This chapter defines the overall Program and key oversight responsibilities and provides guidelines to aid in developing an effective Program. Chapters 3, 4, and 5 cover the details of Program components: environment, housing, and management; veterinary care; and physical plant, respectively. Each institution should establish and provide sufficient resources for a Program that is managed in accord with the Guide and in compliance with applicable regulations, policies, and guidelines.
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Guide for the Care and use of Laboratory Animals: Eighth Edition 2 Animal Care and Use Program The proper care and use of laboratory animals in research, testing, teaching, and production (animal use) require scientific and professional judgment based on the animals’ needs and their intended use. An animal care and use program (hereafter referred to as the Program) comprises all activities conducted by and at an institution that have a direct impact on the well-being of animals, including animal and veterinary care, policies and procedures, personnel and program management and oversight, occupational health and safety, institutional animal care and use committee (IACUC) functions, and animal facility design and management. Program: The activities conducted by and at an institution that have a direct impacton the well-being of animals, including animal and veterinary care, policies and procedures, personnel and program management and oversight, occupational health and safety, IACUC functions, and animal facility design and management. This chapter defines the overall Program and key oversight responsibilities and provides guidelines to aid in developing an effective Program. Chapters 3, 4, and 5 cover the details of Program components: environment, housing, and management; veterinary care; and physical plant, respectively. Each institution should establish and provide sufficient resources for a Program that is managed in accord with the Guide and in compliance with applicable regulations, policies, and guidelines.
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Guide for the Care and use of Laboratory Animals: Eighth Edition REGULATIONS, POLICIES, AND PRINCIPLES The use of laboratory animals is governed by an interrelated, dynamic system of regulations, policies, guidelines, and procedures. The Guide takes into consideration regulatory requirements relevant to many US-based activities, including the Animal Welfare Regulations (USDA 1985; US Code, 42 USC § 289d) and the Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS 2002). The use of the Guide by non-US entities also presumes adherence to all regulations relevant to the humane care and use of laboratory animals applicable in those locations. The Guide also takes into account the U.S. Government Principles for Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training (IRAC 1985; see Appendix B) and endorses the following principles: consideration of alternatives (in vitro systems, computer simulations, and/or mathematical models) to reduce or replace the use of animals design and performance of procedures on the basis of relevance to human or animal health, advancement of knowledge, or the good of society use of appropriate species, quality, and number of animals avoidance or minimization of discomfort, distress, and pain use of appropriate sedation, analgesia, and anesthesia establishment of humane endpoints provision of adequate veterinary care provision of appropriate animal transportation and husbandry directed and performed by qualified persons conduct of experimentation on living animals exclusively by and/or under the close supervision of qualified and experienced personnel. Interpretation and application of these principles and the Guide require knowledge, expertise, experience, and professional judgment. Programs should be operated in accord with the Guide and relevant regulations, policies, and principles. Also, institutions are encouraged to establish and periodically review written procedures to ensure consistent application of Guide standards. Supplemental information on various aspects of animal care and use is available in other publications prepared by the Institute for Laboratory Animal Research (ILAR) and other organizations (Appendix A). References in the Guide provide the reader with additional information that supports statements made in the Guide. In the absence of published literature, some information in the Guide is derived from currently accepted practice standards in laboratory animal science (see Chapter 1). The body
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Guide for the Care and use of Laboratory Animals: Eighth Edition of literature related to animal science and use of animals is constantly evolving, requiring Programs to remain current with the information and best practices. PROGRAM MANAGEMENT An effective Program requires clearly defined roles that align responsibility with regulatory and management authority. US federal law creates a statutory basis for the institutional official (IO), the attending veterinarian (AV), and the institutional animal care and use committee (IACUC). The Guide endorses these concepts as important operating principles for all US and non-US animal care and use programs. Effective leadership in and collaboration among these three components, which not only oversee but also support animal users, are necessary (Lowman 2008; Van Sluyters 2008). In addition, interactions with regulatory and funding agencies and accreditation organizations are an integral part of the Program. As summarized here and discussed throughout the Guide, the primary oversight responsibilities in the Program rest with the IO, the AV, and the IACUC. Their roles fit in a defined organizational structure where the reporting relationships, authorities, and responsibilities of each are clearly defined and transparent. Together they establish policies and procedures, ensure regulatory compliance, monitor Program performance, and support high-quality science and humane animal use. A Program that includes these elements and establishes a balance among them has the best chance of efficiently using resources while attaining the highest standards of animal wellbeing and scientific quality (Bayne and Garnett 2008; Van Sluyters 2008). Program Management Responsibility The Institutional Official The institutional official (IO) bears ultimate responsibility for the Program, although overall Program direction should be a shared responsibility among the IO, AV, and IACUC. The IO has the authority to allocate the resources needed to ensure the Program’s overall effectiveness. Program needs should be clearly and regularly communicated to the IO by the AV, the IACUC, and others associated with the Program (e.g., facilities management staff, occupational health and safety personnel, scientists). As a Institutional official: The individual who, as a representative of senior administration, bears ultimate responsibility for the Program and is responsible for resource planning and ensuring alignment of Program goals with the institution’s mission.
