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OCR for page 32
Physical, Chemical, and
Prolocol-Related Hazards
The diversity of physical, chemical, and protocol-related hazards associated
with animal research is tremendous. Animals bite, scratch, and kick; moving
bulky animal cages can result in sprains and strains; and electricity, machinery,
and noise can cause injury. Chemicals are ubiquitous in the laboratory and animal
room environments; chemicals are used to disinfect and clean surfaces, anesthe-
tize animals, and process tissue samples. Research protocols can introduce toxic
chemicals, human pathogens, or radioactive materials into animals, and these
agents can enter the waste stream of the animal facility. This chapter provides a
brief review of specific physical, chemical, and protocol-related hazards that are
commonly observed in animal care and use programs.
PHYSICAL HAZARDS
Animal care and use by their very nature present many situations that require
safe practices to protect workers from physical hazards. The hazards of bites,
kicks, and scratches are associated inevitably with most laboratory animal con-
tact. A survey of animal-related injuries among veterinarians indicated that 35%
required sutures for lacerations during their career. Working with heavy animals
and equipment, such as metal cages, can stress muscles and joints. The potential
for wet floors in animal rooms and cage washing areas increases risks of slipping
and falling. Workers can also be exposed to physical hazards that are commonly
found in the research environment, such as flammable solvents, ultraviolet radia-
tion, ionizing radiation, pressure vessels, noise, and electric shock. The physical
32
OCR for page 33
PHYSICAL CHEMICAL, AND PROTOCOL-RELATED HAZARDS
33
hazards selected for discussion in this section present the highest potential for
causing serious harm and are likely to be present in most animal facilities.
Animal Bites, Scratches, Kicks, and Related Hazards
Bites, scratches, and kicks are ubiquitous hazards associated with laboratory
animal contact. They are largely preventable through proper training in animal-
handling techniques. People working with large domestic animals might sustain
crushing injuries when the animals kick, fall, or simply shift their body weight.
Personnel should be aware of environmental factors, as well as factors intrin-
sic to the animal, that can precipitate a traumatic event in a research animal
facility. Several factors need to be considered in work with animals (Grandin
1987~. Animals respond to sounds and smells as people do; they also hear, smell,
and react to things that people might not detect. If an animal hears a high-pitched
sound, it might become frightened. Such situations can result in an unexpected
response that results in injury to the animal handler. Many animals have a "flight
zone": approaches by another animal or a person cause an attempt to escape.
Being aware of an animal's flight zone will help to avoid injuries. Many animals,
including monkeys and livestock, are social and show visible signs of distress if
isolated from others of their kind. Knowledge of animal behavior is important in
reducing risks.
Inappropriate handling can induce discomfort, pain, and distress, provoking
an animal to inflict injury on its handler. Personnel should review educational
materials pertinent to safe animal-handling techniques (Fowler 1986; Kesel 1990)
and should have supervised instruction before undertaking new animal-handling
procedures. The institution should be prepared to evaluate the causes of any
injuries that result from newly adopted procedures. The injured persons should
participate in this evaluation.
Special attention should be given to the training of personnel involved in the
handling and restraint of nonhuman primates. In addition to posing a bite and
scratch hazard, nonhuman primates can be challenging and difficult to handle
safely because of their great strength, dexterity, intelligence, and tenacity. Unsus-
pecting personnel have been injured when nonhuman primates have grabbed and
pulled neckties, loose-fitting laboratory coats, or long hair, and some individual
great apes have been known to throw their feces. When it is compatible with the
experimental conditions of animal use and the clinical condition of the particular
animal, consideration should be given to chemical immobilization of nonhuman
primates to facilitate the ease of handling them and to reduce the risk of injury of
personnel. Personnel who work with nonhuman primates should wear face shields
and other protective garments and equipment appropriate for the circumstances
and species involved.
In a survey of animal bites among the general population, dogs were the
species most commonly involved, with cats and rodents second and third (Moore
OCR for page 34
34 OCCUPATIONAL HEALTH AND SAFETY OF RESEARCH-ANIMAL WORKERS
and others 1977~. Comparable data on bites in animal facilities are not available,
but rodent bites probably predominate because of the large number of rodents
used and the broader exposure of personnel to them.
Animal bites, especially those by rodents that inflict little tissue damage, are
sometimes considered inconsequential by personnel who are unfamiliar with the
host of diseases that can be spread by this mechanism and the complications that
can result from wound contamination by the normal oral flora of the animals
involved. Personnel should be alerted to the need to ascertain their current teta-
nus-immunization status, seek prompt medical review of wounds, and initiate
veterinary evaluation of the animal involved if it is warranted. Rabies, B-virus
infection, hantavirus infection, cat-scratch fever, tularemia, rat-bite fever, brucel-
losis, and off are among the specific diseases that can be transmitted by animal
bites with profound consequences (covered in more detail in Chapter 5~.
The early initiation of antimicrobial therapy for all animal bites that are not
trivial appears warranted because there is a high probability of wound contamina-
tion with a potential pathogen. That approach will limit the progression of a
localized infection and avert the more serious complications of wound infection,
which could include cellulitis, abscess, septic arthritis, tenosynovitis, osteomyeli-
tis, sepsis, endocarditis, and meningitis. If infections do not respond to therapy,
additional microbiological studies that encompass unusual and fastidious organ-
isms should be pursued. Fungal agents should not be overlooked as possible
wound contaminants; the transmission of blastomycosis to humans by dog bite
has been reported (Gnann and others 1983~.
