Annotated Bibliography For Members Of Institutional Animal Care And Use Committees

New Edition, 2001

This bibliography may serve as a guide to published and online material assisting non-affiliated and affiliated members of IACUCs
in their commitment to ensure ethically and scientifically acceptable research protocols involving live animals.

Table of Contents

GENERAL
INSTITUTIONAL ANIMAL CARE AND USE COMMITTEES (IACUCs)

LEGISLATION, REGULATIONS AND GUIDE
ETHICS
ALTERNATIVES: GENERAL
ALTERNATIVES: REPLACEMENT/IN VITRO TESTING
ALTERNATIVES: REFINEMENT /REDUCTION
General
Recognition and Alleviation of Pain
Refinement of Handling and Housing Conditions (Enrichment)
Species-specific Requirements for Enrichment
      Exercise for dogs
      Environmental enhancement for primates
ALTERNATIVES IN EDUCATION/TEACHING
WEB RESOURCES FOR THE LITERATURE SEARCH (USDA POLICY #12)
Databases, Directories & Bibliographies
Search Engines, Search Guidelines
Specialized In Vitro Replacement Resources

Last update: 07/20/01


GENERAL

Animal Care Matters. 1993. Committee on Animal Care, Massachusetts Institute of Technology (MIT). Available from MIT, 37 Vassar Street 45-105, Cambridge, MA 02139.
This 25 minute-videotape is designed to aid institutions in providing effective education to animal research personnel. Included are constructive discussions of the ethical and moral issues concerning animal research, the role of laboratory personnel for ensuring humane treatment and species-adequate housing of research animals, applicable legislative and regulatory guidelines, the responsibility of IACUCs, and alternatives to animals in biomedical research.
 
Animals, Science, and Ethics. Donnelley S and Nolan K, eds. 1990. The Hastings Center Report, Supplement May/June.
Invaluable background information addressing ethical theory and the moral status of animals, animals in science, animal suffering and IACUCs.
 
Animal Welfare Information Center Newsletter. Animal Welfare Information Center, National Agricultural Library, USDA. Beltsville, MD.
A quarterly publication providing "current information on animal welfare to investigators, technicians, administrators, exhibitors and the public."
 
Guide to the Care and Use of Experimental Animals, Volume 1 (2nd Edition). Olfert ED, Cross BM and McWilliam AA, eds. 1993. Canadian Council on Animal Care. Ottawa, Ontario.
Very thorough manual with a clear discussion of relevant literature. Pertinent chapters: responsibility for the care and use of experimental animals; laboratory animal facilities; laboratory animal care; social and behavioral requirements of experimental animals; restraint and manipulations; standards for experimental animal surgery; control of animal pain in research, teaching and testing; anesthesia; euthanasia; use of animals in psychology; use of animals in neuroscience research; space requirements; categories of invasiveness in animal experiments; ethics of animal investigation.
 
In the Name of Science: Issues in Responsible Animal Experimentation. Orlans FB. 1993. Oxford University Press. New York, NY.
Comprehensive analysis of the social, political, and ethical conflicts surrounding the use of animals in scientific experiments. The author makes "recommendations for policy changes that are achievable within the foreseeable future and that would improve the lot of animals used for experimentation without hampering the scientific process… A reasonable way of looking at these issues is to ask the question. 'Can the harms be reduced?' "

Laboratory Animal Science. 1987. 37 (Special Issue).
"Case studies of ethical dilemmas." Orlans FB, 59-64.
Five cases based on actual situations are discussed in depth to illustrate opportunities for the IACUC to modify protocols to introduce more humane experimental design.
 
"Reducing pain in laboratory animals." Spinelli JS, 65-70.
Terminology of pain is summarized; simple but effective strategies for the control of pain are proposed.
 
"Assessment of animal pain in experimental animals." Soma LR, 71-77.
The signs and behavioral changes associated with acute and chronic pain in animals are clearly described. Dr. Soma states, "When there is doubt, the bias should be in favor of the animal."
 
"Public concerns for animals in research." Clark J, 120-121.
The author highlights the fundamental dilemma of regulated animal welfare: "If we want to protect laboratory animals from neglect or abuse, we must insist on strong laws that can be enforced."
 
The Monkey Wars. Blum D. 1994. Oxford University Press. New York, NY.
A realistic picture of the scientific and ethical dilemmas that accrue from biomedical and psychological experimentation with animals, in particular with nonhuman primates. Succinct discussions include the standpoints of extremists and moderates and are based primarily on interviews with leading primatologists and animal advocates across the US.
 


INSTITUTIONAL ANIMAL CARE AND USE COMMITTEES (IACUCs)

"Such members shall possess sufficient ability to assess animal care, treatment, and practices in experimental research as determined by the needs of the research facility and shall represent society's concerns regarding the welfare of animal subjects used at such facility."
                                                                                                                                                     AWA Section 13 (b)(1).

"Animal welfare, animal rights: The past, the present, and the 21st century." Silberman MS. 1988. Journal of Zoo Animal Medicine 19, 161-167.
"The real question that faces us today is, do we need more laws, or do we need to enforce the existing regulations honestly and with vigor?" It is the efforts of IACUCs, "as well as the earnestness in which they perform their missions, that will be the basis for future public confidence."
 
