Proper care, use, and humane treatment of animals used in research, testing, and education (referred to in this Guide as animal care and use) require scientific and professional judgment based on knowledge of the needs of the animals and the special requirements of the research, testing, and educational programs. The guidelines in this section are intended to aid in developing institutional policies governing the care and use of animals.
Each institution should establish and provide resources for an animal care and use program that is managed in accord with this Guide and in compliance with applicable federal, state, and local laws and regulations, such as the federal Animal Welfare Regulations, or AWRs (CFR 1985), and Public Health Service Policy on Humane Care and Use of Laboratory Animals, or PHS Policy (PHS 1996). To implement the recommendations in this Guide effectively, an institutional animal care and use committee (IACUC) must be established to oversee and evaluate the program.
Responsibility for directing the program is
generally given either to a veterinarian with training or experience
in laboratory animal science and medicine or to another qualified
professional. At least one veterinarian qualified through experience
or training in laboratory animal science and medicine or in the
species being used must be associated with the program. The institution
is responsible for maintaining records of the activities of the
IACUC and for conducting an occupational health and safety program.
INSTITUTIONAL POLICIES AND RESPONSIBILITIES
9
The responsible administrative official at each institution must appoint an IACUC, also referred to as "the committee," to oversee and evaluate the institution' 5 animal program, procedures, and facilities to ensure that they are consistent with the recommendations in this Guide, the AWRs, and the PHS Policy. It is the institution's responsibility to provide suitable orientation, background materials, access to appropriate resources, and, if necessary, specific training to assist IACUC members in understanding and evaluating issues brought before the committee.
Committee membership should include the following:
The size of the institution and the nature and extent of the research, testing, and educational programs will determine the number of members of the committee and their terms of appointment. Additional information about committee composition can be found in the PHS Policy and the AWRs.
The committee is responsible for oversight and evaluation of the animal care and use program and its components described in this Guide. Its functions include inspection of facilities; evaluation of programs and animal-activity areas; submission of reports to responsible institutional officials; review of proposed uses of animals in research, testing, or education (i.e., protocols); and establishment of a mechanism for receipt and review of concerns involving the care and use of animals at the institution.
The IACUC must meet as often as necessary
to fulfill its responsibilities, but it should meet at least once
every 6 months. Records of committee meetings and of results of
deliberations should be maintained. The committee should review
the animal-care program and inspect the animal facilities and
activity areas at least once every 6 months. After review and
inspection, a written report, signed by a majority of the IACUC,
should be made to the responsible administrative officials of
the institution on the status of the animal care and use program
and
10 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS
other activities as stated herein and as required
by federal, state, or local regulations and policies. Protocols
should be reviewed in accord with the AWRs, the PHS Policy, U.S.
Government Principles for Utilization and Care of Vertebrate Animals
Used in Testing, Research, and Training (IRAC 1985; see Appendix
D), and this Guide (see footnote, p.2).
The following topics should be considered
in the preparation and review of animal care and use protocols:
Occasionally, protocols include procedures
that have not been previously encountered or that have the potential
to cause pain or distress that cannot be reliably controlled.
Such procedures might include physical restraint, multiple major
survival surgery, food or fluid restriction, use of adjuvants,
use of death as an end point, use of noxious stimuli, skin or
corneal irritancy testing, allowance of excessive tumor burden,
intracardiac or orbital-sinus blood sampling, or the use of abnormal
environmental conditions. Relevant objective information regarding
the procedures and the purpose of the study should be sought from
the literature, veterinarians, investigators, and others knowledgeable
about the effects on animals. If little is known regarding a specific
procedure, limited pilot studies designed to assess the effects
of the procedure on the animals, conducted under IACUC oversight,
might be appropriate. General guidelines for evaluation
INSTITUTIONAL POLICIES AND RESPONSIBILITIES 11
of some of those methods are provided in this
section, but they might not apply in all instances.
Physical restraint is the use of manual or mechanical means to limit some or all of an animal' 5 normal movement for the purpose of examination, collection of samples, drug administration, therapy, or experimental manipulation. Animals are restrained for brief periods, usually minutes, in most research applications.
Animals can be physically restrained briefly either manually or with restraint devices. Restraint devices should be suitable in size, design, and operation to minimize discomfort or injury to the animal. Many dogs, nonhuman primates (e.g., Reinhardt 1991, 1995), and other animals can be trained, through use of positive reinforcement, to present limbs or remain immobile for brief procedures.
Prolonged restraint, including chairing of nonhuman primates, should be avoided unless it is essential for achieving research objectives and is approved by the IACUC. Less-restrictive systems that do not limit an animal's ability to make normal postural adjustments, such as the tether system for nonhuman primates and stanchions for farm animals, should be used when compatible with protocol objectives (Bryant 1980; Byrd 1979; Grandin 1991; McNamee and others 1984; Morton and others 1987; Wakeley and others 1974). When restraint devices are used, they should be specifically designed to accomplish research goals that are impossible or impractical to accomplish by other means or to prevent injury to animals or personnel.
The following are important guidelines for
restraint:
Major surgery penetrates and exposes a body
cavity or produces substantial
12 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS
impairment of physical or physiologic function.
Multiple major survival surgical procedures on a single animal
are discouraged but may be permitted if scientifically justified
by the user and approved by the IACUC. For example, multiple major
survival surgical procedures can be justified if they are related
components of a research project, if they will conserve scarce
animal resources (NRC 1990; see also footnote, p.2), or if they
are needed for clinical reasons. If multiple major 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 (AWRs).
When experimental situations require food or fluid restriction, at least minimal quantities of food and fluid should be available to provide for development of young animals and to maintain long-term well-being of all animals. Restriction for research purposes should be scientifically justified, and a program should be established to monitor physiologic or behavioral indexes, including criteria (such as weight loss or state of hydration) for temporary or permanent removal of an animal from the experimental protocol (Van Sluyters and Oberdorfer 1991). Restriction is typically measured as a percentage of the ad libitum or normal daily intake or as percentage change in an animal's body weight.
Precautions that should be used in cases of
fluid restriction to avoid acute or chronic dehydration include
daily recording of fluid intake and recording of body weight at
least once a week (NIH 1990)-or more often, as might be needed
for small animals, such as rodents. Special attention should be
given to ensuring that animals consume a suitably balanced diet
(NYAS 1988) because food consumption might decrease with fluid
restriction. The least restriction that will achieve the scientific
objective should be used. In the case of conditioned-response
research protocols, use of a highly preferred food or fluid as
positive reinforcement, instead of restriction, is recommended.
Dietary control for husbandry or clinical purposes is addressed
in Chapter 2.
Adequate veterinary care must be provided, including access to all animals for evaluation of their health and well-being. Institutional mission, programmatic goals, and size of the animal program will determine the need for full-time, part-time, or consultative veterinary services. Visits by a consulting or part-time veterinarian should be at intervals appropriate to programmatic needs. For specific responsibilities of the veterinarian, see Chapter 3.
Ethical, humane, and scientific considerations
sometimes require the use of sedatives, analgesics, or anesthetics
in animals (see Appendix A). An attending
INSTITUTIONAL POLICIES AND RESPONSIBILITIES 13
veterinarian (i.e., a veterinarian who has
direct or delegated authority) should give research personnel
advice that ensures that humane needs are met and are compatible
with scientific requirements. The AWRs and PHS Policy require
that the attending veterinarian have the authority to. oversee
the adequacy of other aspects of animal care and use. These can
include animal husbandry and nutrition, sanitation practices,
zoonosis control, and hazard containment.
