5
Physical Plant

GENERAL CONSIDERATIONS

A well-planned, well-designed, well-constructed, properly maintained and managed facility is an important element of humane animal care and use as it facilitates efficient, economical, and safe operation (see Appendix A, Design and Construction of Animal Facilities). The design and size of an animal facility depend on the scope of institutional research activities, the animals to be housed, the physical relationship to the rest of the institution, and the geographic location.

Effective planning and design should include input from personnel experienced with animal facility design, engineering, and operation, as well as from representative users of the proposed facility. Computational fluid dynamics (CFD), building information modeling, and literature on postoccupancy analysis of space use may provide benefits when designing facilities and caging (Eastman et al. 2008; Reynolds 2008; Ross et al. 2009). An animal facility should be designed and constructed in accord with all applicable building codes; in areas with substantial seismic activity the building planning and design should incorporate the recommendations of the Building Seismic Safety Council (BSSC 2001; Vogelweid et al. 2005). Because animal model development and use can be expected to change during the life cycle of an animal facility, facilities should be designed to accommodate changes in use. Modular units (such as custom-designed trailers or prefabricated structures) should comply with construction guidelines described in this chapter.



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5 Physical Plant GENERAL CONSIDERATIONS A well-planned, well-designed, well-constructed, properly maintained and managed facility is an important element of humane animal care and use as it facilitates efficient, economical, and safe opera- tion (see Appendix A, Design and Construction of Animal Facilities). The design and size of an animal facility depend on the scope of institutional research activities, the animals to be housed, the physical relationship to the rest of the institution, and the geographic location. Effective planning and design should include input from personnel experienced with animal facility design, engineering, and operation, as well as from representative users of the proposed facility. Computational fluid dynamics (CFD), building information modeling, and literature on postoccupancy analysis of space use may provide benefits when designing facilities and caging (Eastman et al. 2008; Reynolds 2008; Ross et al. 2009). An animal facility should be designed and constructed in accord with all applicable building codes; in areas with substantial seismic activity the building planning and design should incorporate the recommendations of the Building Seismic Safety Council (BSSC 2001; Vogelweid et al. 2005). Because animal model development and use can be expected to change during the life cycle of an animal facility, facilities should be designed to accommodate changes in use. Modular units (such as custom-designed trail- ers or prefabricated structures) should comply with construction guidelines described in this chapter. 133

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134 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS Building materials for animal facilities should be selected to facilitate efficient and hygienic operation. Durable, moisture- and vermin-proof, fire- resistant, seamless materials are most desirable for interior surfaces, which should be highly resistant to the effects of cleaning agents, scrubbing, high- pressure sprays, and impact. Paints and glazes should be nontoxic if used on surfaces with which animals will have direct contact. In the construction of outdoor facilities, consideration should be given to surfaces that withstand the elements and can be easily maintained. Location Quality animal management and human comfort and health protection require separation of animal facilities from personnel areas, such as offices and conference rooms. Separation can be accomplished by having the animal quarters in a separate building, wing, floor, or room. Careful plan- ning should make it possible to place animal housing areas next to or near research laboratories but separated from them by barriers, such as entry locks, corridors, or floors. Additional considerations include the impact of noise and vibration generated from within the facility and from surrounding areas of the building, as well as security of the facility. Animals should be housed in facilities dedicated to or assigned for that purpose, not in laboratories merely for convenience. If animals must be maintained in a laboratory to satisfy the scientific aims of a protocol, that space should be appropriate to house and care for the animals and its use limited to the period during which it is required. If needed, measures should be taken to minimize occupational hazards related to exposure to animals both in the research area and during transport to and from the area. Centralization Versus Decentralization In a physically centralized animal facility, support, care, and use areas are adjacent to the animal housing space. Decentralized animal housing and use occur in space that is not solely dedicated to animal care or support or is physically separated from the support areas and animal care personnel. Centralization often reduces operating costs, providing a more efficient flow of animal care supplies, equipment, and personnel; more efficient use of environmental controls; and less duplication of support services. Centraliza- tion reduces the needs for transporting animals between housing and study sites, thereby minimizing the risks of transport stress and exposure to disease agents; affords greater security by providing the opportunity to control facil- ity access; and increases the ease of monitoring staff and animals. Decentralized animal facilities generally cost more to construct because of the requirement for specialized environmental systems and

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135 PhySICAL PLANT controls in multiple sites. Duplicate equipment (e.g., cage washers) may be needed, or soiled materials may need to be moved distances for pro- cessing. But decentralization may be preferred for certain specialized research services such as imaging, quarantine, and proximity to research facilities, or for biosecurity reasons. Decentralization may be necessary to accommodate large or complex equipment, such as magnetic resonance imaging, or to permit space sharing by users from multiple facilities or institutions. The opportunity for exposure to disease agents is much greater in these situations and special consideration should be given to biosecu- rity, including transportation to and from the site, quarantine before or after use of the specialized research area, and environmental and equip- ment decontamination. The decisions leading to selection of physically centralized versus decentralized animal facilities should be made early and carefully and should involve all stakeholders (NRC 1996; Ruys 1991). FUNCTIONAL AREAS Professional judgment should be exercised in the development of a practical, functional, and efficient physical plant for animal care and use. The size, nature, and intensity of an institutional Program (see Chapter 2) will determine the specific facility and support functions needed. In facili- ties that are small, maintain few animals, or maintain animals under special conditions—such as facilities used exclusively for housing gnotobiotic or specific pathogen-free (SPF) colonies or animals in runs, pens, or outdoor housing—some functional areas listed below may be unnecessary or may be included in a multipurpose area. Space is required for the following: • animal housing, care, and sanitation • receipt, quarantine, separation, and/or rederivation of animals • separation of species or isolation of individual projects when necessary • storage. Most multipurpose animal facilities may also include the following: • specialized laboratories or space contiguous with or near ani- mal housing areas for such activities as surgery, intensive care, necropsy, irradiation, preparation of special diets, experimental procedures, behavioral testing, imaging, clinical treatment, and diagnostic laboratory procedures

