Bibliography For IACUC Members


Recognition and Alleviation of Pain
Refinement of Handling and Housing Conditions (Enrichment)
Species-specific Requirements for Enrichment
     Exercise for dogs
      Environmental enhancement for primates
Databases, Directories & Bibliographies
Search Engines, Search Guidelines
Specialized In Vitro Replacement Resources
Last update: 11/06/09

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.


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 Bulletin. 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.

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"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).

"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.
"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."
"Best practices for animal care committees and animal use oversight." DeHaven WR. 2002 ILAR Journal 43 (Supplement).
There are many "best practices" that can help the animal care committees (ACC) promote institutional compliance and good animal welfare. These practices, although not universally appropriate for all institutions or activities, include ACC coordinator or administrator, designated protocol reviewer, alternate or dual ACC members, generic protocols and standard operating procedures, centralized controls and animal care facilities, conducting pilot studies, and ensuring the most humane endpoints.
"A current perspective on the role and needs of IACUC unaffiliated members." Mondschein SG 2007. Lab Animal 36(6), 21-26.
"The unaffiliated member, whose role on the Committee is to represent the general public, is often a non-scientist with little or no previous exposure to the concepts described in the animal-use protocols he or she is charged with reviewing. The author, himself an unaffiliated IACUC member, provides advice and suggestions."
"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."
"Contemporary topics for Animal Care Committees." 2007. ILAR [Institute for Laboratory Animal Research] Journal 48 (1) Whole issue.
Recent studies, new approaches, and ethical challenges in animal research are presented.
"Defining the animal care and use program." Sandgren EP. 2005. Lab Animal 34(10), 41-44.
"An effective Animal Care and Use program is critical to an institution's ability to ensure that animal research is conducted humanely and follows all applicable regulations and guidelines. The author provides a global view of the key programmatic components, which can be used to improve existing programs or implement new programs."
"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."
"Engaging the IACUC through comprehensive training." Haywood JR, Greene M, James ML and Bayne, K. 2005. Lab Animal 34(10), 33-37.
"The IACUC is one of the most important committees at a research institution and plays a critical role in the success of an animal care and use program. It is the responsibility of the institution to provide IACUC members with adequate and appropriate training. The authors explore various IACUC training options."
"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.
The IACUC Handbook. Silverman J, Suckow MA and Murthy S, eds. 2nd ed. 2006. 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 second edition features comprehensive updates for all pertinent federal laws, regulations, and policies and also contains an expanded survey of IACUC practices from institutions around the nation.
Information Resources for Institutional Animal Care and Use Committees 1985-1999. Allen T, ed. Revised 2000. AWIC Resource Series No. 7. U.S. Department of Agriculture, National Agricultural Library, Animal Welfare Information Center. Beltsville, MD.
Extensive resource. "This publication is divided into 10 sections: Introduction to Animal Care and Use Committees; U.S. Government Principles, Regulations, Policies and Guidelines; Agency Directives for Federal Fund-holders; Professional Guidelines; World Wide Web Resources; Articles and Bibliographies; Primary References; Selected Software Providers; Organizations; and an Appendix."
Institutional Animal Care and Use Committee Guidebook. Applied Research Ethics National Association (ARENA); Office of Laboratory Animal Welfare (OLAW). 2002. 2nd edition. 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. Subject areas covered in the second edition, but not the first, include the following: IACUC operation and administration; training for IACUC members; oversight of the animal care and use program; behavioral management; emergency preparedness; breeding colonies and transgenic animals.