AWRs and PHS Policy require institutions to ensure that people caring for or using animals are qualified to do so. The number and qualifications of personnel required to conduct and support an animal care and use program depend on several factors, including the type and size of 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, and educational activities.
Personnel caring for animals should be appropriately trained (see Appendix A, "Technical and Professional Education"), and the institution should provide for formal or on-the-job training to facilitate effective implementation of the program and humane care and use of animals. According to the programmatic scope, personnel will be required with expertise in other disciplines, such as animal husbandry, administration, laboratory animal medicine and pathology, occupational health and safety, behavioral management, genetic management, and various other aspects of research support.
There are a number of options for the training
of technicians. Many states have colleges with accredited programs
in veterinary technology (AVMA 1995); most are 2-year programs
that result in associate of science degrees, and some are 4-year
programs that result in bachelor of science degrees. Nondegree
training, with certification programs for laboratory animal technicians
and technologists, can be obtained from the American Association
for Laboratory Animal Science (AALAS). There are commercially
available training materials that are appropriate for self-study
(Appendix B). Personnel using or caring for animals should also
participate regularly in continuing-education activities relevant
to their responsibilities. They are encouraged to be involved
in local and national meetings of AALAS and other relevant professional
organizations. On-the-job training should be part of every technician's
job and should be supplemented with institution-sponsored discussion
and training programs and with reference materials applicable
to their jobs and the species with which they work (Kreger 1995).
Coordinators of institutional training programs can seek assistance
from the Animal Welfare Information Center (AWIC) 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
of some other countries are valuable additions to the libraries
of laboratory animal scientists (Appendix B).
14 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS
Investigators, technical personnel, trainees,
and visiting investigators who perform animal anesthesia, surgery,
or other experimental manipulations must be qualified through
training or experience to accomplish these tasks in a humane and
scientifically acceptable manner.
An occupational health and safety program
must be part of the overall animal care and use program (CDC and
NIH 1993; CFR 1984a,b,c; PHS Policy). The program must be consistent
with federal, state, and local regulations and should focus on
maintaining a safe and healthy workplace. The program will depend
on the facility, research activities, hazards, and animal species
involved. The National Research Council publication Occupational
Health and Safety in the Care and Use of Research Animals
(NRC In press) contains guidelines and references for establishing
and maintaining an effective, comprehensive program (also see
Appendix A). An effective program relies on strong administrative
support and interactions among several institutional functions
or activities, including the research program (as represented
by the investigator), the animal care and use program (as represented
by the veterinarian and the IACUC), the environmental health and
safety program, occupational-health services, and administration
(e.g., human resources, finance, and facility-maintenance personnel).
Operational and day-to-day responsibility for safety in the workplace,
however, resides with the laboratory or facility supervisor (e.g.,
principal investigator, facility director, or veterinarian) and
depends on performance of safe work practices by all employees.
Professional staff who conduct and support
research programs that involve hazardous biologic, chemical, or
physical agents (including ionizing and nonionizing radiation)
should be qualified to assess dangers associated with the programs
and to select safeguards appropriate to the risks. An effective
occupational health and safety program ensures that the risks
associated with the experimental use of animals are reduced to
acceptable levels. Potential hazards-such as animal bites, chemical
cleaning agents, allergens, and zoonoses-that are inherent in
or intrinsic to animal use should also be identified and evaluated.
Health and safety specialists with knowledge in appropriate disciplines
should be involved in the assessment of risks associated with
hazardous activities and in the development of procedures to manage
such risks. The extent and level of participation of personnel
in the occupational health and safety program should be based
on the hazards posed by the animals and materials used; on the
exposure intensity, duration, and frequency; on the susceptibility
of the personnel; and on the history of occupational illness and
injury in the particular workplace (Clark 1993).
INSTITUTIONAL POLICIES AND RESPONSIBILITIES
15
Personnel at risk should be provided with dearly defined procedures for conducting their duties, should understand the hazards involved, and should be proficient in implementing the required safeguards.
Personnel should be trained regarding zoonoses,
chemical safety, microbiologic and physical hazards (including
those related to radiation and allergies), unusual conditions
or agents that might be part of experimental procedures (including
the use of genetically engineered animals and the use of human
tissue in immunocompromised animals), handling of waste materials,
personal hygiene, and other considerations (e.g., precautions
to be taken during personnel pregnancy, illness, or decreased
immunocompetence) as appropriate to the risk imposed by their
workplace.
It is essential that all personnel maintain
a high standard of personal cleanliness. Clothing suitable for
use in the animal facility and laboratories in which animals are
used should be supplied and laundered by the institution. A commercial
laundering service is acceptable in many situations; however,
appropriate arrangements should be made to decontaminate clothing
exposed to potential hazards. Disposable gloves, masks, head covers,
coats, coveralls, and shoe covers might be desirable in some circumstances.
Personnel should wash their hands and change clothing as often
as necessary to maintain personal hygiene. Outer garments worn
in the animal rooms should not be worn outside the animal facility.
Personnel should not be permitted to eat, drink, use tobacco products,
or apply cosmetics in animal rooms.
Facilities required to support occupational health and safety concerns associated with animal care and use programs will vary. Because a high standard of personal cleanliness is essential, facilities and supplies for meeting this obligation should be provided. Washing and showering facilities appropriate to the program should be available. Facilities, equipment, and procedures should also be designed, selected, and developed to provide for ergonomically sound operations that reduce the potential of physical injury to personnel (such as might be caused by the lifting of heavy equipment or animals and the use of repetitive movements). Safety equipment should be properly maintained and routinely calibrated.
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, and the design of the experiments. Experimental animals
should be housed so that potentially contaminated food and bedding,
feces,
16 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS
and urine can be handled in a controlled manner. Facilities, equipment, and procedures should be provided for appropriate bedding disposal.
Appropriate methods should be used for assessing
exposure to potentially hazardous biologic, chemical, and physical
agents where the possibility of exceeding permissible exposure
limits (PELs) exists (CFR 1984b).
In selecting specific safeguards for animal experimentation with hazardous agents, careful attention should be given to procedures for animal care and housing, storage and disbursement of the agents, dose preparation and administration, body-fluid and tissue handling, waste and carcass disposal, and personal protection. Special safety equipment should be used in combination with appropriate management and safe practices. As a general rule, safety depends on trained personnel who rigorously follow safe practices.
Institutions should have written policies governing experimentation with hazardous biologic, chemical, and physical agents. An oversight process (such as use of a safety committee) should be developed to involve persons who are knowledgeable in the evaluation of hazards and safety issues. Because the use of animals in such studies requires special considerations, the procedures and facilities to be used should undergo review for specific safety concerns. Formal safety programs should be established to assess the hazards, determine the safeguards needed for their control, ensure that the staff has the necessary training and skills, and ensure that the facilities are adequate for the safe conduct of the research. Technical support should be provided to monitor and ensure compliance with institutional safety policies.
The Centers for Disease Control and Prevention (CDC) and National Institutes of Health (NIH) publication Biosafety in Microbiological and Biomedical Laboratories (1993) and the National Research Council (In press) 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.
Special facilities and safety equipment are
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. Facilities used for animal experimentation
with hazardous agents should be separated from other animal housing
and support areas, research and clinical laboratories, and patient-care
facilities and should be appropriately identified; and access
to them should be limited to authorized personnel. Such facilities
should be designed and constructed to facilitate cleaning and
maintenance of mechanical systems. A properly managed and used
double corridor facility or barrier entry system is an effective
means of reducing cross-
INSTITUTIONAL POLICIES AND RESPONSIBILITIES 17
contamination. Floor drains should always contain liquid or be sealed effectively by other means. Automatic trap priming can be provided to ensure that traps remain filled.