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136 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS • containment facilities or equipment, if hazardous biologic, physi- cal, or chemical agents are to be used • barrier facilities for housing of SPF rodents, especially valuable genetically modified animals, or irreplaceable animal models • receiving and storage areas for food, bedding, pharmaceuticals, biologics, and supplies • space for washing and sterilizing equipment and supplies and, depending on the volume of work, machines for washing cages, bottles, glassware, racks, and waste cans; a utility sink; a sterilizer for equipment, food, and bedding; and separate areas for holding soiled and clean equipment • space for storing wastes before incineration or removal • space for cold storage or disposal of carcasses • space for administrative and supervisory personnel, including space for staff training and education • showers, sinks, lockers, toilets, and break areas for personnel • security features, such as card-key systems, electronic surveillance, and alarms • areas for maintenance and repair of specialized animal housing systems and equipment. CONSTRUCTION GUIDELINES Corridors Corridors should be wide enough to facilitate the movement of person- nel and equipment; a width of 6 to 8 feet can accommodate the needs of most facilities. Floor-wall junctions should be designed to facilitate clean- ing. Protective rails or bumpers are recommended and, if provided, should be sealed or manufactured to prevent vermin access. In corridors leading to dog or swine housing facilities, cage-washing facilities, and other high-noise areas, double-door entry vestibules or other noise traps should be consid- ered. Similar entries are advisable for areas leading to nonhuman primate housing as a means to reduce the potential for escape. Double-door entry vestibules also permit air locks in these and other areas where directional airflow is critical for containment or protection. Wherever possible, water lines, drainpipes, reheat coils and valves, electric service connections, and other utilities should be accessible via interstitial space or through access panels or chases in corridors outside the animal rooms. Fire alarms, fire extinguishers, and telephones should be recessed, installed high enough, or shielded by protective guards to prevent damage from the movement of large equipment.

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13 PhySICAL PLANT Animal Room Doors Doors should be large enough (approximately 42 × 84 in.) to allow the easy passage of racks and equipment and they should fit tightly in their frames. Both doors and frames should be appropriately sealed to prevent vermin entry or harborage. Doors should be constructed of and, where appropriate, coated with materials that resist corrosion. Self-closing doors equipped with recessed or shielded handles, sweeps, and kickplates and other protective hardware are usually preferable. Hospital or terminated stops are useful to aid in cleaning (Harris 2005). For safety, doors should open into animal rooms; if it is necessary that they open toward a corridor, there should be a recessed vestibule. Where room-level security is necessary or it is desirable to limit access (as with the use of hazardous agents), room doors should be equipped with locks or electronic security devices. For personnel safety, doors should be designed to open from the inside without a key. Doors with viewing windows may be needed for safety and other rea- sons, but the ability to cover these windows may be considered if exposure to light or hallway activities would be undesirable (e.g., to avoid disturbing the animals’ circadian rhythm). Red-tinted windows, which do not transmit specific wavelengths of visible light between corridors and animal rooms, have proved useful for mouse and rat holding rooms as both species have a limited ability to detect light in the red portions of the spectrum (Jacobs et al. 2001; Lyubarsky et al. 1999; Sun et al. 1997). Exterior Windows The presence of windows in an animal facility, particularly in animal rooms, creates a potential security risk and should generally be avoided. Windows also create problems with temperature control of the area and prevent strict control of the photoperiod, which is often required in animal- related protocols (and is a critical consideration in rodent breeding colo- nies). However, in specific situations, windows can provide environmental enrichment for some species, such as nonhuman primates. Floors Floors should be moisture resistant, nonabsorbent, impact resistant, and relatively smooth, although textured surfaces may be required in some high-moisture areas and for some species (e.g., farm animals). Floors should be easy to repair and resistant to both the action of urine and other biologic materials and the adverse effects of hot water and cleaning agents. They should be capable of supporting racks, equipment, and stored items without

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138 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS becoming gouged, cracked, or pitted. Depending on their use, floors should be monolithic or have a minimal number of joints. Some materials that have proved satisfactory are epoxy resins, hard-surface sealed concrete, methyl methacrylate, polyurethane, and special hardened rubber-base aggregates. The latter are useful in areas where noise reduction is important. Correct installation is essential to ensure the long-term stability of the surface. If sills are installed at the entrance to a room, they should be designed to allow for convenient passage of equipment. Drainage Where floor drains are used, the floors should be sloped and drain traps kept filled with liquid. To minimize prolonged increases in humid- ity, drainage should allow rapid removal of water and drying of surfaces (Gorton and Besch 1974). Drainpipes should be at least 4 in. (10.2 cm) in diameter, although in some areas, such as dog kennels and agricultural animal facilities, larger drainpipes (>6 in.) are recommended. A rim- and/or trap-flushing drain or an in-line comminutor may be useful for the disposal of solid waste. When drains are not in use for long periods, they should be capped and sealed to prevent backflow of sewer gases, vermin, and other contaminants; lockable drain covers may be advisable for this purpose in some circumstances. Floor drains are not essential in all animal rooms, particularly those housing rodents. Floors in such rooms can be sanitized satisfactorily by wet vacuuming or mopping with appropriate cleaning compounds or disinfec- tants. But the installation of floor drains that are capped when not in use may provide flexibility for future housing of nonrodent species. Walls and Ceilings Walls and ceilings should be smooth, moisture resistant, nonabsor- bent, and resistant to damage from impact. They should be free of cracks, unsealed utility penetrations, and imperfect junctions with doors, ceilings, floors, walls, and corners. Surface materials should be capable of with- standing cleaning with detergents and disinfectants and the impact of water under high pressure. The use of curbs, guardrails or bumpers, and corner guards should be considered to protect walls and corners from damage, and such items should be solid or sealed to prevent access and harborage of vermin. Ceilings formed by the concrete slab above are satisfactory if they are smooth and sealed or painted. Suspended ceilings are generally undesir- able in animal holding rooms unless they are sealed from the space above with gaskets and clips. When used, they should be fabricated of impervi-