A wide variety of poisonous and venomous reptiles (Russell 1983), marine
animals (Halstead 1978), and arthropods (Biery 1977) might be maintained in the
laboratory or animal facility for research or instructional purposes. Institutions
that host these uncommon research animals have a special obligation to perform
a comprehensive review of safety precautions to ensure the security of animal
housing and the appropriate training of personnel who are involved in their care
and use. Institutions also should have a plan for the immediate delivery of defini-
tive medical care in response to envenomation, including the use of antivenin if
available. Many types of envenomation cause massive tissue destruction that
predisposes a wound to secondary bacterial infection and indicates a need for
treatment with tetanus toxoid and antimicrobial therapy (Goldstein 1990a;
Sanford 1985~.
Sharps
Sharps are ubiquitous in animal care. Needles, broken glass, syringes, pi-
pettes, scalpels all are commonly used in animal facilities and laboratories.
Controls include installing puncture-resistant and leakproof containers for sharps
at critical locations in the facilities. Workers should be trained to handle and
dispose of sharps safely. Improper disposal of sharps with regular trash can
OCR for page 35
PHYSICAL CHEMICAL, AND PROTOCOL-RELATED HAZARDS
35
expose custodial staff to puncture wounds and cuts and potentially to exposure to
infectious agents and hazardous chemicals. Many states and some municipalities
have regulations that specify how to dispose of sharps; these regulations should
be checked to ensure that disposal practices are in compliance.
Special care is required in the use of needles and syringes to avoid needlestick
injuries. This hazard presents a substantial risk for occupationally acquired infec-
tion in inoculating or drawing blood from laboratory animals (Miller and others
1987~. Appropriate restraint or sedation of animals during procedures entailing
the use of sharps decreases the risk of sharps injury to workers.
Flammable Materials
The National Fire Protection Association (NFPA) has classified fires into
four types according to the character of the flammable or combustible materials.
Class A, B. and C fires involve general combustible materials (such as wood,
paper, and cloth), flammable gases and liquids (such as oil and paint), and electric
equipment, respectively. Class D fires involve such combustible metals as mag-
nesium, sodium, and potassium. Class A, B. and C materials are found in all
animal care facilities. Common combustible materials in Class A fires found in
animal care facilities include animal bedding, paper gowns, plastic animal cages,
paper towels, and laboratory wipes. Class B flammable solvents might be used in
painting animal care rooms, cleaning floors and surfaces, sterilizing equipment,
administering anesthesia, and performing laboratory analyses of tissues. Com-
mon Class C materials include lighting, wet vacuums, steam-cleaning units, auto-
matic cage-washers, and many types of laboratory equipment. Explosive materi-
als are not commonly used, however, crystallized picric acid and previously
opened and expired cans of ether are common potential explosion hazards. Class
D materials are not common in animal care facilities but might exist in some
laboratories.
Class B liquids are classified according to their flash point, the lowest tem-
perature at which a liquid will produce vapor sufficient to propagate a flame.
Flammable liquids have flash points less than 100°F. Combustible liquids have
flash points greater than 100°F but less than 200°F. The flash points of combus-
tible liquids are higher, so they are more difficult than are flammable liquids to
ignite at room temperature. Knowledge of flash points of materials can be helpful
in selecting a less-flammable material for a particular use so as to lower the
related fire hazard. Material Safety Data Sheets for chemicals include informa-
tion on flash points. (See page 42, Chemical Hazards.) OSHA provides very
strict regulations for the storage and use of flammable and combustible liquids
(29 CFR 1910.106~.
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36 OCCUPATIONAL HEALTH AND SAFETY OF RESEARCH-ANIMAL WORKERS
Pressure Vessels
Compressed-gas cylinders, air receivers, high-pressure washing equipment,
hydraulic lift lines, and steam generators house high-pressure air lines (over 30
psi), and autoclaves contain steam and contents under high pressure. These ves-
sels present a substantial hazard to workers if uncontrolled or improper release of
the pressure occurs. Compressed-gas cylinders should be secured at all times.
Lighting
One characteristic of animal care facilities that is not seen in many other
operations is a fixed light-dark cycle. In animal care rooms, light cycles can vary,
and most animals receive only artificial light. Animals can be kept on light-dark
cycles that do not match the natural daily cycles. Or animals might be kept in
rooms with single-color lights (usually red) or very low light. For humans, poor
lighting can cause visual fatigue or create safety hazards that cause trips, slips, or
falls. They might bump into corners of cages or other objects because they cannot
see them easily in low light. Humans need an adjustment period for their eyes to
become accustomed to the color or light levels in the room. Waiting for this
adjustment will make work in the room easier and safer.