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Guide for the Care and use of Laboratory Animals: Eighth Edition representative of senior administration, the IO is responsible for resource planning and ensuring the alignment of Program goals of quality animal care and use with the institution’s mission. The Attending Veterinarian The attending veterinarian (AV) is responsible for the health and wellbeing of all laboratory animals used at the institution. The institution must provide the AV with sufficient authority, including access to all animals, and resources to manage the program of veterinary care. The AV should oversee other aspects of animal care and use (e.g., husbandry, housing) to ensure that the Program complies with the Guide. Attending veterinarian: The veterinarian responsible for the health and well-being of all laboratory animals used at the institution. Institutional mission, programmatic goals, including the nature of animal use at the institution, and Program size will determine whether fulltime, part-time, or consultative veterinary services are needed. If a full-time veterinarian is not available on site, a consulting or part-time veterinarian should be available in visits at intervals appropriate to programmatic needs. In such instances, there must be an individual with assigned responsibility for daily animal care and use and facility management. While institutions with large animal care and use programs may employ multiple veterinarians, the management of veterinary medicine, animal care, and facility operations by a single administrative unit is often an efficient mechanism to administer all aspects of the Program. The Guide endorses the American College of Laboratory Animal Medicine’s (ACLAM) “Guidelines for Adequate Veterinary Care” (ACLAM 1996). These guidelines include veterinary access to all animals and their medical records, regular veterinary visits to facilities where animals are or may be housed or used, provisions for appropriate and competent clinical, preventive, and emergency veterinary care, and a system for legal animal procurement and transportation. Other responsibilities of the AV are outlined in the Program Oversight section below and in later chapters. For a Program to work effectively, there should be clear and regular communication between the AV and the IACUC. The Institutional Animal Care and Use Committee The IACUC (or institutional equivalent) is responsible for assessment and oversight of the institution’s Program components and facilities. It should have sufficient authority and resources (e.g., staff, training, comput-
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Guide for the Care and use of Laboratory Animals: Eighth Edition ers and related equipment) to fulfill this responsibility. Detailed information on the role and function of the IACUC is provided later in this chapter. Collaborations Interinstitutional collaboration has the potential to create ambiguities about responsibility for animal care and use. In cases of such collaboration involving animal use (beyond animal transport), the participating institutions should have a formal written understanding (e.g., a contract, memorandum of understanding, or agreement) that addresses the responsibility for offsite animal care and use, animal ownership, and IACUC review and oversight (AAALAC 2003). In addition, IACUCs from the participating institutions may choose to review protocols for the work being conducted. Personnel Management Training and Education All personnel involved with the care and use of animals must be adequately educated, trained, and/or qualified in basic principles of laboratory animal science to help ensure high-quality science and animal well-being. The number and qualifications of personnel required to conduct and support a Program depend on several factors, including the type and size of the institution, the administrative structure for providing adequate animal care, the characteristics of the physical plant, the number and species of animals maintained, and the nature of the research, testing, teaching, and production activities. Institutions are responsible for providing appropriate resources to support personnel training (Anderson 2007), and the IACUC is responsible for providing oversight and for evaluating the effectiveness of the training program (Foshay and Tinkey 2007). All Program personnel training should be documented. Veterinary and Other Professional Staff Veterinarians providing clinical and/or Program oversight and support must have the experience, training, and expertise necessary to appropriately evaluate the health and wellbeing of the species used in the context of the animal use at the institution. Veterinarians providing broad Program direction should be trained or have relevant experience in laboratory animal facility administration and management. Depending on the scope of the Program, professionals with expertise in other specific areas may be needed—in, for example, facility design and renovation, human resource management, pathology of laboratory animals, comparative genomics, facility and equipment maintenance, diagnostic laboratory operations, and behavioral management. Laboratory
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Guide for the Care and use of Laboratory Animals: Eighth Edition animal science and medicine are rapidly changing and evolving disciplines. The institution should provide opportunities and support for regular professional development and continuing education to ensure both that professional 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 appropriately 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. There are a number of options for training animal care personnel and technicians (Pritt and Duffee 2007). Many colleges have accredited programs in veterinary technology (AVMA 2010); most are 2-year programs that award Associate of Science degrees, some are 4-year programs that award Bachelor of Science degrees. Nondegree training, via certification programs for laboratory animal technicians and technologists, is available from the American Association for Laboratory Animal Science (AALAS), and there are various commercially available training materials appropriate for self-guided study (Appendix A). Personnel caring for laboratory animals should also regularly engage in continuing education activities and should be encouraged to participate in local and national laboratory animal science meetings and in other relevant professional organizations. On-the-job training, supplemented with institution-sponsored discussion and training programs and reference materials applicable to their jobs and the species in their care, should be provided to each employee responsible for animal care (Kreger 1995). Coordinators of institutional training programs can seek assistance from the Animal Welfare Information Center (AWIC), the Laboratory Animal Welfare and Training Exchange (LAWTE), AALAS, and ILAR (NRC 1991). The Guide to the Care and Use of Experimental Animals by the Canadian Council on Animal Care (CCAC 1993) and guidelines from other countries are valuable additions to the libraries of laboratory animal scientists (Appendix A). The Research Team The institution should provide appropriate education and training to members of research teams—including principal investigators, study directors, research technicians, postdoctoral fellows, students, and visiting scientists—to ensure that they have the necessary knowledge and expertise for the specific animal procedures proposed and the species
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Guide for the Care and use of Laboratory Animals: Eighth Edition 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, ethics 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. Continuing 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 members 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 animal 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 Each institution must establish and maintain an occupational health and safety program (OHSP) as an essential part of the overall Program of animal care and use (CFR 1984a,b,c; DHHS 2009; PHS 2002). The OHSP must be consistent with federal, state, and local regulations and should focus on maintaining a safe and healthy workplace (Gonder 2002; Newcomer 2002; OSHA 1998a). The nature of the OHSP will depend on the facility, research activities, hazards, and animal species involved. The National Research Council’s publication Occupational Health and Safety in the Care and Use of Research Animals (NRC 1997) contains guidelines and references for establishing and maintaining an effective, comprehensive OHSP (also see Appendix A). An effective OHSP requires coordination between the research program (as represented by the investigator), the animal care and use Program (as represented by the AV, IO, and IACUC), the environmental health and safety program, occupational health services, and administration (e.g., human resources, finance, and facility maintenance personnel). Establishment of a safety committee may facilitate communication and promote ongoing evaluation of health and safety in the workplace. In some cases
