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4 Allergens Allergic reactions to animals are among the most common conditions that adversely affect the health of workers involved in the care and use of animals in research. One survey (Lutsky 1987) demonstrated that three-fourths of all institu- tions with laboratory animals had animal-care workers with allergic symptoms. The estimated prevalence of allergic symptoms in the general population of regu- larly exposed animal-care workers ranges from 10% to 44% (Hollander and others 1996, Knysak 1989~. An estimated 10% of laboratory workers eventually develop occupation-related asthma. Attempts have been made to determine whether persons with allergic condi- tions, such as allergic rhinitis (hay fever), are at higher risk than normal persons of developing animal-dander sensitivity when working with laboratory animals. On the basis of current estimates, up to 73% of persons with pre-existing allergic disease eventually develop allergy to laboratory animals (Agrup and others 1986, Platts-Mills and others 1986, Venables and others 1988~. Allergy is most often manifested by nasal symptoms, itchy eyes, and rashes. Symptoms usually evolve over a period of exposure of 1-2 years. Occupation-related asthma, a more seri- ous disorder, might develop in about 10% of persons with allergic disease who work with laboratory animals (Hunskaar and Fosse 1993~. Occupation-related asthma not only can cause symptoms of cough, wheezing, and shortness of breath while the worker is exposed to laboratory animals, but also can lead to chronic symptoms (persisting for months to years) even after exposure ceases. Workers exposed to laboratory animals can be categorized into several risk groups. The information cited above is shown in Table 4-1 for four risk groups based on history of allergic disease and sensitization to animal proteins. Except in 51

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52 OCCUPATIONALHEALTH AND SAFETY OFRESEARCH-ANIMALWORKERS TABLE 4-1 Risk of Developing Allergy to Laboratory Animals Risk Group History Risk of allergic reactions to laboratory animals Comment Normal No evidence of allergic disease ~10% Atopic Pre-existing Up to 73 % allergic disease Asymptomatic Immunoglobulin E Up to 100% antibodies to allergenic animal proteins Clinical symptoms on exposure to allergenic animal proteins 90% of normal group will never develop symptoms in spite of repeated animal contact Workers who become sensitized to animal proteins will eventually develop symptoms on exposure Risk of developing allergic symptoms of rhinitis, asthma, or contact urticaria with continued exposure is high 33% with chest symptoms; 10% of group might develop occupational asthma; even minimal exposure can lead to permanent impairment a few situations, a dose-response relationship that defines sensitization, induction of disease, and production of symptoms in association with specific allergen concentrations has not been established. Contact urticaria ("hives") is typically due to the application of an allergen (usually a protein or glycoprotein) directly onto the skin. A common example is the development of wheel and flare reactions that produce welts when a person's skin and the tail of a mouse or rat come into contact. Scratches by cats and dogs can produce similar responses. Latex in rubber gloves is another cause of contact urticaria. Although symptoms of asthma in laboratory-animal workers are most obvi- ous in the work environment, they can also occur at night and awaken sufferers. In almost all asthmatic people with laboratory-animal allergy, nasal and eye symptoms preceded the development of asthma (Bland and others 1987~. In rare instances, a person who has become sensitized to an animal protein in the saliva of the animal experiences a generalized allergic reaction termed ana