Electricity
Electric hazards can be present whenever electric current is flowing. Electric
hazards are ubiquitous in animal care. Most of the hazards are obvious, such as
the absence of a plate on a wall socket, an open electric panel, or an ungrounded
plug. Less obvious hazards are present on cage-changing tables, biological safety
cabinets, and wet vacuum systems. The electric hazards associated with those and
other kinds of equipment can be minimized or eliminated through such engineer-
ing controls as ground-fault interrupters, such operational procedures as the use
of lockout and tagout procedures to control energy sources during repair and
maintenance of equipment (CFR 1919.147), and vigilance. Equipment that has
frayed or exposed wires or that is designed to be connected to an ungrounded
receptacle (as with a two-pronged plug) should not be used.
Ultraviolet Radiation
Exposure to ultraviolet (UV) radiation can occur in some operations in-
volved in the care and use of laboratory animals. For example, UV germicidal
lamps are used to sterilize clean surfaces in some work areas, and UV radiation is
used in sterilizing water and in the diagnosis of fungal diseases. The most impor-
tant exposures to UV radiation might be those of workers who perform outside
work. UV radiation is divided into three classes designated WV-A, UV-B, and
OCR for page 37
PHYSICAL CHEMICAL, AND PROTOCOL-RELATED HAZARDS
TABLE 3-1 Classification and Description of Ultraviolet Radiation
37
UV Classification Wavelengths (nary) Effects Sources
UV-A 320-400 Pigmentation of skin Sunlight, black light
(black-light region)
UV-B 280-320 Photokeratitis, Sunlight, artificial
(erythemal region) cataracts, erythema sources
UV-C 100-280 Germicidal effects Germicidal lamps
(germicidal region)
Sources: Adapted from National Safety Council 1988, pp. 227-232, and from the Amencan Confer-
ence of Governmental Industrial Hygienists (ACGIH), 1994, p. 100.
WV-C, whose wavelengths, effects, and sources are shown in Table 3-1. UV
radiation reacts with the vapors of chlorinated solvents such as trichloroethyl-
ene, trichloroethane, and chlorofluorocarbons to produce phosgene, a potent
lung irritant. Those solvents should not be used in areas where UV-B or UV-C
radiation is present.
If employees must work in the presence of UV radiation, their eyes and skin
should be protected against UV exposure. Interlocking devices can be used to
turn off UV sources before exposed areas are entered. Window glass is very
effective at filtering out wavelengths less than 320 rim except for very intense
sources.
Lasers
Laser is an acronym for light amplification by the stimulated emission of
radiation. Laser emissions are produced by solid-state, gaseous, and semiconduc-
tor lasers. Most states require lasers to be registered. The American National
Standards Institute (ANSI Z-136.1 1986) has classified lasers on the basis of
their power level and hazard potential as follows:
· Class I. Lasers that under normal operating conditions do not emit a
hazardous level of radiation.
Class II. Low-power lasers that do not have enough power to injure
someone accidentally but do have enough power to cause injury if the beam is
viewed for extended periods.
· Class III. Class IIIa, higher-power lasers that can cause injury if the beam
is concentrated with a viewing device, such as binoculars; Class IIIb, lasers that
can produce injury if viewed directly. The beam reflected off a mirror-like sur-
face is also hazardous.
.
OCR for page 38
38 OCCUPATIONAL HEALTH AND SAFETY OF RESEARCH-ANIMAL WORKERS
· Class IV. Lasers that, in addition to the conditions in Class III, can present
a fire hazard.
The major hazard associated with lasers is related to the beam. The beam can
cause burns, eye damage, lacerations, or fires, depending on its power. In animal
care operations, lasers might be used to perform surgery or to provide medical
treatment. Personnel who work with or around lasers should be trained in the
hazards and the means to protect themselves. In the case of higher-power lasers,
enclosing or shielding the beam (if possible) and providing interlocks on doors
where a laser will be used are effective ways to reduce exposure to the beam.
Laser surgery can also produce substantial aerosols, fumes, and toxic gases.
These hazards should be controlled to prevent harmful exposures of employees.
All lasers use electric power, some in large quantities, so the risk of electric
shock should be considered and reduced. The National Safety Council (NSC
1988) has produced a list of possible steps for reducing the risk of electric shock
associated with lasers.
Ionizing Radiation
Ionizing radiation is ubiquitous in our daily lives. We are exposed to cosmic
radiation, radon gas, natural background radiation, medical x rays, and even
internal radiation from potassium-40. To be classified as ionizing, radiation must
have enough energy to remove electrons from atoms and so create ions. The
ionization can cause chemical changes that can be harmful to a living organism.
Ionizing radiation can be classified as particulate and nonparticulate. Particulate
radiation is composed of particles that are of atomic origin. Alpha particles are
charged particles that each contain two neutrons and two protons. Beta particles
are electrons that are emitted with very high energy from many radioisotopes.
Positively charged counterparts of beta particles are called positrons. Alpha par-
ticles do not travel more than 0.5 in (1.3 cm) in air and cannot penetrate the dead
layer of skin. The distance that beta particles can travel depends on their source:
in air, some of the more energetic beta particles, such as those from phosphorus-
32, can travel up to 30 It (9 m), but beta particles from tritium (hydrogen-3) travel
only 0.02 It (0.6 cm). Beta particles are usually stopped by the skin but can cause
serious damage to skin and eyes.