Institutional Animal Care and Use Committees: A Comprehensive Resource of Online Information. Web site. Duffee N, Barnett L, Cody C and Silver C. 2009*. AALAS. Memphis, TN.
Useful links archive to resources for IACUCs, organized by area of interest.
Public Health Service Policy on Humane Care and Use of Laboratory Animals. Office of Laboratory Animal Welfare (OLAW). 1985. Rev. 1986; amended 2002.
Functions of IACUCs as defined by the Public Health Service policy are clearly outlined. Useful user-friendly tutorial on the PHS policy is offered.
Public Health Service Policy on Humane Care and Use of Laboratory Animals: Frequently Asked Questions. OLAW. Sept 2006.
The purpose of the new page is to provide up-to-date guidance for institutions and IACUCs to use in implementing the Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy). Many of the answers refer to guidance previously published as articles in journals and magazines. The new FAQs provide guidance on the Freedom of Information Act, post-approval monitoring, HVAC malfunctions and failures, rodent cage density, and other issues not previously addressed by OLAW.
"Reliability of protocol reviews for animal research." Plous S and Herzog H. 2001. Science 293 (July), 608-609.
"A random sample of 50 Institutional Animal Care and Use Committees participated in a study of the protocol review process. Each committee submitted three animal behavior protocols it had recently reviewed, and these protocols were reviewed a second time by another participating committee. The result showed that approval decisions were statistically unrelated. On most cases, proposals that were disapproved by one committee were approved by the second committee. "All told, 61% of [150] protocols were judged as either "not very understandable" or "not understandable at all," as having "poor" research designs and procedures, or as justifying the type and number of animals in a way that was deemed "not very convincing" or "not convincing at all."
*Resources for "Lay Members" of Ethics/Animal Care and Use Committees. Ethical review. Web Site, RSPCA, 2009.
Scientific research needs to take place within a framework that allows for ongoing critical evaluation of the ethical and welfare issues relating to the use of animals. This includes consideration of the validity and justification for using animals - the potential harms for animals, likely benefits of the research and how these balance; experimental design; implementation of the 3Rs; animal husbandry and care and other related issues such as staff training.
"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.
"Should IACUCs review scientific merit of animal research projects?" Mann MD and Prentice ED. 2004. Lab Animal 33(1), 26-31.
Whether IACUCs should review animal research protocols for scientific merit is not addressed in the federal regulations, resulting in ongoing confusion on the subject. The authors examine this issue, discuss the pros and cons, suggest how IACUCs can go about reviewing protocols for scientific merit, and question what effect recent changes in regulations will have on this issue. "Lawmakers and regulatory agencies expect the IACUC to serve as a "gatekeeper" that ultimately ensures that research involving animals is justified and humanely conducted."
"A study of three IACUCs and their views of scientific merit and alternatives." Graham K. 2002. Journal of Applied Animal Welfare Science 5(1), 75-81.
Three IACUCs were evaluated using a 19-question survey. "Although 76% of members answered that scientific merit should be more diligently assessed if more than slight pain is caused, 14% believed that assessing scientific merit is not the role of the IACUC. Nearly 86% agreed that the search for alternatives should be more diligent for protocols that incur more than slight pain to the animals involved. Some members believed that alternatives were not actively enough sought after, while others believed no viable alternatives existed."
"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."
What Investigators Need to Know About the Use of Animals. OLAW. 2006.
This brochure educates investigators about their responsibilities under PHS Grants Policy and PHS Policy. It describes the expectations and requirements when using animals in research supported by the PHS.
"What's wrong with the IACUC?" 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.

