Good Research Practices

MONITORING

It is very important that all research animals be monitored on a regular basis. While at least cursory observation of the animals is made by the animal attendants during cage cleaning procedures, this type of inspection may not detect problems in the early stages.

At a minimum, one of the researchers responsible for the animals should check each and every animal once per week.

Depending on the nature of the research being conducted on the animal more frequent monitoring may be necessary, for example: post-operatively, when using strains of animals that are known to develop specific problems at a given age, or when working with colonies of aged animals. If more frequent monitoring is required, the minimum interval of inspection may be determined by checking the “Clinical Endpoints” section of the protocol the animals are covered by. It is important that responsibility for this task be clearly defined and, when that person will be away for any length of time, another person designated to take over. Symptoms of an animal that is feeling pain or stress may vary by species. Some symptoms of pain include isolation from others in the same housing unit, abnormal body posture (i.e. hunching or stiffness), and vocalization, especially if disturbed. If housed singly, it may be possible to detect decreased appetite or reduction in fecal or urine output. Piloerection or lack of grooming is often a sign that animals that are not feeling well. The following table shows some of the common signs of pain and stress and gives an expectation of their occurrence. This table is not intended to be a definitive guide to determining the presence of pain and/or stress, especially since different species may exhibit different responses. Additional information on the species specific signs of pain is available from the CCAC at http://www.ccac.ca/en_/standards/guidelines/additional/vol2_mice.

Sign

Pain

Stress

Protecting injured part (e.g., limb, abdomen) Commonly seen; may be reluctant to move Seldom seen
Vocalizing Especially if forced to move May occur in isolated stressed animal
Respiration Rate increased and may be shallow rate may be increased if animal is also fearful
Attitude May be depressed and unresponsive to stimuli Usually alert and responsive, sometimes depressed
Food and water intake Usually decreased Often decreased; some stressed animals may overeat
Urination and defecation Reduced volume and frequency Both may be increased with diarrhea sometimes
Appearance Unkempt, piloerection, reduced self care Unkempt, piloerection and reduced self care
Eyes may be sunken, occasional discharge Discharge, especially in rats and mice
Measurable Endpoint Criteria Clinical Evaluation
Tumour size 5% of normal body wight for routine tumour passage
or
10% for animals involved in therapeutic experiments

Frequent weighing (see relevant section of protocol)

Frequent measurement of tumour size, preferably using calipers

Tumour appearance Evidence of necrosis or sepsis Ulceration, scabbing, purulent discharge
Tumour location Impairment of normal bodily functions Inability to access or ingest food or water; significant interference with normal bodily functions (walking, urination, defecation, etc)

WORKMAN, P., TWENTYMAN, P., BALKWILL, F., et al. (1998). United Kingdom Coordinating Committee on Cancer Research (UKCCCR) Guidelines for the welfare of animals in experimental neoplasia (Second Edition, July 1997). British Journal of Cancer 77:1-10.

 

Body Condition Score (BCS)

The McGill University Animal Care Committee (UACC) recommends the use of Body Condition Score (BCS) for clinical endpoints. Body condition scoring is a rapid, non-invasive and effective assessment of an animal’s physical well being.

In many instances, BCS is a better clinical endpoint than body weight. The use of body weight alone does not discriminate between body fat or muscle stores. Weight loss can be masked by abnormal (e.g. tumour growth, accumulation of ascetic fluid, organomegaly) or normal (e.g. pregnancy) weight gain. Alternatively, an animal that may have exceeded a 20%weight loss yet maintains a reasonable BCS will not necessarily require immediate euthanasia. Thus, BCS is a more comprehensive and accurate marker for animal health than a fixed percent of body weight loss.

A BCS less than 2 would usually be considered a clinical endpoint. Other clinical endpoints can also be reported such as decreased exploratory behavior, reluctance to move (decreased locomotion/mobility), pronounced hunched posture, piloerection (hair standing on end), moderate to severe dehydration (sunken eyes, prolonged skin tent, lethargy), unrelenting pain (e.g. distress vocalization). Endpoints specific to the project’s procedures should also be included.