Nonparticulate radiation includes x rays and gamma rays. X rays and gamma
rays are electromagnetic radiation with very short wavelengths. They are photons
of energy and can penetrate matter. Photons are relatively difficult to shield.
Gamma rays arise from nuclear decay; x rays arise from electron dislocation.
When a radionuclide decays, it might produce alpha particles, gamma rays, beta
particles, neutrons, or combinations of these. Irradiators and diagnostic x-ray
machines are commonly used in research settings. Appropriate training of per
OCR for page 39
PHYSICAL CHEMICAL, AND PROTOCOL-RELATED HAZARDS
39
sonnet and personal protection should be provided. Preventive maintenance of
equipment is also critical to safe operations.
Radiation can present a hazard through inhalation, ingestion, skin contact, or
proximity. The biological effect of ionizing radiation depends on the type of
radiation, its energy, and the type of tissue that absorbs it. Two types of hazard
must be considered: external and internal. A radionuclide that presents a radiation
hazard when it is outside the body constitutes an external hazard; a radionuclide
that presents a radiation hazard when it is ingested, inhaled, or absorbed consti-
tutes an internal hazard. Alpha and beta particles do not travel very far in air, so
they present mainly internal hazards; they can produce harm by being near tissue.
Some of the more-energetic beta particles can present an external hazard.
Experimentation involving animals and radioisotopes is common in molecu-
lar biology today. Use of radioisotopes in or with animals presents several new
hazards that must be dealt with. For example, some isotopes can be concentrated
in a specific organ, such as iodine in the thyroid. Tissue that has concentrated a
radioactive material might have to be handled or disposed of differently, depend-
ing on the isotope and the concentration. Bedding material from experimental
animals exposed to radioactive materials should be surveyed to determine its
radioactivity and then disposed of according to applicable regulations. If an iso-
tope could be released by exhalation, additional engineering controls might be
required. The use of radioisotopes is strictly controlled by the US Nuclear Regu-
latory Commission (US Congress 19711. Investigators should be authorized to
use radioisotopes by their institutions; authorizations are based in part on evi-
dence of training and established work practices.
Housekeeping
Good housekeeping keeps work surfaces clean and clear of obstructions,
waste, and other material. If boxes, hoses, or bags of bedding material are not
removed from the work area, trip hazards can be created or safe work might be
impossible because working conditions are cramped. The act of cleaning itself
sometimes creates hazards. For example, during steam cleaning of walls and
floors of an animal room, the hoses can cause tripping hazards, high-temperature
steam can cause burns, and wet floors can cause slipping hazards. Material left in
hallways that are used for emergency egress poses a very serious hazard. Imme-
diate removal of blockages of exits is imperative. Poor housekeeping practices
can increase the seriousness of other hazards associated with animal care. For
example, sweeping bedding, hair, and dander from floors, rather than using a
vacuum cleaner with a filtered exhaust, can result in high concentrations of
airborne allergens that can be distributed throughout the animal facility.
OCR for page 40
40 OCCUPATIONAL HEALTH AND SAFETY OF RESEARCH-ANIMAL WORKERS
Ergonomic Hazards
Physical trauma can occur when workers perform tasks that require repeti-
tive motions and lifting of heavy loads. Injuries that result from repetitive small
stresses are often termed cumulative injuries. Cumulative injuries are not associ-
ated with a specific exposure incident. Common cumulative injuries include back
injuries, carpal-tunnel syndrome, tennis elbow, and bursitis. Activities in animal
care operations that contribute to back injuries include lifting heavy bags of feed,
lifting heavy animals, lifting small weights incorrectly, moving or lifting cages,
or clipping animals' fur manually. Adjusting control knobs, using a screwdriver,
using pliers, opening and closing cage doors, moving small animals from cage to
cage, operating video display terminals for extended periods, and mopping floors
can also lead to repetitive-stress injuries. To reduce hazards due to repetitive
motion, vary tasks to lessen the number of repetitions, re-engineer tasks, or
redesign equipment or tools to require fewer repetitions with less strain.
Lifting heavy loads that exceed permissible-load recommendations of the
National Institute for Occupational Safety and Health (NIOSH 1991) is unsafe
and presents a substantial risk of acute injury. Anyone lifting heavy loads should
be physically fit, should avoid sudden movements, and should use a two-handed
lifting technique. Animal care operations that involve a potential for substantial
physical stress include moving and restraining large animals, lifting and moving
cages, lifting large feed bags, and moving high-pressure wet-vacuum systems.
Engineering controls such as the use of lifting equipment, automation of the
lifting operation, or splitting of the load can reduce the risk.
Once a hazard is recognized, employee education and engineering controls
can be applied to reduce the potential for these types of injuries. Training should
be updated if new tools are used in an operation and updated periodically to
remind employees of proper work techniques. Employee involvement should be
part of each solution.