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Guide for the Care and use of Laboratory Animals: Eighth Edition there is a regulatory requirement for such a committee. Operational and day-to-day responsibility for safety in the workplace resides with the laboratory or facility supervisor (e.g., principal investigator, facility director, or a staff veterinarian) and depends on safe work practices by all employees. Control and Prevention Strategies A comprehensive OHSP should include a hierarchy of control and prevention strategies that begins with the identification of hazards and the assessment of risk associated with those hazards. Managing risk involves the following steps: first, the appropriate design and operation of facilities and use of appropriate safety equipment (engineering controls); second, the development of processes and standard operating procedures (SOPs; administrative controls); and finally, the provision of appropriate personal protective equipment (PPE) for employees. Special safety equipment should be used in combination with appropriate management and safety practices (NIH 2002; OSHA 1998a,b). Managing risk using these strategies requires that personnel be trained, maintain good personal hygiene, be knowledgeable about the hazards in their work environment, understand the proper selection and use of equipment, follow established procedures, and use the PPE provided. Hazard Identification and Risk Assessment The institutional OHSP should identify potential hazards in the work environment and conduct a critical assessment of the associated risks. An effective OHSP ensures that the risks associated with the experimental use of animals are identified and reduced to minimal and acceptable levels. Hazard identification and risk assessment are ongoing processes that involve individuals qualified to assess dangers associated with the Program and implement commensurate safeguards. Health and safety specialists with knowledge in relevant disciplines should be involved in risk assessment and the development of procedures to manage such risks. Potential hazards include experimental hazards such as biologic agents (e.g., infectious agents or toxins), chemical agents (e.g., carcinogens and mutagens), radiation (e.g., radionuclides, X-rays, lasers), and physical hazards (e.g., needles and syringes). The risks associated with unusual experimental conditions such as those encountered in field studies or wildlife research should also be addressed. Other potential hazards—such as animal bites, exposure to allergens, chemical cleaning agents, wet floors, cage washers and other equipment, lifting, ladder use, and zoonoses—that are inherent in or intrinsic to animal use should be identified and evaluated. Once potential hazards have been identified, a critical ongoing assessment of the associated risks should be conducted to determine appropriate strategies to minimize or manage the risks. The extent and level of participation of personnel in the OHSP should be based on the hazards posed by the animals and materials used (the
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Guide for the Care and use of Laboratory Animals: Eighth Edition severity or seriousness of the hazard); the exposure intensity, duration, and frequency (prevalence of the hazard); to some extent, the susceptibility (e.g., immune status) of the personnel; and the history of occupational illness and injury in the particular workplace (Newcomer 2002; NRC 1997). Ongoing identification and evaluation of hazards call for periodic inspections and reporting of potential hazardous conditions or “near miss” incidents. Facilities, Equipment, and Monitoring The facilities required to support the OHSP will vary depending on the scope and activities of the Program. Their design should preferentially use engineering controls and equipment to minimize exposure to anticipated hazards (also see Chapter 5). Because a high standard of personal cleanliness is essential, changing, washing, and showering facilities and supplies appropriate to the Program should be available. Where biologic agents are used, the Centers for Disease Control and Prevention (CDC) and National Institutes of Health (NIH) publication Biosafety in Microbiological and Biomedical Laboratories (BMBL; DHHS 2009) and the USDA standards (USDA 2002) should be consulted for appropriate facility design and safety procedures. These design and safety features are based on the level of risk posed by the agents used. Special facilities and safety equipment may be needed to protect the animal care and investigative staff, other occupants of the facility, the public, animals, and the environment from exposure to hazardous biologic, chemical, and physical agents used in animal experimentation (DHHS 2009; Frasier and Talka 2005; NIH 2002). When necessary, these facilities should be separated from other animal housing and support areas, research and clinical laboratories, and patient care facilities. They should be appropriately identified and access to them limited to authorized personnel. Facilities, equipment, and procedures should also be designed, selected, and developed to reduce the possibility of physical injury or health risk to personnel (NIOSH 1997a,b). Engineering controls and equipment that address the risk of ergonomic injury in activities such as the lifting of heavy equipment or animals should be considered (AVMA 2008). Those are also frequently used to limit or control personnel exposure to animal allergens (Harrison 2001; Huerkamp et al. 2009). The potential for repetitive motion injuries in animal facilities (e.g., maintenance of large rodent populations and other husbandry activities) should also be assessed. The selection of appropriate animal housing systems requires professional knowledge and judgment and depends on the nature of the hazards in question, the types of animals used, the limitations or capabilities of the facilities, and the design of the experiments. Experimental animals should be housed so that possibly contaminated food and bedding, feces, and urine can be handled in a controlled manner. Appropriate facilities, equipment,
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Guide for the Care and use of Laboratory Animals: Eighth Edition and procedures should be used for bedding disposal. Safety equipment should be properly maintained and its function periodically validated. Appropriate methods should be used for assessing and monitoring exposure to potentially hazardous biologic, chemical, and physical agents where required (e.g., ionizing radiation) or where the possibility of exceeding permissible exposure limits exists (CFR 1984b). Personnel Training As a general rule, safety depends on trained personnel who rigorously follow safe practices. Personnel at risk should be provided with clearly defined procedures and, in specific situations, personal protective equipment to safely conduct their duties, understand the hazards involved, and be proficient in implementing the required safeguards. They should be trained regarding zoonoses, chemical, biologic, and physical hazards (e.g., radiation and allergies), unusual conditions or agents that might be part of experimental procedures (e.g., the use of human tissue in immunocompromised animals), handling of waste materials, personal hygiene, the appropriate use of PPE, and other considerations (e.g., precautions to be taken during pregnancy, illness, or immunosuppression) as appropriate to the risk imposed by their workplace. Personal Hygiene The use of good personal hygiene will often reduce the possibility of occupational injury and cross contamination. Appropriate policies should be established and enforced, and the institution should supply suitable attire and PPE (e.g., gloves, masks, face shields, headcovers, coats, coveralls, shoes or shoe covers) for use in the animal facility and laboratories in which animals are used. Soiled attire should be disposed of, laundered, or decontaminated by the institution as appropriate, and may require that special provisions be implemented if outside vendors are used. Personnel should wash and/or disinfect their hands and change clothing as often as necessary to maintain good personal hygiene. Outer garments worn in the animal rooms should not be worn outside the animal facility unless covered (NRC 1997). Personnel should not be permitted to eat, drink, use tobacco products, apply cosmetics, or handle or apply contact lenses in rooms and laboratories where animals are housed or used (DHHS 2009; NRC 1997; OSHA 1998a). Animal Experimentation Involving Hazards When selecting specific safeguards for animal experimentation with hazardous agents, careful attention should be given to procedures for animal care and housing, storage and distribution of the agents, dose preparation and administration, body fluid and tissue handling, waste and carcass disposal, items that might be used temporarily and removed from the site (e.g., written records, experimental devices, sample vials), and personal protection.