Body Condition Score for Mice

BC 1 - Mouse is emaciated

  • Skeletal structure extremely prominent; little or no flesh cover.
  • Vertebrae distinctly segmented.

 

BC 2 - Mouse is under-conditioned.

  • Segmentation of vertebral column evident.
  • Dorsal pelvic bones are readily palpable.

BC 3 - Mouse is well-conditioned.

  • Vertebrae and dorsal pelvis not prominent; palpable with slight pressure.

BC 4 - Mouse is over-conditioned.

  • Spine is a continuous column.
  • Vertebrae palpable only with firm pressure.

BC 5 - Mouse is obese.

  • Mouse is smooth and bulky.
  • Bone structure disappears under flesh and subcutaneous fat.

A "+" or a "-" can be added to the body condition score if additional increments are necessary (i.e. ...2+, 2, 2-...)

Body Condition Score for Rats

BCS 1 - Rat is emaciated

  • Segmentation of vertebral column prominent if not visible.
  • Little or no flesh cover over dorsal pelvis. Pins prominent if not visible.
  • Segmentation of caudal vertebrae prominent.

BCS 2 - Rat is under-conditioned.

  • Segmentation of vertebral column prominent.
  • Thin flesh cover over dorsal pelvis, little subcutaneous fat. Pins easily palpable.

BCS 3 - Rat is well-conditioned.

  • Segmentation of vertebral column easily palpable.
  • Moderate subcutaneous fat store over pelvis. Pins easily palpable with slight pressure.
  • Moderate fat store around tail base, caudal vertebrae may be palpable but not segmented.

BCS 4 - Rat is over-conditioned.

  • Segmentation of vertebral column palpable with slight pressure.
  • Thick subcutaneous fat store over dorsal pelvis. Pins of pelvis palpable with firm pressure.
  • Thick fat store over tail base, caudal vertebrae not palpable.

BCS 5 - Rat is obese.

  • Segmentation of vertebral column palpable with firm pressure; may be a continuous column.
  • Thick subcutaneous fat store over dorsal pelvis. Pins of pelvis not palpable with firm pressure.
  • Thick fat store over tail base, caudal vertebrae not palpable.

 

 

 

       

 

 

FACTORS INFLUENCING RESEARCH RESULTS

Variables:

  • Animal
  • Environment
  • Human
  • Miscellaneous

 

ANIMAL

An ideal animal model is an individual that is sound both physically and mentally and is entirely suitable for the project

Healthy laboratory animals will necessarily generate sound experimental data as opposed to their unwell or diseased counterparts

Factors to consider in selecting an animal model

  • Accurate reflection of the system/organ in question
  • Natural vs. induced disease model
  • Genetic variables of model
  • Species availability
  • Size of animal model
  • Life span of animal
  • Housing costs
  • Husbandry expertise
  • Environmental enrichment
  • Special requirements (diet, housing)

Health status

  • Viral, bacterial, parasitic, fungal pathogens
  • Reflection of a single individual or for an entire animal colony
  • Relevant for imported and exported animals
  • Special importance in immunodeficient animals

Species specific diseases

Genetics

  • Inbred vs. outbred
  • Genetically modified animals
  • e.g. disease susceptibility, tumour incidence, lifespan

Nutritional plane

Age

Disease susceptibility generally increases with age

Sex

Reproductive status (e.g. pregnancy, lactation, neutering)

Body condition score

Obesity / emaciation vs ideal body weight

Acclimation period

  • Adequate period of handling by technically skilled individuals prior to experimentation
  • To minimize negative physiologic effects of transportation stress and introduction to a novel environment
  • To allow for establishment of a baseline in terms of physiological parameters

 

Environment

Relative humidity

Disease susceptibility (ringtail in rats if RH less than 40%)

Temperature

Thermoneutral zone varies between species

Housing

  • Conventional vs. barrier facility
  • Static microisolators vs. ventilated racks

Air quality

Ammonia concentrations, allergens, pollutants

Ventilation

  • Number of fresh air changes per hour
  • Recommended 10-15 per hour
  • Removes ammonia, heat, CO2 and airborne particles (allergens)

