GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS
NATIONAL RESEARCH COUNCIL
OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
THE NATIONAL ACADEMIES PRESS
500 Fifth Street, NW
Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the Committee responsible for the report were chosen for their special competences and with regard for appropriate balance.
This study was supported by the Office of Extramural Research, Office of the Director, National Institutes of Health/Department of Health and Human Services under Contract Number N01-OD-4-2139 Task Order #188; the Office of Research Integrity, Department of Health and Human Services; the Animal and Plant Health Inspection Service, U.S. Department of Agriculture; Association for Assessment and Accreditation of Laboratory Animal Care International; American Association for Laboratory Animal Science; Abbott Fund; Pfizer; American College of Laboratory Animal Medicine; American Society of Laboratory Animal Practitioners; Association of Primate Veternarians.
Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the organizations or agencies that provided support for the project. The content of this publication does not necessarily reflect the views or policies of the National Institutes of Health, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.
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THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering, and Medicine
The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles Vest is president of the National Academy of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.
COMMITTEE FOR THE UPDATE OF THE GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS
Janet C. Garber (Chair),
R. Wayne Barbee,
Virginia Commonwealth University
Joseph T. Bielitzki,
University of Central Florida
Leigh Ann Clayton,
National Aquarium, Baltimore
John C. Donovan,
Coenraad F. M. Hendriksen,
Netherlands Vaccine Institute, Bilthoven, The Netherlands (until March 2009)
Dennis F. Kohn,
Columbia University (retired)
Neil S. Lipman,
Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College
Paul A. Locke,
Johns Hopkins Bloomberg School of Public Health
U.S. Senate (retired)
Fred W. Quimby,
Rockefeller University (retired)
Patricia V. Turner,
University of Guelph, Canada
Geoffrey A. Wood,
University of Guelph, Canada
Justus Liebig University of Giessen, Germany
Lida Anestidou, Study Director
Frances Sharples, Acting Director
Kathleen Beil, Administrative Coordinator
Cameron H. Fletcher, Senior Editor
Ruth Crossgrove, Senior Editor
Radiah Rose, Manager of Editorial Projects
Rhonda Haycraft, Senior Project Assistant
Joanne Zurlo, Director (until April 2010)
INSTITUTE FOR LABORATORY ANIMAL RESEARCH COUNCIL
Stephen W. Barthold (Chair),
Center for Comparative Medicine, University of California-Davis
Kathryn A. Bayne,
Association for Assessment and Accreditation of Laboratory Animal Care International, Frederick, Maryland
Myrtle A. Davis,
National Cancer Institute, National Institutes of Health, Bethesda, Maryland
Jeffrey I. Everitt,
Comparative Medicine and Investigator Support, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina (until June 2010)
James G. Fox,
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge
Nelson L. Garnett,
Laboratory Animal Care and Use Programs, Dickerson, MD
Estelle B. Gauda,
Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, Maryland (until June 2010)
Joseph W. Kemnitz,
Institute for Clinical and Translational Research and Department of Physiology, University of Wisconsin-Madison
Judy A. MacArthur Clark,
Animals in Scientific Procedures Inspectorate, Home Office, London, United Kingdom
Martha K. McClintock,
Institute for Mind and Biology, University of Chicago, Illinois
Leticia V. Medina,
Animal Welfare and Compliance, Abbott Laboratories, Abbott Park, Illinois
Timo Olavi Nevalainen,
National Laboratory Animal Center, University of Eastern Finland, Kuopio, Finland
Bernard E. Rollin,
Department of Animal Sciences, Colorado State University, Fort Collins
Abigail L. Smith,
School of Veterinary Medicine, University of Pennsylvania, Philadelphia (until June 2010)
Stephen A. Smith,
Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg
James E. Womack,
Department of Veterinary Pathology, Texas A&M University, College Station (until June 2010)
INSTITUTE FOR LABORATORY ANIMAL RESEARCH PUBLICATIONS
Recognition and Alleviation of Pain in Laboratory Animals (2009)
Scientific and Humane Issues in the Use of Random Source Dogs and Cats for Research (2009)
Recognition and Alleviation of Distress in Laboratory Animals (2008)
Toxicity Testing in the 21st Century: A Vision and a Strategy (2007)
Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models (2006)
Guidelines for the Humane Transportation of Research Animals (2006)
Science, Medicine, and Animals: Teacher’s Guide (2005)