"Appointing animal protectionists to Institutional Animal Care and Use Committees." Levin LA and Stephens ML.1994/95. Animal Welfare Information Center Newsletter 5(4), 1-2 & 8-9.
Authors "propose that animal research facilities, as a show of good-will, voluntarily appoint individuals to their IACUC who are recognized in the local community as advocates for animals." The advantages and potential pitfalls are discussed.
 
"Community members on animal review committees." Orlans FB. 1993. In In the Name of Science: Issues in Responsible Animal Experimentation. 99-117. Oxford University Press. New York, NY.
To be effective, community members "need to be able to withstand role ambiguity and to deal with group pressures. They need …an ability to present a reasoned view with dignity and without hostility to persons who do not agree with them. They must be satisfied with having only moderate or minor impact on the committee and seeing only occasional disapprovals of protocols. Their overall impact of contributing balance and some measure of public accountability to the proceedings must suffice. For this, they must be prepared to devote a considerable amount of their time."
 
The IACUC Handbook. Silverman J, Suckow MA and Murthy S, eds. 2000. CRC Press. Boca Raton, FL.
This practical guide for IACUC members uses a question-and-answer format to address the problems and concerns often confronting IACUCs. The book's chapters not only discuss the structure and responsibilities of the IACUC, they also include such issues as pain and distress, euthanasia, surgery, occupational health and safety, laboratory animal enrichment, and animal mistreatment and protocol noncompliance.
 
"The attending veterinarian as an ally and leader of the IACUC?" Silverman J. 2000. Lab Animal 29(10), 26-27.
The role of the attending veterinarian (AV) is clearly delineated as a moral and scientific leader of the IACUC who must take an active part in the committee's work. "The veterinarian can take an assertive yet non-confrontational role in helping the IACUC ensure the proper care and use of research animals" in the spirit of the 3 Rs, "preferring not to use animals if efficacious alternatives are available." The AV needs job security, i.e. tenure, since "fear of retribution can negatively affect the AV's performance on the IACUC."
 
"Do pressure and prejudice influence the IACUC?" Silverman J. 1997. Lab Animal 26(5), 23-25.
"I believe that the disparity of IACUCs being less rigorous in their deliberations when approving a given number of mice versus the same number of dogs is the more significant dilemma" [than the influence of the perceived power of an investigator]. "IACUCs and laboratory animal specialists must overcome any of our own prejudices and take the lead in speaking out on behalf of animals, all animals."
 
"Ethics of animal welfare in research: The institution's attempt to achieve appropriate social balance." Prentice ED, Zucker IH and Jameton A. 1986. The Physiologist 29(2), 17 & 19-21.
Paper describes 14 ethical principles governing research involving animals adopted by the University of Nebraska Medical Center. These clearly stated principles serve as the protocol review criteria employed by the IACUC.
 
"IACUCs and the world wide web." Boschert K. 1998. Animal Welfare Information Center Bulletin 9 (1-2).
Author provides a comprehensive list of IACUC-related pages on the web.
 
Institutional Animal Care and Use Committee Guidebook. Applied Research Ethics National Association (ARENA); Office for Protection from Research Risks (OPRR). 1993. NIH Publication No. 92-3415. National Institutes of Health. Bethesda, MD.
Information about authority, composition and functions of IACUCs, issues, criteria, oversight of animal care and use program, evaluation of animal welfare concerns, record keeping and reporting, and special considerations such as alternatives to the use of live animals, instructional use of animals, farm animals, and legal concerns.
 
Institutional Animal Care and Use Committees: A Comprehensive Resource of Online Information. Web site. Duffee N, Barnett L, Cody C and Silver C. 2000*. AALAS. Memphis, TN.
Useful links archive to resources for IACUCs, organized by area of interest.
 
"Toward better unaffiliated members: Goal of two unaffiliated members per IACUC offers advantages." Liss C. 2000. Science and Animal Care 11(1), 1-4.
"Outside members on IACUCs have a very tough job. These lone representatives, unaffiliated with the research institutions and unpaid for their services, carry the responsibility of representing the community's concerns for the welfare of the animals used for experimentation, teaching and testing… Bringing in a second unaffiliated member (UM) on the IACUC would relieve some of the pressure. If one of the UMs is unable to attend a meeting, the other will be there thus ensuring that an outside member is always present for committee activities… In addition, each of the UMs should bring an unique perspective to the meetings."
 
"Institutional animal care and use committees: A new set of clothes for the emperor?" Finsen L. 1988. The Journal of Medicine and Philosophy 13, 145-158.
A thorough analysis of the regulatory texts pertaining to IACUCs.
 
Public Health Service Policy on Humane Care and Use of Laboratory Animals. Office for Protection from Research Risks, National Institutes of Health (OPRR). 1985. Rev. 1986, Reprinted 1996.
Functions of IACUCs as defined by the Public Health Service policy are clearly outlined. Useful user-friendly tutorial on the PHS policy is offered.
 
"Research protocol review for animal welfare." Orlans FB. 1987. Investigative Radiology 22, 253-258.
Author addresses the following questions: What is the attitude of investigators toward IACUCs? How is protocol review conducted? What do IACUCs look for in their review, and how can investigators be responsive to IACUCs concerns? In what ways can a research protocol be modified to minimize animal pain and distress?
 
"The SCAW IACUC survey part II: The unaffiliated member." Theran P. 1997. Lab Animal 26(5), 31-32.
An interesting break down of responses from 427 unaffiliated IACUC members. For example: 98% felt able to fulfill their role on the committee; 31% felt their committee was less than thorough to make sure that there is no duplication; 29% indicated that their committee was less than thorough to make sure that alternatives to live animals were not available.
See also "The evolving role of the unaffiliated member" Theran, P. February 26, 1999:
Discussion about the unaffiliated member and suggestions on how to develop the unaffiliated member's role.
 