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Guide for the Care and use of Laboratory Animals: Eighth Edition Institutions should have written policies and procedures governing experimentation with hazardous biologic, chemical, and physical agents. An oversight process (such as the use of a safety committee) should be developed to involve persons who are knowledgeable in the evaluation and safe use of hazardous materials or procedures and should include review of the procedures and facilities to be used for specific safety concerns. Formal safety programs should be established to assess hazards, determine the safeguards needed for their control, and ensure that staff have the necessary training and skills and that facilities are adequate for the safe conduct of the research. Technical support should be provided to monitor and ensure compliance with institutional safety policies. A collaborative approach involving the investigator and research team, attending veterinarian, animal care technician, and occupational health and safety professionals may enhance compliance. The BMBL (DHHS 2009) and NRC (1997) recommend practices and procedures, safety equipment, and facility requirements for working with hazardous biologic agents and materials. Facilities that handle agents of unknown risk should consult with appropriate CDC personnel about hazard control and medical surveillance. The use of highly pathogenic “select agents and toxins” in research requires that institutions develop a program and procedures for procuring, maintaining, and disposing of these agents (CFR 1998, 2002a,b; NRC 2004; PL 107-56; PL 107-188; Richmond et al. 2003). The use of immunodeficient or genetically modified animals (GMAs) susceptible to or shedding human pathogens, the use of human tissues and cell lines, or any infectious disease model can lead to an increased risk to the health and safety of personnel working with the animals (Lassnig et al. 2005; NIH 2002). Hazardous agents should be contained in the study environment, for example through the use of airflow control during the handling and administering of hazardous agents, necropsies on contaminated animals (CDC and NIH 2000), and work with chemical hazards (Thomann 2003). Waste anesthetic gases should be scavenged to limit exposure. Personal Protection While engineering and administrative controls are the first considerations for the protection of personnel, PPE appropriate for the work environment, including clean institution-issued protective clothing, should be provided as often as necessary. Protective clothing and equipment should not be worn beyond the boundary of the hazardous agent work area or the animal facility (DHHS 2009). If appropriate, personnel should shower when they leave the animal care, procedure, or dose preparation areas. Personnel with potential exposure to hazardous agents or certain species should be provided with PPE appropriate to the situation (CFR 1984c); for example, personnel exposed to nonhuman primates should have PPE such
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Guide for the Care and use of Laboratory Animals: Eighth Edition Veterinary care must be provided if lesions or illnesses associated with restraint are observed. The presence of lesions, illness, or severe behavioral change often necessitates the temporary or permanent removal of the animal from restraint. The purpose of the restraint and its duration should be clearly explained to personnel involved with the study. Multiple Survival Surgical Procedures Surgical procedures in the laboratory setting may be categorized as major or minor (USDA 1985). Whether a procedure is major or minor should be evaluated on a case-by-case basis, as determined by the veterinarian and IACUC (NRC 2003b; Silverman et al. 2007; for additional discussion see Chapter 4, Surgical Procedures). Regardless of classification, multiple surgical procedures on a single animal should be evaluated to determine their impact on the animal’s wellbeing. Multiple major surgical procedures on a single animal are acceptable only if they are (1) included in and essential components of a single research project or protocol, (2) scientifically justified by the investigator, or (3) necessary for clinical reasons. Conservation of scarce animal resources may justify the conduct of multiple major surgeries on a single animal, but the application of such a practice on a single animal used in separate protocols is discouraged and should be reviewed critically by the IACUC. When applicable, the IO must submit a request to the USDA/APHIS and receive approval in order to allow a regulated animal to undergo multiple major survival surgical procedures in separate unrelated research protocols (USDA 1985, 1997a). Justifications for allowing animals not regulated by the USDA to undergo multiple survival procedures that meet the above criteria should conform to those required for regulated species. If multiple survival surgery is approved, the IACUC should pay particular attention to animal well-being through continuing evaluation of outcomes. Cost savings alone is not an adequate reason for performing multiple major survival surgical procedures. Some procedures characterized as minor may induce substantial postprocedural pain or impairment and should similarly be scientifically justified if performed more than once in a single animal. Food and Fluid Regulation Regulation of food or fluid intake may be required for the conduct of some physiological, neuroscience, and behavioral research protocols. The regulation process may entail scheduled access to food or fluid sources, so an animal consumes as much as desired at regular intervals, or restriction, in which the total volume of food or fluid consumed is strictly monitored and controlled (NRC 2003b). The objective when these studies are being planned and executed should be to use the
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Guide for the Care and use of Laboratory Animals: Eighth Edition least restriction necessary to achieve the scientific objective while maintaining animal well-being. The development of animal protocols that involve the use of food or fluid regulation requires the evaluation of three factors: the necessary level of regulation, potential adverse consequences of regulation, and methods for assessing the health and well-being of the animals (NRC 2003b). In addition, the following factors influence the amount of food or fluid restriction that can be safely used in a specific protocol: the species, strain, or stock, gender, and age of the animals; thermoregulatory demand; type of housing; time of feeding, nutritive value, and fiber content of the diet (Heiderstadt et al. 2000; Rowland 2007); and prior experimental manipulation. The degree of food or fluid restriction necessary for consistent behavioral performance is influenced by the difficulty of the task, the individual animal, the motivation required of the animal, and the effectiveness of animal training for a specific protocol-related task. The animals should be closely monitored to ensure that food and fluid intake meets their nutritional needs (Toth and Gardiner 2000). Body weights should be recorded at least weekly and more often for animals requiring greater restrictions (NRC 2003b). Written records should be maintained for each animal to document daily food and fluid consumption, hydration status, and any behavioral and clinical changes used as criteria for temporary or permanent removal of an animal from a protocol (Morton 2000; NRC 2003b). In the case of conditioned-response research protocols, use of a highly preferred food or fluid as positive reinforcement, instead of restriction, is recommended. Caloric restriction, as a husbandry technique and means of weight control, is discussed in Chapter 3. Use of Non-Pharmaceutical-Grade Chemicals and Other Substances The use of pharmaceutical-grade chemicals and other substances ensures that toxic or unwanted side effects are not introduced into studies conducted with experimental animals. They should therefore be used, when available, for all animal-related procedures (USDA 1997b). The use of non-pharmaceutical-grade chemicals or substances should be described and justified in the animal use protocol and be approved by the IACUC (Wolff et al. 2003); for example, the use of a non-pharmaceutical-grade chemical or substance may be necessary to meet the scientific goals of a project or when a veterinary or human pharmaceutical-grade product is unavailable. In such instances, consideration should be given to the grade, purity, sterility, pH, pyrogenicity, osmolality, stability, site and route of administration, formulation, compatibility, and pharmacokinetics of the chemical or substance to be administered, as well as animal welfare and scientific issues relating to its use (NIH 2008).