Animal Care and Management at the National Zoo: Final Report (2005) Science, Medicine, and Animals (2004)
The Development of Science-based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop (2004)
Animal Care and Management at the National Zoo: Interim Report (2004)
National Need and Priorities for Veterinarians in Biomedical Research (2004)
Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research (2003)
International Perspectives: The Future of Nonhuman Primate Resources, Proceedings of the Workshop Held April 17-19, 2002 (2003)
Occupational Health and Safety in the Care and Use of Nonhuman Primates (2003)
Definition of Pain and Distress and Reporting Requirements for Laboratory Animals: Proceedings of the Workshop Held June 22, 2000 (2000)
Strategies That Influence Cost Containment in Animal Research Facilities (2000)
Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference (2000)
Microbial and Phenotypic Definition of Rats and Mice: Proceedings of the 1998 US/Japan Conference (1999)
Monoclonal Antibody Production (1999)
The Psychological Well-Being of Nonhuman Primates (1998)
Biomedical Models and Resources: Current Needs and Future Opportunities (1998)
Approaches to Cost Recovery for Animal Research: Implications for Science, Animals, Research Competitiveness and Regulatory Compliance (1998)
Chimpanzees in Research: Strategies for Their Ethical Care, Management, and Use (1997)
Occupational Health and Safety in the Care and Use of Research Animals (1997)
Guide for the Care and Use of Laboratory Animals (1996)
Nutrient Requirements of Laboratory Animals, Fourth Revised Edition (1995)
Laboratory Animal Management: Dogs (1994)
Recognition and Alleviation of Pain and Distress in Laboratory Animals (1992)
Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs (1991)
Companion Guide to Infectious Diseases of Mice and Rats (1991)
Infectious Diseases of Mice and Rats (1991)
Immunodeficient Rodents: A Guide to Their Immunobiology, Husbandry, and Use (1989)
Use of Laboratory Animals in Biomedical and Behavioral Research (1988)
Animals for Research: A Directory of Sources, Tenth Edition and Supplement (1979)
Amphibians: Guidelines for the Breeding, Care and Management of Laboratory Animals (1974)
Copies of these reports may be ordered from the National Academies Press
(800) 624-6242 or (202) 334-3313
This eighth edition of the Guide for the Care and Use of Laboratory Animals has been reviewed in draft form by individuals chosen for their diverse perspectives and expertise, in accordance with procedures approved by the Report Review Committee of the National Research Council. The purpose of this independent review is to provide candid and critical comments that will assist the Committee in making its published report as sound as possible, and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberation process. The Committee thanks the following individuals for their review of the draft report:
Michael B. Ballinger, Amgen
Philippe J.R. Baneux, PreLabs
Stephen W. Barthold, University of California-Davis
Linda C. Cork, Stanford University
Jann Hau, University of Copenhagen, Denmark
Michael J. Huerkamp, Emory University
Michael D. Kastello, sanofi-aventis
Arthur L. Lage, Harvard Medical School
Christian Lawrence, Children’s Hospital Boston
Randall J. Nelson, University of Tennessee College of Medicine-Memphis
Steven M. Niemi, Massachusetts General Hospital
Melinda A. Novak, University of Massachusetts-Amherst
Gemma Perretta, National Research Council, Italy
Marky E. Pitts, IACUC Consultant
George E. Sanders, University of Washington
Allen W. Singer, Battelle Memorial Institute
William J. White, Charles River Laboratories
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by John Dowling, Harvard University, and John Vandenbergh, North Carolina State University. Appointed by the National Research Council, they were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.
The purpose of the Guide for the Care and Use of Laboratory Animals (the Guide), as expressed in the charge to the Committee for the Update of the Guide, is to assist institutions in caring for and using animals in ways judged to be scientifically, technically, and humanely appropriate. The Guide is also intended to assist investigators in fulfilling their obligation to plan and conduct animal experiments in accord with the highest scientific, humane, and ethical principles. Recommendations in the Guide are based on published data, scientific principles, expert opinion, and experience with methods and practices that have proved to be consistent with both high-quality research and humane animal care and use. These recommendations should be used as a foundation for the development of a comprehensive animal care and use program, recognizing that the concept and application of performance standards, in accordance with goals, outcomes, and considerations defined in the Guide, is essential to this process.