"What's wrong with the IACUC? [scroll all the way down]" Opinion. 2000. Lab Animal 29(10), 28-29.
"IACUCs need an IACUC Chair and members who are not concerned about promotion and tenure issues being compromised by their IACUC role.IACUC members told me they would never take serious action against other faculty members because it would be taken against them during promotion and tenure." Diane McClure.


LEGISLATION, REGULATIONS AND GUIDE

ANIMAL WELFARE ACT & REGULATIONS: 3 documents:
1. Animal Welfare Act as Amended. (7 USC, 2131-2156) Federal law.
Chief federal animal protective law, adopted in 1966 and amended in 1970, 1976, 1985 and 1991; sets minimum standards for the care and housing of animals used in research, exhibition and the wholesale pet trade; mandates principal investigators to consult with a veterinarian and to consider alternatives before conducting any procedure likely to produce pain or distress in an experimental animal; requires semi-annual inspections by the IACUC and at least one inspection per year by USDA; places the authority and control of animal usage with the IACUC.
 
2. Code of Federal Regulations, Title 9, Chapter 1, Subchapter A - Animal Welfare. USDA. 1999.
Regulations developed by the USDA that specify how to comply with the Animal Welfare Act and its amendments, divided into 4 sections: definitions, regulations, standards and rules of practice. The bulk of the subchapter is the third section that provides standards for specific species or groups of species such as cats and dogs, guinea pigs and hamsters, rabbits, nonhuman primates, marine mammals, and the general category of "other warm-blooded animals." Standards include those for facilities and operations, health and husbandry systems, and transportation. Updates of sections and paragraphs are accessible at: http://www.access.gpo.gov/nara/cfr/waisidx_00/9cfrv1_00.html
 
3. Animal and Plant Health Inspection Animal Care Policy Manual. USDA. 1999-2000.
"The Animal Care Policy Manual further clarifies the intent of the Animal Welfare Act." Policy and enforcement guidelines that determine many of the actions that IACUCs must take as they inspect facilities and review protocols.
The manual includes:
"
USDA's AWA Policy #11 -- Policy about painful/distressful procedures" - April 14, 1997.
"A painful procedure is defined as any procedure that would reasonably be expected to cause more than slight or momentary pain and/or distress in a human being to which that procedure is applied. The Institutional Animal Care and Use Committee (IACUC) is responsible for ensuring that investigators have appropriately considered alternatives to any procedures that may cause more than slight or momentary pain or distress." Examples of such procedures are given.
   
"USDA's AWA Policy #12 -- Consideration of alternatives to painful/distressful procedures" June 21, 2000."The Animal Welfare Act (AWA) regulations require principal investigators to consider alternatives to procedures that may cause more than momentary or slight pain or distress to the animals and provide a written narrative of the methods used and sources consulted to determine the availability of alternatives, including refinements, reductions, and replacements." Gives guidance on the requirement to provide a written narrative, and search for alternatives.
 
Guide for the Care and Use of Laboratory Animals. Institute of Laboratory Animal Resources, National Research Council. 1996. National Academy Press. Washington, DC
Updated basic reference on housing, handling and care of animals in scientific institutions and government agencies. Includes US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training.
"Unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings may cause pain or distress in other animals."

Related Documents and Articles

Animal Welfare Act 1966-1996: Historical Perspectives and Future Directions. Kreger M, Jensen D'A, and Allen T, eds. 1998. Proceedings of a symposium sponsored by the USDA, held on September 12, 1996 in Riverdale, Maryland. WARDS (Working for Animals in Research, Drugs, and Surgery). Vienna, VA.
"This symposium takes a retrospective look at the development and effectiveness of the Federal animal welfare regulations since 1966. Leaders from government, including those directly involved in writing the regulations of the original act, industry, and humane groups offer their views of the history and impact of the act and their visions for its future."

"Animal Welfare Act - Requirements for the minimization of pain and distress." DeHaven WR. 1998. Pain Management and Humane Endpoints. Johns Hopkins Center for Alternatives to Animal Testing (CAAT) workshop.
Clear explanation of policy No. 11 and 12 and the role of the IACUCs in implementing them.
 
Animal Welfare Report. USDA. 1999.
Annual report on the administration and enforcement activities of the Animal Welfare Act.


ETHICS

"Ethics in our Western world has hitherto been largely limited to the relations of man to man. But that is a limited ethics. We need a boundless ethics which will include the animals also." Albert Schweitzer

Animals, Nature and Albert Schweitzer. Free AC , ed. 1982. Animal Welfare Institute. Washington, DC. Available from Animal Welfare Institute, PO Box 3650, Washington, DC 20007.
A brief outline of Albert Schweitzer's ethic of Reverence for Life. "Whenever an animal is somehow forced into the service of men, every one of us must be concerned for any suffering it bears on that account. No one of us may permit any preventable pain to be inflicted, even though the responsibility for the pain is not ours."
 
"Beyond 'adequate veterinary care'." Anchel M. 1976. Journal of the American Veterinary Medical Association 168, 513-517.
A very clear definition of the laboratory animal veterinarian's professional and ethical obligations. "The veterinarian must have the courage and it will require courage to insist on standards that are absolute, and not relative to the pressures within any institution."
 
