III
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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs III Content Outlines

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs Introduction This section of the guide contains detailed content outlines of the subjects covered in the recommended modules (Part II). The material in the modules is cross-referenced to appropriate subtopics in this section. The number preceding the decimal point indicates the chapter, and the number(s) following the decimal point indicates the place within the chapter that the information appears. Thus, 1.1 indicates the first entry in chapter 1 of part III, and 1.2.1 indicates the first subentry under the second entry in chapter 1. Content experts asked to deliver information or teach skills should be provided with both the module outline and the corresponding outlines in this section to determine the intended depth of presentation. These outlines can also be used to select alternative instructional materials (e.g., audiovisual, computer-aided, and independent-study). Some sections can also be used as handouts. Permission for limited reproduction of portions of this book for educational purposes, but not for sale, may be granted on receipt of a written request to the National Academy Press, 2101 Constitution Avenue, Washington, DC 20418.

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs 1 Laws, Regulations, and Policies That Impact on the Care and Use of Animals 1.1 Federal Regulations and Policies Affecting the Care and Use of Animals in Research, Testing, and Education1 1.1.1 Animal Welfare Regulations (AWRs)   1.1.1.1 Citation: Code of Federal Regulations, Title 9 (Animals and Animal Products), Subchapter A (Animal Welfare), Parts 1–4 (9 CFR 1–4)   1.1.1.2 Law implemented: U.S. Code, Title 7, Sections 2131 et seq. (7 USC 2131 et seq.), popularly called the Animal Welfare Act; most recently amended in 1985 by Public Law (PL) 99-198   1.1.1.3 Enforcing Agency: U.S. Department of Agriculture (USDA), Animal and Plant Health Inspection Service (APHIS), Regulatory Enforcement and Animal Care (REAC)   1.1.1.4 Research institutions to which AWRs are applicable: All research facilities that use or intend to use live animals (as defined by the regulations; see 1.1.1.5) in research, testing, and education   1.1.1.5 Code of Federal Regulations, Title 9, Part 1: Definition of Terms     • Amended regulations became effective October 30, 1989     • Includes in the definition of animal any warmblooded animal used or intended for use in research, testing, or education except birds; rats of the genus Rattus and mice of the genus Mus bred for use in research; and horses and other farm animals used or intended for use in agricultural research and production 1    Because regulations change periodically, it is recommended that the current Code of Federal Regulations be consulted before presenting regulatory material.

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs   1.1.1.6 Code of Federal Regulations, Title 9, Part 2     • Amended regulations became effective October 30, 1989     • Subparts A, B, and D-I set rules for dealers, exhibitors, and owners of auction sales. Describe requirements for licensing or registration, identification of animals, and recordkeeping; detail responsibilities of the attending veterinarian; and prohibit the purchase, sale, use, or transportation of stolen animals     • Subpart C sets rules for research facilities; requires compliance with standards in Part 3   1.1.1.7 Code of Federal Regulations, Title 9, Part 3     • Establishes minimum standards for animal husbandry, care, treatment, and transportation     • Amended regulations published for guinea pigs, hamsters, and rabbits (APHIS, 1990a)     • Proposed rules published for dogs, cats, and nonhuman primates (APHIS, 1990b)     - Revise standards for handling, care, treatment, and transportation of dogs, cats, and nonhuman primates     - Set standards for exercise and socialization for dogs     - Set standards for environment enhancement to promote psychological well-being of nonhuman primates   1.1.1.8 Penalties     • Animal Welfare Act (7 USC 2143f; 2149)     -The institution can be fined up to $2,500 for each violation of the Animal Welfare Act or the AWRs     - An order can be issued that the institution cease and desist violations of the act or the AWRs     - REAC can request federal funding agencies to suspend or revoke funding for research facilities that are in violation of the act or the AWRs     - REAC can temporarily suspend the licenses of dealers, exhibitors, or owners of auction sales in violation of the act or the AWRs     • Code of Federal Regulations, Title 9, Part 4: Rules of Practice     - Confers authority for adjudicatory proceedings as defined in CFR, Title 7, Subtitle A, Part 1, Subpart H     - Gives additional authority for suspending licenses 1.1.2 Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals (PHS, 1986)   1.1.2.1 Description     • Intended to ensure that PHS grantees and contractors care for and use animals humanely