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ALLERGENS 53 phylaxis when bitten by an animal (Teasdale and others 1993~. People working in entomology laboratories can be exposed to stinging insects, such as bees, wasps and ants, which can cause similar reactions. Anaphylaxis can be evident as dif- fuse itching, hives, and swelling of the face, lips, and tongue. Some people experience difficulty in breathing because of laryngeal edema; others develop asthma with wheezing. In some instances, shock can lead to loss of conscious- ness. Anaphylactic reactions vary from mild generalized urticarial reactions to profound life-threatening reactions. MECHANISMS OF ALLERGIC REACTIONS The allergic reactions described above are examples of classic immunoglo- bulin E-mediated reactions. Such reactions are the consequence of a series of immunological and biochemical events. First, a person is exposed to the allergen, which is usually a protein or glycoprotein. In the case of laboratory animal allergy, the route of exposure is most often due to airborne allergens (see Table 4-2~. The allergen is processed by the macrophages or B lymphocytes and presented to T lymphocytes. Helper T lymphocytes stimulate B lymphocytes to produce antibodies of the immunoglobulin E (IgE) class specific for the allergen. TABLE 4-2 Allergic Reactions to Laboratory-Animal Allergens Disorder Symptoms Signs Contact urticaria Redness, itchiness of skin welts, hives Allergic conjunctivitis Sneezing, itchiness, clear nasal drainage, nasal congestion Allergic rhinitis Sneezing, itchiness, clear nasal drainage, nasal congestion Raised, circumscribed erythematous lesions Conjunctival vascular engorgement, cheminosis, clear discharge (usually bilateral) Pale or edematous nasal mucosa, clear rhinorrhea Asthma Cough, wheezing, chest tightness, Decreased breath sounds, shortness of breath prolonged expiratory phase or wheezing, reversible airflow obstruction, airway hyperresponsivenes s Anaphylaxis Generalized itching, hives, Flushing, urticaria, throat tightness, eye or lip swelling, angioedema, strider, wheezing, difficulty in swallowing, hoarseness, hypotension shortness of breath, dizziness, fainting, nausea, vomiting, abdominal cramps, diarrhea

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54 OCCUPATIONALHEALTH AND SAFETY OFRESEARCH-ANIMALWORKERS IgE is found in the circulation in low concentrations and binds to mast cells and basophils. Mast cells are abundant in the respiratory tract, gastrointestinal tract, and skin, the main sites of allergic reactions. When a person so "sensitized" is re- exposed to the same allergen, the allergen binds to IgE molecules and causes the release of histamine and other chemical mediators stored in the mast cells and basophils. The mediators, on contact with the relevant tissues, can produce hives, nasal congestion, sneezing, nasal drainage, coughing, wheezing, and shortness of breath. All those reactions are termed "immediate hypersensitivity" responses be- cause they are noted within 10-15 min of exposure to the allergen. However, it is now recognized that such reactions not only can occur immediately but also have a late component; that is, the symptoms can recur 4-6 h after exposure without further allergen stimulation. Virtually all human beings are capable of developing allergic reactions; however, some individuals are more susceptible. These people (atopics) are more likely to develop IgE antibodies to allergens owing to an inherited tendency. This is an autosomal dominant trait with variable expression that has been linked to genetic markers on chromosome 5 (Blumenthal and Blumenthal 1996, Marsh and others 1994~. Persons with atopy often develop allergic diseases, such as allergic rhinitis, asthma, and atopic dermatitis (eczema) when chronically exposed to allergens. SPECIFIC ANIMALS THAT CAN PROVOKE ALLERGIC REACTIONS Rats Rats are among the most commonly used laboratory animals and are respon- sible for symptoms in a large portion of people who have laboratory-animal allergy. The major sources of rat-allergen exposure appear to be urine and saliva of the animal. A major rat-urine allergen with two isoforms has been identified: Rat n 1A, a pre-albumin, and Rat n 1B (oc2-euglobulin) (Eggleston and others 1989, Longbottom 1980~. These two proteins have some cross-reactivity, al- though they differ in molecular weight and isoelectric point. Their amino acid composition is similar, but their carbohydrate concentration differs. The amino acid sequence of Rat n 1B has been obtained (Laperche and others 1983~. Sampling methods have been developed to measure the amount of airborne allergen and the size of the airborne particles that contain rat allergen (Eggleston and others 1989; Platts-Mills and others 1986~. Particles that contain ret allergen found in air samples from a rat vivarium vary from 20 ,um in aerody- namic equivalent diameter. Disturbance of rat litter leaves a substantial propor- tion of the smaller particles airborne for 15-35 min (Platte-Mills and others 1986~; most of these particles are easily respirable.