Cage population density

Vibrations

Negative impact on reproductive performance

Noise

  • Often out of human auditory range
  • Negative impact on reproductive performance
  • Audiogenic seizures (strain dependent)
  • Traffic flow patterns
  • In animal facility and research laboratory

Water

Quality, quantity, availability

Diet

  • Nutritional plane, availability, palatability
  • Feed contaminants

Enrichment

At cage or room level - Scientifically proven positive impact upon research animals

Light / dark cycle

  • Natural circadian rhythms
  • Photoperiod (12 hours light: 12 hours dark) in rodent rooms
  • As most rodents are nocturnal, consider this when planning the timing and duration of manipulations and experimental interventions
  • Manipulations should be carried out at same time each day to ensure consistent results
  • Intensity of light source (above 300 lux can cause retinal degeneration in albino animals)
  • Light pollution (interference with tumour growth rates)

 

Human

  • Research community
  • Familiarity with appropriate animal models, experimental design and objectives
  • Knowledge of humane endpoints
  • Competent research personnel trained to work with animals and carry out experimental procedures
  • Post operative care and monitoring skills
  • Animal health team (veterinarians and veterinary technicians)
  • Competent and humane animal handling
  • Familiarity with species specific behaviours and diseases
  • Knowledge and recognition of illnesses and diseases
  • Therapeutic intervention and/or alleviation of clinical signs
  • Post operative care and monitoring skills
  • Technical expertise in animal handling and biomethodology techniques (blood collection, compound administration etc)

 

Miscellaneous

On a larger scale, the institutional sentinel program, micro monitoring procedures and quarantine policy will all have an impact upon the health of both individual animals, and the animal community as a whole.

Infectious disease in a laboratory animal facility can kill many of the animals, alter the animal's immune system interfering with research results, can spread to people and there may be a need to depopulate the facility in order to eliminate the threat.

 

STRESS REDUCTION 

It is important to be proactive in reducing stress in research animals. When preparing a research protocol, minimally invasive techniques should be considered where possible. Pilot studies may be used to find the best method of performing an experimental procedure before starting studies on larger group.

Species Initial Acclimation Basic Handling
Rodents 48 hours minimum Can start after 24 hours
Rabbits 72 hours After 72 hours
Cats/Dogs 7 days After 24 hours
Non-human Primates Quarantine period (6 weeks) After 48 hours

When animals are first received in the animal facility, a period of acclimation is necessary to allow the animals to recover from transport stress and to adjust to their new surroundings and, possibly, new cage mates. The table above shows the recommended acclimation periods for various species. Note that basic handling may be begun inside the acclimation period for most species. Research procedures should wait until after the acclimation period.

Maintaining consistency of handlers is a very good way to reduce stress among research animals. Animals often become accustomed to a particular handler and become less stressed when always handled by that person. Personnel should have assigned duties and minimize asking others to take over for them when at all possible. Consistency in the way techniques are performed on the animals is also very important. Husbandry procedures are less stressful if performed regularly by the same person. All handlers should work in a calm and quiet manner, avoiding unnecessary noise and a busy, ‘bustling’ work attitude.

Pair or group housing of social animals is an important method of reducing stress. If removing an animal from a housing unit for testing, bringing a cage mate along can reduce the stress levels felt by the experimental animal.

Using acclimation and operant conditioning to introduce an animal to an experimental procedure can significantly reduce stress levels. Before starting potentially stressful procedures, animals should be given the opportunity to get used to the apparatus on several occasions beforehand, especially in the company of an animal which is used to that apparatus. Placing experimental apparatus in the housing area, at a gradually decreasing distance, is one possibility. Animals, especially larger animals, can be trained in gradual steps to perform required tasks, such as presenting a limb for injection or remaining quietly in a sling or other restraint for prolonged periods of time. This type of acclimation must only start after the initial acclimation upon arrival is completed.

 

ENVIRONMENTAL ENRICHMENT

Experimental animals were traditionally kept in caging which provided little or no social or physical stimulation.  The use of such caging was justified on the basis of reduction of disease spread, ease of sanitation, prevention of fights between animals, easy recognition of illness through measuring food and water intake, etc.  However, at the time, little consideration was given to the behavioural and psychological well-being or the stress induced by social isolation and physical deprivation. It is recognized now, that the well-being of animals is greatly improved if they are provided with opportunities for interaction with each other and their environment.  Furthermore, there is an increasing volume of literature denoting the deleterious effects of impoverished environments on experimental results.   