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs     • Has been in existence since 1971; underwent major revision in 1985 and minor revision in 1986     • Implements and supplements the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training (see Appendix I)   1.1.2.2 Law implemented: U.S. Code, Title 42, Section 289d (42 USC 289d); was amended in 1985 to cover the care and use of animals in research by PL 99–158, the Health Research Extension Act   1.1.2.3 Oversight by the PHS Office for Protection from Research Risks (OPRR)   1.1.2.4 Activities to which policy is applicable: All PHS-conducted or supported activities involving the use of animals; an animal is defined as ''any live, vertebrate animal used or intended for use in research, research training, experimentation, or biological testing or for related purposes"   1.1.2.5 Requirements     • Compliance with the AWRs and the Guide for the Care and Use of Laboratory Animals, which was revised most recently in 1985 (NRC, 1985)     • A written statement of Assurance, including     — A description of the animal care and use program     — The qualifications, authority, and responsibility of the program's veterinarian(s)     — A list of members of the institutional animal care and use committee and procedures these members will follow to fulfill the requirements of PHS policy     — A summary description of the institution's educational or training programs in humane animal care and use     — An assurrance that the institution is accredited by the American Association for Accreditation of Laboratory Animal Care or has been evaluated by the institution   1.1.2.6 Penalty for noncompliance: Revocation of Assurance and loss of PHS support for entire institution 1.1.3 Good Laboratory Practice (GLP) standards   1.1.3.1 Prescribes good laboratory practice in several sections of the Code of Federal Regulations     • 40 CFR 792 concerns studies on health effects, environmental effects, and chemical fate testing of substances regulated by the Environmental Protection Agency pursuant to 15 USC 2603 et seq. (Toxic Substances Control Act)     • 40 CFR 160 concerns studies that support or are intended to support applications for research or marketing permits for pesticides regulated by the Environmental Protection Agency pursuant to 7 USC 136a, 136c, 136f, 1136q, 136v(c) (Federal Insecticide, Fungicide, and Rodenticide Act) and 21 USC 346a, 348 (Federal Food, Drug, and Cosmetic Act)

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs     • 21 CFR 58 concerns studies that support or are intended to support applications for research or marketing permits regulated by the Food and Drug Administration pursuant to 21 USC 406, 408–409, 502–503, 505–507, 510, 512–516, 518–520, 706, 801 (Federal Food, Drug, and Cosmetic Act) and 42 USC 351, 354–360F (Public Health Service Act)   1.1.3.2 Main concern is with reliability of research results   1.1.3.3 Subpart C of each of the GLPs     • Requires separate rooms or areas for separation of species, isolation of individual projects, quarantine, and routine or specialized housing     • Requires, as appropriate, separate rooms or areas for diagnosis, treatment, and control of diseases     • Requires, as needed, storage areas for feed, bedding, supplies, and equipment   1.1.3.4 Subpart E of each of the GLPs     • Requires written standard operating procedures for housing, feeding, handling, and care of animals     • Requires appropriate identification of animals     — 21 CFR 58.90, was amended effective May 22, 1989     — Amendment prohibits toe clipping as a means of identification     • Requires extensive recordkeeping on the environment of the animal rooms 1.2 Selected Requirements of AWRs and PHS Policy 1.2.1 Institutional animal care and use committee (IACUC)   1.2.1.1 Membership     • Must be appointed by institution's chief executive officer     • Number of members: Chairman and at least two additional members (9 CFR 2.31); Chairman and at least four additional members (PHS, 1986)     • At least one member must be a doctor of veterinary medicine with training or experience in laboratory animal science and medicine and with direct or delegated program responsibility for activities involving animals (9 CFR 2.31; PHS, 1986)     • At least one member must not be affiliated with the facility other than as a committee member and must not be a member of the immediate family of anyone affiliated with the institution (9 CFR 2.31; PHS, 1986)     • At least one member must be a practicing scientist with experience in research involving animals (PHS, 1986)     • At least one member must be a nonscientist (PHS, 1986)