The Guide is an internationally accepted primary reference on animal care and use, and its use is required in the United States by the Public Health Service Policy. It was first published in 1963, under the title Guide for Laboratory Animal Facilities and Care, and was revised in 1965, 1968, 1972, 1978, 1985, and 1996. More than 550,000 copies have been printed since its first publication.
In 2006 an ad hoc committee appointed by the Institute for Laboratory Animal Research recommended that the Guide be updated. The Committee for the Update of the Guide for the Care and Use of Laboratory Animals was appointed in 2008 by the National Research Council; its 13 members
included research scientists, veterinarians, and nonscientists representing biomedical ethics and the public’s interest in animal welfare. The Committee widely solicited written and oral comments on the update of the Guide from the scientific community and the general public; comments at open meetings (on September 26, 2008, in Washington, DC; October 16, 2008, in Irvine, California; and November 14, 2008, in Chicago) as well as written comments submitted to or requested by the Committee were considered. In addition, the Committee studied the materials submitted to NIH in response to its 2005 Request for Information (NOT-OD-06-011). All comments contributed substantially to this eighth edition of the Guide.
In approaching its task, the Committee carried forward the balance between ethical and science-based practice that has always been the basis of the Guide, and fulfilled its role to provide an updated resource that enables the research community to proceed responsibly and in a self-regulatory manner with animal experimentation. The Guide is predicated on the understanding that the exercise of professional judgment both upholds the central notion of performance standards and obviates the need for more stringent regulations.
Laboratory animal science is a rapidly evolving field and the Committee identified a number of areas in which current available scientific information is insufficient; additional objective information and assessment are needed to provide a scientific basis for recommendations in future editions of the Guide. Although pursuing these concepts was beyond this Committee’s charge, the following two topics merit further study: (1) space and housing needs of laboratory species and (2) the need and best methods for providing enrichment, exercise, and human contact.
The need for continual updating of the Guide is implicit in its objective “to provide information that will enhance animal well-being, the quality of research, and the advancement of scientific knowledge that is relevant to both humans and animals” (Chapter 1). The irregular and increasing intervals between updates, reaching a 14-year gap between the seventh edition and this eighth edition, mean that important new research findings might wait more than a decade before being reflected in recommended practice. Addressing this concern was beyond the charge of this Committee; we noted, however, that regular and more frequent updates of the information in the Guide will promote laboratory animal welfare and support high-quality scientific data. A formal process for revising the information in the Guide, including the updating of practice standards, could meet this need.
In undertaking this update, the Committee acknowledged the contributions of William I. Gay and Bennett J. Cohen in the development of the original Guide. In 1959, Animal Care Panel (ACP) President Cohen appointed the Committee on Ethical Considerations in the Care of Laboratory Animals to evaluate animal care and use. That Committee was chaired by Dr. Gay,
who soon recognized that the Committee could not evaluate animal care programs objectively without appropriate criteria on which to base its evaluations—that is, standards were needed. The ACP Executive Committee agreed, and the Professional Standards Committee was appointed. NIH later awarded the ACP a contract to “determine and establish a professional standard for laboratory animal care and facilities.” Dr. Cohen chaired the ACP Animal Facilities Standards Committee, which prepared the first Guide for Laboratory Animal Facilities and Care.
This edition of the Guide was financially supported by the National Institutes of Health; the Office of Research Integrity, Department of Health and Human Services; the US Department of Agriculture (USDA); the Association for Assessment and Accreditation of Laboratory Animal Care International; the American Association for Laboratory Animal Science; Abbott Fund; Pfizer, Inc.; the American College of Laboratory Animal Medicine; the American Society of Laboratory Animal Practitioners; and the Association of Primate Veterinarians.
The Committee for the Update of the Guide for the Care and Use of Laboratory Animals expresses its appreciation to the Animal Welfare Information Center, National Agricultural Library, USDA, for its assistance in compiling bibliographies and references. This task would have been formidable without the help of the Center’s staff. Appreciation is also extended to the reviewers of this volume, to Rhonda Haycraft for providing exemplary administrative and logistical assistance, and especially to Lida Anestidou, Study Director, who, through extraordinary patience, persistence, and scientific insight, managed the process from beginning to end.
