Guide for the Care and Use of Laboratory Animals

Institute of Laboratory Animal Resources

Commission on Life Sciences

National Research Council

National Academy Press
Washington, D.C.
1996



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Guide for the Care and Use of Laboratory Animals Institute of Laboratory Animal Resources Commission on Life Sciences National Research Council National Academy Press Washington, D.C. 1996

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NATIONAL ACADEMY PRESS 2101 Constitution Avenue, NW Washington, DC 20418 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, National Academy of Engineering, and 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 report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, National Academy of Engineering, and Institute of Medicine. This study was supported by the Comparative Medicine Program, National Center for Research Resources the Interagency Research Animal Committee, and the Office for Protection from Research Risks, National Institutes of Health/Department of Health and Human Services; the U.S. Department of Agriculture; and the Department of Veterans Affairs. The grant was awarded by the Comparative Medicine Program, National Center for Research Resources, and all agency funding was provided under grant NIH RR08779-02. Core support is provided to the Institute of Laboratory Animal Resources by the Comparative Medicine Program, National Center for Research Resources, National Institutes of Health, through grant number 5P40RR0137; the National Science Foundation through grant number BIR-9024967; the U.S. Army Medical Research and Development Command, which serves as the lead agency for combined U.S. Department of Defense funding also received from the Human Systems Division of the U.S. Air Force Systems Command, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, and U.S. Naval Medical Research and Development Command, through grant number DAMD17-93-J-3016; and by Research Project Grant #RC-1-34 from the American Cancer Society. Any opinions, findings, and conclusions or recommendations expressed in this publication do not necessarily reflect the views of DHHS or other sponsors, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. government or other sponsors. International Standard Book Number 0-309-05377-3 Copyright 1996 by the National Academy of Sciences. All rights reserved. Printed in the United States of America First Printing, July 1996 Second Printing, October 1996 Third Printing, November 1997

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Note The Guide for the Care and Use of Laboratory Animals was released to the sponsors and the public on January 2, 1996, in a prepublication form. After that, the Institute of Laboratory Animal Resources (ILAR) received comments from users and members of the Committee to Revise the Guide. The Guide has always been characterized as a living document, subject to modification with changing conditions and new information. That characterization results in a continuing emphasis on performance goals as opposed to engineering approaches. The use of performance goals places increasing responsibility on the user and results in greater enhancement of animal well-being; but performance goals require careful interpretation, whereas engineering goals leave no room for interpretation. With that difference in mind, the National Research Council and the appointed reviewers strove for accuracy and clarity. However, some errors and ambiguities were identified by readers of the prepublication copy. Some pointed out pagination, spelling, and reference errors. Others noted that some statements were being misinterpreted. After careful consideration, some changes have been made in this edition. For example, punctuation and spelling were corrected, and wording was changed to clarify meaning. An example of changes for clarification is replacement of the word "develop" with "review and approve" in descriptions of animal care and use committee (IACUC) oversight of housing plans, sanitation, and bedding selection; these are responsibilities of animal care personnel, not of the IACUC, as the word ''develop" might have implied. The discussion of monitoring of food and fluid restriction in small animals was clarified by addition of the phrase "such as rodents." Appendix B (Selected Organizations Related to Laboratory Animal Science) of the review copy that was sent to reviewers requested advice from reviewers regarding what organizations should be listed; some were added in the prepublication copy and others later. A footnote added to page 2 and referred to in three places reminds readers that the Guide is written for a broad international audience some of whom are not covered by either the Public Health Service Policy on Humane Care and Use of Laboratory Animals or the Animal Welfare Regulations but that those who are covered by these rules must abide by them even when the Guide recommends a different approach. That admonition is provided throughout the Guide, but its placement in the introduction was thought important. ILAR believes that each of these changes will help users to interpret and apply the recommendations as intended. There was no substantial change in the content of the prepublication version.

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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. Bruce Alberts 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. Harold Liebowitz 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. Kenneth I. Shine is president of the Institute of Medicine. The National Research Council was established 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 National Academy of Engineering in the conduct of their 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. Brnce Alberts and Dr. Harold Liebowitz are chairman and vice-chairman, respectively, of the National Research Council.