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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, 1991 and 2002; 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. Contains the 2002 Farm Bill amendments to the Animal Welfare Act.
2. Code of Federal Regulations, Title 9, Chapter 1, Subchapter A - Animal Welfare. USDA. 2008.
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.
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.

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"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."
Cost of Caring: Recognizing Human Emotions in the Care of Laboratory Animals. AALAS. 2001.
"The human-animal bond in the field of animal research exists in many forms. Kindness and concern for animals are desirable characteristics in animal care and research workers." Acknowledging feelings of grief or bereavement at the death of animals used for research or teaching and providing support in the workplace are important. "The bond between people and animals in the laboratory can minimize certain variables related to stress in the animals. The research community can reap the benefits of these essential relationships."
A Critical Look at Animal Experimentation. Kaufman, SR, Cohen, MJ, Cramer M, Contard PC, Hahner K and Todd B. 1995. Medical Research Modernization Committee, New York, NY.
"The value of animal experimentation has been grossly exaggerated by those with a vested economic interest in its preservation. Because animal experimentation focuses on artificially created pathology, involves confounding variables, and is undermined by differences in human and nonhuman anatomy, physiology, and pathology, it is an inherently unsound way to investigate human disease processes. Billions of dollars invested annually in animal research would be put to much more efficient, humane, and effective use if redirected to clinical and epidemiological research and public health programs."
"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 aspects of relationships between humans and research animals." Herzog H. 2002. ILAR [Institute for Laboratory Animal Research] Journal 43(1), 27-32.
"Ways that research institutions can help individuals cope with the ethical consequences of relationships with research animals include the following: supporting the development of human-animal relationships in laboratories, giving animal care personnel an ethical voice through involvement in the institutional animal care and use committee decision process, publicly acknowledging the emotional and moral costs of human-laboratory animal relationships, and educating animal care staff about the purpose and possible benefits of research projects."
"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 decisions concerning animal biotechnology: what is the role of animal welfare science?" Olsson IAS and Sandoe P. 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: S139-144.
"In this paper we discuss the role of animal welfare science in aiding ethics decisions about animal biotechnology. We give a summary of the different ethical concerns expressed by ethicists and by the general public. Focusing on one of them, animal welfare, we give an introduction to the animal welfare implications of recent developments in reproductive and gene technologies. The importance of animal welfere aspects is discussed in relation to other ethical concerns about animal biotechnology."
"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."
"Ethics and welfare of animals used in education: an overview." King LA. 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: S221-227.
Ethical, regulatory and scientific issues arise from the use of animals in education. The implementation of alternatives to animal use is inconsistent, and barriers to the adoption of alternatives include specific curriculum and legislative requirements, traditional educational methodology, and resource and training limitations, particularly when the alternative methods involve new technologies.
Ethics, Humans and Other Animals: An introduction with readings. Hursthouse, R. 2000. Routledge: London.
The author deals with the three major approaches to our use of animals, namely utilitarianism, deontology and virtue ethics, and the texts are taken from the works of Singer, Regan, Midgley and Scruton. She analyses them in a way that enables the reader to comprehend and criticise each of the theories. She applies them to real situations.
The Ethics of Animal Investigation. 1989. Canadian Council on Animal Care. Ottawa, Ontario.
"Animals should be used only if the researcher's best efforts to find an alternative have failed. A continuing sharing of knowledge, review of the literature, and adherence to the Russell-Burch "3R" tenet of "Replacement, Reduction and Refinement" are also requisites. Those using animals should employ the most humane methods on the smallest number of appropriate animals required to obtain valid information."
The Ethics of Research Involving Animals. Nuffield Council on Bioethics. 2005. London, UK.
"This Report seeks to clarify the debate and aims to help people think through the ethical issues that are raised. The ways in which animals are used in different areas of research are reviewed, including: basic or 'blue sky' research, the development of new medicines and vaccines, and toxicity testing. The Report makes practical recommendations for future policy and practice, relating, among other things, to the use of GM animals, ways of improving the quality of debate, the implementation of the Three Rs (Refinement, Reduction and Replacement), and the responsibilities of researchers, reviewers and funding bodies."
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.
"Implications of human-animal interactions and bonds in the laboratory." 2002. ILAR Journal 43(1) [whole issue]
Number of articles addressing the ethical implications of the human-animal bond in research laboratories, and its impact on caregivers and on animal well-being.
"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."
"Trapped in a guilt cage." Arluke A. 1993. Animal Welfare Information Center Newsletter 4(2).
The author studied laboratories and research centers to investigate the impact of experiments on the people who carry them out. "Episodic feelings of discomfort were common and were expressed as background uneasiness and guilt... Open discussion of these feelings was taboo. Scientists, veterinarians, and administrators tended to deny that laboratory workers could be troubled by their use of animals. Uneasiness was not seen as an issue, and was not allowed to intrude on the normal course of work.... Yet within the laboratory culture were unspoken rules and resources for dealing with unwanted emotions and thoughts, despite the silence surrounding this topic." The surfacing of conflicts that prompt defensive behavior among researchers may be due to the "diffusion into the laboratory of society's heightened awareness of how animals should be viewed and treated. Coping devices will be called out when humanity's standards clash with traditional scientific practice. This is cheering to some who see this as a willingness to pay more attention to humanitarian ideals in animal experimentation."
"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.
The Use of Animals in Higher Education : Problems, Alternatives, & Recommendations. Balcombe J. 2000. Humane Society Press. Washington, DC
"The aim of this monograph is to present a comprehensive examination of the issue of animal use in education from an ethical and humane perspective."