Hazardous agents should be contained within the study environment. Control of airflow (such as through the use of biologic-safety cabinets) that minimizes the escape of contaminants is a primary barrier used in the handling and administration of hazardous agents and the performance of necropsies on contaminated animals (CDC 1995; Kruse and others 1991). Special features of the facility-such as airlocks, negative air pressure, air filters, and redundant mechanical equipment with automatic switching-are secondary barriers aimed at preventing accidental release of hazards outside the facility and work environment.
Exposure to anesthetic waste gases should
be limited. This is usually accomplished by using various scavenging
techniques. If ether is used, personnel safety should be ensured
by proper use of signs and by using equipment and practices to
minimize risks associated with its explosiveness.
Personal protective equipment should be provided,
and other safety measures should be adopted when needed. Animal-care
personnel should wear appropriate institution-issued protective
clothing, shoes or shoe covers, and gloves. Clean protective clothing
should be provided as often as necessary. If it is appropriate,
personnel should shower when they leave the animal-care, procedure,
or dose-preparation areas. Protective clothing and equipment should
not be worn beyond the boundary of the hazardous-agent work area
or the animal facility. Personnel with potential exposure to hazardous
agents should be provided with personal protective equipment appropriate
to the agents (CFR 1984c). For example, personnel exposed to nonhuman
primates should be provided with such protective items as gloves,
arm protectors, masks, and face shields. Hearing protection should
be provided in high-noise areas. Personnel working in areas where
they might be exposed to contaminated airborne particulate material
or vapors should be provided with suitable respiratory protection
(CFR 1984c).
Development and implementation of a program of medical evaluation and preventive medicine should involve input from trained health professionals, such as occupational-health physicians and nurses. Confidentiality and other medical and legal factors must be considered in the context of appropriate federal, state, and local regulations.
A health-history evaluation before work assignment
is advisable to assess potential risks for individual employees.
Periodic medical evaluations are advis-
18 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS
able for people in some risk categories. An appropriate immunization schedule should be adopted. It is important to immunize animal-care personnel against tetanus. In addition, pre-exposure immunization should be offered to people at risk of infection or exposure to such agents as rabies or hepatitis B virus. Vaccination is recommended if research is to be conducted on infectious diseases for which effective vaccines are available. Specific recommendations can be found in the CDC and NIH publication Biosafety in Microbiological and Biomedical Laboratories (1993). Pre-employment or pre-exposure serum collection is advisable only in specific circumstances as determined by an occupational health and safety professional (NRC In press). In such cases, identification, traceability, retention, and storage conditions of samples should be considered and the purpose for which the serum samples will be used must be consistent with applicable state laws and consistent with the Federal Policy for the Protection of Human Subjects (Federal Register 56(117): 28002-28032, June 18, 1991).
Zoonosis surveillance should be a part of an occupational-health program (CDC and NIH 1993; Fox and others 1984; NRC In press). Personnel should be instructed to notify their supervisors of potential or known exposures and of suspected health hazards and illnesses. Clear procedures should be established for reporting all accidents, bites, scratches. and allergic reactions (NRC In press).
Nonhuman-primate diseases that are transmissible
to humans can be serious hazards. Animal technicians, clinicians,
investigators, predoctoral and postdoctoral trainees, research
technicians, consultants, maintenance workers, security personnel,
and others who have contact with nonhuman primates or have duties
in nonhuman-primate housing areas should be routinely screened
for tuberculosis. Because of the potential for Cercopithecine
herpesvirus 1 (formerly Herpesvirus simiae) exposure, personnel
who work with macaques should have access to and be instructed
in the use of bite and scratch emergency-care stations (Holmes
and others 1995). A procedure should be established for ensuring
medical care for bites and scratches.
AVMA (American Veterinary Medical Association). 1995. Accredited programs in veterinary technology. Pp.236-240 in 1995 AVMA Membership Directory and Resource Manual. 44th ed. Schaumburg. Ill.: AVMA.
Bryant. J. M. 1980. Vest and tethering system to accommodate catheters and a temperature monitor for nonhuman primates. Lab. Anim. Sci. 30(4. Part I):706-705.
Byrd. L. D. 1979. A tethering system for direct measurement of cardiovascular function in the caged baboon. Am. J. Physiol. 236:H775-H779.
CCAC (Canadian Council on Animal Care) 1993. Guide to the Care and Use of Experimental Animals. Vol. 1.2nd ed. E. D. Olfert. B. M. Cross. and A. A. McWilliam. eds. Ontario. Canada: Canadian Council on Animal Care. 211 pp.
CDC (Centers for Disease Control and Prevention
and NIH (National Institutes of Health). 1993. Biosafety in Microbiological
and Biomedical Laboratories. 3rd ed. HHS Publication No. (CDC)
93-8395, Washington. D.C.: U.S. Government Printing Office.
INSTITUTIONAL POLICIES AND RESPONSIBILITIES 19
CDC (Centers for Disease Control and Prevention) and NIH (National Institutes of Health). 1995. Primary Containment for Biohazards: Selection. Installation and Use of Biological Safety Cabinets. Washington. D.C.: U.S. Government Printing Office.
CFR (Code of Federal Regulations). 1984a. Title 10; Part 20, Standards for Protection Against Radiation. Washington. D.C.: Office of the Federal Register.
CFR (Code of Federal Regulations). 1984b. Title 29; Part 1910, Occupational Safety and Health Standards; Subpart G. Occupation Health and Environmental Control, and Subpart Z. Toxic and Hazardous Substances. Washington. D.C.: Office of the Federal Register.
CFR (Code of Federal Regulations). 1984c. Title 29: Part 1910. Occupational Safety and Health Standards; Subpart I. Personal Protective Equipment. Washington, D.C.: Office of the Federal Register.
CFR (Code of Federal Regulations). 1985. Title 9 (Animals and Animal Products), Subchapter A (Animal Welfare). Washington. D.C.: Office of the Federal Register.
Clark, J. M. 1993. Planning for safety: biological and chemical hazards. Lab Anim. 22:33-38.
Fox, J. G., C. E. Newcomer, and H. Rozmiarek. 1984. Selected zoonoses and other health hazards. Pp.614-648 in Laboratory Animal Medicine. 3. G. Fox, B. 3. Cohen, and F.M. Loew. eds. New York: Academic Press.
Grandin, T. 1991. Livestock behavior and the design of livestock handling facilities. Pp.96-125 in Handbook of Facilities Planning. Vol.2. Laboratory Animal Facilities. New York: Van Nostrand. 422 pp.
Holmes, G. P., L. E. Chapman, J. A. Stewart, S. E. Straus, 3. K. Hilliard, D. S. Davenport, and the B Virus Working Group. 1995. Guidelines for the prevention and treatment of B-virus infections in exposed persons. Clin. Infect. Dis. 20:421-439.
IRAC (Interagency Research Animal Committee). 1985. U.S. Government Principles for Utilization and Care of Vertebrate Animals Used in Testing. Research, and Training. Federal Register, May 20, 1985. Washington. D.C.: Office of Science and Technology Policy.
Kreger. M. D., 1995. Training Materials for Animal Facility Personnel: AWIC Quick Bibliography Series, 95-08. Beltsville, Md.: National Agricultural Library.
Kruse, R. H., W. H. Puckett, and J. H. Richardson. 1991. Biological safety cabinetry. Clin. Micro. Reviews 4:207-241.