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ALLERGENS 55 In a preliminary study of 335 workers exposed to rats, the risk of respiratory or skin symptoms was related to the duration of exposure to rat urinary protein concentrations of at least 1 ,ug/m3 of air sampled (Tee and others 1993), the concentrations most likely to be encountered by animal-care technicians. Aller- gic symptoms due to exposure to rats were more likely to develop in atopic subjects (those with pre-existing sensitivity to nonanimal allergens) than in nonatopic subjects. Exposure concentrations are clearly task-related. Cage-cleaning resulted in a mean airborne Rat n 1 concentration of 21 ng/m3 (range,8.1-69 ng/m3); handling rats for weighing, shaving, injections, and collection of blood and urine samples yielded a mean of 13 ng/m3 (range, undetectable to 45 ng/m3); and surgery on anesthetized animals or euthanasia of unconscious animals yielded a mean of 3 ng/m3 (range, undetectable to 12 ng/m3 ~ (Eggleston and others 1989~. It should be noted that these levels are an order of magnitude lower than reported by Tee and others (1993~. This difference might be accounted for by the fact that Eggleston and co-workers measured for the specific allergen Rat n 1, whereas Tee and colleagues measured total airborne rat allergenic activity. The importance of these exposures has been demonstrated in environmental challenge studies in which workers are exposed in rooms containing animals. Eggleston and co-workers (1990) measured airborne Rat n 1 in a rat vivarium over the course of 1 h. The allergen concentration ranged from less than 1.5 to 310 ng/m3 and was much higher during cage-cleaning than during quiet activity. Of 12 rat-allergic volunteers working in this environment, all had nasal symp- toms and evidence of histamine release in their nasal secretions during the period of exposure, and five had decreases in pulmonary function greater than 10%. This experiment demonstrated that occupational exposure was directly correlated with the development of nasal symptoms and asthma in the sensitized volunteers. Airborne allergen concentrations depend on the balance between the rate of allergen production and the rate of removal. And the magnitude of exposure to rat allergens is directly proportional to the number of animals in the area. Urine is a major source of allergen, and contact with contaminated litter seems to be a major source of exposure (Gordon and others 1992~. Ventilation might be an effective means to lower exposure when production of allergen is low, because of either a small number of animals or little disturbance of litter, but it might be ineffective when production is high. For example, Swanson and others (1990) found that it might take up to 127 air changes per hour to reduce exposures sufficiently to make symptoms unlikely when many rats were present in the sampling area. Mice Mice are another important source of allergen exposure of laboratory work- ers. The major mouse allergen is a urinary protein, Mus m 1. Mus m l has been molecularly cloned and its amino acid sequence deduced. It is analogous in many

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56 OCCUPATIONAL HEALTH AND SAFETY OF RESEARCH-ANIMAL WORKERS ways to Rat n 1B in that it is produced in the liver and saliva, is secreted in the urine, and has 80% amino acid sequence homology with Rat n 1B (Clark and others 1984~. Urine samples contain Mus m l at a concentration 100 times that in serum, and male mice excrete 4 times as much of it as female mice (Lorusso and others 1986~. Air-sampling techniques have been developed to monitor concentrations of major mouse urinary proteins in the environment (Twiggs and others 1982~. Airborne allergen concentrations range from 1.8 to 825 ng/m3, depending on the number of animals and the type of activity in the environment. The particles that contain most of the allergen vary from 6 to 18 ,um in diameter (Price and Longbottom 1988~. Sakaguchi and others (1989a) found that most of the airborne allergen in undisturbed air in a room containing 350 mice was trapped by a filter with a retention size greater than 7 ,um. In disturbed air (in which cage-cleaning was conducted), allergen concentration increased by up to 5 times and the propor- tion of small particles (1.1 ,um and smaller) increased by 3 times. Airborne concentrations are related to the number of mice present in the sampling area and the degree of work activity (Twiggs and others 1982~. Guinea Pigs Immunochemical studies have identified allergenic components in the dan- der, fur, saliva, and urine of guinea pigs (Walls and others 1985~; urine appears to be the major source of allergen. Most guinea pig allergen activity is associated with particles greater than 5,um, but about 10% is found on particles smaller than 0.8,um, which are small enough to penetrate into the lower respiratory tract (Swanson and others 1984~. Gerbils Gerbils are occasionally used as laboratory animals, and allergic sensitivity to them has been reported (Gutman and Bush 1993~. The allergens involved have not been identified. Rabbits Rabbits are used widely as laboratory an . 1mals and are a recognized cause of allergic symptoms in many workers. A major glycoprotein allergen has been described that appears to occur in the fur of the animals, and minor allergenic components found in rabbit saliva and urine have been identified (Warner and Longbottom 1991~. Allergenic activity is associated with particles less than 2,um in diameter (Price and Longbottom 1988~.