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"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). 2009*.
Up-to-date, comprehensive site on alternatives containing a number of full-text documents, abstracts of journals on alternatives (, a search engine, Frequently-Asked-Questions on alternatives, and further links, including to the John Hopkins Center for Alternatives to Animal Testing (CAAT) ,
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
). 2009*.
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.
The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM ).
NICEATM and ICCVAM seek to promote the validation and regulatory acceptance of toxicological test methods that will enhance the agencies' ability to assess risks and make decisions, and methods that will refine, reduce, and/or replace animal use.
"The interplay between replacement, reduction and refinement: considerations where the Three Rs interact." de Boo MJ, Rennie AE, Buchanan-Smith HM and Hendriksen CFM. 2005. Animal Welfare 14(4), 327-332
This paper explores the interplay between the Three Rs and provides examples where the Three Rs have a positive interaction and where they are in conflict with each other.
Fund for the Replacement of Animals in Medical Experiments: Information Resources (FRAME). 2006*.
This excellent site offers a clear introduction to the three Rs, Replacement, Reduction, Refinement. Annotated links to databases, resources and organizations are provided as are very helpful guidelines in searching for alternatives.
Laboratory Animals — The Three Rs: developments in laboratory animal science. 1994. Laboratory Animals Ltd. London, England. Contains three reprints from Laboratory Animals, 28, 1994.
"Replacement of animal procedures: alternatives in research, education and testing." Balls M, 193-211.
"Reduction of animal use: experimental design and quality of experiments." Festing MFW, 212-221.
"Refinement of animal use–assessment and alleviation of pain and distress." Flecknell PA, 222-231.
National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) Information Portal
The National Centre for the Replacement, Refinement and Reduction of Animals in Research provides a UK focus for the promotion, development and implementation of the 3Rs in animal research and testing. The Information Portal contains annotated links to online databases, websites, journal articles, legislation and other publications. These resources provide information to help apply the 3Rs and ensure the best possible standards in animal welfare.
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."
*Alternatives to Animal Testing and Experimentation. Proceedings of the 6th World Congress on Alternatives & Animal Use in the Life Sciences Tokyo, Japan August 21-25 2007.
Japanese Society for Alternatives to Animal Experiments (JSAAE). AATEX 14 special Issue, 2008.
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.
"Refinement, reduction, and replacement of animal use for regulatory testing: Current best scientific practices; future improvements and implementation within the regulatory environment; recommendations for implementation of best scientific practices." 2002. In: Regulatory Testing and Animal Welfare. Proceedings of an International Symposium. International Council for Laboratory Animal Science & Canadian Council on Animal Care; Quebec City, Canada, June 21-23, 2001. ILAR Journal 43 Supplement.
The main objective of the symposium was to identify best practices to minimize or eliminate pain and distress for animals used in safety evaluation and testing procedures. The presentations and discussions described the current best practices for using animals in regulatory testing procedures. Widespread implementation of these best practices could improve the welfare of animals used for safety testing and contribute to reduced animal use.
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 & 2.
This new volume reflects the progress that has been made in implementing the concept of the Three Rs of reduction, refinement and replacement in animal research, education and testing. It includes papers on replacement and reduction alternatives; refinement and reduction alternatives; policy and ethics; eudcation and information resources; test development, validation and implementation and point-counterpoint debates.
"The '3Rs' model and the concept of alternatives in animal research: A questionnaire survey." Pollo S, Vitale A, Gayle V, and Zucco F. 2004. Lab Animal 33(7), 47-53.
The authors used a questionnaire survey to determine how well-known experts judged issues related to the 3Rs. In the authors' opinion "there is a critical need for an integration between the practical and ethical aspects of the alternatives. The need is for 'a tool-kit to help apply the philosophical ideal to the practical environment of the laboratory'."
"The Three Rs: past, present and future." Russell WMS. 2005. Animal Welfare 14(4), 279-286.
"We originally envisaged refinement as minimising pain and distress, and by 1959, discomfort. It is now clear that we must aim positively at optimal well-being."
"The three Rs: The way forward." Balls M, et al. 1995. ATLA (Alternatives to Laboratory Animals) 23(6), 838-866.
A 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.
University of California Center for Animal Alternatives
Information and bibliographies on animal welfare and alternatives.

