by E Edition · 2011 · Cited by 13215 — report, the updated Guide will be posted on the Internet in a pdf or equiva- a clear and concise sequential description of the procedures involv-.

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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 Govern -ing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineer -ing, 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 Of˜ce of Extramural Research, Of˜ce of the Direc -tor, National Institutes of Health/Department of Health and Human Services under Contract Number N01-OD-4-2139 Task Order #188; the Of˜ce 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; P˜zer; American College of Laboratory Animal Medicine; Ameri -can Society of Laboratory Animal Practitioners; Association of Primate Veternarians. Any opinions, ˜ndings, conclusions, or recommendations expressed in this pub -lication are those of the authors and do not necessarily re˚ect the views of the organizations or agencies that provided support for the project. The content of this publication does not necessarily re˚ect 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. International Standard Book Number-13: 978-0-309-15400-0 (Book) International Standard Book Number-10: 0-309-15400-6 (Book) International Standard Book Number-13: 978-0-309-15401-7 (PDF) International Standard Book Number-10: 0-309-15401-4 (PDF) Library of Congress Control Number: 2010940400 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, NW, Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Copyright 2011 by the National Academy of Sciences. All rights reserved. Printed in the United States of America.

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The National Academy of Sciences is a private, nonpro˜t, self-perpetuating society of distinguished scholars engaged in scienti˜c 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 Acad -emy has a mandate that requires it to advise the federal government on scienti˜c 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 engineer -ing 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 Insti -tute 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 Sci -ences 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 scienti˜c 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.

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vCOMMITTEE FOR THE UPDATE OF THE GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS Members Janet C. Garber (Chair ), Garber Consulting R. Wayne Barbee , Virginia Commonwealth University Joseph T. Bielitzki , University of Central Florida Leigh Ann Clayton , National Aquarium, Baltimore John C. Donovan , BioResources, Inc. 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 WeillWeill Cornell Medical College Paul A. Locke , Johns Hopkins Bloomberg School of Public Health John Melcher , U.S. Senate (retired) Fred W. Quimby , Rockefeller University (retired) Patricia V. Turner , University of Guelph, Canada Geoffrey A. Wood , UniversityofGuelph,Canada University of Guelph, Canada Hanno Würbel , Justus Liebig University of Giessen, Germany Staff Lida Anestidou , Study Director Frances Sharples , Acting Director Kathleen Beil ,AdministrativeCoordinator AdministrativeCoordinator Administrative Coordinator Cameron H. Fletcher , Senior Editor Ruth Crossgrove , Senior Editor Radiah Rose , Manager of Editorial Projects Rhonda Haycraft ,SeniorProjectAssistant SeniorProjectAssistant Senior Project Assistant Joanne Zurlo , Director (until April 2010)

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vi INSTITUTE FOR LABORATORY ANIMAL RESEARCH COUNCIL Members 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 Scienti˜c Procedures Inspectorate, Home Of˜ce, 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)

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viii INSTITUTE FOR LABORATORY ANIMAL RESEARCH PUBLICATIONS Recognition and Alleviation of Pain in Laboratory Animals (2009) Scienti˜c 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) De˜nition of Pain and Distress and Reporting Requirements for Laboratory Animals: Proceedings of the Workshop Held June 22, 2000 (2000) Strategies That In˚uence 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 De˜nition 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)

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ix Occupational Health and Safety in the Care and Use of Research Animals (1997) Guide for the Care and Use of Laboratory Animals (1996) Rodents (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) Immunode˜cient 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

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xi Reviewers 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 proce -dures 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 con˜dential to protect the integrity of the deliberation process. The Committee thanks the follow -ing 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, sano˜-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

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