"Editorial: Caring for animals, caring for ourselves." Spaeth GL. 1994. Ophthalmic Surgery 25, 426.
"When we act uncaringly toward experimental animals we become uncaring human beings. What is the worth of medical miracle achieved at the cost of inflicting trauma on others that cannot help but scar our own characters?"
 
"Ethical consideration in toxicology." Zbinden G. 1985. Food and Chemical Toxicology 23, 137-138.
"Toxicologists must realize that their important mission ... does not give them an unconditional license to kill as many laboratory animals as they wish and to hide behind regulatory requirements, testing guidelines and bureaucratic prescriptions for good laboratory practice."
 
"Ethical guidelines for investigations of experimental pain in conscious animals." Zimmermann M. 1983. Pain 16, 109-110.
Guidelines of the International Association for the Study of Pain. "It is essential that intended experiments on pain in conscious animals be reviewed beforehand by scientists and lay-persons." Investigators "should accept a general attitude in which the animal is regarded not as an object for exploitation, but as a living individual."
 
"The ethical socialization of animal researchers." Arluke A. 1994. Lab Animal 23(6), 30-32 & 34-35.
"Newcomers face a closed moral universe where issues of morality are defined institutionally, and hence are rarely confronted openly by individuals. Anti-ethical training processes support ideological claims for the importance of knowledge production, the need for objectivity and professionalism, and the priority of the concerns of humans over those of animals."
 
The Human Use of Animals: Case Studies in Ethical Choice. Orlans FB, Beauchamp TL, Dresser R, Morton DB and Gluck JP. 1998. Oxford University Press: New York.
This easy-to-read book includes an introductory chapter on morality providing a broad background information and describing several methods useful to resolve ethical dilemmas. Subsequent chapters are individual case studies covering most major areas of animal use, and discussing the ethical issues and welfare concerns involved. This book helps readers reflect on their own ethical outlook.
 
"Sacrificial symbolism in animal experimentation: Object or pet." Arluke AB. 1988. Anthrozoos 2, 98-117.
"Many principal investigators do not handle animals at all, although a few may do surgery after the animal has been prepared fully by a technician Laboratories should adopt a moral attitude that sanctions the expression of emotions and condones the human side of scientific work."
 
"Seeking common ground. [abstracts; login as guest]" 1999. Special section on animal experimentation in Cambridge Quarterly of Healthcare Ethics 8(1), 9-87.
Inspired by Henry Spira's search for common ground on animal testing, this section provides contributions to bridging the gap between scientists and animal welfare advocates.
 
"Understanding the emotional experiences of animal research personnel." Halpern-Lewsi JG. 1996. Contemporary Topics 35(6), 58-60.
Research personnel "who demonstrate caring and compassionate behaviors add to the integrity of the animals, which ultimately results in higher quality research protocols. Individuals interacting with animals ... should be encouraged to engage in caring behaviors without fear of reprisal." Suggestions are provided to help research participants to do their work without compromising humane relationships with experimental animals.


ALTERNATIVES: GENERAL

"Alternatives or alternative methods are generally regarded as those that incorporate some aspect of replacement, reduction, or refinement of animal use in pursuit of the minimization of animal pain and distress consistent with the goals of the research. These include methods that use non-animal systems or less sentient animal species to partially or fully replace animals (for example, the use of an in vitro or insect model to replace a mammalian model), methods that reduce the number of animals to the minimum required to obtain scientifically valid data, and methods that refine animal use by lessening or eliminating pain or distress and, thereby, enhancing animal well-being." USDA AWA's policy #12.

Alternatives to Animal Testing: Refinement, Reduction, Replacement (ALTWEB Web Site). 2001*.
Up-to-date, comprehensive site on alternatives containing a number of full-text documents, abstracts of journals on alternatives (http://altweb.jhsph.edu/publications/publications.htm), a search engine, Frequently-Asked-Questions on alternatives, and further links, including to the John Hopkins Center for Alternatives to Animal Testing (CAAT) , http://caat.jhsph.edu/
 
Alternatives to Laboratory Animals (ATLA Journal). FRAME (Fund for the Replacement of Animal in Medical Experiments.)
This quarterly journal covers "all aspects of the development, validation, introduction and use of alternatives to laboratory animals in biomedical research and toxicology testing."
 
Alternatives to Pain in Experiments on Animals. Pratt DP. 1980. Argus Archives. New York, NY.
Well written account of ethically and scientifically unacceptable practices in animal experimentation. The author describes specific experiments and matches them with alternatives.

Alternatives Page of The Animal Welfare Information Center's Web Site (AWIC
). 2001*.
This site contains online articles; a list of databases and organizations; and help with the literature search in the form of guidelines, a thesaurus of alternatives terminology, worksheets and an AWIC alternatives workshop on the web. A number of bibliographies are available from AWIC's publications page relating to animal care, use and welfare; ethical and moral issues; and IACUCs.
 
Alternatives Page of the Fund for the Replacement of Animals in Medical Experiments (FRAME). 2001*.
This excellent site offers a wealth of information about alternatives including a clear introduction to the three Rs and a comprehensive overview of alternatives with a summary of each category such as computer-based systems, physico-chemical techniques, lower organisms and embryos, human studies, cell, tissue and organ culture. Annotated links to databases, resources and organizations are provided as are very helpful guidelines in searching for alternatives.
 