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"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

Alternative Toxicological Methods. Salem H and Katz S. 2003. CRC Press. Boca Raton.
Explores the development and validation of replacement, reduction, and refinement alternatives (the 3 Rs) to animal testing. Contributions present what has been accomplished thus far in developing acceptable alternatives to traditional animal toxicological assessment and provide potentially new initiatives.
"Evaluation of some in vitro tests to reduce and replace the sub-acute animal toxicity studies." Chhabra RS, Ress NB, Harbell JW and Curren RD. 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, 43-49. ATLA 32, Supplement 1 & 2.
"At present, in addition to refining the current testing protocols, the NTP is evaluating the potential for in vitro test methods to partially or completely avoid the need for 14-day toxicity studies, especially for chemicals where the dermal route of exposure is used. The in vitro assays used were the EpiDerm™ bioassay to estimate dermal irritation, the neutral red uptake (NRU) bioassay to estimate systemic toxicity and the primary rat hepatocyte cytotoxicity (PRHC) assay to estimate hepatotoxicity."
"In vitro and other non-animal experiments in the biomedical sciences." Blaauboer BJ. 1996. Australian and New Zealand Council for the Care of Animals in Research and Teaching (ANZCCART) News 9(4), insert: 1-4. An ANZCCART News Fact Sheet.
"Developments in cellular and molecular biology, as well as computerised modelling, provide ample opportunities for change and the incorporation of knowledge of the mechanisms of toxicity. New procedures must be validated in order to assess their reliability and relevance. Validation should have a sound scientific basis and should also be practical. In this validation process an important driving force should be the improvement of the relevance of toxicological risk assessment."
In Vitro Methods for Assessing Acute Systemic Toxicity. ICCVAM and NICEATM. 2007. National Institute of Environmental Health Sciences. National Institutes of Health. U.S. Public Health Service. Department of Health and Human Services.
The workshop evaluated the status of available in vitro methods for assessing acute toxicity. It also developed recommendations for validation efforts.
Institute for In Vitro Sciences. (IIVS website) 2009*
The Institute (1) provides non-animal research and testing services, (2) sponsors workshops and training courses in in vitro methods, and (3) creates a forum where Industry, Government and Animal Welfare proponents can meet to determine constructive programs which effectively reduce animal use.
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.
"The use of human cells in biomedical research and testing." Combes R. 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, 43-49. ATLA 32, Supplement 1 & 2.
It is only comparatively recently that the safe and controlled acquisition of surgical waste and non-transplantable human tissues has become feasible with the establishment of several human tissue banks. Recently, the formation of a UK and European centralised network for human tissue supply has been initiated. The problems of short longevity and loss of specialisation in culture are being approached.

Specific Topics in In Vitro Testing

 Eye irritation

"Using In Vitro prediction models instead of the rabbit eye irritation test to classify and label new chemicals: a post hoc data analysis of the international EC/HO validation study." Modlenhauer F. 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.

"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.

72.5% of the chemicals in the undivided sample were correctly classified when applying the in vitro endpoints lgNRU of the neutral red uptake test and IgBCoPo5 of the bovine opacity and permeability test. The accuracy increased to 80.9% when six in vitro features wre used, and the sample was subdivived. The subset of surfactants was correctly classified in more than 90% of cases, which is an excellent performance.
"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.


 "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.

 "In vitro methods for predicting human toxicity." Silber P, Ruegg CE and Myslinski N. 1994. Lab Animal 23(2), 33-37.

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

"Integrated In Vitro approaches for assessing systemic toxicity." Forsby A and Blaauboer B. 2003. In Alternative Toxicological Methods. Salem H and Katz S. 2003. CRC Press. Boca Raton.

 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 .

A brief but very clear introduction to in vitro prediction of target organ-specific toxicity using human tissues and cells.

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.

"It is necessary to find a strategy by which cellular toxic concentrations determined in vitro can be 'converted' to doses that are relevant for risk assessment. One approach is to integrate the in vitro data with computer-based biokinetic models.


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

"Update on the validation and regulatory acceptance of alternative tests for skin corrosion and irritation" Fentem JH and Botham PA. 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, 683-688. ATLA 32, Supplement 1 & 2.

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

Discussion of validation issues. Includes tables giving an overview and summary of the validation and regulatory acceptance of in vitro methods for skin corrosion and irritation.

"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.

Note: *Web sites and databases are updated regularly.

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Recognition and Alleviation of Pain

Refinement of Handling and Housing Conditions (Enrichment)

Species-Specific Requirements for Enrichment




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* Newest entries