McNamee, G. A.. Jr., R. W. Wannemacher, Jr.. R. E. Dinterman. H. Rozmiarek, and R. D. Montrey. 1984. A surgical procedure and tethering system for chronic blood sampling, infusion, and temperature monitoring in caged nonhuman primates. Lab. Anim. Sci. 34(3):303-307.
Morton, W. R., G. H. Knitter, P. M. Smith, T. G. Susor. and K. Schmitt. 1987. Alternatives to chronic restraint of nonhuman primates. J. Am. Vet. Med. Assoc. 191(10):1282-1286.
NIH (National Institutes of Health). 1990. Guidelines for Diet Control in Behavioral Study. Bethesda, Md.: Animal Research Advisory Committee. NIH.
NRC (National Research Council). 1990. Important laboratory animal resources: selection criteria and funding mechanisms for their preservation. A report of the Institute of Laboratory Animal Resources Committee on Preservation of Laboratory Animal Resources. ILAR News 32(4):A1-A32.
NRC (National Research Council). 1991. Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs. A report of the Institute of Laboratory Animal Resources Committee on Educational Programs in Laboratory Animal Science. Washington. D.C.: National Academy Press. 152 pp.
NRC (National Research Council). In press.
Occupational Health and Safety in the Care and Use of Research
Animals. A report of the Institute of Laboratory Animal Resources
Committee on Occupational Safety and Health in Research Animal
Facilities. Washington. D.C.: National Academy Press.
20 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS
NYAS (New York Academy of Sciences). 1988. Interdisciplinary Principles and Guidelines for the Use of Animals in Research, Testing and Education. New York: New York Academy of Sciences.
PHS (Public Health Service). 1996. 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. [PL 99-158, Health Research Extension Act, 1985]
Reinhardt, V.1991. Training adult male rhesus monkeys to actively cooperate during in-homecage venipuncture. Anim. Technol. 42(l):1 1-17.
Reinhardt, V.1995. Restraint methods of laboratory non-human primates: a critical review. Anim. Welf. 4:221-238.
Van Sluyters, R. C., and M. D. Oberdorfer, eds. 1991. Preparation and Maintenance of Higher Mammals During Neuroscience Experiments. Report of National Institute of Health Workshop. NIH No.91-3207. Bethesda, Md.: National Institutes of Health.
Wakeley, H., J. Dudek. and J. Kruckeberg.
1974. A method for preparing and maintaining rhesus monkeys with
chronic venous catheters. Behav. Res. Methods Instrum. 6:329-331.
Proper housing and management of animal facilities are essential to animal well-being, to the quality of research data and teaching or testing programs in which animals are used, and to the health and safety of personnel. A good management program provides the environment, housing, and care that permit animals to grow, mature, reproduce, and maintain good health; provides for their well-being; and minimizes variations that can affect research results. Specific operating practices depend on many factors that are peculiar to individual institutions and situations. Well-trained and motivated personnel can often ensure high-quality animal care, even in institutions with less than optimal physical plants or equipment.
Many factors should be considered in planning
for adequate and appropriate physical and social environment,
housing, space, and management. These include
22 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS
Animals should be housed with a goal of maximizing species-specific behaviors and minimizing stress-induced behaviors. For social species, this normally requires housing in compatible pairs or groups. A strategy for achieving desired housing should be developed by animal-care personnel with review and approval by the IACUC. Decisions by the IACUC in consultation with the investigator and veterinarian, should be aimed at achieving high standards for professional and husbandry practices considered appropriate for the health and well-being of the species and consistent with the research objectives. After the decision-making process, objective assessments should be made to substantiate the adequacy of animal environment, husbandry, and management.
The environment in which animals are maintained should be appropriate to the species, its life history, and its intended use. For some species, it might be appropriate to approximate the natural environment for breeding and maintenance. Expert advice might be sought for special requirements associated with the experiment or animal subject (for example, hazardous-agent use, behavioral studies, and immunocompromised animals, farm animals, and nontraditional laboratory species).
The following sections discuss some considerations
of the physical environment related to common research animals.
The microenvironment of an animal is the physical environment immediately surrounding it-the primary enclosure with its own temperature, humidity, and gaseous and particulate composition of the air. The physical environment of the secondary enclosure-such as a room, a barn, or an outdoor habitat-constitutes the macroenvironment. Although the microenvironment and the macro-environment are linked by ventilation between the primary and secondary enclosures, the environment in the primary enclosure can be quite different from the environment in the secondary enclosure and is affected by the design of both enclosures.
Measurement of the characteristics of the
microenvironment can be difficult in small primary enclosures.
Available data indicate that temperature, humidity, and concentrations
of gases and particulate matter are often higher in an animal's
microenvironment than in the macroenvironment (Besch 1980; Flynn
1959; Gamble and Clough 1976; Murakami 1971; Serrano 1971). Microenvironmental
ANIMAL ENWRONMENT, HOUSING, AND MANAGEMENT 23
conditions can induce changes in metabolic
and physiologic processes or alterations in disease susceptibility
(Broderson and others 1976; Schoeb and others 1982; Vesell and
others 1976).
Primary Enclosures
The primary enclosure (usually a cage, pen,
or stall) provides the limits of an animal's immediate environment.
Acceptable primary enclosures
Primary enclosures should be constructed with materials that balance the needs of the animal with the ability to provide for sanitation. They should have smooth, impervious surfaces with minimal ledges, angles, corners, and overlapping surfaces so that accumulation of dirt, debris, and moisture is reduced and satisfactory cleaning and disinfecting are possible. They should be constructed of durable materials that resist corrosion and withstand rough handling without chipping, cracking, or rusting. Less-durable materials, such as wood, can provide a more appropriate environment in some situations (such as runs, pens, and outdoor corrals) and can be used to construct perches, climbing structures, resting areas, and perimeter fences for primary enclosures. Wooden items might need to be replaced periodically because of damage or difficulties with sanitation.
All primary enclosures should be kept in good
repair to prevent escape of or injury to animals, promote physical
comfort, and facilitate sanitation and servicing. Rusting or oxidized
equipment that threatens the health or safety of the animals should
be repaired or replaced.
24 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS
Some housing Systems have special caging and ventilation equipment, including filter-top cages, ventilated cages, isolators, and cubicles. Generally, the purpose of these systems is to minimize the spread of airborne disease agents between cages or groups of cages. They often require different husbandry practices, such as alterations in the frequency of bedding change, the use of aseptic handling techniques, and specialized cleaning, disinfecting, or sterilization regimens to prevent microbial transmission by other than the airborne route.
Rodents are often housed on wire flooring,
which enhances sanitation of the cage by enabling urine and feces
to pass through to a collection tray. However, some evidence suggests
that solid-bottom caging, with bedding, is preferred by rodents
(Fullerton and Gilliatt 1967; Grover-Johnson and Spencer 1981;
Ortman and others 1983). Solid-bottom caging, with bedding, is
therefore recommended for rodents. Vinyl-coated flooring is often
used for other species, such as dogs and nonhuman primates. IACUC
review of this aspect of the animal care program should ensure
that caging enhances animal well-being consistent with good sanitation
and the requirements of the research project.
Sheltered or Outdoor Housing
Sheltered or outdoor housing-such as barns, corrals, pastures, and islands-is a common primary housing method for some species and is acceptable for many situations. In most cases, outdoor housing entails maintaining animals in groups.