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ALLERGENS 57 Cats Domestic cats are kept as pets by many people, and sensitization can occur outside the laboratory environment. Furthermore, allergy to cats might predis- pose workers to the development of allergy to laboratory animals, such as mice and rats (Hollander and others 1996~. There is a close link between immunologi- cal sensitization and development of asthma in people sensitive to cats (Desjardins and others 1993~. Those with pre-existing sensitivity might encounter worsening of their symptoms and possibly develop asthma during the course of their work exposure. The major cat allergen is the protein Fel d 1 (Kleine-Tebbe and others 1993~. Fel d 1 was first described by Ohman and colleagues (1974~. It is produced in the sebaceous glands of the skin and coats the hair shafts (Woodfolk and others 1992~. Itis also producedin the saliva (Anderson and others 1985~. Fel d 1 has been molecularly cloned, its amino acid sequenced, and its allergenic structure analyzed (Morgenstern and others 1991~. Fel d 1 is found in all cats, and cross reactivity occurs throughout all species of cats. However, individual cats shed different amounts of the allergen (Wentz and others 1990), and male cats might shed more than female cats. A few people can become sensitized to cat albumin. The size of particles that contain cat allergen varies, but many are less than 0.25,um in diameter (Findlay and others 1983) and are easily carried deeply into the lung. Exposure to two cats that produced allergen at a concentration of 1.1- 128 ng/m3 was sufficient to cause symptoms of rhinitis and asthma in 10 persons with cat sensitivity (VanMetre and others 1986~. Cumulative doses of 80-98 ng of Fel d 1 inhaled over 2 min can cause a sufficient decrease in pulmonary function to produce an asthma attack. Placing one cat in a room with a volume of 33 m3 increases the concentration of Fel d 1 from nondetectable to 30-90 ng/m3, which would be sufficient to cause an asthma attack within 25 min in a sensitized person (VanMetre and others 1986~. Airborne Fel d 1 remains suspended for long periods because of its small particles (Luczynska and others 1990~. The allergen appears to be highly electro- statically charged and therefore sticks to surfaces, such as walls and laboratory benches (Wood and others 1992~. It can be transferred from those materials to hands, or the materials can act as reservoirs and can hold large quantities of allergen in the absence of cats. Decreasing the airborne concentrations of cat allergen can be attempted by washing the animal (Middleton 1991; Ohman and others 1983~. Using a filtered vacuum cleaner, removing carpeting, running a high-efficiency air cleaner, and washing the caters) can decrease concentrations in the air (deBlay and others 1991~. Simply increasing ventilation rates from eight to 40 air changes per hour in a room containing two female cats did not reduce the clearance of airborne cat allergen (Wood and others 1993~. After removal of cats from the environment,

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58 OCCUPATIONAL HEALTH AND SAFETY OF RESEARCH-ANIMAL WORKERS the time for concentrations to reach those seen in areas where there has been no cat can be 20 weeks or more (Wood and others 1989~. In addition to cats themselves, it is now recognized that cat fleas can produce allergic symptoms in some people (Baldo 1993~. Dogs Like exposure to cats, exposure to domestic dogs outside the work environ- ment can lead to sensitization and is also a risk factor for laboratory animal allergy (Hollander and others 1996~. The major allergens of dogs are not as well studied as cat allergens, but an important allergen, Can f 1, has been identified (deGroot and others 1991; Schou and others l991b). Collections of dust samples from homes with a dog in residence showed a Can f 1 concentration of 120,ug/g of dust, compared with 3,ug/g where there was no dog (Schou and others 1991a). There is some question about cross reactivity among breeds of dogs, but the relevant information is not complete. Sources of exposure to dog allergens appear to be saliva, hair, and skin (Spitzauer and others 1993~. Dog albumin has also been shown to be an important allergen (Spitzauer and others 1994~. About 35% of people who are allergic to dogs have IgG antibody to albumin. The allergen has been molecularly cloned and shares amino acid sequence homology with other albumins. Primates Sensitization to primates is unusual. Despite widespread exposure to pri- mates in research settings, few cases of sensitivity to primate allergens have been documented. Cases of sensitivity to lesser bushbaby (galago) and cottontop tama- rin have been identified (Petry and others 1985~. Allergenic activity was found in the dander of the latter. Whether other sources, such as saliva, are important is not clear. Pigs Asthma and other respiratory symptoms have been attributed to pig expo- sures, particularly in farm operations. In general, the symptoms do not appear to be allergic but more often are related to exposure to high nitrogen concentrations, especially in confinement operations (Matson and others 1983; Zhou and others 1991~. Occupational asthma was described in a person who apparently had aller- gic sensitivity to a urinary protein from pigs (Harries and Cromwell 1982~. Cattle Sensitivity to cattle has been reported in 15-20% of dairy farmers. The

