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REVIEWERSThis eighth edition of the Guide for the Care and Use of Laboratory Animalshas been reviewed in draft form by individuals chosen for their diverseperspectives and expertise, in accordance with procedures approved by theReport Review Committee of the National Research Council. The purpose of thisindependent review is to provide candid and critical comments that will assistthe Committee in making its published report as sound as possible, and toensure that the report meets institutional standards for objectivity, evidence, andresponsiveness to the study charge. The review comments and draft manuscriptremain confidential to protect the integrity of the deliberation process. TheCommittee thanks the following individuals for their review of the draft report:Michael B. Ballinger, AmgenPhilippe J. R. Baneux, Northwestern UniversityStephen W. Barthold, University of California, DavisLinda C. Cork, Stanford UniversityJann Hau, University of Copenhagen, DenmarkMichael J. Huerkamp, Emory UniversityMichael D. Kastello, sanofi-aventisArthur L. Lage, Harvard Medical SchoolChristian Lawrence, Children’s Hospital BostonRandall J. Nelson, University of Tennessee Health Science CenterSteven M. Niemi, Massachusetts General HospitalMelinda A. Novak, University of MassachusettsGemma Perretta, National Research Council, ItalyMarky E. Pitts, IACUC ConsultantGeorge E. Sanders, University of WashingtonAllen W. Singer, Battelle Memorial InstituteWilliam J. White, Charles River LaboratoriesAlthough the reviewers listed above have provided many constructivecomments and suggestions, they were not asked to endorse the conclusions orrecommendations 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 theNational Research Council, they were responsible for making certain that anindependent examination of this report was carried out in accordance withinstitutional procedures and that all review comments were carefully considered.xiPREPUBLICATION COPY

Responsibility for the final content of this report rests entirely with the authoringcommittee and the institution.PREPUBLICATION COPYxii

PREFACEThe Guide for the Care and Use of Laboratory Animals (the Guide) was first publishedin 1963 under the title Guide for Laboratory Animal Facilities and Care and wasrevised in 1965, 1968, 1972, 1978, 1985, and 1996. More than 550,000 copies havebeen printed since its first publication. The Guide is an internationally acceptedprimary reference on animal care and use. Use of the Guide is required by thePublic Health Service Policy.The purpose of the Guide, as expressed in the charge to the Committee toUpdate the Guide for the Care and Use of Laboratory Animals, is to assist institutionsin caring for and using animals in ways judged to be scientifically, technically,and humanely appropriate. The Guide is also intended to assist investigators infulfilling their obligation to plan and conduct animal experiments in accord withthe highest scientific, humane, and ethical principles. The recommendations arebased on published data, scientific principles, expert opinion, and experiencewith methods and practices that have proved to be consistent with high-qualityhumane animal care and use. These recommendations should be used as afoundation for the development of a comprehensive animal care and useprogram, recognizing that the concept and application of performance standards,in accordance with goals, outcomes and considerations defined in the Guide, isessential to this process.This Committee has carried forward the balance between ethical andscience-bassed practice that has always been the basis of the Guide. In doing so,the Committee has fulfilled its role to provide the research community with anupdated tool that allows it to responsibly carry on in a self-tregulatory mannerwith animal experimentation. Consequently, as professional judgment isexercised, the central notion of performance standards is upheld while the needfor more stringent regulations is obviated.The need for continual updating of the Guide is implicit in its objective“ to provide information that will enhance animal well-being, the quality ofresearch, and the advancement of scientific knowledge that is relevant to bothhumans and animals” (Chapter 1). The irregular and increasing intervalsbetween updates, reaching a 14-year gap between the seventh edition and thiseighth edition, means that important new research findings might wait morexiiiPREPUBLICATION COPY