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13 PhySICAL PLANT ous materials, have a washable surface, and be free of imperfect junctions. Exposed plumbing, ductwork, and light fixtures are undesirable unless the surfaces can be readily cleaned. Heating, Ventilation, and Air Conditioning (HVAC) A properly designed and functioning HVAC system is essential to provide environmental and space pressurization control. Temperature and humidity control minimizes variations due either to changing climatic conditions or to differences in the number and kind of animals and equipment in an animal holding space (e.g., a room or cubicle). Pressurization assists in controlling airborne contamination and odors by providing directional airflow between spaces. Areas for quarantine, housing and use of animals exposed to hazard- ous materials, and housing of nonhuman primates should be kept under rela- tive negative pressure, whereas areas for surgery or clean equipment storage should be kept under relative positive pressure with clean air. HVAC systems should be designed for reliability (including redundancy where applicable), ease of maintenance, and energy conservation; able to meet requirements for animals as discussed in Chapter 3; and flexible and adaptable to the changing types and numbers of animals and equipment maintained during the life of the facility (ASHRAE 2007a). They should be capable of adjustments in and ideally maintain dry-bulb temperatures of ±1°C (±2°F). Relative humidity should generally be maintained within a range of 30-70% throughout the year. Although maintenance of humidifi- cation within a limited range over extended periods is extremely difficult, daily fluctuations (recognizing the effects of routine husbandry especially when caring for large animal species) in relative humidity should be mini- mized; if excursions outside the desired range are infrequent, minimal, and of short duration, they are unlikely to negatively affect animal well-being. Ideally relative humidity should be maintained within ±10% of set point; however, this may not be achievable under some circumstances. Constant-volume systems have been most commonly used in animal ost facilities, but variable-volume (VAV) systems may offer design and opera- tional advantages, such as allowing ventilation rates to be set in accordance with heat load and other variables. These systems offer considerable advan- tages with respect to flexibility and energy conservation (see Chapter 3). Previously specified temperature and humidity ranges can be modified to meet special animal needs in circumstances in which all or most of the animal facility is designed exclusively for acclimated species with similar requirements (e.g., when animals are held in a sheltered or outdoor facility). In addition, modifications may need to take into account the microenvi- ronment in some primary enclosures, such as rodent isolator cages, where humidity and temperature may exceed room levels.

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140 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS Temperature is best regulated by having thermostatic control for each holding space. Use of zonal control for multiple spaces can result in tem- perature variations between spaces in the zone because of differences in animal densities and heat gain or loss in ventilation ducts and other surfaces within the zone. Individual space control is generally accomplished by pro- viding each space with a dedicated reheat coil. Valves controlling reheat coils should fail in the closed position; steam coils should be avoided or equipped with a high-temperature cut-off system to prevent space overheat- ing and animal loss with valve failure. Humidification is typically controlled and supplemented on a system or zone basis. Control of humidification in individual holding spaces may be desirable for selected species with reduced tolerance for low relative (e.g., nonhuman primates) or high humidity (e.g., rabbits). Most HVAC systems are designed for average high and low tempera- tures and humidities experienced in a geographic area within ±5% variation (ASHRAE 2009). Moderate fluctuations in temperature and relative humidity outside suggested ranges are generally well tolerated by most species com- monly used in research as long as they are brief and infrequent; holding spaces should be designed to minimize drafts and temperature gradients. Consideration should be given to measures that minimize fluctuations in temperature and relative humidity outside the recommended ranges due to extremes in the external ambient environment. Such measures can include partial redundancy, partial air recirculation, altered ventilation rates, or the use of auxiliary equipment. In the event of an HVAC system or component failure, systems should at the minimum supply facility needs at a reduced level, address the adverse effects of loss of temperature control, and, where necessary, maintain critical pressurization gradients. It is essential that life- threatening heat accumulation or loss be prevented during mechanical failure. Temporary needs for ventilation of sheltered or outdoor facilities can usually be met with auxiliary equipment. Air handling system intake locations should avoid entrainment of fumes from vehicles, equipment, and system exhaust. While 100% outside air is typically provided, when recirculated air is used its quality and quantity should be in accord with recommendations in Chapter 3. The type and efficiency of supply and exhaust air treatment should be matched to the quantity and types of contaminants and to the risks they pose. Supply air is usually filtered with 85–95% dust spot efficient filters (ASHRAE 2008). In certain instances, higher efficiency filters (e.g., HEPA) may be beneficial for recirculated supply air and air supplied to or exhausted from specialized areas such as surgical and containment facilities (Kowalski et al. 2002).

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141 PhySICAL PLANT Power and Lighting The electrical system should be safe and provide appropriate lighting, a sufficient number of power outlets, and suitable amperage for specialized equipment. In the event of power failure, an alternative or emergency power supply should be available to maintain critical services (e.g., the HVAC system, ventilated caging systems [Huerkamp et al. 2003], or life support systems for aquatic species) or support functions (e.g., freezers and isolators) in animal rooms, operating suites, and other essential areas. Consideration should be given to outfitting movable equipment for which uninterrupted power is essential (e.g., ventilated racks), with twist-lock plugs to prevent accidental removal from the power supply. Light fixtures, timers, switches, and outlets should be properly sealed to prevent vermin access. Recessed energy-efficient fluorescent lights are commonly used in animal facilities. Spectral quality of lights may be important for some species when maintained in the laboratory; in these cases full spectrum lamps may be appropriate. A time-controlled lighting system should be used to ensure a uniform diurnal lighting cycle. Override systems should be equipped with an automatic timeout or a warning light to indicate the system is in override mode, and system performance and override functions should be regularly evaluated to ensure proper cycling. Dual-level lighting may be considered when housing species that are sen- sitive to high light intensity, such as albino rodents; low-intensity lighting is provided during the light phase of the diurnal cycle, and higher-intensity lighting is provided as needed (e.g., when personnel require enhanced visibility). Light bulbs or fixtures should be equipped with protective cov- ers to ensure the safety of the animals and personnel. Moisture-resistant switches and outlets and ground-fault interrupters should be used in areas with high water use, such as cage-washing areas and aquarium-mainte- nance areas. Storage Areas Adequate space should be available for storage of equipment, supplies, food, bedding, and refuse. Corridors are not appropriate storage areas. Storage space can be decreased when delivery of materials and supplies is reliable and frequent; however, it should be ample enough to accommo- date storage of essential commodities to ensure the animals’ uninterrupted husbandry and care (e.g., if delivery is delayed). Bedding and food should be stored in a separate area free from vermin and protected from the risk of contamination from toxic or hazardous substances. Areas used for food storage should not be subject to elevated temperatures or relative humidity for prolonged periods. Refuse storage areas should be separated from other