Machinery
Conveyor belts, sanders, floor polishers, cage washers, room washing equip-
ment, and other machinery have potential to cause injury. The common types of
hazards presented by machinery are in-running nip points, crush points, and
pinch points. In-running nip points are places on a roller or similar moving
surface where a body part of an exposed worker could be pulled into the machin-
ery. Crush points and pinch points are areas of a machine where two surfaces
could come together to crush or pinch part of the body. These all occur in machin-
ery that has exposed moving parts. Each machine should be evaluated to deter-
mine whether a worker's hand or arm could be placed in an area where it could be
injured. If a hazardous area is identified, guarding should be installed to eliminate
the hazard. Guarding is important even when workers know that they are not to
OCR for page 41
PHYSICAL CHEMICAL, AND PROTOCOL-RELATED HAZARDS
41
place their hands in a dangerous area. Slips, falls, and loss of awareness of the
hazard can cause injury if guarding is not in place. In large equipment that
requires operators or repair mechanics to work in the operating chamber, such as
cage washers, an internal release mechanism should be available to allow emer-
gency escape if the equipment is inadvertently started.
Noise
Exposure to intense noise can result in loss of hearing. Chronic noise-in-
duced hearing loss is a permanent condition and cannot be treated medically. This
type of hearing loss is usually characterized by declining sensitivity to frequen-
cies above 2,000 Hz. Exposure to an intense noise for a short period can cause
temporary or permanent loss of hearing. OSHA limits employee exposure to
noise to 90 decibels measured on the A scale of a standard sound-level meter at
slow response (dBA) averaged over an 8-h workshift (29 CFR 1910.95~. The
time-weighted average must be lower than 90 dBA if the workshift is longer than
8 h (29 CFR 1910.95~. Where levels exceed 85dBA, the exposed employees need
to participate in a hearing-conservation program that includes monitoring, audio-
metric testing, hearing protection, training, and record-keeping (29 CFR 1910.95
c though o). Hearing loss is not the only adverse effect of exposure to noise.
Noise can make speech difficult, cause loss of concentration, distract workers,
and increase fatigue (NSC 1988~.
In an animal care facility, noise can result from animals, particularly pigs and
dogs, and from equipment, such as cage washers, high pressure air cleaning
equipment, and wet vacuum systems operated in a confined space. A useful way
of assessing whether a noise exposure might be excessive is to visit the area and
attempt to converse with another person or attempt to talk on the telephone. The
noise is probably excessive if normal speech or talking on the telephone is diffi-
cult or impossible. When this condition is observed, the noise levels should be
assessed by a person knowledgeable about noise, noise-measurement techniques,
and data interpretation. Most often, such a person will be an industrial hygienist
or an acoustical engineer. OSHA requires that engineering controls be applied
first to control the hazard. Engineering controls include shielding, quieter equip-
ment, and installation of sound-deadening materials on the walls and ceilings. If
acceptable noise levels are not achieved that way, administrative controls or
personal protective equipment will be necessary. Administrative controls include
limiting the time that an employee works in the noise-hazard area. It is prudent to
provide workers who are exposed to a noise hazard earplugs, earmuffs, or other
protective equipment during the noise-evaluation period.
Ultrasonography is used in laboratories and animal care facilities for imag-
ing internal structures. If the frequency is below 20 kHz, it is covered by the
OSHA noise standard. Even if it is above 20 kHz, noise exposure is possible
because of subharmonics at these higher frequencies (Strickoff and Walters 1990~.
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42 OCCUPATIONALHEALTH AND SAFETY OFRESEARCH-ANIMALWORKERS
Chemical Hazards
Most employees engaged in the care and use of research animals are familiar
with the hazards of chemicals used in animal care and laboratory environments.
Employee knowledge of chemical hazards and of relevant protective measures
has been focused and increased in recent years through employers' responses to
two important health and safety standards promulgated by OSHA: the Hazard
Communication Standard (29 CFR 1910.1200) and the Occupational Exposure to
Hazardous Chemicals in Laboratories (29 CFR 1910.1450), which is known as
the laboratory standard. The recognition and control of chemical hazards in re-
search institutions have also been aided by Prudent Practices for Handling Haz-
ardous Chemicals in Laboratories (NRC 1981~. That volume was extensively
revised and updated in 1995, and the new edition, Prudent Practices in the
Laboratory: Handling and Disposal of Chemicals (NRC 1995), provides practi-
cal guidance for evaluating chemical hazards and for working safely with chemi-
cals in the research setting. It extensively discusses sources of hazard information
and principles for evaluating and elucidating toxic effects of chemicals. It consti-
tutes a relevant and comprehensive reference document on the recognition and
control of chemical hazards, and it should be consulted by all who have responsi-
bility for the planning, conduct, and support of safe research.
Flammability, corrosiveness, reactivity, and explosivity are hazardous prop-
erties of chemicals that are usually well understood. Toxicity is the least-predict-
able hazardous property of chemicals. Exposure to toxic chemicals can cause
acute or chronic health effects. General classes of toxic chemicals that might be
handled in a research environment are carcinogens, allergens, asphyxiants, corro-
sives, hepatotoxicants, irritants, mutagens, nephrotoxicants, neurotoxicants, and
teratogens. Health risks associated with toxicants depend on both the inherent
toxicity of the chemicals and the nature and extent of exposure to them. Animal
care activities can seriously influence the potential for employee exposure. Thus,
animal care practices that might contribute to employee exposures need to be
carefully assessed so that toxic hazards of chemicals associated with the care and
use of research animals can be recognized and controlled. A comprehensive
review of chemical-hazard assessment and control is provided in Prudent Prac-
tices in the Laboratory: Handling and Disposal of Chemicals (NRC 1995~.