Although the term "environmental enrichment" is used to describe efforts aimed at improving the living conditions for animals, the move is really from a very impoverished environment to a less impoverished environment. It is unlikely that the level of complexities encountered by wild counterparts will ever be achieved within the laboratory. Furthermore, it is possible that the well-being of an animal will not be increased by our ideas of increased complexity in its environment. Nevertheless, the wild species are often taken as the norm against which the environment of the captive animal is measured. Some argue that the wild and laboratory animals are no longer the same behaviourally, but most wild behaviours are seen in the laboratory animal. 

The presence of a normal range of behaviours and the absence of abnormal behaviours or stereotypies (behaviors that do not appear to be goal-directed) is a reasonable indication that the animal is coping with its environment. To make such judgements, we must be able to recognize normal and abnormal behaviours. Those species that are prey animals in nature, seldom reveal that they are hurting in any way as this would be an invitation for predation.

Another approach to evaluating well-being is to use the Five Freedoms of the UK Farm Animal Welfare Council. These freedoms were defined to give guidance to farmers on the goals of husbandry. However, the freedoms are easily adapted to other animals and have been accepted by various groups including the World Veterinary Association and Humane Societies.

The five freedoms are:

  1. Freedom from hunger and thirst (by ready access to fresh water and a diet to maintain full health and vigour)
  2. Freedom from discomfort (by providing an appropriate environment including shelter and a comfortable resting area)
  3. Freedom from pain, injury and disease (by prevention or rapid diagnosis and treatment)
  4. Freedom to express normal behaviour (by providing sufficient space, proper facilities and company of the animal's own kind)
  5. Freedom from fear and distress (by ensuring conditions and treatment which avoid mental suffering)

The freedoms are general enough to allow them to be used for any animal species and to allow for interpretation related to particular species. They must be applied carefully with an understanding of the biology of each species and care must be taken to avoid using our own ideas as animal standards. For example, it is customary to keep newly weaned piglets at a temperature of about 27° 0 C, day and night. However, when the piglets had the opportunity to control the temperature themselves, they preferred a temperature of about 29°0 C during the day and about 15°0 C at night.


Terms like "discomfort" make us think about the animal's living conditions and while we tend to think of the extremes of heat and cold, or wet and dry, there are grades of discomfort in between the extremes as we know from our own experience. A cool room is uncomfortable if we do not wear enough clothes and a hairless animal without any means of building a nest or others to huddle with may be uncomfortable at the normally recommended temperatures in the animal facility.

We can assume, given our present knowledge, that the health, nutrition and general environment needs of the common laboratory animal species are being met in present day laboratory animal facilities. The major challenge for us is to provide them with social and physical opportunities to live and behave in a normal manner. To do that we must have some knowledge of what a particular animal needs based on understanding their preferences. Most important, all animals require social interactions although for some this interaction is intermittent and occurs only at breeding times. Most wild animals occupy their days in the search for food and water. The threat of predation is a fact of life for many small animals, including those in the laboratory where we are the predators. To be frightened without having any means of protecting yourself is a stressful experience. Lack of space or structure to exercise or play, in the case of young animals, is detrimental to bone and muscle development and maintenance.

 
The major factors to be considered then are:

  • Opportunities to socialize or not
  • Opportunities to occupy time during waking hours
  • Opportunities to hide
  • Opportunities and structure for exercise

Improving the environment is not just a nicety for research animals. There is a considerable body of literature now that demonstrates the influence of an animal's physical and social environment on research results. One of the earlier demonstrations showed that social and physical stimulation of rats resulted in a thicker cerebral cortex with more dendritic connections. Tumours in isolated mice grow faster than the same tumours in mice housed at appropriate densities. Isolation of mice has been shown to increase the toxic effects of some drugs.