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142 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS storage areas. Refrigerated storage, separated from other cold storage, is essential for storage of dead animals and animal tissue waste; this storage area should be kept below 7°C (44.6°F) to reduce putrefaction of wastes and animal carcasses and should be constructed in a manner that facilitates cleaning. Noise Control Noise control is an important consideration in an animal facility and should be addressed during the planning stages of new facility design or renovation (see Chapter 3). Noise-producing support functions, such as cage washing, are commonly separated from housing and experimen- tal functions. Masonry walls, due to their density, generally have excel- lent sound-attenuating properties, but similar sound attenuation can be achieved using many different materials and partition designs. For example, sanitizable sound-attenuating materials bonded to walls or ceilings may be appropriate for noise control in some situations, whereas acoustic materi- als applied directly to the ceiling or as part of a suspended ceiling in an animal room present problems for sanitation and vermin control and are not recommended. Experience has shown that well-constructed corridor doors, sound-attenuating doors, or double-door entry vestibules can help to control the transmission of sound along corridors. An excellent resource on partition design for sound control is available in Noise Control in buildings: A Practical Guide for Architects and Engineers (Warnock and Quirt 1994). Attention should be paid to attenuating noise generated by equipment (ASHRAE 2007b). Fire and environmental-monitoring alarm systems and public address systems should be selected and positioned to minimize potential animal disturbance. The location of equipment capable of gener- ating sound at ultrasonic frequencies is important as some species can hear such high frequencies. Selecting equipment for rodent facilities that does not generate noise in the ultrasonic range should be considered. Vibration Control Vibration may arise from mechanical equipment, electrical switches, and other building components, or from remote sources (via groundborne transmission). Regarding the latter, special consideration should be given to the building structure type especially if the animal facility will be located over, under, or adjacent to subways, trains, or automobile and truck traffic. Like noise, different species can detect and be affected by vibrations of dif- ferent frequencies and wavelengths, so attempts should be made to identify all vibration sources and isolate or dampen them with vibration suppression systems (ASHRAE 2007b).

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143 PhySICAL PLANT Facilities for Sanitizing Materials A dedicated central area for sanitizing cages and ancillary equipment should be provided. Mechanical cage-washing equipment is generally needed and should be selected to match the types of caging and equipment used. Consideration should be given to such factors as the following: • location with respect to animal rooms and waste disposal and stor- age areas • ease of access, including doors of sufficient width to facilitate movement of equipment • sufficient space for staging and maneuvering of equipment • soiled waste disposal and prewashing activities • ease of cleaning and disinfection of the area • traffic flow that separates animals and equipment moving between clean and soiled areas • air pressurization between partitioned spaces to reduce the poten- tial of cross contamination between soiled and clean equipment • insulation of walls and ceilings where necessary • sound attenuation • utilities, such as hot and cold water, steam, floor drains, and electric power • ventilation, including installation of vents or canopies and provi- sions for dissipation of steam and fumes from sanitizing processes • vibration, especially if animals are housed directly above, below, or adjacent to the washing facility • personnel safety, by ensuring that safety showers, eyewash stations, and other equipment are provided as required by code; exposed hot water and steam lines are properly insulated; procedures with a propensity to generate aerosols are appropriately contained; and equipment, such as cage/rack washers, and bulk sterilizers, which personnel enter, are equipped with functioning safety devices that prevent staff from becoming trapped inside. Environmental Monitoring Monitoring of environmental conditions in animal holding spaces and other environmentally sensitive areas in the facility should be considered. Automated monitoring systems, which notify personnel of excursions in environmental conditions, including temperature and photoperiod, are advisable to prevent animal loss or physiologic changes as a result of sys- tem malfunction. The function and accuracy of such systems should be regularly verified.

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144 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS SPECIAL FACILITIES Surgery The design of a surgical facility should accommodate the species to be operated on and the complexity of the procedures to be performed (Hessler 1991; see also Appendix A, Design and Construction of Animal Facilities). The facility, including that used for rodents, by necessity becomes larger and more complex as the number and size of animals or the complexity of procedures increase. For instance, a larger facility may be required to accommodate procedures on agricultural species, large surgical teams, imaging devices, robotic surgical systems, and/or laparoscopic equipment towers. Surgical facilities for agricultural species may additionally require floor drains, special restraint devices, and hydraulic operating tables. For most survival surgery performed on rodents and other small spe- cies such as aquatics and birds, an animal procedure laboratory is recom- mended; the space should be dedicated to surgery and related activities when used for this purpose, and managed to minimize contamination from other activities conducted in the room at other times. The association of surgical facilities with diagnostic laboratories, imaging facilities, animal housing, staff offices, and so on should be considered in the overall context of the complexity of the surgical program. Centralized surgical facilities are cost-effective in equipment, conservation of space and personnel resources, and reduced transit of animals. They also enable enhanced personnel safety and professional oversight of both facilities and procedures. For most surgical programs, functional components of aseptic surgery include surgical support, animal preparation, surgeon’s scrub, operating room, and postoperative recovery. The areas that support those functions should be designed to minimize traffic flow and separate the related non- surgical activities from the surgical procedure in the operating room. The separation is best achieved by physical barriers (AORN 1993) but may also be achieved by distance between areas or by the timing of appropriate cleaning and disinfection between activities. Surgical facilities should be sufficiently separate from other areas to minimize unnecessary traffic and decrease the potential for contamination (Humphreys 1993). The number of personnel and their level of activity have been shown to be directly related to the level of bacterial contamination and the incidence of postoperative wound infection (Fitzgerald 1979). Traf- fic in the operating room can be reduced by the installation of an observa- tion window, a communication system (such as an intercom system), and judicious location of doors. Control of contamination and ease of cleaning should be key consid- erations in the design of a surgical facility. The interior surfaces should be