When animals are maintained in outdoor runs, pens, or other large enclosures, there must be protection from extremes in temperature or other harsh weather conditions and adequate protective and escape mechanisms for submissive animals. These goals can be achieved by such features as windbreaks, shelters, shaded areas, areas with forced ventilation, heat-radiating structures, or means of retreat to conditioned spaces, such as an indoor portion of a run. Shelters should be accessible to all animals, have sufficient ventilation, and be designed to prevent buildup of waste materials and excessive moisture. Houses, dens, boxes, shelves, perches, and other furnishings should be constructed in a manner and made of materials that allow cleaning or replacement in accord with generally accepted husbandry practices when the furnishings are excessively soiled or worn.
Floors or ground-level surfaces of outdoor housing facilities can be covered with dirt, absorbent bedding, sand, gravel, grass, or similar material that can be removed or replaced when that is needed to ensure appropriate sanitation. Excessive buildup of animal waste and stagnant water should be avoided by, for example, using contoured or drained surfaces. Other surfaces should be able to withstand the elements and be easily maintained.
Successful management of outdoor housing relies
on consideration of
ANIMAL ENVIRONMENT, HOUSING, AND MANAGEMENT 25
Naturalistic Environments
Areas like pastures and islands afford opportunities
to provide a suitable environment for maintaining or producing
animals and for some types of research. Their use results in the
loss of some control over nutrition, health care and surveillance,
and pedigree management. These limitations should be balanced
against the benefits of having the animals live in more natural
conditions. Animals should be added to, removed from, and returned
to social groups in this setting with appropriate consideration
of the effects on the individual animals and on the group. Adequate
supplies of food, fresh water, and natural or constructed shelter
should be ensured.
An animal's space needs are complex, and consideration of only the animal's body weight or surface area is insufficient. Therefore, the space recommendations presented here are based on professional judgment and experience and should be considered as recommendations of appropriate cage sizes for animals under conditions commonly found in laboratory animal housing facilities. Vertical height, structuring of the space, and enrichments can clearly affect animals' use of space. Some species benefit more from wall space (e.g., "thigmotactic" rodents), shelters (e.g., some New World primates), or cage complexities (e.g., cats and chimpanzees) than from simple increases in floor space (Anzaldo and others 1994; Stricklin 1995). Thus, basing cage-size recommendations on floor space alone is inadequate. In this regard, the Guide might differ from the AWRs (see footnote 1, p.2).
Space allocations should be reviewed and modified
as necessary to address individual housing situations and animal
needs (for example, for prenatal and postnatal care, obese animals,
and group or individual housing). Such animalperformance indexes
as health, reproduction, growth, behavior, activity, and use of
space can be used to assess the adequacy of housing. At a minimum,
an animal must have enough space to turn around and to express
normal postural adjustments, must have ready access to food and
water, and must have enough cleanbedded or unobstructed area to
move and rest in. For cats, a raised resting surface should be
included in the cage. Raised resting surfaces or perches are also
often
26 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS
desirable for dogs and nonhuman primates. Low resting surfaces that do not allow the space under them to be comfortably occupied by the animal should be counted as part of the floor space. Floor space taken up by food bowls, water containers, litter boxes, or other devices not intended for movement or resting should not be considered part of the floor space.
The need for and type of adjustments in the amounts of primary enclosure space recommended in the tables that follow should be approved at the institutional level by the IACUC and should be based on the performance outcomes described in the preceding paragraph with due consideration of the AWRs and PHS Policy (see footnote 1, p.2). Professional judgment, surveys of the literature and current practices, and consideration of the animals' physical, behavioral, and social needs and of the nature of the protocol and its requirements might be necessary (see Crockett and others 1993, 1995). Assessment of animals' space needs should be a continuing process. With the passage of time or long-term protocols, adjustments in floor space and height should be considered and modified as necessary.
It is not within the scope or size constraints of the Guide to discuss the housing requirements of all species used in research. For species not mentioned, space and height allocations for an animal of equivalent size and with a similar activity profile and similar behavior can be used as a starting point from which adjustments that take species-specific and individual needs into account can be made.
Whenever it is appropriate, social animals should be housed in pairs or groups, rather than individually, provided that such housing is not contraindicated by the protocol in question and does not pose an undue risk to the animals (Brain and Bention 1979). Depending on a variety of biologic and behavioral factors, group-housed animals might need less or more total space per animal than individually housed animals. Recommendations provided below are based on the assumption that pair or group housing is generally preferable to single housing, even when members of the pair or group have slightly less space per animal than when singly caged. For example, each animal can share the space allotted to the animals with which it is housed. Furthermore, some rodents or swine housed in compatible groups seek each other out and share cage space by huddling together along walls, lying on each other during periods of rest, or gathering in areas of retreat (White 1990; White and others 1989). Cattle, sheep, and goats exhibit herding behavior and seek group associations and close physical contact. Conversely, some animals, such as various species of nonhuman primates, might need additional individual space when group-housed to reduce the level of aggression.
The height of enclosures can be important
in the normal behavior and postural adjustments of some species.
Cage heights should take into account typical postures of an animal
and provide adequate clearance for normal cage components, such
as feeders and water devices, including sipper tubes. Some species
of
ANIMAL ENVIRONMENT, HOUSING, AND MANAGEMENT 27
nonhuman primates use the vertical dimensions of the cage to a greater extent than the floor. For them, the ability to perch and to have adequate vertical space to keep the whole body above the cage floor can improve their well-being.
Space allocations for animals should be based on the following tables, but might need to be increased, or decreased with approval of the IACUC, on the basis of criteria previously listed.
Table 2.1 lists recommended space allocations for commonly used laboratory rodents housed in groups. If they are housed individually or exceed the weights in the table, animals might require more space.
Table 2.2 lists recommended space allocations
for other common laboratory animals. These allocations are based,
in general, on the needs of individually housed animals. Space
allocations should be re-evaluated to provide for enrichment of
the primary enclosure or to accommodate animals that exceed the
weights in the table. For group housing. determination of the
total space needed is not necessarily based on the sum of the
amounts recommended for individually housed animals. Space for
group-housed animals should be based on individual species needs,
behavior, compatibility of the animals, numbers of animals, and
goals of the housing situation.
TABLE 2.1 Recommended Space for Commonly Used
Group-Housed Laboratory Rodents
| Animals | Weight, g | Floor Area/Animal, in2 a | Height.b inc |
| Mice | <10 | 6 | 5 |
| Up to 15 | 8 | 5 | |
| Up to 25 | 12 | 5 | |
| >25d | >15 | 5 | |
| Rats | <100 | 17 | 7 |
| Up to 200 | 23 | 7 | |
| Up to 300 | 29 | 7 | |
| Up to 400 | 40 | 7 | |
| Up to 500 | 60 | 7 | |
| >500d | >70 | 7 | |
| Hamsters | <60 | 10 | 6 |
| Up to 80 | 13 | 6 | |
| Up to 100 | 16 | 6 | |
| >100d | >19 | 6 | |
| Guinea pigs | <350 | 60 | 7 |
| >350d | >101 | 7 |
aTo convert square inches to square centimeters. multiply by 6.45.
bFrom cage floor to cage top.
cTO convert inches to centimeters. multiply by 2.54.
dLarger
animals might require more space to meet the performance standards
(see text).
