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Laboratory Animal
Allergy
Definition of Terms
Laboratory Animal Allergy (LAA) can
be defined as the presence of clinical symptoms (such as rhinitis,
conjunctivitis, sore throat, urticaria, cough, wheeze, tightness of the chest)
combined with evidence of sensitization to laboratory animals (such as history,
skin test, RAST, or total IgE).{4012,4011} It has been studied for several
years in people who work with laboratory animals. Atopy is a term invented in 1923.{4007}
It is an hereditary predisposition for prolonged IgE reactions to environmental
allergens. IgE is a type of antibody that binds to mast cells and triggers
histamine release, causing signs such as hay fever, urticaria, or asthma.
People with prior evidence of sensitization to an allergen are called atopic.
Someone’s history of atopy may be measured in different ways in research
studies. The easiest way, for example in large studies with lots of people, is
to fill out a questionnaire in which they are asked if they have a family
history of allergies. A more definitive, but also more time-consuming, way is
to ask if they themselves have had any personal history of allergies to things
such as house dust, ragweed, cats, pollen, or trees. Finally, a more
quantifiable way to find out if someone has atopy is to ask if they have ever
had a positive skin test for allergies, or a blood test called a RAST (Radio-Allergo-Sorbent Test) or a RIST (which measures only total IgE
antibodies, not the specific ones as a RAST does).{4013} It is very
important to note that someone can be atopic, but not allergic. In other words,
you might have a positive skin test to an allergen, but never have symptoms such
as sneezing or conjunctivitis. Asthma is a lower respiratory
disease that generally develops after months or years of allergy.{4013}
Symptoms include cough, wheeze, and a tight feeling in the chest. Asthma is the
most common chronic disease of childhood{4011}. Fortunately, asthma is a
rare disease. People with LAA generally are
classified in one of three categories: oculonasal symptoms, skin symptoms, or
asthma. There is some overlap in the frequency and types of symptoms people may
have, as shown in the following diagram {4013}. Laboratory Animal Allergens
Allergens are tiny proteins that are capable of inducing an immune response in the body. Most of the time this response is appropriate, i.e. it helps the body rid itself of foreign substances. However, in some people, the response is too exuberant—this is called hypersensitivity. The following drawing depicts the cells and cytokines involved in the development of allergy{4165}.
Some allergens from animals have
been studied. The best-known allergens from laboratory animals come from rats
and mice; those from other species are less well-understood. In pet species,
cats are known to produce at least a dozen allergens, but dogs only two.{4007}
There are probably hundreds of possible allergens in every species of animal.
Animals produce
allergens in different amounts. Male animals often produce more allergen than
females.
This is because the production of some of these proteins is affected
by the levels of sex hormones. One theory of why rodents are often a cause of
hypersensitivity in people is that many rodent species normally excrete proteins
in their urine. Dogs, cats and other large animals rarely do this. In addition,
old rats often develop kidney disease (nephropathy), producing even more
protein in their urine. Animals with skin disease may produce more dander.
There will be more allergens in materials that contain animal hair, dander
(skin flakes), urine, feces, and saliva. Furthermore, the size of these
allergens is very tiny—on the order of 1-20 micrometers{4007}—so they are
easily transported on fomites and in the air. They remain in the environment
for a long time. Cat allergens are electrically charged, so they are
"sticky". Size of particles is important because the body’s natural
defenses against respiratory allergens may not be able to remove the tiny
particles. The nose removes particles greater than 10m m.
The trachea and bronchi remove particles between 4 and 10m m.
Particles that are smaller than 4m m make it all the way to the alveoli.{4008} Questions
Rat: Mouse: Guinea pig: Rabbit: Cat: Dog: Risk Factors for Developing Laboratory
Animal Allergy
The first thing to know about the
risks of developing laboratory animal allergy (LAA) is that there are no hard-and-fast
rules. Even though LAA has been studied on several continents for decades, each
study is done differently and comes up with different results. No single study
should be taken as incontrovertible evidence of the truth. Clinical immunology
as a science has only been around for about 50 years. In general, the prevalence of LAA
in lab animal workers is about 20%{4013,3734}; that is, if you were to take
a snapshot today of all people who work with laboratory animals (including
animal care staff, researchers and their technicians, and administrative
staff), two out of every ten would have LAA. The range varies from
approximately 14-44% {3734}.There are not enough studies to tell if the
prevalence is decreasing as we develop better occupational health practices.
Some of the studies were performed as far back as the 1960s. The most important risk factor in
most studies is atopy, the genetic predisposition to develop hypersensitivity.
People with a family or personal history of allergies, or with positive skin
tests or blood (RAST) tests, are much more likely to go on to develop LAA than
those who do not have such a genetic background. Even the children of
laboratory animal workers are more likely to be hypersensitive to laboratory
rats, mice and hamsters {4011}. People who are hypersensitive to their
cats or dogs at home seem more likely to develop LAA{4014}. In one review
of nine studies, it was concluded that 36% of atopic people had allergic
symptoms, compared with only 15% of non-atopic people{4007}. When only
rat allergy was studied, another researcher determined that 13-17% of atopic
animal workers were positive, compared with 2-4% of non-atopic workers{4010}.