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145 PhySICAL PLANT constructed of materials that are monolithic and impervious to moisture. Ventilation systems supplying filtered air at positive pressure can reduce the risk of postoperative infection (Ayscue 1986; Bartley 1993; Schonholtz 1976). Careful location of air supply and exhaust ducts and appropriate room ventilation rates are also recommended to minimize contamination (Ayliffe 1991; Bartley 1993; Holton and Ridgway 1993; Humphreys 1993). To facilitate cleaning, the operating rooms should have as little fixed equip- ment as possible (Schonholtz 1976; UFAW 1989). Other operating room features to consider include surgical lights to provide adequate illumina- tion (Ayscue 1986); sufficient electric outlets for support equipment; gases to support anesthesia, surgical procedures, and gas-powered equipment; vacuum; and gas-scavenging capability. The surgical support area should be designed for washing and sterilizing instruments and for storing instruments and supplies. Autoclaves are com- monly placed in this area. It is often desirable to have a large sink in the animal preparation area to facilitate cleaning of the animal and the operat- ing facilities. A dressing area should be available for personnel to change into surgical attire; a multipurpose locker room can serve this function. There should be a scrub area for surgeons, equipped with foot, knee, or electric-eye surgical sinks (Knecht et al. 1981). To minimize the potential for contamination of the surgical site by aerosols generated during scrubbing, the scrub area should usually be outside the operating room and animal preparation area. A postoperative recovery area should provide the physical environ- ment to support the needs of the animal during the period of anesthetic and immediate postsurgical recovery and should be sited to allow adequate observation of the animal during this period. The electric and mechanical requirements of monitoring and support equipment should be considered. The type of caging and support equipment will depend on the species and types of procedures but should be designed to be easily cleaned and to support physiologic functions, such as thermoregulation and respiration. Depending on the circumstances, a postoperative recovery area for farm animals may be modified or nonexistent in some field situations, but pre- cautions should be taken to minimize risk of injury to recovering animals. barrier Facilities Barrier facilities are designed and constructed to exclude the introduc- tion of adventitious infectious agents from areas where animals of a defined health status are housed and used. They may be a portion of a larger facility or a free-standing unit. While once used primarily for rodent production facilities and to maintain immunodeficient rodents, many newer facilities incorporate barrier features for housing specific pathogen-free (SPF) mice

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146 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS and rats, especially valuable genetically engineered animals, and SPF ani- mals of other species. Barrier facilities typically incorporate airlock or special entries (e.g., air or wet showers) for staff and supplies. Staff generally wear dedicated cloth- ing and footwear, or freshly laundered, sterile, or disposable outer garments such as gowns, head and shoe covers, gloves, and sometimes face masks prior to entry. Consumables, such as feed or bedding, that may harbor infectious agents are autoclaved or are gamma-irradiated by the supplier and surface decontaminated on entry. Drinking water may be autoclaved or subject to specialized treatment (e.g., reverse osmosis filtration) to remove infectious agents. Caging and other materials with which the animals have direct contact may be sterilized after washing before reuse. Strict opera- tional procedures are frequently established to preclude intermingling of clean and soiled supplies and personnel groups, depending on work func- tion. Only animals of defined health status are received into the barrier, and once they leave they are prohibited from reentering without retesting. Personnel entry is restricted and those with access are appropriately trained in procedures that minimize the introduction of contaminants. Engineering features may include high-level filtration of supply air (e.g., HEPA or 95% efficient filters), pressurization of the barrier with respect to surrounding areas, and directional airflow from clean to potentially con- taminated areas. Specialized equipment augmenting the barrier may include isolator cages, individually ventilated cages, and animal changing stations. Detailed information on barrier design, construction, and operations has been recently published (Hessler 2008; Lipman 2006, 2008). Imaging In vivo imaging offers noninvasive methods for evaluating structure and function at the level of the whole animal, tissue, or cell, and allows for the sequential study of temporal events (Chatham and Blackband 2001; Cherry and Gambhir 2001). Imaging devices vary in the technology used to generate an image, body targets imaged, resolution, hazard exposure, and requirements for use. The devices may be self-shielded and require no modifications of the surrounding structure to operate safely, or they may require concrete, solid core masonry, lead-, steel-, or copper-lined walls, or other construction features to operate safely or minimize interference with devices and activities in adjacent areas. Because imaging devices are often expensive to acquire and maintain, and may require specialized sup- port space and highly trained personnel to operate, shared animal imaging resources may be preferable. Consideration should be given to the location of the imaging resource. Whether located in the animal facility or in a separate location, cross

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14 PhySICAL PLANT contamination between groups of animals, different animal species, or between animals and humans (if the device is used for both animal and human subjects) is possible because these devices may be difficult to sani- tize (Klaunberg and Davis 2008; Lipman 2006). If the imaging resource is located outside the animal facility, appropriate transportation methods and routes should be developed to avoid inappropriate exposure of humans to animals in transit. If possible, animals should not be moved past offices, lunch rooms, or public areas where people are likely to be present. As imaging may require the subject to be immobile, often for extended time periods during image acquisition, provisions should be made for deliv- ery of anesthetics and carrier gas, the scavenging of waste anesthetic gas, and adequate animal monitoring (Balaban and Hampshire 2001). Remote storage of gas tanks is generally required in facilities where magnetic reso- nance (MR) scanners are used as the magnetic field requires ferrous materi- als to be kept a safe distance away from the magnet. Site selection of MR scanners requires special attention because of their weight, the fringe field generated (especially from unshielded magnets), and the impact of ferrous elements of the building structure or its components, especially those that are not static (e.g., elevators), as they may affect field homogeneity. Most MR scanners are superconducting and require the use of cryogens. Because cryogen boil-off can lead to asphyxiation of both personnel and animals, rooms with MR scanners or in which cryogen gases are stored must be equipped with oxygen sensors and a method for increasing room ventilation to exhaust inert gases during cryogen filling (Klaunberg and Davis 2008). Many imaging devices, especially those designed for small animals, are self-contained and require no special physical plant considerations. Provi- sions should be made to locate the operating console away from imaging devices that emit ionizing or magnetic radiation. Imaging devices with com- ponents that are difficult to sanitize should be covered with a disposable or sanitizable material when not in use. Whole body Irradiation Total body irradiation of small laboratory animals may be accom- plished using devices that emit either gamma- or X-rays. Devices are usu- ally self-shielded and, because of the weight of the shielding material, may require special site considerations. Devices with gamma-emitting sources are subject to regulations that require adherence to specific security, moni- toring, and personnel clearance requirements (Nuclear Regulatory Commis- sion 2008). The site selected for irradiators should also take into account whether they are to be used for animals and biologics, as well as the source and microbial status of the animals to be irradiated. Locating them in the animal facility may require access for personnel who would normally not