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Guide for the Care and use of Laboratory Animals: Eighth Edition Field Investigations 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. Additionally, occupational health and safety issues, including zoonoses, should be reviewed by the institution’s health and safety committee or office, with assurances to the IACUC that the field study does not compromise the health and safety of either animals or persons in the field. Principal investigators conducting field research should be knowledgeable about relevant zoonotic diseases, associated safety issues, and any laws or regulations that apply. Exceptions to the above should be clearly defined and evaluated by the IACUC. In preparing the design of a field study, investigators are encouraged to consult with relevant professional societies and available guidelines (see Appendix A). Veterinary input may be needed for projects involving capture, individual identification, sedation, anesthesia, surgery, recovery, holding, transportation, release, or euthanasia. Issues associated with these activities are similar if not identical to those for species maintained and used in the laboratory. When species are removed from the wild, the protocol should include plans for either a return to their habitat or their final disposition, as appropriate. The Guide does not purport to be a compendium of all information regarding field biology and methods used in wildlife investigations, but the basic principles of humane care and use apply to animals living under natural conditions. IACUCs engaged in the review of field studies are encouraged to consult with a qualified wildlife biologist. Agricultural Animals The use of agricultural animals in research is subject to the same ethical considerations as for other animals in research, although it is often categorized as either biomedical or agricultural because of government regulations and policies, institutional policies, administrative structure, funding sources, and/or user goals (Stricklin et al. 1990). This categorization has led to a dual system with different criteria for evaluating protocols and standards of housing and care for animals of the same species on the basis of stated biomedical or agricultural research objectives (Stricklin and Mench 1994). With some studies, differences in research goals may lead to a clear distinction between biomedical and agricultural research. For example, animal models of human diseases, organ transplantation, and major surgery are considered biomedical uses; and studies on food and fiber production, such as feeding trials, are usually considered agricultural uses. But when the distinction is unclear, as in the case of some nutrition and
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Guide for the Care and use of Laboratory Animals: Eighth Edition 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. Regardless of the category of research, institutions are expected to provide oversight of all research animals and ensure that pain and distress are minimized. The protocol, rather than the category of research, should determine the setting (farm or laboratory). Housing systems for agricultural animals used in biomedical research may or may not differ from those used in agricultural research; animals used in either type of research can be housed in cages, stalls, paddocks, or pastures (Tillman 1994). Some agricultural studies need uniform conditions to minimize environmental variability, and some biomedical studies are conducted in farm settings. Agricultural research often necessitates that animals be managed according to contemporary farm production practices (Stricklin and Mench 1994), and natural environmental conditions might be desirable for agricultural research, whereas control of environmental conditions to minimize variation might be desirable in biomedical research (Tillman 1994). The Guide applies to agricultural animals used in biomedical research, including those maintained in typical farm settings. For animals maintained in a farm setting, the Guide for the Care and Use of Agricultural Animals in Research and Teaching (FASS 2010) is a useful resource. Information about environmental enrichment, transport, and handling may be helpful in both agricultural and biomedical research settings. Additional information about facilities and management of farm animals in an agricultural setting is available from the Midwest Plan Service (1987) and from agricultural engineers or animal science experts. Postapproval Monitoring Continuing IACUC oversight of animal activities is required by federal laws, regulations, and policies. A variety of mechanisms can be used to facilitate ongoing protocol assessment and regulatory compliance. Postapproval monitoring (PAM) is considered here in the broadest sense, consisting of all types of protocol monitoring after the IACUC’s initial protocol approval. PAM helps ensure the well-being of the animals and may also provide opportunities to refine research procedures. Methods include continuing protocol review; laboratory inspections (conducted either during regular facilities inspections or separately); veterinary or IACUC observation of selected procedures; observation of animals by animal care, veterinary, and IACUC staff and members; and external regulatory inspections and assess-
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Guide for the Care and use of Laboratory Animals: Eighth Edition ments. The IACUC, veterinary, animal care, and compliance staff may all conduct PAM, which may also serve as an educational tool. Continuing protocol review typically consists of an annual update or review as well as the triennial review required by the PHS. The depth of such reviews varies from a cursory update to a full committee review of the entire protocol. Some institutions use the annual review as an opportunity for the investigator to submit proposed amendments for future procedures, to provide a description of any adverse or unanticipated events, and to provide updates on work progress. For the triennial review, many institutions require a complete new protocol submission and may request a progress report on the use of animals during the previous 3 years. Both the Health Research Extension Act and the AWA require the IACUC to inspect animal care and use facilities, including sites used for animal surgeries, every 6 months. As part of a formal PAM program some institutions combine inspection of animal study sites with concurrent review of animal protocols. Based on risks to animals and their handlers, other study areas may require more or less frequent inspections. Examples of effective monitoring strategies include examination of surgical areas, including anesthetic equipment, use of appropriate aseptic technique, and handling and use of controlled substances review of protocol-related health and safety issues review of anesthetic and surgical records regular review of adverse or unexpected experimental outcomes affecting the animals observation of laboratory practices and procedures and comparison with approved protocols. Institutions may also consider the use of veterinary staff and/or animal health technicians to observe increased risk procedures for adverse events (e.g., novel survival surgeries, pain studies, tumor growth studies) and report their findings for review by the IACUC. The level of formality and intensity of PAM should be tailored to institutional size and complexity, and in all cases should support a culture of care focusing on the animals’ well-being (Klein and Bayne 2007). Regardless of the methods used or who conducts and coordinates the monitoring, PAM programs are more likely to succeed when the institution encourages an educational partnership with investigators (Banks and Norton 2008; Collins 2008; Dale 2008; Lowman 2008; Plante and James 2008; Van Sluyters 2008).
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Guide for the Care and use of Laboratory Animals: Eighth Edition DISASTER PLANNING AND EMERGENCY PREPAREDNESS Animal facilities may be subject to unexpected conditions that result in the catastrophic failure of critical systems or significant personnel absenteeism, or other unexpected events that severely compromise ongoing animal care and well-being (ILAR 2010). Facilities must therefore have a disaster plan. The plan should define the actions necessary to prevent animal pain, distress, and deaths due to loss of systems such as those that control ventilation, cooling, heating, or provision of potable water. If possible the plan should describe how the facility will preserve animals that are necessary for critical research activities or are irreplaceable. Knowledge of the geographic locale may provide guidance as to the probability of a particular type of disaster. Disaster plans should be established in conjunction with the responsible investigator(s), taking into consideration both the priorities for triaging animal populations and the institutional needs and resources. Animals that cannot be relocated or protected from the consequences of the disaster must be humanely euthanized. The disaster plan should identify essential personnel who should be trained in advance in its implementation. Efforts should be taken to ensure personnel safety and provide access to essential personnel during or immediately after a disaster. Such plans should be approved by the institution and be part of the overall institutional disaster response plan that is coordinated by the IO or another senior-level administrator. Law enforcement and emergency personnel should be provided with a copy of the plan for comment and integration into broader, areawide planning (Vogelweid 1998). REFERENCES AAALAC [Association for Assessment and Accreditation of Laboratory Animal Care] International. 2003. Who’s responsible for offsite animals? Connection Spring:6-11, 13. Available at www.aaalac.org/publications. ACLAM [American College of Laboratory Animal Medicine]. 1996. Adequate Veterinary Care. Available at www.aclam.org/education/guidelines/position_adequatecare.html; accessed May 10, 2010. Anderson LC. 2007. Institutional and IACUC responsibilities for animal care and use education and training programs. ILAR J 48:90-95. AVMA [American Veterinary Medical Association]. 2008. Introduction to Ergonomics Guidelines for Veterinary Practice. April. Available at www.avma.org/issues/policy/ergonomics.asp; accessed May 10, 2010. AVMA. 2010. Programs accredited by the AVMA Committee on Veterinary Technician Education and Activities (CVTEA). Available at www.avma.org/education/cvea/vettech_programs/vettech_programs.asp; accessed January 4, 2010. Banks RE, Norton JN. 2008. A sample postapproval monitoring program in academia. ILAR J 49:402-418. Bayne KA, Garnett NL. 2008. Mitigating risk, facilitating research. ILAR J 49:369-371.