The Principles of Humane Experimental Techniques. Russell WMS and Burch RL. 1959. Methuen and Co. London, UK.
The authors introduce the concept of the 3 Rs: Replacement, Reduction, Refinement. "Desirable as replacement is, it would be a mistake to put all our humanitarian eggs in this basket alone. The progress of replacement is gradual, nor is it ever likely to absorb the whole of experimental biology. Refinement may reach such a pitch that a given procedure employing animals is absolutely humane, but in any given field there is bound to be a latent period before such success is attained. Reduction remains of great importance, and of all modes of progress it is the one most obviously, immediately, and universally advantageous in terms of efficiency."
 
Progress in the Reduction, Refinement and Replacement of Animal Experimentation. Ball M , van Zeller AM and Halder ME , eds. 2000. Developments in Animal and Veterinary Science. Vol. 31A and 31B. Proceedings of the 3rd World Congress on Alternatives and Animal Use in the Life Sciences, Bologna, Italy, 29 Aug. to 2 Sept 1999. Elsevier. Amsterdam, Netherlands.
Excellent and expert contributions reflect the present state of knowledge in many areas including adverse effects; animal models; biologicals; barrier systems in vitro; carcinogenicity testing; ethical committees; ethical aspects of transgenesis; humane endpoints; outreach on the Three Rs to scientists and the general public; experimental design, data analysis and reduction; refinements in animal housing and husbandry; refinement in experimental design and techniques; skin and eye irritation testing; toxicogenomics; use of animals in education and training; and use of reconstituted tissues and co-cultures.
 
"The three Rs: The way forward." Balls M et al. 1995. ATLA (Alternatives to Laboratory Animals) 23(6), 838-866.
A very clear and comprehensive explanation of the ethical, scientific and methodological ramifications of the three Rs. "The Three Rs should be seen as a challenge and as an opportunity for reaping benefits of every kind scientific, economic and humanitarian not as a threat."


ALTERNATIVES: REPLACEMENT/IN VITRO TESTING

"We shall use the term `replacement technique' for any scientific method employing non-sentient material which may, in the history of animal experimentation, replace methods which use conscious living vertebrates." Russell W and Burch R

"Alternatives to animal testing in the USP-NF: Present and future." Underhill LA, Dabbah R, Grady LT and Rhodes CT. 1994. Drug Development and Industrial Pharmacy 20, 165-216.
A comprehensive review of replacement options to animal testing, including physiochemical tests, tissue cultures, electronic and computer processing tests, bioassays, combination tests, hormone potency assays, and general safety tests. Advantages of in vitro tests are outlined and discussed.
 
"How far advanced is the replacement of animal experimentation?" Balls M. 1993. In Vitro Toxicology 6, 149-161.
The concept of replacement alternatives and the impact of societal changes on animal experimentation are reviewed. The range of replacement methods, and progress toward their incorporation into research and, in particular, toxicity testing are discussed. It is concluded that much greater effort should be put into overcoming the barriers to the acceptance of replacement alternatives, which currently limit the contributions they have to make toward greater humanity and better biomedical science.
 
" In vitro methods in toxicology." Spielmann H and Goldberg AM. 1999. Toxicology. Marquardt H. , ed. 1999. Academic Press. San Diego, CA.
Validation and valid methods are discussed and current use of in vitro methods in toxicology testing is reviewed. "In vitro methods can and should play a much more important role in the risk assessment process and, in fact, with the appropriate data in vitro methods might completely bypass animal use." Several tests and methods are examined, and an integrated strategy proposed.
 
"In vitro methodologies for enhanced toxicity testing." DelRaso NJ. 1993. Toxicology Letters 68, 91-99.
An excellent introduction to in vitro studies of toxicology. Advantages and limitations of in vitro systems as alternatives to whole animals are discussed. "It is not realistic, at this time, to expect that in vitro methods will totally replace the whole animal. However, the use of in vitro systems to reduce animal numbers and to refine in vivo experiments has been documented."
 
"In vitro methods for predicting human toxicity." Silber P, Ruegg CE and Myslinski N. 1994. Lab Animal 23(2), 33-37.
A brief but very clear introduction to in vitro prediction of target organ-specific toxicity using human tissues and cells. "The in vitro methods born in the laboratories of academic researchers have been increasingly transferred to the commercial sector, where they are being used with great success to accelerate product development, significantly reduce the numbers of animals required to satisfy research requirements, and most important, to provide a means for predicting the interactions of drugs and chemicals with human systems long before clinical tests are ethically possible."
 
"Science in Vitro." Zurlo J, Rudacille D and Goldberg AM.1994. Animals and Alternatives in Testing: History, Science, and Ethics. MA Liebert. Larchmont, NY.
Clear, easy-to-read survey of in vitro alternatives.
 
Selection and Use of Replacement Methods in Animal Experimentation. UFAW, FRAME, 1998. Available from UFAW, The Old School, Brewhouse Hill, Wheathampstead, Herts AL4 8AN UK.
The booklet is "a practical guide to help ensure that those considering animal experimentation have explored all opportunities to avoid animal use and attempted to minimize the numbers involved." Detailed overview of replacement options, including a summary of the current uses, advantages and limitations for each method.

Specific Topics in In Vitro Testing

 Eye irritation

"A battery of cell toxicity assays as predictors of eye irritation: a feasibility study" Rosenkranz HS and Cunningham AR. 2000. ATLA 28(4).