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148 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS require it or may necessitate bringing animals into a facility where they are not normally housed. Hazardous Agent Containment The goal of containment is to “reduce or eliminate exposure of laboratory workers, other persons, and the outside environment to potential hazardous agents” (DHHS 2010). This is accomplished by employing appropriate prac- tices and equipment, vaccinating personnel if a vaccine is available, and ensuring the proper design and operation of the physical plant. Animal facilities used to study biologic agents that are infectious to humans are categorized into different biosafety levels of escalating con- tainment requirements as described in biosafety in Microbiological and biomedical Laboratories (BMBL; DHHS 2009 or most recent version). Each animal biosafety level (ABSL) reflects a combination of practices, safety equipment, and facilities based on risk of human infection. As described in the 2009 edition of the BMBL, ABSL-1 contains agents not known to cause human infection; ABSL-2 contains agents of moderate risk that cause human disease by ingestion or percutaneous or mucosal exposure; ABSL-3 contains agents that cause serious and potentially lethal infections and have known potential for aerosol transmission; and ABSL-4 contains nonindigenous (exotic) agents that pose high individual risk of life-threatening disease and for which there is no available vaccine or treatment. Facility design, engi- neering criteria, construction methods and materials, commissioning, and validation become more important with each increasing level. The BMBL should be consulted for specific design and engineering requirements. Considerable care should be taken when selecting the team of professionals responsible for the design, engineering, construction, and commissioning of a containment facility. Guidelines have also been developed for containing agricultural patho- gens (USDA ARS 2002), recombinant DNA molecules (NIH 2002), arthro- pod vectors (ACME, ASTMH 2003), and hazardous chemicals (NRC 1995). Biologic agents and toxins pose a threat to animal and plant health or public health and safety, and facilities in which they are used must adhere to APHIS, USDA, and CDC Select Agent Regulations (CFR 2005; CDC and DHHS 1996; PL 107-56; PL 107-188;) and/or other applicable federal, state, or local regulations. These regulations stipulate, among other requirements, that the institution registered to use select agents establish and adhere to stringent security measures. The specific facility features, equipment, and safety practices to be employed will depend, to a considerable extent, on whether a specific hazard is a particulate, volatile, or both. Facility features applicable to all hazards include isolation of the animals and their waste, provision of sealed

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14 PhySICAL PLANT monolithic room surfaces that do not promote dust accumulation and are easy to sanitize, increased air exchange rates to dilute environmental con- tamination if it occurs, air pressure differentials to ensure that areas con- taining hazards have negative pressure with respect to surrounding areas, specialized housing systems, if available, and appropriate safety equipment such as a biologic safety cabinet or chemical hood (CDC and NIH 2007). A number of references are available to provide an overview of the issues related to hazardous material containment (Frazier and Talka 2005; Lehner et al. 2008; Lieberman 1995; NRC 1989, 1995) behavioral Studies When planning a behavioral facility, special attention should be given to all aspects of facility design, construction, equipment, and use that may generate conditions that inappropriately stimulate the senses of the test animals. It is frequently necessary to maintain animals in an environment, especially during periods of testing and observation, with strict control over auditory, visual, tactile, and olfactory stimuli. The facility site, as well as the engineering and construction methods used, should be carefully selected to minimize airborne transmission of noise and groundborne transmission of vibration. Noise and vibration may arise from the building’s structure, its equip- ment, or from human activities (see section on Noise). The frequencies and intensity of sound, which stimulate auditory responses in the species being investigated, should guide the selection of construction materials, techniques, and equipment to minimize intrusions. For instance, the HVAC system should be designed and components selected to ensure that noise, including ultrasonic frequencies, is not generated; fire alarm annunciators that emit sound at a frequency not audible to rodents should be used; hard- ware should be provided on doors to enable them to close quietly; nones- sential noise-generating equipment should be housed outside the study area; and personnel traffic should be minimized both in animal testing areas and in areas contiguous to them (Heffner and Heffner 2007). Attention should be given to the control of aberrant visual cues, especially in circadian studies. The selection of the type, intensity, and control of lighting will likely differ from other animal facility areas. A variety of specialized housing and testing systems may also need to be accommodated in the facility. Special construction features may also be desirable. Double-door ves- tibule entries to the behavioral facility, testing suites, or individual testing rooms may be useful as they can prevent noise, odors, and light from entering the behavioral testing area. Floor coverings that reduce sound transmission should be selected. Testing rooms may require floor drains, water sources, and increased floor loading to support specific behavioral testing apparatus.

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150 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS Consideration should be given to the types and amount of electronics and other equipment used to ensure that the HVAC system can accommodate the associated heat loads. Airlocks and air pressure differentials between spaces can provide olfactory segregation of species and activities and thus reduce the risk of altered behavioral responses (ASHRAE 2007c). When possible, testing equipment should be designed in such a way as to allow surface disinfection between studies. Components that cannot be cleaned or disinfected, such as computers and recording equipment, should be located in areas where contact with animals is unlikely and should be covered when not in use (the use of computer keyboard covers may also be beneficial). Provision of sufficient space for storage of behavioral apparatus and equipment should also be considered. As transportation to and from the testing area may alter behavioral responses, consideration should be given to providing housing areas contiguous with those used for testing; if such areas are provided, they should meet the requirements specified in the Guide. Aquatic Species Housing Many of the construction features described above are applicable to those for aquatic species, but particular consideration should be given to the housing systems used and the methods for maintaining the aquatic environment. The complexity of the life support system depends on the species housed and the size, type, and number of tanks and animals supported. All systems require a water source, which may require prior treatment (e.g., ultraviolet sterilization and particulate, carbon, and ultrafiltration). Hold- ing areas for aquatic species should be provided with drains of a suitable size and number to accommodate water released during system operation and maintenance or as a result of life support system or tank failure. Drains should not permit passage of animals or hazardous materials into the sani- tary system without appropriate treatment. Materials used for floors, walls, and ceilings should be impervious to water while floors should be slip resistant and able to withstand the loads inherent with large quantities of water. Electrical receptacles or circuits should be ground-fault interrupted to prevent electrocution of personnel and animals. Doors and frames, supply diffusers, exhaust registers, lighting fixtures, HVAC ducts and components (exposed to high levels of moisture or corrosives), and other metallic elements should be made of moisture- and corrosion-resistant materials. Housing systems, life support system components, and plumbing used to distribute water after treatment, including adhesives to connect components, should be constructed of materials that are nontoxic and bio- logically inert. If the macroenvironmental/room HVAC system is used as the primary method for tempering the aquatic environment, sufficient ventila-

