Environmental Enrichment for Nonhuman Primates
Resource Guide. It covers literature published from 1999-Jan
2009. The bibliographic chapters are divided into subject areas
that cover the concept of environmental enrichment, enrichment
for nonhuman primates overall, abnormal behavior exhibited by
nonhuman primates, great apes and gibbons, macaques, old world
monkeys other than macaques, marmosets and tamarins, other new
world monkeys, lemurs, lorises, and tarsiers, animal training
as an enrichment strategy, and books and proceedings from conferences
focused on environmental enrichment or nonhuman primate management."
Enrichment for Rodents and Rabbits: An Annotated Bibliography.
Reinhardt A. 2007. Animal Welfare
Institute. Washington, DC.
- This bibliography offers
animal caregivers, animal technicians, veterinarians, and students
guidance to practical information
on refinement and environmental
enrichment for rodents and rabbits kept in research institutions.
- "Free web resources on alternatives." Donnelly
TM. 2004. Lab Animal 33(3), 46-48.
- Access to many online databases for alternatives searches
requires a paid subscription and these fees may be expensive
for small or not-for-profit institutions. The author provides
a list of free sites that can be used to fulfill the legal requirement
for an alternatives search.
- Institute for In Vitro Sciences . IIVS Publications:
- Searchable bibliography of in
vitro resources with access to online documents . Articles include
the following categories: eye, ocular; skin ; photoxicity; percutaneous
penetration; acute toxicity; validation; alternative methods.
- Practical Enrichment Options for Animals
Kept in Research Institutions.
Reinhardt A. 2009*. Animal
Welfare Institute. Washington, DC.
- This database disseminates enrichment
ideas and practical tips from the "Laboratory Animals Refinement
and Enrichment Forum" and from other published information.
and Environmental Enrichment for All Laboratory Animals.
Reinhardt V and Reinhardt A. 2009*.
Animal Welfare Institute. Washington, DC.
- This information resource is a merger
of the two databases on refinement & enrichment for non-primate and primate laboratory
animals. It contains nearly three
thousand annotated entries, 17% full-text,
on all aspects of refinement of housing and handling
conditions and environmental enrichment for ALL animals kept in research, testing and
teaching institutions. Access
to the database is free. It is searchable by citation and keywords
and updated at least once every two months.
- ECVAM Database Service on Alternative Methods
to Animal Experimentation.
ECVAM (European Centre for
the Validation of Alternative Methods).
- DB-ALM provides factual and evaluated
information on advanced non-animal test development and validation
for toxicology assessments coming from a wide range of international
information sources. It includes various databases on method descriptions,
validation studies, INVITTOX protocols, compounds and test results,
ECVAM workshop reports.
guide to searching for alternatives to the use of laboratory
animals." Bottrill K. FRAME Web Site.
- Very useful and comprehensive
guide, including basic principles for searching the Internet
or any online database, comparison of search engines, suggestions
for how to approach a search on the Three Rs; a description,
including links, of some of the databases which can be accessed
free on the Internet, as well as a listing of commercial databases
and database hosts of potential relevance.
- "The search for refinement
alternatives: When you've just got to use animals." Kreger,
MD. 2000. Lab Animal 29(4), 22-25, 28-29.
- Tips for researchers and IACUCs
on how to conduct a literature search for refinement. "Refinements
to animal-use protocols can help reduce animal pain and distress,
thus producing cleaner data. Yet, most researchers neglect a
refinement search, despite legal mandates, because the information
is not readily available. What's more, IACUCs may have difficulty
assessing researchers' refinement searches. The author offers
for searching for alternatives to animal research and testing."
Smith CP. 1994. Lab Animal 23(3), 46-48.
- "Investigators can assist
information specialists who perform the search by being prepared
to give precise and specific information about their research
or testing procedures." The type of information the investigator
may be asked to provide is listed, and the two phases of a search
strategy, 1. reduction and refinement, and 2. replacement, are
delineated. Sample searches are given. Worksheets (requesting
information that the researcher must provide in order to run
a multi-database literature search for alternatives) with instructions
and a search summary form can be found at: http://awic.nal.usda.gov/nal_display/index.php?info_center=3&tax_level=1&tax_subject=184
- EXPERT HELP WITH THE ALTERNATIVES
In Vitro Replacement Resources
"AWIC (Animal Welfare Information
Center) offers expertise in formulation of the search strategy
and selection of key words and databases, access to unique databases,
on- and off-site training of institute personnel in conducting
effective alternatives searches, and is able to perform no-cost
or low-cost electronic database searches. AWIC can be contacted
at (301) 504-6212, via E-mail at email@example.com [cited
from USDA Policy #12]
The University of California Center for Animal
Alternatives: The UC Center
for Animal Alternatives offers help with the alternatives search,
including search strategy, database selection, and general guidance
and performs low-cost searches. Email: ( firstname.lastname@example.org ).
Web site: http://www.vetmed.ucdavis.edu/Animal_Alternatives/service.htm
Note: * Date when last accessed while compiling the
bibliography. Web sites and databases are updated regularly.
to Table of Contents
Compiled by Annie
and Viktor Reinhardt, Animal Welfare Institute and reviewed by
Barbara Orlans, Kennedy Institute of Ethics.
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