It has also been shown that environmental enrichment is beneficial at any stage of an animal's life. The effects may be different between young and old animals but the old will also benefit. For this reason it is important to consider environmental enrichment as a variable in an experiment and to account for it. It is not an option, however, to omit environmental enrichment to reduce the variables in a study unless the investigator is prepared to include all the deleterious effects of an impoverished environment on the study. Even then, it would be difficult to say that the results represent the normal state of the animal. However, if an investigator feels that attempts at environmental enrichment will jeopardize the results of a study, then this should be justified to the Animal Care Committee.

Environmental enrichment encompasses more than just the physical and social environment of a group of animals. Because we interact with them at various levels, we may have a profound effect on their life. We should treat animals in a manner that minimizes any discomfort or stress they may experience at our hands. All the environmental enrichment in the world will not be of any value if an animal fears the arrival of a human being at its cage. It may not be just the presence of a person but it may also include the sounds and smells associated with an experimental procedure, for example.

Our activities in the animal facility may be disturbing, even if they do not directly involve the animals. Noise is disturbing to animals and we should minimize extraneous noises as much as possible. Some people bustle and have an air of urgency about them that is unsettling to animals. Doors are allowed to slam shut or objects fall on the floor. Equipment like cage washers, vacuums etc. may be upsetting, particularly to pregnant animals.

If we try to see things as the animals might see them, we will probably be able to improve their living conditions. In return, people working with the animals, particularly the animal care technicians, feel better about their jobs when they see the animals responding to their enriched environment.

It must be emphasized that changing an animal's environment, whether it be giving it a clean cage devoid of familiar "homey" smells or adding toys or other objects for enrichment, will be a variable that should be accounted for. It is important, then, not to make changes to the environment without the agreement of the principal investigator and if changes are made, they should be applied consistently to all animals in the study. It should be remembered that there may be effects of withdrawing enrichment, for example, if the animals move from a facility with very complex environments to one where there is minimal complexity.

In the past, animals were kept in cages or pens that provided very little substrate for them to engage in many of their natural behaviours. Environmental enrichment is a phrase used to cover a wide range of additions or modifications of the environment to allow animals a more varied life. Although many of the changes are indeed to the physical environment, changes in social opportunities for the animals are also important; and social opportunities include interactions with people. A major benefit of environmental enrichment is the reduction in stress in the animals with beneficial influences on the research projects they are involved in.

Animal Users must know that environmental enrichment is part of the set of guidelines from the CCAC. It is not a matter of choice but a requirement. Animal facilities will include enrichment devices to single housed animals as part of the normal process. Investigators who do not want such devices, clear justification must be supplied to the local animal care committee.

Examples of enrichment

Mice

  • Study design
  • Housing - wire-bottom vs. solid bottom cages
  • Social interaction - single vs. pair vs. group housing
  • Feed - ad libitum
  • Enrichment devices - tubes, running wheels, marbles
  • Human interaction - minor value

Rats

  • Study design
  • Housing - wire-bottom vs. solid bottom cages
  • Social interaction - single vs. pair vs. group housing
  • Feed - ad libitum vs. diet optimization
  • Enrichment devices - tubes, marbles, hanging toys
  • Human interaction - possible value

Rabbits

  • Study design
  • Housing - flooring considerations
  • Social interaction - single housing with visual contact
  • Feed - limit feed, treats
  • Enrichment devices - toys, music
  • Human interaction - probable benefit

Other Species

For other species, a search on the Web will bring plenty of information regarding what is best for the animal you are working with.

 

 

 

CONTROLLED SUBSTANCES

Definition:

A controlled substance is any type of drug that the federal government has categorized as having a higher-than-average potential for abuse or addiction and has taken measures to control its use such as limiting the type of users and requiring a written application for permission to use.

Permits:

Due to the potential for abuse, permits and/or valid practice licenses are required for the purchase, distribution and administration of opioids as well other controlled substances such as ketamine. Each investigator who plans to use a controlled substance must complete an “Application Form for an Exemption to Use a Controlled Substance for Scientific Purposes” and submit it to the Office of Controlled Substances at Health Canada. Justification for the amount of drug to be purchased must be provided as well as the name and address of the supplier (e.g. The Animal Resources Centre is a licensed distributor for many of the controlled drugs used in research at McGill University). Both applicant and supplier will receive copies of the permit once the request has been approved. Call Health Canada at 613-952-2219 for further information.