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs   1.2.1.2 Functions (see also content outline section 4.2)     • Reviews semiannually institutional animal facilities and the institutional program for humane animal care and use and reports on these reviews to the institutional official     • Reviews and approves protocols and modifications to protocols     • Reviews concerns about care and use of animals     • Suspends activities found no longer to be in compliance with the AWRs and PHS policy     • Makes recommendations to the responsible institutional official concerning the animal care and use program, animal facilities, or personnel training 1.2.2 Training and Instruction   1.2.2.1 Must be made available to all personnel involved in the care, treatment, and use of species covered by the AWRs and PHS policy   1.2.2.2 Must include at least the following areas     • Humane methods of animal maintenance and experimentation     • Methods that limit the use of animals or minimize distress     • Proper use of anesthetics, analgesics, and tranquilizers for any species used by the facility     • Methods for reporting deficiencies in care and treatment     • Utilization of services, such as the National Agricultural Library, that provide information that could prevent unintended or unnecessary duplication of animal research and details about appropriate methods of animal care and use, alternatives to the use of live animals in research, and the intent and requirements of the Animal Welfare Act 1.2.3 Records that facilities must keep   1.2.3.1 Records of the IACUC     • Minutes of meetings     • Records of applications     • Proposed significant changes in animal care and use and whether approval was given or withheld     • Semiannual reports   1.2.3.2 Records on the description, identification, purchase, sale, transportation, and previous ownership of live dogs and cats (AWRs)   1.2.3.3 Records of accrediting body determinations (PHS policy) 1.2.4 Required reports   1.2.4.1 AWRs (9 CFR 2.31, 2.36)     • Requires annual report to REAC made by the facility and certified by the responsible institutional official or the chief executive officer     — Must contain assurance that professionally acceptable standards were followed in care, treatment, and use; that principal investigators have considered alternatives to painful procedures; and that the facility is adhering to the standards and regulations and has IACUC approval for all exceptions

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs     — Must state the location of all facilities where animals, as defined by the AWRs, were housed or used     — Must give the numbers and common names of animals, as defined by the AWRs, used in nonpainful or nondistressing procedures, painful or distressing procedures in which appropriate pain-relieving or tranquilizing drugs were given, and painful or distressing procedures in which pain-relieving or tranquilizing drugs were withheld because they would have interfered with experimental results     — Must give the numbers and common names of animals, as defined by the AWRs, bred for use in research, testing, and education but not yet used for such purposes     • Requires prompt notification, with a full explanation, of any suspended activity   1.2.4.2 PHS policy (PHS, 1986)     • Requires annual report to OPRR by the IACUC through the institutional official     — Must note significant changes in the institution's programs, facilities, or animal care and use program     — Must list changes in IACUC membership     — Must provide dates of semiannual IACUC evaluations     • Requires prompt notification with a full explanation of     — Any serious or continuing noncompliance with PHS policy or the Guide for the Care and Use of Laboratory Animals     — Any suspension of activity by the IACUC 1.3 State and Local Regulations Affecting the Care and Use of Animals in Research, Testing, and Education (if applicable) 1.4 Institutional Policies Affecting the Care and Use of Animals in Research, Testing, and Education 1.4.1 Policies that affect research protocols 1.4.2 Policy on dealing with alleged misconduct REFERENCES APHIS (Animal and Plant Health Inspection Service). 1990a. 9 CFR Part 3. Animal welfare; guinea pigs, hamsters, and rabbits. Fed. Regist. 55(136):28879–28884. APHIS (Animal and Plant Health Inspection Service). 1990b. 9 CRF Part 3. Animal welfare; standards; proposed rule. Fed. Regist. 55(158):33448–33531. Code of Federal Regulations, Title 9 (Animals and Animal Products), Subchapter A (Animal Welfare), Parts 1–3. Available from: Regulatory Enforcement and Animal Care, APHIS, USDA, Federal Building, Room 268, Hyattsville, MD 20782. Code of Federal Regulations, Title 9 (Animals and Animal Products), Subchapter A (Animals Welfare),

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs Amendments to Part 3. 1990a. Fed. Regist. 55(136):28879–28884. Code of Federal Regulations, Title 9 (Animals and Animal Products), Subchapter A (Animals Welfare), Proposed amendments to Part 3. 1990b. Fed. Regist. 55(158):33448–33531. NRC (National Research Council). 1985. Guide for the Care and Use of Laboratory Animals. A report of the Institute of Laboratory Animal Resources Committee on Care and Use of Laboratory Animals. NIH Pub. No. 86-23. Washington, D.C.: U.S. Department of Health and Human Services . 83 pp. PHS (Public Health Service). 1986. Public Health Service Policy on Humane Care and Use of Laboratory Animals. Washington, D.C.: U.S. Department of Health and Human Services. 28 pp. Available from: Office for Protection from Research Risks, Building 31, Room 4B09, NIH, Bethesda, MD 20892.