28 GUIDE FOR THE CARE AND USE OF LABORATORY
ANIMALS
TABLE 2.2 Recommended Space for Rabbits, Cats,
Dogs, Nonhuman Primates, and Birds
| Animals | Weight, kga | Floor Area/Animal, ft2 b | Height c ind |
| Rabbits | <2 | 1.5 | 14 |
| Up to 4 | 3.0 | 14 | |
| Up to 5.4 | 4.0 | 14 | |
| >5.4e | >5.0 | 14 | |
| Cats | <4 | 3.0 | 24 |
| >4e | >4.0 | 24 | |
| Dogsf | <15 | 8.0 | - |
| Up to 30 | 12.0 | - | |
| >30e | >24.0 | - | |
| Monkeysg, h | |||
| (including baboons) | |||
| Group 1 | Up to 1 | 1.6 | 20 |
| Group 2 | Up to 3 | 3.0 | 30 |
| Group 3 | Up to 10 | 4.3 | 30 |
| Group 4 | Up to 15 | 6.0 | 32 |
| Group 5 | Up to 25 | 8.0 | 36 |
| Group 6 | Up to 30 | 10.0 | 46 |
| Group 7 | >30e | 15.0 | 46 |
| Apes (pongidae)h | |||
| Group 1 | Up to 20 | 10.0 | 55 |
| Group 2 | Up to 35 | 15.0 | 60 |
| Group 3 | >35 | 25.0 | 84 |
| Pigeons/ | - | 0.8 | - |
| Quail/ | - | 0.25 | - |
| Chickens/ | <0.25 | 0.25 | - |
| Up to 0.5 | 0.50 | - | |
| Up to 1.5 | 1.00 | - | |
| Up to 3.0 | 2.00 | - | |
| >3.0e | >3.00 | - |
Table 2.3 lists recommended space allocations
for farm animals commonly used in a laboratory setting. When animals,
housed individually or in groups, exceed the weights in the table,
more space might be required. If they are grouphoused, adequate
access to water and feeder space should be provided (Larson and
Hegg 1976; Midwest Plan Service 1987).
Regulation of body temperature within normal
variation is necessary for the well-being of homeotherms. Generally,
exposure of unadapted animals to temperatures above 850F
(29.40C) or below 400F (4.40C),
without access to shelter or other protective mechanisms, might
produce clinical effects (Gordon 1990),
ANIMAL ENVIRONMENT, HOUSING, AND MANAGEMENT
29
TABLE 2.2 Continued
aTo convert kilograms to pounds, multiply by 2.2.
bTo convert square feet to square meters, multiply by 0.09.
cFrom cage floor to cage top.
dTo convert inches to centimeters. multiply by 2.54.
eLarger animals might require more space to meet performance standards (see text).
fThese recommendations might require modification according to body conformation of individual animals and breeds. Some dogs, especially those toward upper limit of each weight range, might require additional space to ensure compliance with the regulations of the Animal Welfare Act. These regulations (CFR 1985) mandate that the height of each cage be sufficient to allow occupant to stand in "comfortable position" and that the minimal square feet of floor space be equal to "mathematical square of the sum of the length of the dog in inches (measured from the tip of its nose to the base of its tail) plus 6 inches; then divide the product by 144."
gCallitrichidae, Cebidae. Cercopithecidae, and Papio. Baboons might require more height than other monkeys.
hFor some species (e.g., Brachyreles, Hylobares, Symphalangus, Pongo, and Pan), cage height should be such that an animal can, when fully extended, swing from the cage ceiling without having its feet touch the floor. Cage-ceiling design should enhance brachiating movement.
iApes weighing over 50 kg are more effectively housed in permanent housing of masonry, concrete, and wire-panel structure than in conventional caging.
jCage
height should be sufficient for the animals to stand erect with
their feet on the floor.
which could be life-threatening. Animals can adapt to extremes
by behavioral, physiologic, and morphologic mechanisms, but such
adaptation takes time and might alter protocol outcomes or otherwise
affect performance (Garrard and others 1974; Gordon 1993; Pennycuik
1967).
Environmental temperature and relative humidity can depend on husbandry and housing design and can differ considerably between primary and secondary enclosures. Factors that contribute to variation in temperature and humidity include housing material and construction, use of filter tops, number of animals per cage, forced ventilation of the enclosures, frequency of bedding changes, and bedding type.
Some conditions might require increased environmental temperatures, such as postoperative recovery, maintenance of chicks for the first few days after hatching, housing of some hairless rodents, and housing of neonates that have been separated from their mothers. The magnitude of the temperature increase depends on the circumstances of housing; sometimes, raising the temperature in the primary enclosure alone (rather than raising the temperature of the secondary enclosure) is sufficient.
In the absence of well-controlled studies,
professional judgment and experience have resulted in recommendations
for dry-bulb temperatures (Table 2.4) for several common species.
In the case of animals in confined spaces, the range of
30 GUIDE FOR THE CARE AND USE OF LABORATORY
ANIMALS
TABLE 2.3 Recommended Space for Commonly Used
Farm Animals
| Animals/Enclosure | Weight. kga | Floor Area/Animal. ft2 b |
| Sheep and Goats | ||
| <25 | 10.0 | |
| Up to 50 | 15.0 | |
| >50c | 20.0 | |
| 2-5 | <25 | 8.5 |
| Up to 50 | 12.5 | |
| >50c | 17.0 | |
| >5 | <25 | 7.5 |
| Up to 50 | 11.3 | |
| >50c | 15.0 | |
| Swine | ||
| Up to 25 | 12.0 | |
| Up to 50 | 15.0 | |
| Up to 100 | 24.0 | |
| Up to 200 | 48.0 | |
| >200c | >60.0 | |
| 2-5 | <25 | 6.0 |
| Up to 50 | 10.0 | |
| Up to 100 | 20.0 | |
| Up to 200 | 40.0 | |
| >200c | >52.0 | |
| >5 | <25 | 6.0 |
| Up to 50 | 9.0 | |
| Up to 100 | 18.0 | |
| Up to 200 | 36.0 | |
| >200c | >48.0 |
daily temperature fluctuations should be kept
to a minimum to avoid repeated large demands on the animals' metabolic
and behavioral processes to compensate for changes in the thermal
environment. Relative humidity should also be controlled, but
not nearly as narrowly as temperature; the acceptable range of
relative humidity is 30 to 70%. The temperature ranges in Table
2.4 might not apply to captive wild animals, wild animals maintained
in their natural environment, or animals in outdoor enclosures
that are given the opportunity to adapt by being exposed to seasonal
changes in ambient conditions.
The purposes of ventilation are to supply
adequate oxygen; remove thermal loads caused by animal respiration,
lights, and equipment; dilute gaseous and particulate contaminants;
adjust the moisture content of room air; and, where
ANIMAL ENWRONMENT. HOUSING, AND MANAGEMENT
31
TABLE 2.3 Continued
| Animals/Enclosure | Weight. kga | Floor Area/Animal, ft2 b |
| Cattle | ||
| 1 | <75 | 24.0 |
| Up to 200 | 48.0 | |
| Up to 350 | 72.0 | |
| Up to 500 | 96.0 | |
| Up to 650 | 124.0 | |
| >650c | >144.0 | |
| 2-5 | <75 | 20.0 |
| Up to 200 | 40.0 | |
| Up to 350 | 60.0 | |
| Up to 500 | 80.0 | |
| Up to 650 | 105.0 | |
| >650c | >120.0 | |
| >5 | <75 | 18.0 |
| Up to 200 | 36.0 | |
| Up to 350 | 54.0 | |
| Up to 500 | 72.0 | |
| Up to 650 | 93.0 | |
| >650c | >108.0 | |
| Horses | 144.0 | |
| Ponies | ||
| 1-4 | 72.0 | |
| >4/Pen | <200 | 60.0 |
| >200c | >72.0 |
aTo convert kilograms to pounds. multiply by 2.2.
bTo convert square feet to square meters. multiply by 0.09.
cLarger animals might require more space to
meet performance standards (see text).
appropriate, create static-pressure differentials between adjoining
spaces. Establishing a room ventilation rate, however, does not
ensure the adequacy of the ventilation of an animal's primary
enclosure and hence does not guarantee the quality of the microenvironment.