Records:

Up-to-date record keeping logs are mandatory. A sample log is available online at: Controlled drugs dispensing form [.xls] or see sample form below. The log should permit recording of the type of drug the record is for, the name of the Principal Investigator under whose permit the drug was ordered and the date of issue/receipt.

 

OTHER ISSUES

 

A. FACILITY SPECIFIC ISSUES

A laboratory animal facility must facilitate research by minimizing undesirable experimental variables while providing for the physiological, social and behavioural requirements of the animal. Different research projects and/or different species of animals often require differing facilities and environments. To accommodate such needs, an animal facility must have separate areas for carrying out different functions, specialized rooms and equipment, and closely controlled environments.

Animal facilities providing the appropriate environment are expensive to build. It is, therefore, imperative that every effort be made to ensure that any proposed new facility is programmed, designed, and built to meet the size and scope of current animal use, and yet to be versatile enough to allow flexibility in the years to come.

A number of alternative design approaches to achieve any given functional need are available. It is strongly recommended that the CCAC be involved at an early stage in the planning phase and that plans be evaluated by the Council before the start of construction.

Important issues include:

  • location (secured, clean and dirty material kept separate),
  • mechanical services (heating, ventilation and air conditioning systems,
  • design (size of room, easy to sanitize, easy to access for authorized personnel)
  • major functional divisions (animal holding rooms separate from procedure rooms, reception area, one species per room, hazardous material used in separate rooms, quarantine rooms, washing facilities, waste disposal, food and bedding storage area, office area)
  • security (controlled access to facility)
  • construction (floor drains, no cracks in walls & ceilings, windows that do not open)
  • caging (appropriate for species, easy to clean, allow view of animals, with a solid bottom)

Information on housing of large domestic animals and fowl may be found in Agriculture Canada's Canadian Farm Building Handbook (Agriculture Canada, 1988) as well as Social and Behavioural Requirements of Experimental Animals on the CCAC Web site at http://www.ccac.ca/en_/standards/guidelines.

For information on cages for wild animals, contact the Secretary-Treasurer of the Canadian Association of Zoos and Aquariums (http://www.caza.ca).

Information on shipping crates and transport cages for a wide range of domestic, wild and laboratory animals may be obtained from the most recent volume of Live Animals Regulations (1992) of the International Air Transport Association (IATA).

B. THE ENVIRONMENT

There are many physical, chemical, and biological factors which may influence experimental animals and thus modify the results of the investigations. The experimental results obtained are, in principle, only valid for the conditions under which they were obtained and only useful for comparison if all the relevant information concerning experimental conditions is made available.

Among the environmental factors which should be recorded for possible inclusion in scientific reports are: temperature (C and range), relative humidity (% and range) and whether or not these are regulated; air exchanges/hour, proportion of fresh and recirculated air, and gas or particle concentrations in the air; lighting (natural and/or artificial, photoperiod, and intensity); water type, quality, and pretreatment; bedding type, quality, and pretreatment; housing density; housing equipment; and physical measures to protect microbiological status. The microbiological status of the animal should be reported [conventional, Specific Pathogen Free (SPF) for stated pathogens, or gnotobiotic with microorganisms specified].

CLIMATE CONTROL

Environmental requirements vary with the species and the experimental protocol. Environmental parameters are usually measured at the level of the room. More important, however, is the microenvironment established at the cage level, since the conditions between the two may differ dramatically. A summary of some environmental parameters for individual species is given in Appendix I of the CCAC guidelines.

The design of the animal facility should permit adjustment of environmental controls to meet the needs of the species and the experimental protocol. Ideally, each animal room would be controlled independently. In facilities not originally constructed with this capability, this ideal could be approached through proper management and the installation of ancillary automatic light timers, rheostats, thermostatically controlled exhaust fans, humidifiers, and air conditioning units.