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs 2 Ethical and Scientific Issues It is important that the person who presents the issues discussed in this chapter emphasizes the need for tolerance of differing points of view. 2.1 Definitions 2.1.1 Ethics: A discipline within philosophy concerned with the examination and establishment of criteria for making judgments concerning value (good and bad) and judgments concerning responsibility and duty (right and wrong) 2.1.2 Applied ethics: Ethical reflection, as defined above, applied to a specific area of concern, e.g., the use of laboratory animals 2.2 Conceptual Framework for Ethical Decisions (Robb, 1989) 2.2.1 A framework provides a method or formal structure for making decisions 2.2.2 Utilitarian or teleological ethical approach to decision making   2.2.2.1 Involves risk/benefit analysis; the best action is determined by the effects of the action in a particular circumstance or on the effects on all concerned (the social utility of the action)   2.2.2.2 Can be used by both animal-rights and animal-use advocates   2.2.2.3 Is too often based on short-term rather than long-term effects 2.2.3 Deontological ethical approach to decision making   2.2.3.1 Determines an action by comparison with a highest duty (e.g., respect for dignity, beneficience, justice) or with universal moral obligations derived from cultural or religious principles   2.2.3.2 Is used primarily by animal-rights advocates   2.2.3.3 By definition, ignores the short- and long-term consequences of an action; however, in actual experience, moral principles have exceptions

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs 2.3 Arguments Used by those Advocating the Humane Use of Animals for Human Purposes (Caplan, 1984) 2.3.1 Research with animals has made possible the advancement of knowledge in the medical and veterinary sciences in ways that otherwise would not have been possible (NRC, 1988)   2.3.1.1 Benefits of basic research   2.3.1.2 Benefits to health and welfare of humans and animals 2.3.2 Society accepts the idea of a hierarchy of species in its attitude toward other animal species (NRC, 1988, p. 16) 2.3.3 Humankind has the moral responsibility to enhance the well-being of other humans and also the moral duty to use wisely and prudently all resources that nature provides, including the use of animals for good purposes 2.4 Arguments Used by Animal-Rights Advocates (Singer, 1975; Regan, 1983) 2.4.1 Animals are intelligent and sentient beings, with feelings not too unlike our own 2.4.2 Animals have inherent value and have a right to fulfill their destiny as independent beings 2.4.3 As independent beings, they are "subjects-of-a-life," that is, they have desires and intentions that should be respected 2.4.4 Therefore, humankind has no right to exploit them for human purposes because this violates their integrity as separate species 2.5 The Role of Laws, Regulations, and Policies 2.5.1 Function to prescribe common standards that prevent the abuse of humane standards for the care of animals 2.5.2 Recent policies and guidelines have refined earlier standards and have had a salutary effect on the well-being of laboratory animals 2.6 Suggested Ethical Principles (See U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training; Appendix I) 2.6.1 Design procedures relevant to the improvement of health, advancement of knowledge, or good of society (Principle II) 2.6.2 Use appropriate models and consider alternatives (Principle III) 2.6.3 Avoid or minimize pain and distress (Principle IV) 2.6.4 When painful procedures are necessary, use appropriate sedation, analgesia, or anesthesia (Principle V) 2.6.5 Humanely kill animals that would suffer severe or chronic pain (Principle VI) 2.6.6 If an exception to these principles is necessary, it should be assessed and approved by a review group such as the institutional animal care and use committee (Principle IX)

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs   8.7.12.2 Electrocution     • Requires special equipment that passes electrical current directly through the brain to cause immediate loss of consciousness     • Is potentially hazardous to personnel 8.8 Carcass Disposal 8.8.1 Conduct the process in a way that demonstrates respect for the animal 8.8.2 Occupational hazards   8.8.2.1 Evaluate possible hazards to human handlers when animals are known to be carrying a zoonotic agent or were treated with radioisotopes or toxic chemicals   8.8.2.2 Ensure that personnel handling such carcasses take the necessary precautions to protect themselves and others 8.8.3 Follow institutional guidelines for packaging carcasses and moving them to the incinerator to ensure proper disposal REFERENCES Ad Hoc Committee on Animal Research. 1988. Interdisciplinary Principles and Guidelines for the Use of Animals in Research, Testing, and Education. New York: New York Academy of Sciences. Arluke, A. B. 1988. Sacrificial symbolism in animal experimentation: Object or pet? Anthrozoös 2(2):98-117. AVMA (American Veterinary Medical Association). 1986. 1986 Report of the AVMA Panel on Euthanasia. J. Am. Vet. Med. Assoc. 188:2522-268. CCAC (Canadian Council on Animal Care). 1980. Euthanasia. Pp. 70–76 in Guide to the Care and Use of Experimental Animals, vol. 1. Ottawa: Canadian Council on Animal Care. Code of Federal Regulations, Title 9 (Animals and Animal Products), Subchapter A (Animal Welfare), Parts 1–3. Copies available from: Animal Care Staff, Regulatory Enforcement and Animal Care, Federal Building, Room 268, Hyattsville, MD 20782. Everitt, J. I., and W. Griffon. 1988. Recent laboratory animal legislation and toxicology research and testing. CIIT Activities 8(11):4. Copies available from: Information Services, Chemical Industry Institute of Toxicology, P.O. Box 12137, Research Triangle Park, NC 27709. PHS (Public Health Service). 1986. Public Health Service Policy on Humane Care and Use of Laboratory Animals. Washington, D.C.: U.S. Department of Health and Human Services. 28 pp. Copies available from: Office for Protection from Research Risks, Building 31, Room 4B09, National Institutes of Health, Bethesda, MD 20892.