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Guide for the Care and use of Laboratory Animals: Eighth Edition 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 emotions 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. 2001. Assessment and treatment of laboratory animal allergy. ILAR J 42:55-64. Bush RK, Stave GM. 2003. Laboratory animal allergy: An update. ILAR J 44:28-51. CCAC [Canadian Council on Animal Care]. 1993. Guide to the Care and Use of Experimental Animals, vol 1, 2nd ed. Olfert ED, Cross BM, McWilliam AA, eds. Ontario: CCAC. CCAC. 1998. Guidelines on Choosing an Appropriate Endpoint in Experiments Using Animals for Research, Teaching and Testing. Ottawa. Available at www.ccac.ca/en/CCAC_Programs/Guidelines_Policies/gdlines/endpts/appopen.htm; accessed May 10, 2010. CDC [Centers for Disease Control and Prevention] and NIH [National Institutes of Health]. 2000. Primary Containment for Biohazards: Selection, Installation and Use of Biological Safety Cabinets, 2nd ed. Washington: Government Printing Office. Available at www.cdc.gov/od/ohs/biosfty/bsc/bsc.htm; accessed May 25, 2010. CFR [Code of Federal Regulations]. 1984a. Title 10, Part 20. Standards for Protection against Radiation. Washington: Office of the Federal Register. CFR. 1984b. Title 29, Part 1910, Occupational Safety and Health Standards, Subpart G, Occupational Health and Environmental Control, and Subpart Z, Toxic and Hazardous Substances. Washington: Office of the Federal Register. CFR. 1984c. Title 29, Part 1910. Occupational Safety and Health Standards; Subpart I, Personal Protective Equipment. Washington: Office of the Federal Register. CFR. 1998. Title 29, Section 1910.120. Inspection Procedures for the Hazardous Waste Operations and Emergency Response Standard. Washington: Office of the Federal Register. April 24. CFR. 2002a. Title 42, Part 73. Possession, Use and Transfer of Select Agents and Toxins. Washington: Office of the Federal Register. December 13. CFR. 2002b. Title 7, Part 331; and Title 9, Part 121. Agricultural Bioterrorism Protection Act of 2002: Possession, Use and Transfer of Select Agents and Toxins. Washington: Office of the Federal Register. December 13. Cohen JI, Davenport DS, Stewart JA, Deitchmann S, Hilliard JK, Chapman LE, B Virus Working Group. 2002. Recommendations for prevention of and therapy for exposure to B virus (Cercopithecine herpesvirus 1). Clin Infect Dis 35:1191-1203. Colby LA, Turner PV, Vasbinder MA. 2007. Training strategies for laboratory animal veterinarians: Challenges and opportunities. ILAR J 48:143-155. Collins JG. 2008. Postapproval monitoring and the IACUC. ILAR J49:388-392. Conarello SL, Shepard MJ. 2007. Training strategies for research investigators and technicians. ILAR J 48:120-130. Crawley JN. 1999. Behavioral phenotyping of transgenic and knockout mice: Experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests. Brain Res835:18-26. Dale WE. 2008. Postapproval monitoring and the role of the compliance office. ILAR J 49:393-401. Dennis MB. 1999. Institutional animal care and use committee review of genetic engineering. In: Gonder JC, Prentice ED, Russow L-M, eds. Genetic Engineering and Animal Welfare: Preparing for the 21st Century. Greenbelt MD: Scientists Center for Animal Welfare. Dennis MB. 2000. Humane endpoints for genetically engineered animal models. ILAR J 41:94-98.
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Guide for the Care and use of Laboratory Animals: Eighth Edition DHHS [Department of Health and Human Services]. 2009. Biosafety in Microbiological and Biomedical Laboratories, 5th ed. Chosewood LC, Wilson DE, eds. Washington: Government Printing Office. Available at http://www.cdc.gov/biosafety/publications/bmbl5/index.htm; accessed July 30, 2010. FASS [Federation of Animal Science Societies]. 2010. Guide for the Care and Use of Agricultural Animals in Research and Teaching, 3rd ed. Champlain, IL: FASS. Fechter LD. 1995. Combined effects of noise and chemicals. Occup Med 10:609-621. Foshay WR, Tinkey PT. 2007. Evaluating the effectiveness of training strategies: Performance goals and testing. ILAR J 48:156-162. Frasier D, Talka J. 2005. Facility design considerations for select agent animal research. ILAR J 46:23-33. Gonder JC. 2002. Regulatory compliance. In: Suckow MA, Douglas FA, Weichbrod RH, eds. Management of Laboratory Animal Care and Use Programs. Boca Raton, FL: CRC Press. p 163-185. Gondo Y. 2008. Trends in large-scale mouse mutagenesis: From genetics to functional genomics. Nat Rev Genet 9:803-810. Gordon S. 2001. Laboratory animal allergy: A British perspective on a global problem. ILAR J 42:37-46. Gordon S, Wallace J, Cook A, Tee RD, Newman Taylor AJ. 1997. Reduction of exposure to laboratory animal allergens in the workplace. Clin Exp Allergy 27:744-751. Greene ME, Pitts ME, James ML. 2007. Training strategies for institutional animal care and use committee (IACUC) members and the institutional official (IO). ILAR J 48:131-142. Harrison DJ. 2001. Controlling exposure to laboratory animal allergens. ILAR J 42:17-36. Heiderstadt KM, McLaughlin RM, Wright DC, Walker SE, Gomez-Sanchez CE. 2000. The effect of chronic food and water restriction on open-field behaviour and serum corticosterone levels in rats. Lab Anim 34:20-28. Hendriksen CFM, Steen B. 2000. Refinement of vaccine potency testing with the use of humane endpoints. ILAR J 41:105-113. Huerkamp MJ, Gladle MA, Mottet MP, Forde K. 2009. Ergonomic considerations and allergen management. In: Hessler JR, Lerner NMD, eds. Planning and Designing Research Animal Facilities. San Diego: Elsevier. p 115-128. ILAR [Institute for Laboratory Animal Research, National Research Council]. 2000. Humane Endpoints for Animals Used in Biomedical Research and Testing. ILAR J 41:59-123. ILAR. 2010. Disaster planning and management. ILAR J 51:101-192. IRAC [Interagency Research Animal Committee]. 1985. US Government Principles for Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training. Federal Register, May 20, 1985. Washington: Office of Science and Technology Policy. Available at http://oacu.od.nih.gov/regs/USGovtPrncpl.htm; accessed May 10, 2010. Klein HJ, Bayne KA. 2007. Establishing a culture of care, conscience, and responsibility: Addressing the improvement of scientific discovery and animal welfare through science-based performance standards. ILAR J 48:3-11. Kreger MD. 1995. Training Materials for Animal Facility Personnel: AWIC Quick Bibliography Series, 95-08. Beltsville MD: National Agricultural Library. Lassnig C, Kolb A, Strobl B, Enjuanes L, Müller M. 2005. Studying human pathogens in human models: Fine tuning the humanized mouse. Transgenic Res 14:803-806. Laule GE, Bloomsmith MA, Schapiro SJ. 2003. The use of positive reinforcement training techniques to enhance the care, management, and welfare of primates in the laboratory. J Appl Anim Welf Sci 6:163-173. Lowman RP. 2008. The institutional official and postapproval monitoring: The view from 10,000 feet. ILAR J49:379-387.