"Justification of the enucleated eye test with eyes of slaughterhouse animals as an alternative to the Draize eye irritation test with rabbits." Prinsen MK and Koeter HBWM. 1993. Food and Chemical Toxicology 31, 69-76.

"Results indicate that a battery of cytotoxicity tests could provide a viable alternative to the animal-based procedure."
  

The authors examined 21 test materials and concluded that the enucleated eye test provides a very accurate means of assessing eye irritant potential without using laboratory animals.

 Monoclonal antibodies

"Small-Scale monoclonal antibody production in vitro: Methods and resources" Jackson LR, Trudel LJ and Lipman NS. 1999. Lab Animal 28( 3), 20-30.

"Proceedings of the Production of Monoclonal Antibodies Workshop August 29, 1999, Bologna, Italy." McArdle JE and Lund CJ , eds. Alternatives Research and Development Foundation and the 3rd World Congress on Alternatives and Animal Use in the Life Sciences.

"Guidance Document for IACUC Evaluation of Monoclonal Antibody Production Protocols." Adapted from DeTolla and Smith. Available from Alternatives Research and Development Foundation, 14280 Golf View Drive, Eden Prairie, MN 55346

 Review of in vitro production of MAbs. Highlights some of the in vitro technologies most commonly used and points to consider when selecting an in vitro method for MAb production.

Useful contributions including animal welfare implications of the ascites method; description of advantages and disadvantages of in vivo and in vitro methods; up-to-date review of laboratory-scale in vitro methods for producing MAbs; IACUC guidance for protocol review of MAbs.
 

Applicable concepts and guidelines appropriate for protocol review of Mabs are presented. Each of the questions listed in the IACUC checklist are discussed.

 Toxicology

 "The integrated use of alternative methods in toxicological risk evaluation." Blaauboer B. 1999. ATLA 27(2), 229-238.

"Predictive value of in vitro model systems in toxicology. " Davila JC, Rodriguez RJ, Melchert RB and Acosta D. 1998. Annual Review of Pharmacology and Toxicology. 38, 63-96.
 

"Integrating computer prediction systems with in vitro methods towards a better understanding of toxicology." Barratt MD. 1998. Toxicology Letters Dec. 102-103:617-21.

 In this report, a generic scheme for local/systemic toxicity, and a specific scheme for target organ toxicity, are proposed. The scope and limitations of the approaches are discussed.

Overview of the use of in vitro model systems to investigate target organ toxicity of drugs and chemicals; also provides selective examples of these model systems to better understand cutaneous and ocular toxicity and the role of drug metabolism in the hepatotoxicity of selected agents .

Ways in which computer prediction systems and in vitro toxicology can complement each other in the development of alternatives to live animal experiments are described.

 Validation

"Practical aspects of the validation of toxicity test procedures. " Balls M. 1995. ATLA 23(1), 129-147.
 

"The validation and acceptance of alternatives to animal testing." Balls M and Fentem JH 1999. Toxicology In Vitro13(4-5), 837-46.

Recommendations are made concerning the practical and logistical aspects of validating alternative toxicity testing procedures .

Discussion of validation issues.

 Cosmetics
"The potential use of non-invasive methods in the safety assessment of cosmetic products." Rogiers, V et al. 1999. ATLA 27(4), 515-537. The potential of using non-invasive techniques in safety assessment with human volunteers is reviewed.




ALTERNATIVES: REFINEMENT/REDUCTION

"Techniques that 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 N.
"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).

General

"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.
 
"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 unethical."
 
"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 16(4), 3-4.
"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."
 
"The Importance 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."
 
"Innovations in research animal care." Benn DM. 1995. Journal of the American Veterinary Medicine Association 205, 465-468.
An excellent introduction.
 
"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.
 
"Reducing the use of laboratory animals in biomedical research: problems and possible solutions." Festing MFW, et al. 1998. ATLA (Alternatives to Laboratory Animals) 26(3), 283-301.
Practical ways in which reduction in animal use might be achieved are discussed including the application of a better research strategy; improving experimental design by using controlled studies, sequential experimentation, reducing variability; and better statistical analysis of experiments as a means of extracting more useful information.



Recognition and Alleviation of Pain

"Adverse effects in animals and their relevance to refining scientific procedures." Morton DB. 1990. ATLA (Alternatives to Laboratory Animals) 18, 29-39.
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."
 
Animal Anesthesia and Analgesia. Web page. Chandler Medical Center, Office of the University Veterinarian. 1998*. University of Kentucky. Lexington, KY.
Anesthesia and analgesia guidelines and regulations. Valuable guidance on the use of anesthetics, analgesics, and other categories of drugs for the prevention or relief of pain and distress in laboratory animals. Additional notes describe several commonly-used anesthetics and analgesic medications including tables of drugs used for preanesthesia, anesthesia, analgesia, sedation, tranquilization, and restraint of mice, rats, hamsters, guinea pigs, rabbits, dogs, cats, nonhuman primates and pigs.
 
"Assessment and alleviation of post-operative pain." Flecknell P. 1997/98. Animal Welfare Information Center Newsletter 8(3-4) 8-14.
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."
 
"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 for Recognizing Animal Pain. Web page. Office of Research, Technology, and Graduate Education. 2001*. University of Florida. Gainesville FL.
Concise and practical series of guidelines: description of typical behavioral signs of acute pain in laboratory animals including a table listing potential signs associated with pain or distress in rodents and rabbits; pain assessment by means of pain scales in dogs, large animals, rodents rabbits, birds with corresponding action plans; guidelines helpful in relieving unnecessary pain and distress; and guidelines for recognizing post-surgical animal pain.
 