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs 9 Husbandry, Care, and the Importance of the Environment 9.1 Legal Requirements for Husbandry and Care 9.1.1 Animals covered   9.1.1.1 AWRs: Any warmblooded animal used or intended for use in research, testing, or education except birds, rats of the genus Rattus and mice of the genus Mus bred for use in research, and horses and other farm animals used or intended for use in agricultural research and production (see 9 CFR 1.1)   9.1.1.2 PHS Policy: All live vertebrates used in PHS-conducted or supported activities   9.1.1.3 State and local laws, as applicable 9.1.2 Scope of Coverage   9.1.2.1 Facilities and operating procedures in facilities, including temperature and humidity, lighting, cage construction and maintenance, cage size, and waste disposal   9.1.2.2 Animal health and husbandry, including feeding, watering, sanitation, staffing, classification and separation, and veterinary care   9.1.2.3 Transportation, including construction, size, and ventilation of transportation cage; identification of animals; and care in transit 9.2 Importance of Proper Husbandry and a Stable Environment 9.2.1 Improves validity and reliability of experimental data 9.2.2 Conserves research resources   9.2.2.1 Reduces number of animals necessary   9.2.2.2 Reduces time required to complete experiments   9.2.2.3 Reduces cost

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs 9.2.3 Improves staff morale and community relations 9.3 Environmental Variables that can be Controlled 9.3.1 The micro- and macroenvironments   9.3.1.1 Definitions     • Microenvironment: The physical environment immediately surrounding the animal, for example, temperature and humidity in the cage or primary enclosure (NRC, 1985)     • Macroenvironment: The physical conditions in the room or secondary enclosure (NRC, 1985)   9.3.1.2 Importance of the microenvironment     • Profoundly affects metabolism, behavior, and susceptibility to diseases     • May vary greatly from macroenvironment, depending on cage design (e.g., ammonia levels will be higher in an enclosed cage than in an open one)     • Can be more difficult to monitor and regulate than the macroenvironment 9.3.2 Examples of variables that can affect animal health and research outcomes   9.3.2.1 Temperature and humidity   9.3.2.2 Ventilation   9.3.2.3 Population density   9.3.2.4 Illumination   9.3.2.5 Noise (frequency, loudness, suddenness of onset   9.3.2.6 Food and water   9.3.2.7 Type of bedding   9.3.2.8 Sanitation   9.3.2.9 Handling (age of animal, frequency of handling) 9.4 Dealing with Emergencies (e.g., power failure, flooding, air-handlingfailure, heating or cooling failure, fire) REFERENCE NRC (National Research Council). 1985. Guide for the Care and Use of Laboratory Animals. A report of the Institute of Laboratory Animal Resources Committee on Care and Use of Laboratory Animals. NIH Pub. No. 86-23. Washington, D.C.: U.S. Department of Health and Human Services.

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs 10 Species-Specific Overview The following outline is intended as a guide for preparing a series of programs, each designed to provide information on a specific animal (e.g., dogs, nonhuman primates) or group of animals (e.g., rodents). Topics are broken down by animal type only in those instances in which the material to be covered depends on animal type. With the exception of the Specific Techniques section, which is intended to be hands-on training, the material in this section can be presented in a variety of formats, as appropriate to institutional needs and constraints. Outline 10.1 Factors Associated with Selection of Animals 10.1.1 Rodents   10.1.1.1 Types of stocks     • Inbred: Each animal of the strain is virtually genetically identical to all the others of that strain     • Hybrid: The first generation offspring of two inbred strains; known genetic background, but heterozygous at most loci     • Mutant: Each animal carries an inherited trait or a combination of traits that allows the study of a specific biologic process or disease     • Outbred: Genetics unknown; very heterogeneous     • Other specialized stocks (e.g., transgenic animals)