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ALLERGENS 59 allergens have not been completely described, but components of dander and urine have been identified as allergenic (Ylonen and others 1992~. A purified allergen with a molecular weight of 20-25 kilodaltons (kD) and an isoelectric point of 4.1 has been described (Ylonen and others 1994~. Airborne cow-dander allergen concentrations in animal sheds range from 137 to 19,800 ng/m3. Horses Horses constitute a highly potent source of allergens. The nature of the allergens has not been established, but a 27-kD allergen from horse dander, skin scrapings, and albumin are important (Fjeldsgaard and Paulsen 1993~. They ap- pear to be shed by the skin and are highly sensitizing in some people. Formerly, the use of horse antiserum in treatment of infectious diseases led to serious reactions in sensitized persons, but the risk has been substantially reduced in recent years since the advent of human antisera. Sheep Little information is available regarding sensitivity to sheep. Major allergens have not been identified. Contact dermatitis, possibly due to lanolin in the wool, can occur (Slavin 1993~. Deer Some people have been shown to be sensitized to deer proteins. There is evidence of cross sensitivity between deer and horse allergens (Huwyler and Wuthrich 1992~. Airborne reindeer epithelial allergens have been detected at 0.1 - 3.9 ,ug/m3 (Reijula and others 1992~. Birds Exposure to birds can cause rhinitis and asthma symptoms. Birds are also a potential source of hypersensitivity pneumonitis, a lung condition in which a pneumonia-like illness develops after repeated exposure to the antigen. These allergic and hypersensitivity reactions are not mediated by IgE antibody. The symptoms and signs usually occur several hours after exposure and consist of cough, fever, chills, myalgia, and shortness of breath. People with hypersensitiv- ity pneumonitis often have precipitating IgG antibodies to the protein in question. Various bird proteins have been identified as sources of antigens involved in both allergic reactions and hypersensitivity pneumonitis. These proteins are found in pigeon serum and droppings that contain serum.

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60 OCCUPATIONALHEALTH AND SAFETY OFRESEARCH-ANIMALWORKERS Reptiles Human sensitivity to reptiles and amphibians is rare. Cases of occupational asthma caused by frog proteins have been described (Chang-Yeung and Malo 1994), but otherwise the information is sparse. Fish Fish proteins are a source of problems for people sensitized through inhala- tion. In the fish- and crab-processing industry and through the use of fish as a source of animal feed, some people have developed allergic rhinitis and asthma symptoms (Malo and Cartier 1993~. Crustaceans and mollusks also pose prob- lems in some laboratory workers. There is evidence that sensitization to airborne allergens from these sources can result in asthma (Malo and Cartier 1993~. Insects Entomologists are at risk for developing sensitivity to insect proteins. People working in laboratories can be exposed to scales of moths, caterpillars, and other insects that result in sensitization. Beetles, mealworms, cockroaches, and other insects have been described as causing contact urticaria, rhinitis, and possibly asthma symptoms in laboratory workers (Gutman and Bush 1993~. PREVENTIVE MEASURES AND INTERVENTIONS Prudence suggests that efforts to minimize exposure to animal allergens would result in a reduction in the frequency of sensitization in laboratory-animal workers and a reduction in symptoms in those who have developed sensitivity. But there are few data to support that suggestion. In spite of a number of attempts to reduce or minimize exposure, laboratory-animal allergy remains an important problem. Further research is needed to determine which measures are effective in preventing and controlling symptoms of laboratory-animal allergy. Screening Programs Preplacement screening evaluations can be helpful in identifying and alert- ing persons who might be at risk for developing laboratory-animal allergy or asthma and educating them to take protective measures. The extent of the evalu- ations depends on the resources of the facility; at a minimum, a simple question- naire that asks for a personal and family history of allergy (seasonal rhinitis or "hay fever," asthma, eczema, hives) and specifically allergy to laboratory ani- mals (pets, as well as laboratory animals) should be completed. The presence of pre-existing allergic conditions in a person might increase likelihood of develop