OCR for page 38
Guide for the Care and use of Laboratory Animals: Eighth Edition Mann MD, Prentice ED. 2004. Should IACUCs review scientific merit of animal research projects? Lab Anim (NY) 33:26-31. McCullough NV. 2000. Personal respiratory protection. In: Fleming DO, Hunt DL, eds. Biological Safety Principles and Practices. Washington: ASM Press. p 383-404. Meunier LD. 2006. Selection, acclimation, training and preparation of dogs for the research setting. ILAR J 47:326-347. Midwest Plan Service. 1987. Structures and Environment Handbook, 11th ed. rev. Ames: Midwest Plan Service, Iowa State University. Miller G. 2007. Science and the public: Animal extremists get personal. Science 318:1856-1858. Moorehead RA, Sanchez OH, Baldwin RM, Khokha R. 2003. Transgenic overexpression of IGF-II induces spontaneous lung tumors: A model for human lung adenocarcinoma. Oncogene 22:853-857. Morton DB. 2000. A systematic approach for establishing humane endpoints. ILAR J 41:80-86. Morton WR, Knitter GH, Smith PV, Susor TG, Schmitt K. 1987. Alternatives to chronic restraint of nonhuman primates. JAVMA 191:1282-1286. Mumphrey SM, Changotra H, Moore TN, Heimann-Nichols ER, Wobus CE, Reilly MJ, Moghadamfalahi M, Shukla D, Karst SM. 2007. Murine norovirus 1 infection is associated with histopathological changes in immunocompetent hosts, but clinical disease is prevented by STAT1-dependent interferon responses. J Virol 81:3251-3263. Newcomer CE. 2002. Hazard identification and control. In: Suckow MA, Douglas FA, Weichbrod RH, eds. Management of Laboratory Animal Care and Use Programs. Boca Raton, FL: CRC Press. p 291-324. NIH [National Institutes of Health]. 2002. Guidelines for Research Involving Recombinant DNA Molecules. April. Available at http://oba.od.nih.gov/rdna/nih_guidelines_oba.html; accessed May 20, 2010. NIH. 2008. Guidelines for the Use of Non-Pharmaceutical-Grade Chemicals/Compounds in Laboratory Animals. Animal Research Advisory Committee, Office of Animal Care and Use, NIH. Available at http://oacu.od.nih.gov/ARAC/documents/Pharmaceutical_Compounds.pdf; accessed May 20, 2010. NIOSH [National Institute for Occupational Safety and Health]. 1997a. Elements of Ergonomics Programs: A Primer Based on Workplace Evaluations of Musculoskeletal Disorders (NIOSH Publication No. 97-117). Cincinnati: NIOSH. p 16-24. NIOSH. 1997b. Musculoskeletal Disorders and Workplace Factors: A Critical Review of Epidemiologic Evidence for Work-Related Musculoskeletal Disorders of the Neck, Upper Extremity, and Low Back. Bernard B, ed. Cincinnati: DHHS, PHS, CDDC, NIOSH. p 1-12. NRC [National Research Council]. 1991. Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs. Washington: National Academy Press. NRC. 1997. Occupational Health and Safety in the Care and Use of Research Animals. Washington: National Academy Press. NRC. 2003a. Occupational Health and Safety in the Care and Use of Nonhuman Primates. Washington: National Academies Press. NRC. 2003b. Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research. Washington: National Academies Press. NRC. 2004. Biotechnology Research in an Age of Terrorism. Washington: National Academies Press. OECD [Organisation for Economic Co-operation and Development]. 1999. Guidance Document on Humane Endpoints for Experimental Animals Used in Safety Evaluation Studies. Paris: OECD.