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs   10.1.1.2 Standardized nomenclature     • Importance of using standardized nomenclature     • Sources for rules of standardized nomenclature (International Committee on Laboratory Animals, 1972; Lyon and Searle, 1989; Greenhouse, in press)   10.1.1.3 Microbiologic status     • Effects of clinical and subclinical infections on research outcomes (NRC, in press a,b)     • Definitions of terms describing microbial status (NRC, in press a)     - Germfree: A hysterectomy-derived animal that has been reared and maintained in an isolator by germfree techniques and demonstrated free of associated forms of life, including viruses, bacteria, fungi, protozoa, and other saprophytic or parasitic forms     - Gnotobiote: A hysterectomy-derived animal that has been reared and maintained in an isolator by germfree techniques and that has one or more associated nonpathogenic agents, all of which are known     - Defined flora: A germfree animal that has been intentionally associated with one or more microorganisms and maintained continuously in an isolator to prevent contamination by other agents (term may be used synonymously with gnotobiote)     - Pathogen free: An animal free of all demonstrable pathogens; proper usage of the term requires that the pathogen-free status be supported by current results from a battery of tests appropriate for all pathogens of a specific species (term differs little from specific pathogen free)     - Specific pathogen free (SPF) or barrier maintained: An animal free of a specified list of pathogens; proper usage of the term requires that the absence of the specified pathogens be supported by current test results from a battery of tests appropriate for those pathogens     - Virus antibody free: An animal free of antibodies to viral pathogens; proper usage requires that the absence of viral pathogens be supported by current test results from a battery of appropriate serologic tests     - Clean conventional: An animal housed in a low-security barrier and demonstrated to be free of major pathogens     - Conventional: An animal whose microbial burden is not known and not controlled; the animal is generally housed in open rooms with unrestricted access     • Animal resource policy

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs 10.1.2 Rabbits   10.1.2.1 Breeds   10.1.2.2 Microbiologic status 10.1.3 Dogs and cats   10.1.3.1 Breeds     • Purebred     • Mixed breed   10.1.3.2 Purpose bred or random source     • Availability     • Health and vaccination history 10.1.4 Nonhuman primates   10.1.4.1 Genus and species   10.1.4.2 Colony-born, wild-caught, or previously used in experimentation     • Availability     • History (e.g., date of birth)     • Health records     • Previous experimental procedures 10.1.5 Other animals (as appropriate to the audience) 10.2 Procurement of Animals 10.2.1 Information on sources of animals   10.2.1.1 Institutional animal resource   10.2.1.2 Institute of Laboratory Animal Resources   10.2.1.3 Primate Information Clearing House 10.2.2 Requirements for purchasing animals   10.2.2.1 Legal requirements     • Dogs and cats     • Threatened or endangered species   10.2.2.2 Institutional requirements     • Requirement for purchasing only from USDA-licensed dealers, if applicable     • Microbiologic status     • Health records     • Quarantine and stabilization 10.3 Caging 10.3.1 Types of caging regularly available in the institution   10.3.1.1 Advantages and disadvantages     • Species needs     • Safety (people and animals)     • Security     • Visibility     • Accessibility     • Disease control     • Sanitation

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs   10.3.1.2 Maximum population density permitted     • Size of individuals     • Age of individuals     • Aggressive animals     • Physiologic and metabolic signs of overcrowding     — Increased corticosterone levels     — Loss of fertility     • Behavioral effects of overcrowding     — Aggression     — Cannibalism     — Self-mutilation 10.3.2 Special caging   10.3.2.1 Metabolic   10.3.2.2 Intensive care or therapy   10.3.2.3 Special construction 10.4 Environmental Enrichment 10.4.1 Legal requirements   10.4.1.1 Dogs   10.4.1.2 Nonhuman primates 10.4.2 Institutional policies 10.4.3 Group housing and socialization 10.4.4 Special equipment 10.5 Food 10.5.1 Advantages and disadvantages of food-delivery methods available   10.5.1.1 Appropriateness for age of animal   10.5.1.2 Appropriateness for health status of animal   10.5.1.3 Adequate availability for all individuals in a social group (subordinates are not food deprived) 10.5.2 Nutrition   10.5.2.1 Supplementation of standard diets available   10.5.2.2 Diet control     • Batch date     • Frequent content assessment   10.5.2.3 Special dietary needs     • Unusual amounts of food, such as for pregnant and nursing animals     • Special types of food     • Caloric restriction   10.5.2.4 Availability and sources of experimental diets 10.5.3 Delivery of experimental agents 10.5.4 Food deprivation carried out under approved experimental protocol 10.6 Water 10.6.1 Advantages and disadvantages of available water delivery methods