Parameters:

temperature
humidity
ventilation
lighting
noise
chemicals
bedding
population density and space limitations

 

DESIRABLE CRITERIA FOR RODENT CONTACT BEDDING (Kraft, 1980) : Moisture absorbent, dust free, unable to support bacterial growth, inedible, non-staining, non-traumatic, ammonia binding, sterilizable, deleterious products not formed as a result of sterilization, easily stored, non-desiccating to the animal, uncontaminated, non-nutritious, non-palatable, unlikely to be chewed or mouthed, non-toxic, non-malodorous, nestable, disposable by incineration, readily available, relatively inexpensive, fire resistant, remains chemically stable during use, manifests batch to batch uniformity, optimizes normal animal behaviour, non-deleterious to cage-washers, non-injurious and non-hazardous to personnel

Unsterilized materials are a possible source for the introduction of disease into rodent colonies. Wild rodents enjoy nesting in packages of bedding, and cats will defecate in loose bedding.

MICROBIOLOGICAL CONTROL

The effects that microbiological agents can have on experimental results and the health of laboratory animals have been widely documented. Control of the microbiological status of the experimental animal and its environment is necessary for valid scientific results and animal well-being. The sources of microbial contamination include vermin, experimentally infected and spontaneously ill laboratory animals or their tissues or tumours, air, food, water, bedding, ancillary equipment, and personnel. Good facility management practices and constant surveillance are necessary to minimize the introduction of unwanted microbes. Insect and rodent vermin should be strictly controlled or excluded from the facility.

Whenever possible, the health status of all animals should be ascertained before the animal is brought into the facility. Animals having an unknown health status should be quarantined and tested before being admitted to the facility. Additionally, all tumour and cell lines should be tested before being introduced. Research on contagious diseases must be carried out in appropriate containment facilities.

Biohazard Containment

Containment is required for animals exposed to known infectious microorganisms. Required containment and management procedures vary with the biohazard classification of the microorganism, based on the degree of risk to man and other animals. Personnel may be required to shower before leaving the containment unit. All cages and materials are sterilized upon leaving the area. Air pressures are balanced so that the highest pressure is outside the containment area. Air exiting the facility is diluted with clean air, filtered, or incinerated.

Because it is hazardous to staff and animals, UV light is not generally recommended for routine disinfection of laboratory air. The infectious disease unit should be segregated as much as possible from the rest of the animal facility. Specific requirements will differ with the degree of risk. Depending on the hazard, containment of small groups of animals may be accomplished with flexible film isolators or microisolation cages. The use of laminar airflow racks to prevent cross-contamination between cages should be carefully evaluated as the transfer of certain pathogens may be enhanced in some instances. Infectious disease units should be disinfected immediately following use.

Recommendations for control of biohazards can be found in Laboratory Biosafety Guidelines (http://www.hc-sc.gc.ca/pphb-dgspsp/publicat/lbg-ldmbl-96/index.html) and elsewhere. Biological safety cabinets approved for the appropriate biohazard level must be used for experimental manipulations. These cabinets must be inspected and tested annually by trained personnel.

Persons working in infectious disease units should be protected with a comprehensive occupational health and safety program.

CHEMICAL AND RADIOISOTOPE UNITS

In Canada, laboratory use of radioisotopes is regulated by the (federal) Canadian Nuclear Safety Commission (CNSC, http://www.nuclearsafety.gc.ca/eng). The CNSC issues licences to the institution for the possession of radioactive material. When radioisotopes are used in animals experimentally, Standard Operating Procedures (SOPs) to ensure that related hazards are minimized should be defined and enforced; these SOPs are considered by the CNSC when it issues the Radiation Licence. As well, the CNSC recommends that the institution's Radiation Safety Officer sit on the Occupational Health and Safety Committee in an ex-officio capacity.

The Workplace Hazardous Materials Information System (WHMIS) is regulated by federal and provincial health and safety authorities. It legislates labeling requirements, availability of Material Safety Data Sheets (MSDS), and training programs required for personnel to work safely with certain hazardous materials.

The chemical and radiation hazard area should be separated from other animal housing and work areas. The hazardous area must be clearly posted and entry restricted to necessary personnel. Contaminated cages should not be transported through corridors. Safe transport equipment and procedures should be developed if necessary. Laminar flow cage-changing stations are recommended to protect the staff from aerosolized contaminants.

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