The total percentages may vary, but the trends are usually the same. In patients with LAA who have been
studied, the effect of atopy can be quite pronounced. One researcher suggested
that there are two syndromes of LAA, depending mostly on whether the patient is
atopic. These two syndromes can be symbolized by the following diagrams{4013}.
This information suggests that
those with atopy must consider both their short-term risks (development of LAA)
and long-term risks (development of asthma years later) if they continue to
work with animals. Remember, though, that if one-third of the atopic people
develop LAA, the other two-thirds will not! A very controversial risk factor is
the level of exposure a person has to laboratory animals. It is tempting to
hope that if we could only keep a person’s exposure to allergens to some very
low level, we could prevent their allergic symptoms. Unfortunately, this has
not yet been demonstrated for LAA. It does seem to be true that people with
allergic symptoms do better when they stay away from activities that generate a
lot of allergens like dander or urine; for example, an allergic person in a quiet
rat room with no activity is less likely to develop symptoms than when cages
are being changed in the room. However, the truth is most likely that "no
one is unexposed" {3734}; there is no
"safe" threshold
level for exposure. An example of a study attempting to
equate exposure with risk was published in 1997. It was found that there was
some relationship between the number of hours per week working with rats and
the prevalence of hypersensitization (important note: this was hypersensitization,
not allergy symptoms). The results are shown in this table{4012}.
One determinant of a
person’s exposure level is the length of time they have worked with laboratory
animals. In the study above, only people with less than 4 years’ experience
were used in the calculations. If the authors used all the data they could not
find a statistically significant relationship between exposure and sensitization.
Several studies have demonstrated that about half of those who will ultimately
go on to develop LAA will do so in their first two years of employment{4013}.
Asthma, however, will develop in only about 2%{4013}. Some factors that have not been shown to affect the development of LAA are age, gender, and whether or not you smoke. Questions
Control of Laboratory Animal Allergy
Concerns over employee health and
safety while on the job have resulted in numerous improvements and changes in
the workplace, with new ideas emerging all the time. In some cases these
changes have resulted in documented improvements in health, while in others the
data are somewhat slow in coming, particularly for rare diseases or conditions
requiring large studies. Balanced against improved or enhanced workplace
factors must be the costs and time they require. As in all things, the
risk:benefit ratio should be taken into account before making any global
changes in management. Reduction of laboratory animal allergy (LAA) may involve
modifications in facility design, employee work practices and use of protective
equipment. Engineering controls for reduction
of LAA include maintaining proper airflow and relative humidity. Most animal
rooms are negative with respect to the hallway—that is, air flows into the room
from the hall to prevent escape of pathogens and allergens into areas of human
traffic flow. In order for the airflow to remain "balanced" the doors
must be closed, the filters and ducts kept clean, and the arrangement of caging
remain roughly the same as it was when the airflow was measured. Air in animal
facilities should be 100% fresh, not recirculated. In general, a downward flow
of air from the inlet to the outlet may aid in removal of allergens and other
particles {3734}. Increasing the number of air changes per hour has not
been conclusively shown to have an effect on LAA{4008}. Raising the
relative humidity from 15 to 65% will help keep the allergen levels down, but
workers and animals may be uncomfortable at such high humidity {4008}. Improvements in animal caging are
constantly becoming available. Use of filter tops or bonnets has been
documented to decrease allergen levels in a quiet room by up to 84% {4008}.
Unfortunately, the levels of CO2 and ammonia may build up rapidly in
filtered cages, requiring more frequent changes. New types of ventilated rodent
caging decrease the allergen levels, even if they are maintained in positive
pressure mode, because the air is HEPA filtered. Handling animals in a
ventilated cabinet, and using a negative pressure dump station are other ways
to decrease the amount of airborne allergens. Using corncob rather than wood
shavings for bedding is also thought to generate less dust {4008}. Personal protective equipment (PPE)
should be worn by all people who handle animals. Those who are at higher risk
for developing LAA must be particularly vigilant in their use of PPE.
Respirators or helmets may remove up to 98% of airborne allergen from mice {3734};
however these must be professionally fitted and the user must follow the SOP
for their use. Use of a dust-mist respirator may be effective. A surgical mask
provides minimal protection. Avoidance of skin contact is accomplished by
wearing long sleeves and gloves, and also hair and shoe covers. Clothes should
be changed frequently, and the employee might consider showering to wash away
any residual allergens. Hands must be washed frequently. Training and encouraging awareness
of the risks and avoidance of LAA are key factors in the facility’s management
program. Annual re-training should be conducted to refresh the employees’
memories. Medical surveillance is provided by
the occupational health program. During the physical examination, the employee
should discuss any changes in health status, especially if symptoms of allergy
have begun since the previous exam. Those who begin practicing risk-reduction
habits early may be able to avoid the development of asthma later on. Work practices can decrease
exposure significantly, and each employee should be very clear about what these
practices are:
Questions
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©1999, Janet Becker Rodgers, DVM, MS All rights reserved. Comments? Send an email to rodgers@uky.edu |