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COMMITTEE TO REVISE THE GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS J. Derrell Clark (Chairman), University of Georgia, College of Veterinary Medicine, Athens, Georgia Ransom L. Baldwin, University of California, Davis, California Kathryn A. Bayne, American Association for Accreditation of Laboratory Animal Care, Rockville, Maryland Marilyn J. Brown, Dartmouth College, Lebanon, New Hampshire G. F. Gebhart, University of Iowa, College of Medicine, Iowa City, Iowa Janet C. Gonder, Baxter Healthcare Corporation, Round Lake, Illinois Judith K. Gwathmey, Harvard Medical School, Boston, Massachusetts Michale E. Keeling, University of Texas M.D. Anderson Cancer Center, Bastrop, Texas Dennis F. Kohn, Columbia University, College of Physicians & Surgeons, New York, New York J. Wesley Robb, Professor Emeritus, University of Southern California, Los Angeles, California Orville A. Smith, University of Washington, Seattle, Washington Jo Ann D. Steggerda, Champaign, Illinois John G. Vandenbergh, North Carolina State University, Raleigh, North Carolina William J. White, Charles River Laboratories, Wilmington, Massachusetts Sarah Williams-Blangero, Southwest Foundation for Biomedical Research, San Antonio, Texas John L. VandeBerg, Southwest Foundation for Biomedical Research, San Antonio, Texas (ex officio member) Staff Thomas L. Wolfie, Program Director Carol M. Rozmiarek, Project Assistant Norman Grossblatt, Editor

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INSTITUTE OF LABORATORY ANIMAL RESOURCES COUNCIL John L. VandeBerg (Chairman), Southwest Foundation for Biomedical Research, San Antonio, Texas Christian R. Abee, University of South Alabama, Mobile, Alabama J. Derrell Clark, University of Georgia, College of Veterinary Medicine, Athens, Georgia Muriel T. Davisson, The Jackson Laboratory, Bar Harbor, Maine Bennett Dyke, Southwest Foundation for Biomedical Research, San Antonio, Texas Neal L. First, University of Wisconsin, Madison, Wisconsin James W. Glosser, Massillon, Ohio John P. Hearn, Wisconsin Regional Primate Research Center, Madison Margaret S. Landi, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania Gail Martin, University of California, San Francisco, California Charles R. McCarthy, Kennedy Institute of Ethics, Georgetown University, Washington, D.C. Robert J. Russell, Harlan Sprague Dawley, Frederick, Maryland Richard C. Van Sluyters, University of California, Berkeley, California John G. Vandenbergh, North Carolina State University, Raleigh, North Carolina Peter A. Ward, University of Michigan Medical School, Ann Arbor, Michigan Thomas D. Pollard, The Johns Hopkins University School of Medicine, Baltimore, Maryland (ex officio member) Staff Eric A. Fischer, Director Thomas L. Wolfie, Program Director Mara L. Glenshaw, Research Assistant Carol M. Rozmiarek, Project Assistant The Institute of Laboratory Animal Resources (ILAR) was founded in 1952 under the auspices of the National Research Council. A component of the Commission on Life Sciences, ILAR develops guidelines and disseminates information on the scientific, technological, and ethical use of animals and related biological resources in research, testing, and education. ILAR promotes high-quality, humane care of animals and the appropriate use of animals and alternatives. ILAR functions within the mission of the National Academy of Sciences as an advisor to the federal government, the biomedical research community, and the public.

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COMMISSION ON LIFE SCIENCES Thomas D. Pollard (Chairman), The Johns Hopkins University School of Medicine, Baltimore, Maryland Frederick R. Anderson, Cadwalader, Wickersham & Taft, Washington, D.C. John C. Bailar, III, McGill University, Montreal, Canada John E. Burris, Marine Biological Laboratory, Woods Hole, Massachusetts Michael T. Clegg, University of California, Riverside, California Glenn A. Crosby, Washington State University, Pullman, Washington Ursula W. Goodenough, Washington University, St. Louis, Missouri Susan E. Leeman, Boston University School of Medicine, Boston, Massachusetts Richard E. Lenski, Michigan State University, East Lansing, Michigan Thomas E. Lovejoy, Smithsonian Institution, Washington, D.C. Donald R. Mattison, University of Pittsburgh, Pittsburgh, Pennsylvania Joseph E. Murray, Wellesley Hills, Massachusetts Edward E. Penhoet, Chiron Corporation, Emeryville, California Emil A. Pfitzer, Research Institute for Fragrance Materials, Inc., Hackensack, New Jersey Malcolm C. Pike, University of Southern California School of Medicine, Los Angeles, California Henry C. Pitot, III, McArdle Laboratory for Cancer Research, Madison, Wisconsin Jonathan M. Samet, The Johns Hopkins University, Baltimore, Maryland Harold M. Schmeck, Jr., North Chatham, Massachusetts Carla J. Shatz, University of California, Berkeley, California John L. VandeBerg, Southwest Foundation for Biomedical Research, San Antonio, Texas Staff Paul Gilman, Executive Director