The degree to which air movement (drafts)
causes discomfort or biologic consequences has not been established
for most species. The volume and physical characteristics of the
air supplied to a room and its diffusion pattern influence the
ventilation of an animal's primary enclosure and so are important
determinants of its microenvironment. The relationship of the
type and location of supply-air diffusers and exhaust vents to
the number, arrangement, location, and type of primary enclosures
in a room or other secondary enclosure affects how well the primary
enclosures are ventilated and should therefore be considered.
The use of computer modeling for assessing those factors in relation
to heat loading and air diffusion patterns can be helpful in optimizing
ventilation of primary and
32 GUIDE FOR THE CARE AND USE OF LABORATORY
ANIMALS
TABLE 2.4 Recommended Dry-Bulb Temperatures
for Common Laboratory Animals
| Dry-Bulb Temperature | ||
| Animal | 0C | 0F |
| Mouse. rat. hamster. gerbil. guinea pig | 18-26 | 64-79 |
| Rabbit | 16-22 | 61-72 |
| Cat. dog. nonhuman primate | 18-29 | 64-84 |
| Farm animals and poultry | 16-27 | 61-81 |
secondary enclosures (for example, Hughes and Reynolds 1995; Reynolds and Hughes 1994).
The guideline of 10-15 fresh-air changes per hour has been used for secondary enclosures for many years and is considered an acceptable general standard. Although it is effective in many animal-housing settings, the guideline does not take into account the range of possible heat loads; the species, size, and number of animals involved; the type of bedding or frequency of cage-changing; the room dimensions; or the efficiency of air distribution from the secondary to the primary enclosure. In some situations, the use of such a broad guideline might pose a problem by overventilating a secondary enclosure that contains few animals and thereby wasting energy or by underventilating a secondary enclosure that contains many animals and thereby allowing heat and odor accumulation.
To determine more accurately the ventilation required, the minimal ventilation rate (commonly in cubic feet per minute) required to accommodate heat loads generated by animals can be calculated with the assistance of mechanical engineers. The heat generated by animals can be calculated with the average-total-heat-gain formula as published by the American Society of Heating, Refrigeration, and Air-Conditioning Engineers (ASHRAE, 1993). The formula is species-independent, so it is applicable to any heat-generating animal. Minimal required ventilation is determined by calculating the amount of cooling required (total cooling load) to control the heat load expected to be generated by the largest number of animals to be housed in the enclosure in question plus any heat expected to be produced by nonanimal sources and heat transfer through room surfaces. The total-cooling-load calculation method can also be used for an animal space that has a fixed ventilation rate to determine the maximal number of animals (based on total animal mass) that can be housed in the space.
Even though that calculation can be used to
determine minimal ventilation needed to prevent heat buildup,
other factors-such as odor control, allergen control, particle
generation, and control of metabolically generated gases-might
necessitate ventilation beyond the calculated minimum. When the
calculated minimal required ventilation is substantially less
than 10 air changes per hour, lower ventilation rates might be
appropriate in the secondary enclosure, provided
ANIMAL ENWRONMENT, HOUSING, AND MANAGEMENT 33
that they do not result in harmful or unacceptable concentrations of toxic gases, odors, or particles in the primary enclosure. Similarly, when the calculated minimal required ventilation exceeds 15 air changes per hour, provisions should be made for additional ventilation required to address the other factors. In some cases, fixed ventilation in the secondary enclosure might necessitate adjustment of sanitation schedules or limitation of animal numbers to maintain appropriate environmental conditions.
Caging with forced ventilation that uses filtered room air and other types of special primary enclosures with independent air supplies (i.e., air not drawn from the room) can effectively address the ventilation requirements of animals without the need to ventilate secondary enclosures to the extent that would be needed if there were no independent primary-enclosure ventilation. Nevertheless, a secondary enclosure should be ventilated sufficiently to provide for the heat loads released from its primary enclosures. If the specialized enclosures contain adequate particulate and gaseous filtration to address contamination risks, recycled air may be used in the secondary enclosures.
Filtered isolation caging without forced ventilation, such as that used in some types of rodent housing, restricts ventilation. To compensate, it might be necessary to adjust husbandry practices-including sanitation, placement of cages in the secondary enclosure, and cage densities-to improve the microenvironment and heat dissipation.
The use of recycled air to ventilate animal rooms saves considerable amounts of energy but might entail some risk. Many animal pathogens can be airborne or travel on fomites, such as dust, so exhaust air to be recycled into heating, ventilation, and air conditioning (HVAC) systems that serve multiple rooms presents a risk of cross contamination. The exhaust air to be recycled should be HEPA filtered (high-efficiency particulate air-filtered) to remove airborne particles before it is recycled; the extent and efficiency of filtration should be proportional to the estimated risk. HEPA filters are available in various efficiencies that can be used to match the magnitude of risk (ASHRAE 1992, 1993). Air that does not originate from animal-use areas but has been used to ventilate other spaces (e.g., some human-occupancy areas and food, bedding, and supply storage areas) may be recycled for animal-space ventilation and might require less-intensive filtration or conditioning than air recycled from animal-use space. The risks in some situations, however, might be too great to consider recycling (e.g., in the case of nonhuman-primate and biohazard areas).
Toxic or odor-causing gases, such as ammonia,
can be kept within acceptable limits if they are removed by the
ventilation system and replaced with air that contains either
a lower concentration or none of these gases. Treatment of recycled
air for these substances by chemical absorption or scrubbing might
be effective; however, the use of nonrecycled air is preferred
for ventilation of animal use and holding areas. The use of HEPA-filtered
recycled air without
34 GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS
gaseous filtration (such as with activated-charcoal
filters) can be used but only in limited applications, provided
that
Frequent bedding changes and cage-cleaning coupled with husbandry practices, such as low animal density within the room and lower environmental temperature and humidity, can also reduce the concentration of toxic or odor-causing gases in animal-room air. Treatment of recycled air for either particulate or gaseous contaminants is expensive and can be rendered ineffective by improper or insufficient maintenance of filtration systems. These systems should be properly maintained and monitored appropriately to maximize their effectiveness.
The successful operation of any HVAC system
requires regular maintenance and evaluation, including measurement
of its function at the level of the secondary enclosure. Such
measurements should include supply- and exhaust-air volumes, as
well as static-pressure differentials, where applicable.
Light can affect the physiology, morphology, and behavior of various animals (Brainard and others 1986; Erkert and Grober 1986; Newbold and others 1991; Tucker and others 1984). Potential photostressors include inappropriate photoperiod, photointensity, and spectral quality of the light (Stoskopf 1983). Numerous factors can affect animals' needs for light and should be considered when an appropriate illumination level is being established for an animal holding room. These include light intensity, duration of exposure, wavelength of light, light history of the animal, pigmentation of the animal, time of light exposure during the circadian cycle, body temperature, hormonal status, age, species, sex, and stock or strain of animal (Brainard 1989; Duncan and O'Steen 1985; O'Steen 1980; Saltarelli and Coppola 1979; Semple-Rowland and Dawson 1987; Wax 1977).