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."
 
"Implementing 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 25(6), 23-25.
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."
 
"Pain–assessment, 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 Management and Humane Endpoints. Johns Hopkins Center for Alternatives to Animal Testing (CAAT). 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.
 
"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. 1992. 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."
 
"Post-operative care and analgesia of farm animals used in biomedical research.[scroll down]" Randolph MM. 1994. Animal Welfare Information Center 5(1), 11-13.
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.
 
"2000 Report of the AVMA Panel on Euthanasia." 2001. Journal of the American Veterinary Medical Association 218(5), 669-696.
Useful reference to insure that appropriate methods of euthanasia are being used for different laboratory animal species.
 
Research Animal Anesthesia, Analgesia and Surgery. Smith AC and Swindle MM , eds. 1994. Scientists Center for Animal Welfare. Greenbelt, MD.
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.



Refinement of Handling and Housing Conditions (Enrichment)

"Proper housing 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 Animals

"Behavioral indexes of poor welfare in laboratory rats." Patterson-Kane EG, Hunt M and Harper DN. 1999. Journal of Applied Animal Welfare 2, 97-110.
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 31(4), 33.
"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 , ed. 1997. 8th edition, Animal Welfare Institute. Washington, DC. Available from Animal Welfare Institute, PO Box 3650, Washington, DC 20007.
A collection of 12 articles outlining refined, i.e., species-appropriate housing conditions and handling techniques for rats, mice, guinea pigs, rabbits, amphibians and reptiles, chickens, dogs, cats, primates, pigs, cattle, sheep and goats. 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 33, 101-107.
"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 4, 207-220.
"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."
 
"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 Animals, Vol. 2, Gilman J , ed. 1984. Canadian Council on Animal Care. Ottawa, Ontario.
Excellent guidelines for the species-appropriate keeping of fish, amphibians, reptiles, and pigeons in the research laboratory setting. Chapters can be accessed individually: fish; amphibians; reptiles; pigeons.
 
"Pair-housing 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."
 
"Restraint methods of laboratory nonhuman primates: A critical review." Reinhardt V, Liss C and Stevens C. 1995. Animal Welfare 4, 221-238.
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."
 
"Social 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 behaviors; 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."
 
"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.
 
See also:
Annotated Database on Refinement of Housing and Handling Conditions and Environmental Enrichment for Laboratory Animals. Part I and Part II.
Environmental Enrichment Information Resources for Laboratory Animals.

in the databases and bibliographies section below.

Species-Specific Requirements for Enrichment

Exercise for Dogs

"...Research facilities 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 for exercise."
                                                                                                                         
              AWA Regulations. Part 3. Standards. A73.8 Exercise for dogs.

Guidelines for Exercising Dogs. Web page. Office of Research, Technology, and Graduate Education. 2000*. University of Florida. Gainesville FL.
A practicable exercise program for dogs is outlined. "A record of exercise and/or contact shall be maintained by the attending veterinarian, and shall be displayed and easily accessible on each cage/run/room. This record shall show the animal ID #, the date(s) and time(s) of each exercise and/or contact, social/medical problems, and shall be signed by the handler who exercised/visited the dog."
 
"Comfortable quarters for laboratory dogs." Hubrecht RC. 1997. In Comfortable Quarters for Laboratory Animals, 8th Edition. Reinhardt V , ed, 63-74. 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: (1) Space considerations and minimum space allowances. (2) Socialization during development. (3) Group-housing versus single-housing. (4) Exercise. (5) Structures within the dog enclosure. (6) Social contact of adult dogs with animal care staff. (7) Minimization of stress during handling procedures. (8) Noise in kennels, and (9) Dog supply and surplus animals.
 
"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 pens.

Environmental Enhancement for Primates

"...Research facilities 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 species-typical activities."
                                                 
AWA Regulations. Part 3. Standards. A73.81 Environmental enhancement to promote psychological well-being.

Environmental Enrichment for Caged Rhesus Macaques (Macaca mulatta): Photographic Documentation and Literature Review. Reinhardt V and Reinhardt A. 2001. Animal Welfare Institute. Washington, DC . Available free from Animal Welfare Institute, PO Box 3650, Washington, DC 20007.
A collection of 108 annotated photos dealing with all aspects of environmental enrichment including refinement of housing and handling conditions for caged macaques. "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. Washington, DC.
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.
 
"Social-housing 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 research protocols.
See also
   Environmental Enrichment for Primates: Annotated Database...
   Environmental Enrichment for Nonhuman Primates: An Annotated Bibliography...

in the databases and bibliographies section below.

ALTERNATIVES IN EDUCATION/TEACHING

"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 of alternatives.
 
Alternatives to the Harmful Use of Nonhuman Animals In Veterinary Medical Education, Buyukmihci, NC. 1989-1998. Web version updated 01/15/1999. Association of Veterinarians for Animal Rights. Davis, CA.
"The purpose of this booklet is to inform veterinary medical students, and those aspiring to be, and educators about some of the alternatives to the harming or killing of nonhuman animals in veterinary medical education". and give a sampling of what is available." Available alternatives in the various disciplines of veterinary medicine are listed including information on format, source, price and description of alternative method."
 
AVAR (Association of Veterinarians for Animal Rights) Alternatives in Education Database. 1990-2000. 2001*. 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.
 