Typical sources of chemical exposure in the care and use of research animals
involve the use of disinfectants, pesticides, anesthetic gases, and chemicals for
preserving tissues. Sources can include animals that have been intentionally
exposed to highly toxic chemicals. Another important source is the disposal of
bedding and other waste materials from experimental procedures.
Disinfectants and detergents include soaps, cleaning chemicals, acid-con-
taining chemicals, alcohols (most commonly ethanol and isopropanol), aldehydes
(including formaldehyde and gluteraldehyde), and halogenated materials (such as
chlorinated and iodinated bleaches). Some phenolic compounds (including potas
OCR for page 43
PHYSICAL CHEMICAL, AND PROTOCOL-RELATED HAZARDS
43
slum o-phenylphenate and potassium o-benzyl-p-chlorophenate) and quaternary
ammonium compounds are also used as disinfectants. Various pesticides can be
used within animal facilities, but most animal facilities restrict the use of pesti-
cides because of their potential effects on the animals. The primary chemical used
as a preservative is formalin as a 10% neutral-buffered solution, but other mate-
rials are used from time to time.
Several occupational diseases including cancer, spontaneous abortion, and
liver disease have been associated with exposure to waste anesthetic gases.
Monitoring exposures to waste anesthetic gases in animal operating rooms is an
important part of the health and safety program because of the difficulty in
matching anesthetic-delivery equipment to the animals.
Burns and irritation of the skin are the most common chemical injuries
associated with animal care and use. Some chemicals, such as formaldehyde and
gluteraldehyde used for preserving tissue, can cause an allergic response in sen-
sitized people. The risk of injury and illness associated with chemical use can be
minimized by practices that reduce or prevent exposure.
HAZARDS ASSOCIATED WITH EXPERIMENTAL PROTOCOLS
A fundamental principle in the conduct of research is the need to determine
the potential hazards associated with an experiment before beginning it. That is
extremely important in planning experiments that involve research animals, be-
cause investigators might be unfamiliar with the intrinsic hazards presented by
the animal species of choice or tissues derived from them, and managers and their
employees who care for the research animals should be informed of the hazards
presented by the experimental protocol. Consideration of both animal-related
hazards and protocol-related hazards would benefit from a collaborative assess-
ment in which the investigator, the institutional veterinarian, the animal care
supervisor, and a health and safety professional participate. A collaborative as-
sessment is strongly encouraged if the animal experimentation involves either the
testing of chemicals for their toxic properties or research with experimentally or
naturally infected animals. Whether or not a collaborative initiative is pursued,
investigators have an obligation to identify hazards associated with their research
and to select the safeguards that are necessary to protect employees involved in
the care and use of their research animals.
Hazards associated with experimental protocols are influenced by two prin-
cipal factors: the dangerous qualities of the experimental agents and the complex-
ity or type of the experimental operations. For example, toxicity, reactivity, flam-
mability, and explosivity should be considered when an experimental protocol
involving chemical agents is being planned, and virulence, pathogenicity, and
communicability are possible hazardous qualities of biological agents.
The complexity and type of an experimental operation have a direct impact
on the extent of potential exposure that an employee receives while carrying out
OCR for page 44
44 OCCUPATIONALHEALTH AND SAFETY OFRESEARCH-ANIMALWORKERS
or participating in an experimental protocol. For example, during incorporation
of a test chemical into feed for ingestion studies, a contaminated dust created
during milling and mixing and during transfer of the diet could result in respira-
tory and dermal exposures. Test material applied to the skin of experimental
animals might be disseminated by handling of animals, clipping of hair, changing
of bedding, and sweeping of the animal room floor. Vapors are potential sources
of exposure during the application of test material to the skin. Exposing an animal
to an agent by injection will create a risk of accidental self-inoculation. Inhala-
tion challenges are particularly hazardous and should be conducted only by in-
vestigators who have appropriate experience and containment equipment.
Protocols Involving Chemicals of Unknown Hazard
A comprehensive, rigidly followed plan is necessary for testing chemicals of
unknown hazard for their toxic properties. It should be presumed that a chemical
is hazardous to humans, and the plan should describe specific procedures for
handling the chemical from receipt through disposal of animal waste and process-
ing of tissues for histopathological or biochemical examination. Prudent Prac-
tices in the Laboratory: Handling and Disposal of Chemicals (NRC 1995) pro-
vides an excellent general model for planning experiments that involve hazardous
chemicals. It was specifically structured to follow the sequence of stages that
should be considered in planning a safe experiment: evaluating hazards and as-
sessing risks in the laboratory, management of chemicals, working with chemi-
cals, working with equipment, disposal of chemicals, laboratory facilities, and
government regulation of laboratories. It is important not to underestimate the
risk presented by experimental chemicals. But most references on chemical safety
provide little guidance that is directly applicable to the care and use of research
animals. Therefore, developing plans for a specific research protocol that in-
volves research animals and chemicals of unknown hazard will require ingenuity,
a quality best derived from a collaborative planning process.