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Guide for the Care and use of Laboratory Animals: Eighth Edition Olfert ED, Godson DL. 2000. Humane endpoints for infectious disease animal models. ILAR J 41:99-104. OSHA [Occupational Safety and Health Administration]. 1998a. Occupational Safety and Health Standards. Subpart G, Occupational Health and Environmental Controls (29 CFR 1910). Washington: Department of Labor. OSHA. 1998b. Occupational Safety and Health Standards. Subpart Z, Toxic and Hazardous Substances, Bloodborne Pathogens (29 CFR 1910.1030). Washington: Department of Labor. OSHA. 1998c. Occupational Safety and Health Standards. Subpart G, Occupational Health and Environmental Controls, Occupational Noise Exposure (29 CFR 1910.95). Washington: Department of Labor. OSHA. 1998d. Occupational Safety and Health Standards. Subpart I, Personal Protective Equipment, Respiratory Protection (29 CFR 1910.134). Washington: Department of Labor. Paster EV, Villines KA, Hickman DL. 2009. Endpoints for mouse abdominal tumor models: Refinement of current criteria. Comp Med 59:234-241. PHS [Public Health Service]. 2002. Public Health Service Policy on Humane Care and Use of Laboratory Animals. Department of Health and Human Services, National Institutes of Health, Office of Laboratory Animal Welfare. Available at http://grants.nih.gov/grants/olaw/references/phspol.htm; accessed January 14, 2010. PL [Public Law] 104-191. 1996. Health Insurance Portability and Accountability Act (HIPAA) of 1996. Washington: Government Printing Office. PL 107-56. 2001. Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism (USA PATRIOT) Act of 2001. Washington: Government Printing Office. October 26. PL 107-188. 2002. Public Health Security and Bioterrorism Preparedness and Response Act of 2002. Washington: Government Printing Office. June 12. Plante A, James ML. 2008. Program oversight enhancements (POE): The big PAM. ILAR J 49:419-425. Prescott MJ, Buchanan-Smith HM. 2003. Training nonhuman primates using positive reinforcement techniques. J Appl Anim Welf Sci6:157-161. Pritt S, Duffee N. 2007. Training strategies for animal care technicians and veterinary technical staff. ILAR J 48:109-119. Reeb-Whitaker CK, Harrison, DJ, Jones RB, Kacergis JB, Myers DD, Paigen B. 1999. Control strategies for aeroallergens in an animal facility. J Allergy Clin Immunol 103:139-146. Reinhardt V. 1991. Training adult male rhesus monkeys to actively cooperate during in-homecage venipuncture. Anim Technol 42:11-17. Reinhardt V. 1995. Restraint methods of laboratory non-human primates: A critical review. Anim Welf 4:221-238. Richmond JY, Hill RH, Weyant RS, Nesby-O’Dell SL, Vinson PE. 2003. What’s hot in animal biosafety? ILAR J 44:20-27. Rowland NE. 2007. Food or fluid restriction in common laboratory animals: Balancing welfare considerations with scientific inquiry. Comp Med 57:149-160. Sargent EV, Gallo F. 2003. Use of personal protective equipment for respiratory protection. ILAR J 44:52-56. Sass N. 2000. Humane endpoints and acute toxicity testing. ILAR J 41:114-123. Sauceda R, Schmidt MG. 2000. Refining macaque handling and restraint techniques. Lab Anim29:47-49. Schweitzer IB, Smith E, Harrison DJ, Myers DD, Eggleston PA, Stockwell JD, Paigen B, Smith AL. 2003. Reducing exposure to laboratory animal allergens. Comp Med 53:487-492. Seward JP. 2001. Medical surveillance of allergy in laboratory animal handlers. ILAR J 42:47-54. Silverman J, Sukow MA, Murthy S, eds. 2007. The IACUC Handbook, 2nd ed. Boca Raton, FL: CRC Press.
OCR for page 40
Guide for the Care and use of Laboratory Animals: Eighth Edition Stokes WS. 2000. Reducing unrelieved pain and distress in laboratory animals using humane endpoints. ILAR J 41:59-61. Stokes WS. 2002. Humane endpoints for laboratory animals used in regulatory testing. ILAR J 43:S31-S38. Stricklin WR, Mench JA. 1994. Oversight of the use of agricultural animals in university teaching and research. ILAR News 36:9-14. Stricklin WR, Purcell D, Mench JA. 1990. Farm animals in agricultural and biomedical research. In: The Well-Being of Agricultural Animals in Biomedical and Agricultural Research: Proceedings from a SCAW-Sponsored Conference, September 6-7. Washington: Scientists Center for Animal Welfare. p 1-4. Thomann WR. 2003. Chemical safety in animal care, use, and research. ILAR J 44:13-19. Thulin H, Bjorkdahl M, Karlsson AS, Renstrom A. 2002. Reduction of exposure to laboratory animal allergens in a research laboratory. Ann Occup Hyg 46:61-68. Tillman P. 1994. Integrating agricultural and biomedical research policies: Conflicts and opportunities. ILAR News 36:29-35. Toth LA. 1997. The moribund state as an experimental endpoint. Contemp Top Lab Anim Sci 36:44-48. Toth LA. 2000. Defining the moribund condition as an experimental endpoint for animal research. ILAR J 41:72-79. Toth LA, Gardiner TW. 2000. Food and water restriction protocols: Physiological and behavioral considerations. Contemp Top Lab Anim Sci 39:9-17. UKCCCR [United Kingdom Coordinating Committee on Cancer Research]. 1997. Guidelines for the Welfare of Animals in Experimental Neoplasia, 2nd ed. London: UKCCCR. USC [United States Code]. Title 42, Chapter 6a, Subchapter III, Part H, Section 289d: Animals in Research. Available at http://uscode.house.gov/download/pls/42CGA.txt. USDA [US Department of Agriculture]. 1985. 9 CFR 1A. (Title 9, Chapter 1, Subchapter A): Animal Welfare. Available at http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?sid=8314313bd7adf2c9f1964e2d82a88d92andc=ecfrandtpl=/ecfrbrowse/Title09/9cfrv1_02.tpl; accessed January 14, 2010. USDA. 1997a. APHIS Policy #14, “Multiple Survival Surgery: Single vs. Multiple Procedures” (April 14). Available at www.aphis.usda.gov/animal_welfare/downloads/policy/policy14.pdf; accessed January 4, 2010. USDA. 1997b. APHIS Policy #3, “Veterinary Care” (July 17). Available at www.aphis.usda.gov/animal_welfare/downloads/policy/policy3.pdf; accessed January 9, 2010. USDA. 2002. Facilities Design Standards. Manual 242.1. Available at www.afm.ars.usda.gov/ppweb/PDF/242-01M.pdf; accessed May 10, 2010. Van Sluyters RC. 2008. A guide to risk assessment in animal care and use programs: The metaphor of the 3-legged stool. ILAR J49:372-378. Yeates JW, Main DCJ. 2009. Assesment of positive welfare: A review. Vet Rev 175:293-300. Vogelweid CM. 1998. Developing emergency management plans for university laboratory animal programs and facilities. Contemp Top Lab Anim Sci 37:52-56. Wallace J. 2000. Humane endpoints and cancer research. ILAR J 41:87-93. Wolff A, Garnett N, Potkay S, Wigglesworth C, Doyle D, Thornton, D. 2003. Frequently asked questions about the Public Health Service Policy on Humane Care and Use of Laboratory Animals. Lab Anim 32(9):33-36. Wolfle TL, Bush RK. 2001. The science and pervasiveness of laboratory animal allergy. ILAR J 42:1-3. Wood RA. 2001. Laboratory animal allergens. ILAR J 42:12-16.