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ALLERGENS 61 ment of asthma in an occupational setting where there is exposure to laboratory animals. Because most people will not develop sensitivities beyond pre-existing conditions, this evaluation should not preclude employment. Skin testing or in vitro tests to detect the presence of specific IgE antibodies to animals and other allergens should be available but not required. Positive results can be used to place people with pre-existing sensitivity to laboratory animals in low-risk as- signments or used diagnostically to demonstrate the development of sensitization in people who might later become symptomatic. Skin tests are usually applied by the prick or puncture method. Proteins are extracted from the allergen source, usually in a saline buffer, and applied to the skin of the subject, and the skin is pricked with a needle. The demonstration of a wheel and flare response within 10-15 min after application suggests the presence of an IgE-mediated allergic mechanism. In some instances, a serological immunoassay, such as the radioallergo- sorbent test (RAST), or an enzyme-linked immunosorbent assay (ELISA) is used to detect the presence of specific IgE antibodies as an alternative to skin tests. In these immunoassays, the person's serum is incubated with the relevant allergenic protein bound to a support material, and the binding of IgE antibodies is detected with a radiolabeled (RAST) or enzyme-linked (ELISA) anti-IgE antibody sys- tem. Both skin tests and in vitro assays are reasonably reliable and sensitive in detecting allergy to animal protein, although the quality of materials available commercially for testing is variable. Clearly, people with pre-existing laboratory animal sensitivity should avoid repetitive exposure. Sensitized people who have had 2 yr or more of experience working with laboratory animals might be at risk for developing airway hyper- responsiveness (asthma) as a result of laboratory animal exposure (Newill and others 1992~. In addition to a screening questionnaire for the presence of asthma or asthma symptoms (coughing, wheezing, chest tightness, or shortness of breath), objective measurement of pulmonary function is encouraged. Spirometry, or peak expiratory flow rates, before and after the inhalation of a bronchodilator, are useful in detecting, evaluating the severity of, and monitoring occupation-related asthma. In people who are chronically exposed to laboratory animals, annual screen- ing should be done to detect those who are developing allergic symptoms (sneez- ing, nasal congestion, itchy eyes, cough, wheezing, shortness of breath, or hives) so that appropriate intervention measures can be taken to prevent long-term diffi- culties. Such screening should, at a minimum, consist of a questionnaire regard- ing allergic or asthma symptoms, and may include skin testing or an in vitro test for specific IgE antibodies to identify sensitization. Periodic monitoring of pul- monary function is recommended if asthma symptoms appear.

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62 OCCUPATIONALHEALTH AND SAFETY OFRESEARCH-ANIMALWORKERS Facility Design Attention to facility design can be helpful in reducing the incidence of labo- ratory animal allergy. The airborne-allergen load in an animal room depends on the rate of production, which is a function of the numbers of animals present, and the rate of removal, which is a function of ventilation. Achieving a substantial reduction of airborne allergen in a heavily populated area requires extremely high ventilation rates in excess of 100 air changes per hour (Swanson and others 1990~. That might be possible with the use of high-efficiency-particulate-air- filtered (HEPA-filtered) laminar-flow units, but such measures can be extremely expensive. Airborne concentrations of rat allergens also depend on the relative humidity of the environment. An increase in relative humidity from 54% to 77% was shown to reduce airborne rat-allergen concentrations substantially (Edwards and others 1983~. This simple maneuver could be of benefit in reducing exposure in some facilities; however, raising humidity to 77% might exceed the optimal range for animals, produce employee discomfort, and induce mold growth. Cage-emptying where loose bedding is used results in particularly high lev- els of allergen exposure. Use of ventilated hoods or work stations for cage- emptying and cage-cleaning with filtered, recirculated air can reduce exposure. More detailed discussions of ventilation systems can be found in Hunskaar and Fosse (1993) and Bland and others (1987~. The type of caging will undoubtedly influence exposure to airborne aller- gens. Filter-top cages have been shown to reduce concentrations of airborne allergens, compared with conventional open-top cages (Gordon and others 1992; Sakaguchi and others 1990~. Ventilated cage and rack systems that can reduce exposure are commercially available. Cage and rack systems that exhaust air through a HEPA filter system before returning it into the room substantiatially reduce the concentration of airborne rat allergen, Rat n 1, compared with non- HEPA-filtered cage racks (Ziemann and others 1992~. However, data to support the routine use of these devices to prevent sensitization or reduce symptoms in workers have not appeared. Work Practices Several work practices can reduce the potential development of laboratory animal allergy and perhaps alter its severity. Educational programs and codes of practice can greatly reduce the incidence (37% to 12% over 4 yr) and severity of allergic symptoms (Bothan end others 1987; Olfert 1993~. Workers should tee made aware of the risks and be instructed in proper measures to control and avoid exposure as much as possible. Those with a history of allergies and particularly those with known sensitivities to animals are at highest risk and so should be