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs 10.6.2 Delivery of experimental agents 10.6.3 Water deprivation carried out under approved experimental protocol 10.7 Handling and Restraint 10.7.1 Regulations and policies 10.7.2 Importance of proper handling (cite examples)   10.7.2.1 Avoid injury to animals   10.7.2.2 Avoid injury to personnel   10.7.2.3 Minimize stress   10.7.2.4 Aesthetics 10.7.3 Techniques for handling 10.7.4 Methods of restraint   10.7.4.1 Physical   10.7.4.2 Chemical   10.7.4.3 Mechanical 10.7.5 Prolonged restraint   10.7.5.1 Regulations and policies   10.7.5.2 Procedures to reduce stress     • Selection of the least restrictive system compatible with research objectives     • Selection of the minimal restraint time needed to accomplish the research objectives     • Conditioning of animals to restraint devices before beginning research     • Prevention or treatment of problems resulting from restraint, including contusions, decubital ulcers, dependent edema, weight loss, and traumatic injury 10.8 Identification and Records 10.8.1 Legal requirements   10.8.1.1 PHS policy (Guide for the Care and Use of Laboratory Animals) (NRC, 1985)   10.8.1.2 Animal welfare regulations (9 CRF 2.35): Dogs and cats   10.8.1.3 Good Laboratory Practices (21 CFR 58.90) 10.8.2 Advantages and disadvantages of identification methods: Tattoos, color or dye markings, natural markings, ear punch, toe clipping, ear tags, collars 10.8.3 Recordkeeping   10.8.3.1 Cage card: Species and strain of animals, sex, weights, source, identification number, responsible investigator, other pertinent data   10.8.3.2 Individual identification: Species and strain or breed of animal, source 10.9 Animal Health 10.9.1 Normal parameters   10.9.1.1 Life cycle   10.9.1.2 Behavior patterns, including reproduction

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs   10.9.1.3 Physiologic parameters   10.9.1.4 Clinical chemistry 10.9.2 Health surveillance   10.9.2.1 Importance of the health-surveillance program     • Minimizes pain and discomfort associated with disease, injury, or distress     • Reduces number of animals required by minimizing loss     • Improves the reliability and validity of experimental data     • Enables early intervention in cases of disease and injury     • Reduces probability of spread of disease   10.9.2.2 Role of the research team     • Assists in detection of distress and disease through frequent observation     • Reports signs of distress and disease to veterinary staff and consults on plan of action 10.9.3 Signs of distress and disease   10.9.3.1 Gross signs     • Cutaneous: Alopecia, cutaneous or subcutaneous swelling, dermatitis, abnormal hair coat, necrosis, discoloration     • Gastrointestinal: Diarrhea, constipation, cramping (hunched posture), anorexia, ptyalism, rectal prolapse, pendulous abdomen     • Respiratory: Dyspnea, abnormal respiratory sounds, nasal and ocular discharges     • Urinary: Polydipsia, excessive or reduced volume, content or color abnormalities, unusual odor, straining to urinate     • Neuromuscular and skeletal: Paresis or paralysis, seizures, torticollis, incoordination, lameness     • Reproductive: Infertility, abortions, discharges, still births, litter desertion, orchitis, mastitis     • Miscellaneous: Unexpected deaths, loss of appendages, weight loss, anemia, eye lesions   10.9.3.2 Physiologic signs     • Blood: Anemia; cell size, count, or type     • Urinary: Abnormalities in specific gravity, color, content, chemistry, volume, odor     • Decreased or elevated body temperature, pulse or respiratory rate     • Miscellaneous: Changes in synovial or cerebrospinal fluids, nerve impulse transmission, bone density, liver and pancreatic function, endocrine function, mineral and pH balance   10.9.3.3 Behavioral signs     • Inappetance     • High or low levels of activity