than a decade before being reflected in recommended practice. Althoughaddressing this concern is beyond the charge of this Committee, we note thatregular and more frequent updates of the information in the Guide promotelaboratory animal welfare and support high quality scientific data. A formalprocess for revising the information in the Guide, including updating of practicestandards, could meet this need.Laboratory animal science is a rapidly evolving field and the Committeehas identified a number of areas in which current available scientific informationis insufficient; additional objective information and assessment is needed toprovide a scientific basis for recommendations in future editions of the Guide.Although pursuing these concepts is beyond this Committee’s charge, thefollowing two topics merit further study: space and housing needs of laboratoryspecies and the need and the best methods for providing enrichment, exerciseand human contact.This edition of the Guide was financially supported by the NationalInstitutes of Health; the Office of Research Integrity, Department of Health andHuman Services; the United States Department of Agriculture; the Associationfor Assessment and Accreditation of Laboratory Animal Care, International; theAmerican Association for Laboratory Animal Science; Abbott Fund; Pfizer, Inc;the American College of Laboratory Animal Medicine; the American Society ofLaboratory Animal Practitioners; and the Association of Primate Veterinarians,and was published by the National Academies Press.In 2006 an ad hoc committee appointed by the Institute for LaboratoryAnimal Research recommended that the Guide be updated. The Committee toUpdate the Guide for the Care and Use of Laboratory Animals was appointed in 2008by the National Research Council; its 13 members included research scientists,veterinarians, and nonscientists representing biomedical ethics and the public’sinterest in animal welfare.Written and oral comments on the Update of the Guide were widelysolicited from the scientific community and the general public. Open meetingswere held on September 26, 2008 in Washington, DC; on October 16, 2008 inIrvine, CA; and on November 14, 2008 in Chicago, IL. Comments made at thosemeetings as well as additional written comments submitted to or requested bythe Committee were considered. In addition, the Committee studied thematerials submitted to NIH in response to its 2005 Request for Information NOTOD-06-011. All comments contributed substantially to this eighth edition of theGuide.PREPUBLICATION COPYxiv

The Committee acknowledges the contributions of William I. Gay andBennett J. Cohen in the development of the original Guide. In 1959, Animal CarePanel (ACP) President Cohen appointed the Committee on EthicalConsiderations in the Care of Laboratory Animals to evaluate animal care anduse. That Committee was chaired by Dr. Gay, who soon recognized that theCommittee could not evaluate animal-care programs objectively withoutappropriate criteria on which to base its evaluations; that is, standards wereneeded. The ACP executive committee agreed, and the Professional StandardsCommittee was appointed. NIH later awarded the ACP a contract to “determineand establish a professional standard for laboratory animal care and facilities.”Dr. Cohen chaired the ACP Animal Facilities Standards Committee, whichprepared the first Guide for Laboratory Animal Facilities and Care.The Committee to Update the Guide for the Care and Use of LaboratoryAnimals expresses its appreciation to the Animal Welfare Information Center,National Agricultural Library, USDA, for its assistance in compilingbibliographies and references. This task would have been formidable withouttheir help. Appreciation is also extended to the reviewers of this volume, toCameron Fletcher for editing the manuscript, to Rhonda Haycraft for providingexemplary administrative and logistical assistance, and especially to LidaAnestidou, Study Director, who, through extraordinary patience, persistence andscientific insight, managed the process from beginning to end.Readers who detect errors of omission or commission are invited to sendcorrections and suggestions to the Institute for Laboratory Animal Research,National Research Council, 500 Fifth Street NW, Washington, DC 20001.Janet C. Garber, ChairCommittee to Update the Guide for the Care and Use of LaboratoryAnimalsxvPREPUBLICATION COPY

OVERVIEWThis eighth edition of the Guide is divided into five chapters and four appendices.Chapter 1 incorporates some of the material from the Introduction to the lastedition and presents key concepts and terminology essential to the premise andutilization of the Guide. The Chapter highlights a commitment to the concepts ofthe Three Rs (Replacement, Reduction and Refinement) and presents anenhanced discussion of the ethics of animal use and investigator/institutionalobligations. The goals and intended audiences of the Guide are also discussed.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. Itdefines the evolved concept of Program and provides a framework for its intrainstitutional integration, including a focus on institutional policies andresponsibilities; regulatory considerations; Program and personnel management(including training and occupational health and safety); and Program oversight.The latter includes institutional animal care and use committee (IACUC)functions; protocol and Program review, a new section on post-approvalmonitoring, and discussion of special considerations, such as humane endpointsand multiple survival surgical procedures. The American College of LaboratoryAnimal Medicine’s “Guidelines for Adequate Veterinary Care” are endorsed.Chapter 3 focuses on the animals themselves and unlike prior editions, addressesterrestrial and aquatic animals in separate sections reflecting the growing role ofaquatic animals in biomedical research. In this chapter, recommendations forhousing and environment and enhanced sections on environmental enrichment,animal well-being and scientific validity are presented. The importance of socialhousing is also emphasized.In this chapter, space recommendations were minimally expanded basedon the Committee’s professional and expert opinion and currently appliedhousing methods. The cage sizes have historically been interpreted as minimumspace needs by the users of the Guide, and were labeled as such (“recommendedminimum space”) in this edition. The use of the word “minimum” does notfurther restrict users of the Guide because although the space requirements arenumbers (i.e., engineering standards), they are utilized within a performancestandards framework. In light of many comments submitted to the Committeerequesting more information on performance goals and how to achieve them,xixPREPUBLICATION COPY