Protocols Involving Infectious Agents
Experiments involving experimentally or naturally infected research animals
present recognized risks of occupationally acquired infections. In the largest
survey of laboratory-acquired infections conducted to date, research animals or
their ectoparasites were associated with about 17% of the reported infections
(Pike 1976~. In the few cases (under 3%) in which infections were attributed to a
recognized accident, the primary source was a bite or scratch from an infected
animal. That survey and others (Sullivan and others 1978) have shown that trained
scientific personnel and technicians were most likely to be infected, although
animal care providers and janitorial and maintenance workers have been proved
to be at risk for occupationally acquired infection. Most of the zoonotic infections
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PHYSICAL CHEMICAL, AND PROTOCOL-RELATED HAZARDS
45
cited in these surveys were associated with research activities involving experi-
mentally infected animals. Transmission of zoonotic disease in an animal facility
that is not involved with infectious disease research is rare. CDC and NIH have
identified 17 infectious agents or genera other than arboviruses as proven hazards
for personnel who use and care for experimentally or naturally infected research
animals (CDC-NIH 1993~. The agents and genera are summarized in Table 3-2.
Arboviruses most notably Venezuelan equine encephalomyelitis virus, yellow
fever virus, Rift Valley virus, and Chikungunya virus have also been respon-
sible for laboratory animal-associated infections (Hanson and others 1950~. The
Subcommittee on Arbovirus Laboratory Safety (SALS) of the American Com-
mittee on Arthropod-Borne Viruses reported 818 occupationally acquired infec-
tions caused by 62 different arboviruses or related viruses (SALS 1980~. A total
of 19 of these infections, which were associated with 10 viruses Semliki Forest,
Venezuelan equine encephalitis, Western equine encephalitis, yellow fever, Hypr,
Rift Valley fever, Congo-Crimean hemorrhagic fever, Junin, Lassa, and
Machupo resulted in death.
Investigators who are planning research activities involving experimentally
or naturally infected vertebrate animals should carefully review Biosafety in Mi-
crobiological and Biomedical Laboratories (CDC-NIH 1993~. It defines four
levels of control that are appropriate for animal research with infectious agents
that present occupational risks ranging from no risk of disease for healthy people
to high individual risk of life-threatening disease, and it recommends guidelines
for specific agents. The four levels of control, referred to as animal biosafety
levels 1-4, each have appropriate microbiological practices, safety equipment,
and features of animal facilities. The selection of an animal biosafety level is
influenced by several characteristics of the infectious agent, the most important
of which are the severity of the disease, the documented mode of transmission of
the infectious agent, the availability of protective immunization or effective
therapy, and the relative risk of exposure created by manipulation in handling the
agent and caring for infected animals.
Animal biosafety level 1 is the basic level of protection appropriate for well-
characterized agents that are not known to cause disease in healthy humans.
Animal biosafety level 2 is appropriate for handling a broad spectrum of moder-
ate-risk agents that cause human disease by ingestion or through percutaneous or
mucous-membrane exposure. Extreme precautions with needles or sharp instru-
ments are emphasized at this level. Animal biosafety level 3 is appropriate for
agents that present risks of respiratory transmission and that can cause serious
and potentially lethal infections. Emphasis is placed on the control of aerosols by
containing all manipulations and housing infected animals in isolators or venti-
lated cages. At this level, the animal facility is designed to control access to areas
where animals are kept and includes a specialized ventilation system that is
designed to maintain directional airflow. Exotic agents that pose a high indi-
vidual risk of life-threatening disease by the aerosol route and for which no
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46 OCCUPATIONAL HEALTH AND SAFETY OF RESEARCH-ANIMAL WORKERS
TABLE 3-2 Reported Occupationally Acquired Infections Associated with
Expenmentally or Naturally Infected Research Animals
Pathogenic Agent Animals Comment References
Viral Agents
B virus Macaques Contact with Holmes and others
(Circopithecine experimentally and 1990, Palmer 1987
herpesvirus 1) (formerly naturally infected
Herpesvirus simiae) animals
Hepatitis A virus Nonhuman Contact with Pike 1979
primates experimentally and
naturally infected
animals
Lymphocytic Mice, hamsters, Contact with Bowen and others
choriomeningitis virus guinea pigs experimentally and 1975, Jahrling and
naturally infected Peters 1992, Pike
animals 1976
Marburg virus African Green Contact with Martini & Siegert
monkeys naturally infected 1971
animals Martini 1973
Simian Macaques Handling of blood CDC 1992a,
immunodeficiency virus from experimentally Khabbaz and others
infected animals 1992
Vesicular stomatitis virus Livestock Contact with naturally Hanson and others
infected animals 1950, Patterson and
others 1958
Rickettsial Agents
Coxiella burnetii Sheep Contact with naturally CDC 1979, Spinelli
infected animals and others 1981
Bacterial Agents
Brucella (B. abortus, Cattle, dogs, Contact with Pike 1976
B. cants, B. melitensis, goats, swine experimentally and
B. suds) naturally infected
animals, presumed
aerosol exposure
Campylobacter jejuni Dogs, primates, Fox and others 1989
coyotes, etc.