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs     • Withdrawal to a cage corner     • Inter- or intraspecies aggression     • Unusual or repetitive movement patterns     • Excessive self grooming     • Sexual and maternal abnormalities     • Self-mutilation 10.9.4 Common disease   10.9.4.1 Rodents     • Mice: Acariasis, pneumonias, abscesses, mammary neoplasia, subclinical viral infections such as MHV and Sendai     • Rats: Incisor malocclusion, chronic respiratory disease, mammary (benign) neoplasia, nephrosis, sialodacryoademitis, chromodacryorrhea, moist dermatitis     • Guinea pigs: Pneumonia, enteropathies, dermatophytosis, hypo-vitaminosis C, premolar malocclusion, mastitis, pregnancy toxemia, pediculosis, urolithiasis, limb fractures     • Hamsters: Demodecosis, renal amyloidosis, limb fractures, enteropathies, cutaneous and adrenal neoplasia   10.9.4.2 Rabbits: Otic acariasis, coccidiosis, enteropathies, malocclusion, lumbar fracture, moist dermatitis, pasteurellosis, ulcerative pododermatitis   10.9.4.3 Dogs: Bordetella infection; distemper; parvovirus infection; herpesvirus infection; heartworms; intestinal and cutaneous parasitism; hepatitis, adenovirus, and parainfluenza infections; neoplasia   10.9.4.4 Cats: Infectious peritonitis, panleukopenia, respiratory disorders, toxoplasmosis, parasitism, leukemia, urologic syndrome, otic acariasis   10.9.4.5 Nonhuman primates: Enteropathies, tuberculosis, trauma, caloric insufficiency, hypovitaminosis C or D3, herpesvirus infections   10.9.4.6 Other animals: Include as appropriate to audience 10.9.5 Experimentally produced disorders: Physical, electrophysiologic, microbiologic, or chemical alteration of any part so as to produce an abnormal sign; must be differentiated (based on history) from signs associated with spontaneous diseases 10.9.6 Institutional procedures for emergency or special care 10.10 Zoonoses (Describe Signs and Symptoms in Animals and Humans) 10.10.1 Types   10.10.1.1 Naturally occurring     • Rodents: Lymphocytic choriomeningitis, rat-bite fever, Korean hemorrhagic fever and related diseases (animals imported from Europe and Asia)     • Dogs: Rabies, brucellosis, ringworm, endoparasite-induced disease

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Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs     • Cats: Cat-scratch fever, toxoplasmosis, endoparasite-induced disease     • Nonhuman primates: Tuberculosis, herpesvirus B infection, Marburg disease, infectious hepatitis, monkeypox     • Ungulates: Encephalomyelitis, Q fever, leptospirosis, tetanus, contagious ecthyma, cowpox     • Birds: Psitticosis (ornithosis), salmonellosis, encephalomyelitis     • Wild rodents/racoons: Rat bite fever, tularemia, plague, rabies   10.10.1.2 Experimentally produced (any agent injected, fed, or introduced by biotechnology) 10.10.2 Techniques for handling animals carrying or at high risk for carrying zoonotic agents 10.11 Specific Techniques: Hands-on Training in Techniques Such as Blood Withdrawal, Injections, Specimen Collection, Measurement of Vital Signs, and Euthanasia References Code of Federal Regulations, Title 9 (Animals and Animal Products), Subchapter A (Animal Welfare), Parts 1–3. Copies available from: Animal Care Staff, Regulatory Enforcement and Animal Care, Federal Building, Room 268, Hyattsville, MD 20782. Greenhouse, D. D., M. F. W. Festing, S. Hasan, and A. L. Cohen. In press. Inbred strains of rats. In Genetic Monitoring of Inbred Strains of Rats. A Manual on Colony Management, Basic Monitoring Techniques, and Genetic Variants of the Laboratory Rat, H. J. Hedrich, ed. Stuttgart: Gustav Fischer Verlag. International Committee on Laboratory Animals (now known as the International Council for Laboratory Animal Science or ICLAS). 1972. International standardized nomenclature for outbred stocks of laboratory animals. A report of the Working Party to prepare an International Nomenclature System for Outbred Animals. ICLA Bull. 30:4–17. Copies available from: Institute of Laboratory Animal Resources, National Research Council, 2101 Constitution Avenue, Washington, DC 20418. Lyon, M. F., and A. G. Searle, eds. 1989. Genetic Variants and Strains of the Laboratory Mouse, 2nd ed. Oxford: Oxford University Press. 876 pp. NRC (National Research Council). 1985. Guide for the Care and Use of Laboratory Animals. A report of the Institute of Laboratory Animal Resources Committee on Care and Use of Laboratory Animals. NIH Pub. No. 86-23. Washington, D.C.: U.S. Department of Health, Education, and Welfare. NRC (National Research Council). In press a. Infectious Diseases of Mice and Rats. A report of the ILAR Committee on Infectious Diseases of Mice and Rats. Washington, D.C.: National Academy Press. NRC (National Research Council). In press b. Companion Guide to Infectious Diseases of Mice and Rats. A report of the ILAR Committee on Infectious Diseases of Mice and Rats. Washington, D.C.: National Academy Press.