The NORINA (A Norwegian Inventory of Alternatives) Database: Audiovisual Alternatives to Laboratory Animals in Teaching. Smith K and Smith A , eds. 2001*. 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.


WEB RESOURCES FOR THE LITERATURE SEARCH (USDA Policy #12)

Databases, Directories, Bibliographies

Alternatives to the Use of Live Vertebrates in Biomedical Research and Testing. A Bibliography with Abstracts. Hudson VW and Nguyen Q. 1999. 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.
Overview; 1999 no. 2, latest issue.
 
Annotated Database on Refinement of Housing and Handling Conditions and Environmental Enrichment for Laboratory Animals. Part I: Amphibians, Cats, Degus, Dogs, Ferrets, Fishes, Gerbils, Guinea pigs, Hamsters, Mice, Pigeons, Rabbits, Rats, Reptiles. Reinhardt V and Reinhardt A. 2001*. Animal Welfare Institute. Washington, DC.
More than 400 annotated entries 13% full-text on all aspects of environmental enrichment and refinement of housing and handling conditions of small laboratory animals. Access to the database is free. It is searchable by citation and keywords and updated at least once every two months.
 
Annotated Database on Environmental Enrichment and Refinement of Husbandry for Laboratory Animals. Part II: Cattle, Calves, Chickens, Goats, Horses, Quails, Pigs, Sheep. Reinhardt V and Reinhardt A. 2001*. Animal Welfare Institute. Washington, DC.
More than 400 annotated entries on all aspects of environmental enrichment and refinement of housing and handling conditions of 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 available on the Internet at no cost." FRAME Web Page. 2001*.
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.
 
Directory of Resources on Alternatives and Animal Use in the Life Sciences. Larson JA, Criscio R and Jensen D'A. 1998. U.S. Department of Agriculture, National Agricultural Library, Animal Welfare Information Center. Beltsville, MD.
Comprehensive directory of newsletters, databases, publications, audio-visuals, computer models and websites. "Each entry includes information on sponsor's name, address, telephone/fax, e-mail address, url address, descriptive information, costs, availability, audience, language, and a contact person. There is often a note for information considered important but which doesn't fit neatly into the above."
 
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 Nonhuman Primates: An Annotated Bibliography for Animal Care Personnel. Reinhardt V and Reinhardt A. January 2001. 3rd Edition. Animal Welfare Institute. Washington, DC.
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.
 
Environmental Enrichment for Primates: Annotated Database on Environmental Enrichment and Refinement of Husbandry for Nonhuman Primates. Reinhardt V and Reinhardt A. 2001*. New Edition. 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. TAccess 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 Information Resources for Nonhuman Primates: 1987-1992. Swanson JC, Kreger MD, Berry D'AJ, Lyons-Carter JL and Larson, JA. 1992. National Agricultural Library, Animal Welfare Information Center, Beltsville, MD.
A comprehensive, well structured bibliography consisting of citations downloaded from the Agricola database with an appendix on primate information resources.
 
ZEBET Database. Spielmann H, Grune B, Dorendahl A and Skolik S. 1989, 2000. 5th version. 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.
[From the search page: "Access to DIMDI Databases", choose Free Access: "Free Grips-WebSearch". From the "Grips-WebSearch - Start Up Page," choose: Search in "Free Medline And More", you will then be able to select ZEBET from the list.]
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 of charge.

Search Engines, Search Guidelines

"Altweb search engine." ALTWEB Web Site.
"The Altweb search engine is designed to allow users to search several information sets simultaneously: the databases MEDLINE, TOXLINE and AGRICOLA as well as the entire contents of the Altweb site and a list of related Internet sites that contain information on alternatives or animal welfare." User-friendly, the search results from the various databases appear on the screen.
 
"A guide to searching for alternatives to the use of laboratory animals." Bottrill K. FRAME Web Site. 2001*.
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 some solutions."
 
"Tips 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://www.nal.usda.gov/awic/alternatives/searches/searches.htm
 
EXPERT HELP WITH THE ALTERNATIVES SEARCH:

Specialized In Vitro Replacement Resources

Skin irritation

Alternatives to Skin Irritation Testing in Animals. Huggins, J. compiler.

SkinEthic Laboratories Web site

Searchable database containing approx. 340 citations with abstracts.

Useful information about a variety of human tissue equivalents

Monoclonal antibodies

Altweb special section on monoclonal antibodies, ALTWEB
 

Suppliers of monoclonal antibodies produced in vitro, FRAME
 

Resource List of In Vitro MAB Producers, ARDF
 
 
Companies and Institutes Providing New Technologies in Mabs. Jensen A and Smith CP, compilers.

Introduction and resources, various in vitro listings of facilities that produce MAbs.

Two lists: Europe and US.

List created by the Alternatives Research and Development Foundation

AWIC Selected list of company and institute resources in Mabs with annotations
.

Toxicity
MEIC/MEMO (Multicentre Evaluation of In Vitro Cytotoxicity) The same 50 chemicals were tested by a large number of laboratories worldwide in their own in vitro systems.

Cell lines
Cell lines databases, FRAME Annotated links to searchable collections of cell lines.

In Vitro Tests
INVITTOX protocols In Vitro Testing Industrial Platform (Europe) Up-to-date listing of in vitro tests currently available.

Compiled by Annie and Viktor Reinhardt, Animal Welfare Institute and reviewed by Barbara Orlans, Kennedy Institute of Ethics.


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