Chlamydia psittaci Birds Contact with Miller and others
experimentally and 1987, Pike 1976
naturally infected
animals, presumed
aerosol exposure
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PHYSICAL CHEMICAL, AND PROTOCOL-RELATED HAZARDS
TABLE 3-2 Continued
47
Pathogenic Agent Animals Comment References
Francisella tularensis Rabbits
Leptospira interrogans
Rabbits, dogs,
rats, mice,
. .
guinea pigs
Contact with Pike 1976
experimentally and
naturally infected
animals or their
ectoparasites
Contact with Richardson 1973
experimentally and
naturally infected
animals
Legionella pneumophila Guinea pigs Aerosol or droplet CDC 1976
exposure during
animal challenge
Mycobacterium Nonhuman
tuberculosis primates
Salmonella spp. Mice, rats,
dogs, cats
Contact with Kaufmann and
experimentally and Anderson 1978
naturally infected
animals
Contact with
experimentally and
naturally infected
animals
Grist and Emslie
1987, Miller and
others 1987, Pike
1976
Shigella spp. Guinea pigs, rats, Contact with Pike 1976
mice, nonhuman experimentally
primates infected animals
Streptobacillus Rats Contact with Pike 1976
moniliformis experimentally and
naturally infected
animals
Fungal Agents
Sporothrix schenckii Rats Bite from an Jeanselme and
experimentally Chevallier 1910,
infected animal 1911
Microsporum, Mice, rabbits,
Trichophyton guinea pigs
Contact with
experimentally and
naturally infected
animals
Hanel and Kruse
1967, McAleer
1980; Pike 1976
Source: CDC-NIH 1993.
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48 OCCUPATIONAL HEALTH AND SAFETY OF RESEARCH-ANIMAL WORKERS
treatment is available are restricted to animal biosafety level 4 high-containment
facilities. Worker protection in these facilities is provided by the use of physi-
cally sealed glove boxes or fully enclosed barrier suits that supply breathing air.
Most research involving experimentally and naturally infected vertebrate animals
will be conducted at animal biosafety level 2 or 3. A summary of hazard control
elements for these two animal biosafety levels is presented in Table 3-3. Animal
biosafety level 1 is not addressed here because it represents normal housing
without special precautions. Animal biosafety level 4 is not discussed because
containment facilities for this work are limited to a few highly specialized institu-
tions that have considerable experience in the handling of dangerous and exotic
pathogens.
Research protocols involving emerging and re-emerging pathogens require
careful planning and might require review of previous studies. Most of the litera-
ture on safety in handling infectious agents was published 3-4 decades ago, but it
is still invaluable in planning safe experiments. Modern research can also present
novel hazards that require careful review. For example, the potential occupa-
tional health and safety risks need to be considered before animal experiments are
undertaken to evaluate the safety to humans of viral vectors that are being pro-
posed for use in gene therapies. Similarly, studies with transgenic animals that
express receptors for human pathogens or whose genomes contain proviral DNA
for an infectious virus should be evaluated to determine whether safeguards
appropriate for handling the wild-type infectious agent should be applied. Assis-
tance in the determination of risk and the selection of appropriate safeguards can
be found in the NIH Guidelines for Research Involving Recombinant DNA Mol-
ecules (NIH 1994~. A recent revision of its Appendix B has a section (B-V) on
frequently used viral agents, including viral vectors. These protocols might
require approval of the institution or funding agency. The institution's biosafety
committee and biosafety officer are valuable resources and should be consulted
when experiments are being planned.
Several authoritative reference works provide excellent guidance for the safe
handling of infectious microorganisms in research. Three that are particularly
noteworthy are Biosafety in the Laboratory: Prudent Practices for the Handling
and Disposal of Infectious Materials (NRC 1989), Laboratory Safety: Principles
and Practices (Fleming and others 1995), and Biosafety in Microbiological and
Biomedical Laboratories (CDC-NIH 1993~.
Most-helpful practices to prevent occupationally acquired infections associ
ated with the care and use of research animals are the following:
· Avoid the use of sharps whenever possible. Take extreme care when
using a needle and syringe for inoculating research animals or when using sharps
during necropsy procedures.
· Keep hands away from mouth, nose, and eyes.
OCR for page 49
49
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OCR for page 50
50 OCCUPATIONAL HEALTH AND SAFETY OF RESEARCH-ANIMAL WORKERS
· Wear protective gloves and a laboratory coat or gown in areas where
research animals are kept.
· Remove gloves and wash hands after handling animals or tissues derived
from them and before leaving areas where animals are kept.
· Use mechanical pipetting devices.
· Never eat, drink, smoke, handle contact lenses, apply cosmetics, or take
or apply medicine in areas where research animals are kept.
· Perform procedures carefully to reduce the possibility of creating splashes
or aerosols.
· Contain operations that generate hazardous aerosols in biological safety
cabinets or other ventilated enclosures.
· Wear eye protection.
· Keep doors closed to rooms where research animals are kept.
· Promptly decontaminate work surfaces after spills of viable materials and
when procedures are completed.
· Decontaminate infectious waste before disposal.
· Use secondary leakproof containers to store or transfer cultures, tissues,
or specimens of body fluids.
Representative terms from entire chapter:
research animals