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151 PhySICAL PLANT tion should be provided to prevent moisture buildup on room surfaces and maintain suitable temperatures for the species housed. SECURITy AND ACCESS CONTROL Recent episodes of domestic terrorism have heightened awareness of the importance of animal facility security, but there are other reasons why security and access control should be provided. Most animals maintained for research are vulnerable to infection with adventitious agents and there- fore access to them should be strictly controlled and made available only to personnel who have received appropriate training and have a legitimate need for access. Animals used in studies with hazardous materials require special precautions for personnel before access, and staff entering the ani- mal facility should have completed the institution’s occupational health and safety training. When possible, the animal facility should be located within another structure with its own independent set of security features. Vehicular access should be limited and, when provided, controlled and monitored. Security and access control are generally provided in zones, starting at the perimeter with areas of highest security located within other zones. Con- trol measures may consist of security personnel, physical barriers, and control devices. The scope of the security system should depend on the size of the facility as well as the nature of the activities conducted within. Increasingly, access control is extended from the facility’s perimeter to each animal holding room. Microprocessor-controlled security systems are frequently employed because of the large number of control points and staff requiring access. These systems typically use electronic key or proximity cards and associated readers, which, in addition to controlling access, enable recording of the time, location, and personal identification of each entry. In more sensitive areas, biometric reading devices such as thumb or palm readers or retinal scanners may be more suitable because key cards can be shared. Security may be enhanced with electronic and video surveillance systems. These systems may be monitored by personnel or motion-activated recording devices. REFERENCES ACME, ASTMH [American Committee of Medical Entomology, American Society of Tropical Medicine and Hygiene]. 2003. Arthropod Containment Guidelines. Vector-Borne Zoo- notic Dis 3:61-98. AORN [Association of Operating Room Nurses]. 1993. Recommended practices: Traffic pat- terns in the surgical suite. AORN J 57:730.

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152 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS ASHRAE [American Society of Heating, Refrigeration, and Air Conditioning Engineers]. 2007a. Chapter 22: Environmental control for animals and plants. In 2007 ASHRAE Handbook: Fundamentals, I-P ed. Atlanta. ASHRAE. 2007b. Chapter 47: Sound and vibration control. In 2007 ASHRAE Handbook: HVAC Applications. Atlanta. ASHRAE. 2007c. Chapter 45: Control of gaseous indoor air contaminants. In 2007 ASHRAE Handbook: HVAC Applications. Atlanta. ASHRAE. 2008. Chapter 28: Air cleaners for particulate contaminants. In 2008 ASHRAE Hand - book: HVAC Systems and Equipment. Atlanta. ASHRAE. 2009. Chapter 14: Climatic design information. In 2009 ASHRAE Handbook: Fun- damentals. Atlanta. Ayliffe GAJ. 1991. Role of the environment of the operating suite in surgical wound infection. Rev Infect Dis 13(Suppl 10):S800-S804. Ayscue D. 1986. Operating room design: Accommodating lasers. AORN J 41:1278-1285. Balaban RS, Hampshire VA. 2001. Challenges in small animal noninvasive imaging. ILAR J 42:248-262. Bartley JM. 1993. Environmental control: Operating room air quality. Today’s OR Nurse 15:11-18. BSSC [Building Seismic Safety Council]. 2001. National Earthquake Hazards Reduction Pro- gram Recommended Provisions for Seismic Regulations for New Buildings and Other Structures, 2000 ed, FEMA 369. Washington: FEMA. CDC and DHHS [Centers for Disease Control and Prevention and Department of Health and Human Services]. 1996. Additional requirements for facilities transferring or receiving select agents. Final Rule, Federal Register 61:55189-55200. October 24. CDC and NIH [Centers for Disease Control and Prevention and National Institutes of Health]. 2007. Primary Containment for Biohazards: Selection, Installation and Use of Biological Safety Cabinets, 3rd ed. Washington: Government Printing Office. Available at www.cdc .gov/biosafety/publications/bmbl5/BMBL5_appendixA.pdf; accessed July 15, 2010. CFR [Code of Federal Regulations]. 2005. 7 CFR Part 331 and 9 CFR Part 121, Agricultural Bioterrorism Protection Act of 2002. USDA, APHIS, Possession, use and transfer of biological agents and toxins. 42 CFR Part 1003, Final Rule, Department of Health and Human Services, March. Chatham JC, Blackband SJ. 2001. Nuclear magnetic resonance spectroscopy and imaging in animal research. ILAR J 42:189-208. Cherry SR, Gambhir SS. 2001. Use of positron emission tomography in animal research. ILAR J 42:219-232. DHHS [Department of Health and Human Services]. 2009. Biosafety in Microbiological and Biomedical Laboratories, 5th ed. Chosewood LC, Wilson DE, eds. Washington: Gover- nment Printing Office. Available at http://www.cdc.gov/biosafety/publications/bmbl5/ index.htm; accessed July 30, 2010. Eastman C, Teicholz P, Sacks R, Liston K. 2008. BIM Handbook: A Guide to Building Informa- tion Modeling for Owners, Managers, Designers, Engineers, and Contractors. Hoboken, NJ: John Wiley and Sons. Fitzgerald RH. 1979. Microbiologic environment of the conventional operating room. Arch Surg 114:772-775. Frazier D, Talka J. 2005. Facility design considerations for select agent animal research. ILAR J 46:23-33. Gorton RL, Besch EL. 1974. Air temperature and humidity response to cleaning water loads in laboratory animal storage facilities. ASHRAE Trans 80:37-52. Harris CM. 2005. Dictionary of Architecture and Construction, 4th ed. Columbus, OH: McGraw-Hill.