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Preface The Guide for the Care and Use of Laboratory Animals (the Guide) was first published in 1963 under the title Guide for Laboratory Animal Facilities and Care and was revised in 1965, 1968, 1972, 1978, and 1985. More than 400,000 copies have been distributed since it was first published, and it is widely accepted as a primary reference on animal care and use. The changes and new material in this seventh edition are in keeping with the belief that the Guide is subject to modification with changing conditions and new information. The purpose of the Guide, as expressed in the charge to the Committee to Revise the Guide for the Care and Use of Laboratory Animals, 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. The recommendations are based on published data, scientific principles, expert opinion, and experience with methods and practices that have proved to be consistent with high-quality, humane animal care and use. Previous editions of the Guide were supported solely by the National Institutes of Health (NIH) and published by the Government Printing Office. As an indication of its wide use, this edition was financially supported by NIH, the Department of Agriculture, and the Department of Veterans Affairs and was published by the National Academy Press. The Guide is organized into four chapters on the major components of an animal care and use program: institutional policies and responsibilities; animal environment, housing, and management; veterinary medical care; and physical

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plant. Responsibilities of institutional officials, institutional animal care and use committees, investigators, and veterinarians are discussed in each chapter. In 1991, an ad hoc committee appointed by the Institute of Laboratory Animal Resources (ILAR) recommended that the Guide be revised. The Committee to Revise the Guide for the Care and Use of Laboratory Animals was appointed in 1993 by the National Research Council; its 15 members included research scientists, veterinarians, and nonscientists representing bioethics and the public's interest in animal welfare. Before revision began, written and oral comments on the Guide were solicited widely from the scientific community and the general public. Open meetings were held in Washington, D.C., on December 1, 1993; in San Francisco, California, on February 2, 1994; and in St. Louis, Missouri, on February 4, 1994. Comments made at those meetings and written comments were considered by the committee and contributed substantially to this revision of the Guide. The committee acknowledges 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. The Committee to Revise the Guide for the Care and Use of Laboratory Animals expresses its appreciation to the Animal Welfare Information Center, National Agricultural Library, U.S. Department of Agriculture, for its assistance in compiling bibliographies and references. This task would have been quite formidable without their help. Appreciation is also extended to the reviewers of the volume, to Norman Grossblatt for editing the manuscript, to Carol Rozmiarek for providing exemplary secretarial assistance and preparing multiple drafts, and to Thomas L. Wolfle, who 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 of Laboratory Animal Resources, National Research Council, 2101 Constitution Avenue, NW, Washington, DC 20418. DERRELL CLARK, Chairman Committee to Revise the Guide for the Care and Use of Laboratory Animals

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Contents     Introduction   1     Regulations, Policies, and Principles   2     Evaluation Criteria   3     Farm Animals   4     Nontraditional Species   5     Field Investigations   5     Overview   5     References   6 1   Institutional Policies and Responsibilities   8     Monitoring the Care and Use of Animals   9     Veterinary Care   12     Personnel Qualifications and Training   13     Occupational Health and Safety of Personnel   14     References   18 2   Animal Environment, Housing, and Management   21     Physical Environment   22     Behavioral Management   36     Husbandry   38     Population Management   46     References   48

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3   Veterinary Medical Care   56     Animal Procurement and Transportation   57     Preventive Medicine   57     Surgery   60     Pain, Analgesia, and Anesthesia   64     Euthanasia   65     References   66 4   Physical Plant   71     Functional Areas   72     Construction Guidelines   73     Facilities for Aseptic Surgery   78     References   79 Appendix A:   Selected Bibliography   81 Appendix B:   Selected Organizations Related to Laboratory Animal Science   102 Appendix C:   Some Federal Laws Relevant to Animal Care and Use   114 Appendix D:   Public Health Service Policy and Government Principles Regarding the Care and Use of Animals   116     Index   119