rodent breeding recommendations are accompanied by substantial guidance onimportant considerations, and recommended minimum space for female rodentswith litter has been added. Further, the cage height recommendation for rabbitsincreased to 16”.With respect to NHPs the Committee endorses social housing as thedefault and has provided some species-specific guidance. Additional NHPgroups have been added to include baboons, while the chimpanzees wereseparated in a new category. These changes were motivated by the Committee’srecognition (affirmed by the solicited comments from NHP experts) that theseanimals need more vertical space, at least in some groups, to exercise theirnatural habits.Chapter 4 discusses veterinary care and the responsibilities of the attendingveterinarian. It introduces the concept of animal biosecurity to affirm its centralrole in assuring the health of laboratory animals. It includes recommendationsrelative to animal procurement, transportation and preventive medicine, andexpands the sections on clinical care and management; surgery (introducesintraoperative monitoring); pain and distress; and euthanasia.Chapter 5 discusses physical plant-related topics and includes updated and newmaterial on such topics as vibration control; physical security and access control;hazardous agent containment; and special facilities for imaging and whole bodyirradiation, barrier housing, behavioral studies, and aquatic species housing.Detailed discussion of centralized vs. decentralized animal facilities is providedand the concept of variable-volume HVAC systems is introduced with a nodtoward energy conservation and efficiency.Appendix A is the updated bibliography; Appendix B contains the U.S.Government Principles for the Utilization and Care of Vertebrate Animals Usedin Testing, Research, and Training; Appendix C presents the Statement of Task;and Appendix D contains the biographical sketches of the Committee members.In accordance with the Statement of Task, “ .In addition to thepublished report, the updated Guide will be posted on the Internet in a pdf orequivalent format such that users will be able to search the entire document atone time”, the Guide may be found in searchable pdf format on the website of theNational Academies Press, http://www.nap.edu.PREPUBLICATION COPYxx

XICHAPTER 1. KEY CONCEPTS1APPLICABILITY AND GOALSINTENDED AUDIENCES AND USES OF THE GUIDEETHICS AND ANIMAL USETHE THREE RSKEY TERMS USED IN THE GUIDEHUMANE CAREANIMAL CARE AND USE PROGRAMENGINEERING AND PERFORMANCE STANDARDSPRACTICE STANDARDSPOLICIES, PRINCIPLES AND PROCEDURESMUST, SHOULD AND MAYCHAPTER 1 REFERENCESCHAPTER 2. ANIMAL CARE AND USE PROGRAMREGULATIONS, POLICIES, AND PRINCIPLESPROGRAM MANAGEMENTPROGRAM MANAGEMENT RESPONSIBILITYThe Institutional OfficialThe Attending VeterinarianThe Institutional Animal Care and Use CommitteeCollaborationsPERSONNEL MANAGEMENTTraining and EducationOccupational Health and Safety of PersonnelPersonnel SecurityInvestigating and Reporting Animal Welfare ConcernsPROGRAM OVERSIGHTTHE ROLE OF THE IACUCIACUC Constitution and FunctionProtocol ReviewSpecial Considerations for IACUC 5252728PREPUBLICATION COPY

POST-APPROVAL MONITORINGDISASTER PLANNING AND EMERGENCY PREPAREDNESSCHAPTER 2 REFERENCESCHAPTER 3. ENVIRONMENT, HOUSING, AND MANAGEMENTTERRESTRIAL ANIMALSTERRESTRIAL ENVIRONMENTMicroenvironment and MacroenvironmentTemperature and HumidityVentilation and Air QualityIlluminationNoise and VibrationTERRESTRIAL HOUSINGMicroenvironment (Primary Enclosure)Environmental EnrichmentSheltered or Outdoor HousingNaturalistic EnvironmentsSpaceTERRESTRIAL MANAGEMENTBehavioral and Social ManagementHusbandryPopulation ManagementAQUATIC ANIMALSAQUATIC ENVIRONMENTMicroenvironment and MacroenvironmentWater QualityLife Support SystemTemperature, Humidity and VentilationIlluminationNoise and VibrationAQUATIC HOUSINGMicroenvironment (Primary Enclosure)Environmental Enrichment and Social HousingSheltered, Outdoor, and Naturalistic HousingSpaceAQUATIC MANAGEMENTBehavior and Social ManagementHusbandryPopulation ManagementCHAPTER 3 REFERENCESCHAPTER 4. VETERINARY 86888888888989909090919495113ANIMAL PROCUREMENT AND TRANSPORTATIONANIMAL PROCUREMENTTRANSPORTATION OF ANIMALSPREVENTIVE MEDICINEPREPUBLICATION COPY353737xxii114114115117

