Guide for the care and use of laboratory animals

GUIDE LABORATORYANIMALS FOR THE CARE AND USE OF Eighth Edition 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 Office of Extramural Research, Office 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 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; Ameri – can Society of Laboratory Animal Practitioners; Association of Primate Veternarians.Any opinions, findings, conclusions, or recommendations expressed in this pub – lication 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.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.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 Acad – emy 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.

Guide for the care and use of laboratory animals

1The 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 scientific and engineering communities.

2The 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  COMMITTEE FOR THE UPDATE OF THE GUIDE FOR THE CARE AND USE OF LAbORATORy ANIMALS i INSTITUTE FOR LAbORATORy ANIMAL RESEARCH COUNCIL ii Staff Frances Sharples, Acting Director Lida Anestidou, Senior Program Officer Kathleen beil , Administrative Coordinator Administrative Coordinator Administrative Coordinator Cameron H.Fletcher , Managing Editor, ILAR Journal Rhonda Haycraft, Program Associate Program AssociateProgram Associate Joanne Zurlo , Director (until April 2010) iii 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) 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) 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) 334-3313www. xi Reviewers T xii REVIEWERS xiii Preface T xi PREFACE PREFACE x xii Overview T xiii OVERVIEW OVERVIEW xix xxi Contents xxii CONTENTS CONTENTS xxiii xxi CONTENTS CONTENTS xx 1 1 Key Concepts T 2 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS KEy CONCEPTS 3 4 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS KEy CONCEPTS 5 6 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS Humane Care KEy CONCEPTS  8 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS MUST, SHOULD, AND MAy KEy CONCEPTS  NRC [National Research Council].1992.Report on Responsible Science.Washington: Na- tional Academy Press.Perry P.2007.The ethics of animal research: A UK perspective.ILAR J 48:42-46.PHS [Public Health Service].

42002.Public Health Service Policy on Humane Care and Use of Laboratory Animals.Publication of the Department of Health and Human Services, Na – tional Institutes of Health, Office of Laboratory Animal Welfare.Available at; accessed June 9, 2010.Russell WMS, Burch RL.1959.The Principles of Humane Experimental Technique.

5London: Methuen and Co.[Reissued: 1992, Universities Federation for Animal Welfare, Herts, UK].USDA [US Department of Agriculture].1985.9 CFR 1A.(Title 9, Chapter 1, Subchapter A): Animal Welfare.Available at 7adf2c9f1964e2d82a88d92andc=ecfrandtpl=/ecfrbrowse/Title09/9cfrv1_02.tpl; accessed January 14, 2010.

611 2 Animal Care and Use Program T 12 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS REGULATIONS, POLICIES, AND PRINCIPLES ANIMAL CARE ANd USE PROGRAM 13 14 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS ANIMAL CARE ANd USE PROGRAM 15 16 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS animal science and medicine are rapidly changing and evolving disciplines.The institution should provide opportunities and support for regular profes- sional development and continuing education to ensure both that profes – sional staff are knowledgeable about the latest practices and procedures and that laboratory animals receive high-quality care (Colby et al.2007).Animal Care Personnel Personnel caring for animals should be appropri – ately trained (see Appendix A, Education), and the institution should provide for formal and/or on-the-job training to facilitate effective implementation of the Program and the humane care and use of animals.Staff should receive training and/or have the experience to complete the tasks for which they are responsible.According to the Program scope, personnel with expertise in various disciplines (e.g., animal husbandry, administration, veterinary medical technology) may be required.ANIMAL CARE ANd USE PROGRAM 1 used (Conarello and Shepard 2007).Training should be tailored to the particular needs of research groups; however, all research groups should receive training in animal care and use legislation, IACUC function, eth- ics of animal use and the concepts of the Three Rs, methods for reporting concerns about animal use, occupational health and safety issues pertaining to animal use, animal handling, aseptic surgical technique, anesthesia and analgesia, euthanasia, and other subjects, as required by statute.