In general, lighting should be diffused throughout
an animal holding area and provide sufficient illumination for
the well-being of the animals and to allow good housekeeping practices,
adequate inspection of animals-including the bottom-most cages
in racks-and safe working conditions for personnel. Light in
ANIMAL ENVIRONMENT, HOUSING, AND MANAGEMENT 35
animal holding rooms should provide for adequate vision and for neuroendocrine regulation of diurnal and circadian cycles (Brainard 1989).
Photoperiod is a critical regulator of reproductive behavior in many species of animals (Brainard and others 1986; Cherry 1987) and can also alter body-weight gain and feed intake (Tucker and others 1984). Inadvertent light exposure during the dark cycle should be minimized or avoided. Because some species will not eat in low light or darkness, such illumination schedules should be limited to a duration that will not compromise the well-being of the animals. A time-controlled lighting system should be used to ensure a regular diurnal cycle, and timer performance should be checked periodically to ensure proper cycling.
The most commonly used laboratory animals are nocturnal. Because the albino rat is more susceptible to phototoxic retinopathy than other species, it has been used as a basis for establishing room illumination levels (Lanum 1979). Data for room light intensities for other animals, based on scientific studies, are not available. Light levels of about 325 lux (30 ft-candles) about 1.0 m (3.3 ft) above the floor appear to be sufficient for animal care and do not cause clinical signs of phototoxic retinopathy in albino rats (Belihorn 1980), and levels up to 400 lux (37 ft-candles) as measured in an empty room 1 m from the floor have been found to be satisfactory for rodents if management practices are used to prevent retinal damage in albinos (Clough 1982). However, the light experience of an individual animal can affect its sensitivity to phototoxicity; light of 130-270 lux above the light intensity under which it was raised has been reported to be near the threshold of retinal damage in some individual albino rats according to histologic, morphometric, and electrophysiologic evidence (Semple-Rowland and Dawson 1987). Some guidelines recommend a light intensity as low as 40 lux at the position of the animal in midcage (NASA 1988). Young albino and pigmented mice prefer much-lower illumination than adults (Wax 1977), although potential retinal damage associated with housing these rodents at higher light levels is mostly reversible. Thus, for animals that have been shown to be susceptible to phototoxic retinopathy, light at the cage level should be between 130 and 325 lux.
Management practices, such as rotating cage
position relative to the light source (Greenman and others 1982)
or providing animals with ways to modify their own light exposure
by behavioral means (e.g., via tunneling or hiding in a structure),
can be used to reduce inappropriate light stimulation of animals.
Provision of variable-intensity light controls might be considered
as a means of ensuring that light intensities are consistent with
the needs of animals and personnel working in animal rooms and
with energy conservation. Such controls should have some form
of vernier scale and a lockable setting and should not be used
merely to turn room lighting on and off. The Illuminating Engineering
Society of North America (IESNA) handbook (Kaufman 1984, 1987)
can assist in decisions concerning lighting uniformity, color-rendering
index, shielding, glare control, reflection, lifetime, heat generation,
and ballast selection.
36 GUIDE FOR THE CAREAND USE OF LABORATORY
ANIMALS
Noise produced by animals and animal-care activities is inherent in the operation of an animal facility (Pfaff and Stecker 1976). Therefore, noise control should be considered in facility design and operation (Pekrul 1991). Assessment of the potential effects of noise on an animal warrants consideration of the intensity, frequency, rapidity of onset, duration, and vibration potential of the sound and the hearing range, noise-exposure history, and sound-effect susceptibility of the species, stock, or strain.
Separation of human and animal areas minimizes disturbances to both the human and animal occupants of the facility. Noisy animals-such as dogs, swine, goats, and nonhuman primates-should be housed away from quieter animals, such as rodents, rabbits, and cats. Environments should be designed to accommodate animals that make noise, rather than resorting to methods of noise reduction. Exposure to sound louder than 85 dB can have both auditory and nonauditory effects (Fletcher 1976; Peterson 1980), including eosinopenia and increased adrenal weights in rodents (Geber and others 1966; Nayfield and Besch 1981), reduced fertility in rodents (Zondek and Tamari 1964), and increased blood pressure in nonhuman primates (Peterson and others 1981). Many species can hear frequencies of sound that are inaudible to humans (Brown and Pye 1975; Warfield 1973), 50 the potential effects of equipment and materials that produce noise in the hearing range of nearby animals-such as video display terminals (Sales 1991) should be carefully considered. To the greatest extent possible, activities that might be noisy should be conducted in rooms or areas separate from those used for animal housing.
Because changes in patterns of sound exposure
have different effects on different animals (Armano and others
1985; Clough 1982), personnel should try to minimize the production
of unnecessary noise. Excessive and intermittent noise can be
minimized by training personnel in alternatives to practices that
produce noise and by the use of cushioned casters and bumpers
on carts, trucks, and racks. Radios, alarms, and other sound generators
should not be used in animal rooms unless they are parts of an
approved protocol or an enrichment program.
The structural environment consists of components
of the primary enclosure-cage furniture, equipment for environmental
enrichment, objects for manipulation by the animals, and cage
complexities. Depending on the animal species and use, the structural
environment should include resting boards, shelves or perches,
toys, foraging devices, nesting materials, tunnels, swings, or
other ob-
ANIMAL ENVIRONMENT, HOUSING, AND MANAGEMENT 37
jects that increase opportunities for the
expression of species-typical postures and activities and enhance
the animals' well-being. Much has been learned in recent years
about the natural history and environmental needs of many animals,
but continuing research into those environments that enhance the
well-being of research animals is encouraged. Selected publications
that describe enrichment strategies for common laboratory animal
species are listed in Appendix A and in bibliographies prepared
by the Animal Welfare Information Center (AWIC 1992; NRC In press).
Consideration should be given to an animal's social needs. The social environment usually involves physical contact and communication among members of the same species (conspecifics), although it can include noncontact communication among individuals through visual, auditory, and olfactory signals. When it is appropriate and compatible with the protocol, social animals should be housed in physical contact with conspecifics. For example, grouping of social primates or canids is often beneficial to them if groups comprise compatible individuals. Appropriate social interactions among conspecifics are essential for normal development in many species. A social companion might buffer the effects of a stressful situation (Gust and others 1994), reduce behavioral abnormality (Reinhardt and others 1988, 1989), increase opportunities for exercise (Whary and others 1993), and expand species-typical behavior and cognitive stimulation. Such factors as population density, ability to disperse, initial familiarity among animals, and social rank should be evaluated when animals are being grouped (Borer and others 1988; Diamond and others 1987; Drickamer 1977; Harvey and Chevins 1987; Ortiz and others 1985; Vandenbergh 1986, 1989). In selecting a suitable social environment, attention should be given to whether the animals are naturally territorial or communal and whether they should be housed singly, in pairs, or in groups. An understanding of species-typical natural social behavior will facilitate successful social housing.
However, not all members of a social species can or should be maintained socially; experimental, health, and behavioral reasons might preclude a successful outcome of this kind of housing. Social housing can increase the likelihood of animal wounds due to fighting (Bayne and others 1995), increase susceptibility to such metabolic disorders as atherosclerosis (Kaplan and others 1982), and alter behayior and physiologic functions (Bernstein 1964; Bernstein and others 1974a,b). In addition, differences between sexes in compatibility have been observed in various species (Crockett and others 1994; Grant and Macintosh 1963; Vandenbergh 1971; vom Saal 1984). These risks of social housing are greatly reduced if the animals are socially compatible and the social unit is stable.
It is desirable that social animals be housed in groups; however, when they must be housed alone, other forms of enrichment should be provided to compen-