ANIMAL BIOSECURITYQUARANTINE AND STABILIZATIONSEPARATION BY HEALTH STATUS AND SPECIESSURVEILLANCE, DIAGNOSIS, TREATMENT, AND CONTROL OF DISEASECLINICAL CARE AND MANAGEMENTMEDICAL MANAGEMENTEMERGENCY CARERECORDKEEPINGSURGERYTRAININGPRESURGICAL PLANNINGSURGICAL FACILITIESSURGICAL PROCEDURESASEPTIC TECHNIQUEINTRAOPERATIVE MONITORINGPOSTOPERATIVE CAREPAIN AND DISTRESSANESTHESIA AND ANALGESIAEUTHANASIACHAPTER 4 REFERENCESCHAPTER 5. PHYSICAL 128129130132133143LOCATIONCENTRALIZATION VERSUS DECENTRALIZATIONFUNCTIONAL AREASCONSTRUCTION GUIDELINESCORRIDORSANIMAL-ROOM DOORSEXTERIOR WINDOWSFLOORSDRAINAGEWALLS AND CEILINGSHEATING, VENTILATION AND AIR-CONDITIONING (HVAC)POWER AND LIGHTINGSTORAGE AREASNOISE CONTROLVIBRATION CONTROLFACILITIES FOR SANITIZING MATERIALSENVIRONMENTAL MONITORINGSPECIAL FACILITIESSURGERYBARRIER FACILITIESIMAGINGWHOLE BODY IRRADIATIONHAZARDOUS AGENT CONTAINMENTBEHAVIORAL 1152152153154154154156157158158159PREPUBLICATION COPY

AQUATIC SPECIES HOUSINGSECURITY AND ACCESS CONTROLCHAPTER 5 REFERENCES160161162APPENDIX A: ADDITIONAL SELECTED REFERENCESUSE OF LABORATORY ANIMALSALTERNATIVESETHICS AND WELFAREEXPERIMENTAL DESIGN AND STATISTICSRESEARCH AND TESTING METHODOLOGYPROGRAM MANAGEMENTGENERAL REFERENCESLAWS, REGULATIONS, AND POLICIESEDUCATIONMONITORING THE CARE AND USE OF ANIMALSOCCUPATIONAL HEALTH AND SAFETYENVIRONMENT, HOUSING AND MANAGEMENTGENERAL REFERENCESENVIRONMENTAL ENRICHMENTGENETICS AND GENETICALLY MODIFIED ANIMALSSPECIES-SPECIFIC REFERENCES – ENVIRONMENT, HOUSING AND MANAGEMENTAgricultural AnimalsAmphibians, Reptiles and FishBirdsCats and DogsExotic, Wild and Zoo AnimalsNonhuman PrimatesRodents and RabbitsOther AnimalsVETERINARY CARETRANSPORTATIONANESTHESIA, PAIN AND SURGERYDISEASE SURVEILLANCE, DIAGNOSIS AND TREATMENTPATHOLOGY, CLINICAL PATHOLOGY, AND PARASITOLOGYSPECIES-SPECIFIC REFERENCES – VETERINARY CAREAgricultural AnimalsAmphibians, Reptiles and FishBirdsCats and DogsExotic, Wild and Zoo AnimalsNonhuman PrimatesRodents and RabbitsDESIGN AND CONSTRUCTION OF ANIMAL 202202202203204204204205207APPENDIX B: U.S. GOVERNMENT PRINCIPLES FOR THE UTILIZATION ANDCARE OF VERTEBRATE ANIMALS USED IN TESTING, RESEARCH, ANDTRAINING209PREPUBLICATION COPYxxiv

APPENDIX C: STATEMENT OF TASK211APPENDIX D: ABOUT THE AUTHORS213xxvPREPUBLICATION COPY

CHAPTER 1. Key ConceptsThis edition of the Guide for the Care and Use of Laboratory Animals (the Guide)strongly affirms the principle that all who care for, use or produce animals forresearch, testing or teaching must assume responsibility for their well-being. TheGuide plays an important role in decision- making regarding the use of vertebratelaboratory animals, because it establishes the minimum ethical, practice and carestandards for researchers and their institutions. The use

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, 1985, and 1996. More than 550,000 copies have been printed since its first publication. The Guide is an internationally accepted Guide Guide