Readers who detect errors of omission or commission are invited to send corrections and suggestions to the Institute for Laboratory Animal Research, National Research Council, 500 Fifth Street NW, Washington, DC 20001.
Janet C. Garber, Chair
Committee for the Update of the Guide for the Care and Use of Laboratory Animals
This eighth edition of the Guide is divided into five chapters and four appendices.
Chapter 1 presents the goals and intended audiences of the Guide as well as key concepts and terminology essential to its premise and use. Incorporating some of the material from the Introduction to the last edition, the chapter highlights a commitment to the concepts of the Three Rs—Replacement, Reduction, and Refinement—and provides an enhanced discussion of the ethics of animal use and investigator/institutional obligations.
Chapter 2 focuses on the overall institutional animal care and use program (Program), in addition to many of the topics previously covered in Chapter 1 of the seventh edition. It defines the evolved concept of Program and provides a framework for its intra-institutional integration, taking into account institutional policies and responsibilities, regulatory considerations, Program and personnel management (including training and occupational health and safety), and Program oversight. Discussions of the latter include institutional animal care and use committee (IACUC) functions, protocol and Program review, postapproval monitoring (a new section), and considerations such as humane endpoints and multiple survival surgical procedures. The Committee endorses the American College of Laboratory Animal Medicine’s “Guidelines for Adequate Veterinary Care.”
Chapter 3 focuses on the animals themselves and, unlike previous editions, addresses terrestrial and aquatic species in separate sections, reflect-
ing the growing role of aquatic animals in biomedical research. The chapter provides recommendations for housing and environment, discusses the importance of social housing, and includes enhanced sections on environmental enrichment, animal well-being, and scientific validity.
Space recommendations were nominally expanded based on the Committee’s professional and expert opinion and on current housing methods. Cage sizes have historically been interpreted as minimum space needs by users of the Guide, and were labeled as such (“recommended minimum space”) in this edition. The use of the word “minimum” does not further restrict users of the Guide because, although the space requirements are numbers (i.e., engineering standards), they are used in a performance standards framework. The Committee recommends minimum space for female rodents with litter and an increase of the cage height for rabbits to 16”. Further, in light of many comments submitted to the Committee requesting more information on performance goals and how to achieve them, rodent breeding recommendations are accompanied by substantial guidance.
With respect to nonhuman primates (NHPs), the Committee endorses social housing as the default and has provided some species-specific guidance. An additional group has been added for monkeys, and chimpanzees are separated in a new category. These changes were motivated by the Committee’s recognition (affirmed in comments solicited from NHP experts) that these animals need more floor and vertical space, at least in some groups, to exercise their natural habits.
Chapter 4 discusses veterinary care and the responsibilities of the attending veterinarian. It introduces the concept of animal biosecurity and upholds its central role in ensuring the health of laboratory animals. The chapter includes recommendations relative to animal procurement, transportation, and preventive medicine, and expands the sections on clinical care and management, surgery (with a new section on intraoperative monitoring), pain and distress, and euthanasia.
Chapter 5 discusses physical plant–related topics and includes updated and new material on vibration control; physical security and access control; hazardous agent containment; and special facilities for imaging and whole body irradiation, barrier housing, behavioral studies, and aquatic species housing. The chapter provides detailed discussion of centralized versus decentralized animal facilities and introduces the concept of variable-volume HVAC systems with a nod toward energy conservation and efficiency.
Appendix A is the updated bibliography; Appendix B presents the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training; Appendix C presents the Statement
of Task; and Appendix D provides the biographical sketches of the Committee members.
In accordance with the Statement of Task (“In addition to the published report, the updated Guide will be posted on the Internet in a pdf or equivalent format such that users will be able to search the entire document at one time”), the Guide is available in searchable pdf format on the National Academies Press website, www.nap.edu.
Species-Specific References—Environment, Housing, and Management,
B U.S. GOVERNMENT PRINCIPLES FOR THE UTILIZATION AND CARE OF VERTEBRATE ANIMALS USED IN TESTING, RESEARCH, AND TRAINING