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7Continu – ing education programs should be offered to reinforce training and provide updates that reflect changes in technology, legislation, and other relevant areas.Frequency of training opportunities should ensure that all animal users have adequate training before beginning animal work.The IACUC It is the institution’s responsibility to ensure that IACUC mem – bers are provided with training opportunities to understand their work and role.Such training should include formal orientation to introduce new members to the institution’s Program; relevant legislation, regulations, guidelines, and policies; animal facilities and laboratories where animal use occurs; and the processes of animal protocol and program review (Greene et al.2007).Ongoing opportunities to enhance their understanding of ani – mal care and use in science should also be provided.For example, IACUC members may meet with animal care personnel and research teams; be provided access to relevant journals, materials, and web-based training; and be given opportunities to attend meetings or workshops.Occupational health and Safety of Personnel 18 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS ANIMAL CARE ANd USE PROGRAM 1 20 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS ANIMAL CARE ANd USE PROGRAM 21 22 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS as gloves, arm protectors, suitable face masks, face shields, and goggles (NRC 2003a).Hearing protection should be available in high-noise areas (OSHA 1998c).Personnel working in areas where they might be exposed to contaminated airborne particulate material or vapors should have suitable respiratory protection (Fechter 1995; McCullough 2000; OSHA 1998d), with respirator fit testing and training in the proper use and maintenance of the respirator (OSHA 1998d; Sargent and Gallo 2003).

8Medical Ealuation and Preentie Medicine for Personnel Development and implementation of a program of medical evaluation and preventive medicine should involve input from trained health professionals, such as occupational health physicians and nurses.Confidentiality and other medi – cal and legal factors must be considered in the context of appropriate fed – eral, state, and local regulations (e.g., PL 104-191).ANIMAL CARE ANd USE PROGRAM 23 24 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS ANIMAL CARE ANd USE PROGRAM 25 26 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS ANIMAL CARE ANd USE PROGRAM 2 Special Considerations for IACUC Reiew 28 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS ANIMAL CARE ANd USE PROGRAM 2 30 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS ANIMAL CARE ANd USE PROGRAM 31 least restriction necessary to achieve the scientific objective while maintain- ing animal well-being.32 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS Field Inestigations Investigations may involve the observation or use of nondomesticated vertebrate species under field conditions.Many field investigations require international, federal, state, and/or local permits, which may call for an evaluation of the scientific merit of the proposed study and a determination of the potential impact on the population or species to be studied.ANIMAL CARE ANd USE PROGRAM 33 disease studies, administrators, regulators, and IACUCs face a dilemma in deciding how to handle such studies (Stricklin et al.1990).Decisions on categorizing research uses of agricultural animals and defining standards for their care and use should be made by the IACUC based on both the researcher’s goals and concern for animal well-being.

9Regardless of the category of research, institutions are expected to provide oversight of all research animals and ensure that pain and distress are minimized.34 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS ANIMAL CARE ANd USE PROGRAM 35 DISASTER PLANNING AND EMERGENCy PREPAREDNESS 36 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS Boissy A, Manteuffel G, Jensen MB, Moe RO, Spruijt B, Keeling L, Winckler C, Forkman B, Dimitrov I, Langbein J, Bakken M, Veissier I, Aubert A.2007.Assesment of positive emo – tions in animals to improve their welfare.Physiol Behav 92:375-397.Brown RE, Stanford L, Schellinck HM.2000.Developing standardized behavioral tests for knockout and mutant mice.ILAR J 41:163-174.Bush RK.

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The science and pervasiveness of laboratory animal allergy.ILAR J 42:1-3.Wood RA.2001.Laboratory animal allergens.ILAR J 42:12-16.41 3 Environment, Housing, and Management T 42 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS ENVIRONMENT, hOUSING, ANd MANAGEMENT 43 Temperature and humidity 44 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS ENVIRONMENT, hOUSING, ANd MANAGEMENT 45 46 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS ENVIRONMENT, hOUSING, ANd MANAGEMENT 4 48 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS ENVIRONMENT, hOUSING, ANd MANAGEMENT 4 50 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS ENVIRONMENT, hOUSING, ANd MANAGEMENT 51 52 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS 1 1 ENVIRONMENT, hOUSING, ANd MANAGEMENT 53 exercise, manipulative activities, and cognitive challenges according to species-specific characteristics (NRC 1998a; Young 2003).Examples of enrichment include structural additions such as perches and visual barriers for nonhuman primates (Novak et al.2007); elevated shelves for cats (Overall and Dyer 2005; van den Bos and de Cock Buning 1994) and rabbits (Stauffacher 1992); and shelters for guinea pigs (Baumans 2005), as well as manipulable resources such as novel objects and foraging devices for nonhuman primates; manipulable toys for nonhuman primates, dogs, cats, and swine; wooden chew sticks for some rodent species;….

Guide for the care and use of laboratory animals

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