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153 PhySICAL PLANT Heffner HE, Heffner RS. 2007. Hearing ranges of laboratory animals. JAALAS 46:20-22. Hessler JR. 1991. Facilities to support research. In: Ruys T, ed. Handbook of Facility Planning, vol 2: Laboratory Animal Facilities. New York: Van Nostrand. p 34-55. Hessler JR. 2008. Barrier housing for rodents. In: Hessler J, Lehner N, eds. Planning and De- De- signing Animal Research Facilities. Amsterdam: Academic Press. p 335-345. Holton J, Ridgway GL. 1993. Commissioning operating theatres. J Hosp Infect 23:153-160. Huerkamp MJ, Thompson WD, Lehner NDM. 2003. Failed air supply to individually ventilated caging system causes acute hypoxia and mortality of rats. Contemp Top Lab Anim Sci 42:44-45. Humphreys H. 1993. Infection control and the design of a new operating theatre suite. J Hosp Infect 23:61-70. Jacobs GH, Fenwick JA, Williams GA. 2001. Cone-based vision of rats for ultraviolet and vis- ible lights. J Exp Biol 204:2439-2446. Klaunberg BA, Davis JA. 2008. Considerations for laboratory animal imaging center design and setup. ILAR J 49:4-16. Knecht CD, Allen AR, Williams DJ, Johnson JH. 1981. Fundamental Techniques in Veterinary Surgery, 2nd ed. Philadelphia: WB Saunders. Kowalski WJ, Bahnfleth WP, Carey DD. 2002. Engineering control of airborne disease transmis- sion in animal laboratories. Contemp Top Lab Anim Sci 41:9-17. Lehner NDM, Crane JT, Mottet MD, Fitzgerald ME. 2008. Biohazards: Safety practices, opera- tions, and containment facilities. In: Hessler J, Lehner N, eds. Planning and Designing Research Animal Facilities. London: Academic Press. p 347-364. Lieberman D. 1995. Biohazards Management Handbook, 2nd ed. New York: Marcel Dekker. Lipman NS. 2006. Design and management of research facilities for mice. In: Fox J, Barthold S, Newcomer C, Smith A, Quimby F, Davisson M, eds. The Mouse in Biomedical Research, 2nd ed, vol III. London: Academic Press. p 270-317. Lipman NS. 2008. Rodent facilities and caging systems. In: Hessler J, Lehner N, eds. Planning and Designing Animal Research Facilities. Amsterdam: Academic Press. p 265-288. Lyubarsky AL, Falsini B, Pennesi ME, Valentini P, Pugh ENJ. 1999. UV- and midwave sensitive cone-driven retinal responses of the mouse: A possible phenotype for coexpression of cone photopigments. J Neurosci 19:442-455. NIH [National Institutes of Health]. 2002. Guidelines for Research Involving Recombinant DNA Molecules. Available at http://oba.od.nih.gov/rdna/nih_guidelines_oba.html; ac- cessed May 15, 2010. NRC [National Research Council]. 1989. Biosafety in the Laboratory: Prudent Practices for Handling and Disposal of Infectious Materials. Washington: National Academy Press. NRC. 1995. Prudent Practices in the Laboratory: Handling and Disposal of Chemicals. Wash- ington: National Academy Press. NRC. 1996. Laboratory Animal Management: Rodents. Washington: National Academy Press. Nuclear Regulatory Commission. 2008. NRC Regulatory Issue Summary 2008-02, Actions to Increase the Security of High Activity Radioactive Sources. Washington: NRC Office of Federal and State Materials and Environmental Management Programs. PL [Public Law] 107-56. 2001. Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism (USA PATRIOT) Act of 2001. Wash- ington: Government Printing Office. PL 107-188. 2002. Public Health Security and Bioterrorism Preparedness and Response Act of 2002. Washington: Government Printing Office. Reynolds SD. 2008. Using computational fluid dynamics (CFD) in laboratory animal facilities. In: Hessler J, Lehner N, eds. Planning and Designing Research Animal Facilities. Amster- dam: Academic Press. p 479-488.

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154 GUIdE FOR ThE CARE ANd USE OF LAbORATORy ANIMALS Ross S, Schapiro S, Hau J, Lukas K. 2009. Space use as an indicator of enclosure appropriate- ness: A novel measure of captive animal welfare. Appl Anim Behav Sci 121:42-50. Ruys T. 1991. Handbook of Facilities Planning, vol 2. New York: Van Nostrand Reinhold. Schonholtz GJ. 1976. Maintenance of aseptic barriers in the conventional operating room. J Bone Joint Surg 58:439-445. Sun H, Macke JP, Nathans J. 1997. Mechanisms of spectral tuning in the mouse green cone pigment. Proc Natl Acad Sci USA 94:8860-8865. UFAW [Universities Federation for Animal Welfare]. 1989. Guidelines on the Care of Labora- tory Animals and Their Use for Scientific Purposes, III: Surgical Procedures. Herts, UK. USDA ARS [United States Department of Agriculture Animal Research Services]. 2002. ARS Facilities Design Standards. Pub. 242.01 Facilities Division, Facilities Engineering Branch, AFM/ARS. Washington: Government Printing Office. Vogelweid CM, Hill JB, Shea RA, Johnson DB. 2005. Earthquakes and building design: A primer for the laboratory animal professional. Lab Anim (NY) 34:35-42. Warnock ACC, Quirt JD. 1994. Chapter 5: Airborne Sound Insulation and Appendix 5 Tables on Sound Transmission Loss. In: Harris CM, ed. Noise Control in Buildings: A Practical Guide for Architects and Engineers. Columbus OH: McGraw-Hill. p 5.1-5.32; 5.33-5.77.