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ALLERGENS 63 especially sought out for education. Sensitized workers who develop asthma should be made aware that they might experience such symptoms not only when exposed to animals but also when they engage in exercise and other physical activities. The Guide for the Care and Use of Laboratory Animals (NRC 1996) recom- mends that solid-bottom cages with bedding be used for mice and rats. Selection of bedding materials can be beneficial in reducing worker exposure. Use of noncontact absorbent pads, rather than such wood-based contact litter as chips and sawdust, substantially reduced airborne concentrations of rat urinary allergen (Gordon and others 1992~. Job assignment on entry into the laboratory animal work environment should be assessed. People with known risks are best assigned to tasks that minimize exposure. Some tasks such as simple feeding, weighing, or necropsy produce low levels of exposure, whereas cage cleaning can lead to high levels of expo- sure. Selection of job assignment is the first step to minimize exposure of people who have become sensitized or have developed symptoms. Personal Protective Equipment The use of protective equipment and clothing can minimize the chance of sensitization. Few data are available to determine which methods are most effec- tive. However, surgical (cloth or paper) disposable masks are probably not effec- tive. The use of gloves, laboratory coats, shoe covers, and other kinds of protec- tive clothing that are worn only in the animal rooms should be encouraged. Frequent hand washing is important and showering after work might be of value. Once a person develops allergic symptoms, surgical (cloth or paper) dispos- able masks are usually not effective. Some commercial dust respirators can ex- clude up to 98% of mouse urinary allergens (Sakaguchi and others 1989b). High- efficiency respirators are most likely to be of value, but they are cumbersome and often are not used appropriately (Hunskaar and Fosse 1993~. At a minimum, for symptomatic workers, the use of a dust-mist respirator certified by the National Institute for Occupational Safety and Health should be required to control symptoms. A filtered airhood device (Airstream Dustmaster(D hood, Racal, Middlesex, UK) has been shown to be effective (Price and Longbottom 1988~. The use of these devices and protective clothing is most successful in highly motivated workers who have some control over their expo- sure frequency. Employees using effective respiratory protection (respirators) will need respiratory fit-testing and medical clearance. EVALUATION OF THE ALLERGIC WORKER When people develop allergic symptoms (sneezing, nasal congestion, itchy eyes, cough, wheezing, chest tightness, shortness of breath, or hives) related to

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64 OCCUPATIONALHEALTH AND SAFETY OFRESEARCH-ANIMALWORKERS laboratory animal exposures, consultation with appropriate physicians (allergists, pulmonologists, or occupational medicine specialists) is necessary so that an accurate diagnosis and effective management can be achieved. The American Academy of Allergy, Asthma, and Immunology can provide assistance (AAAAI, 611 East Wells St., Milwaukee, WI 53202. Ph: 414-272-6071; Fax: 276-3349; Web site http://www.AAAAI.org). For personnel in research animal facilities suspected of having allergic problems, the diagnosis of animal sensitivity is based largely on the history of symptoms in conjunction with exposure. The diagnosis is confirmed by the demonstration of specific IgE antibodies to the allergen in question. Pulmonary-function measurements should be done to diag- nose or assess asthma severity. Exposure-reduction and -avoidance measures should be undertaken when people become sensitized and develop symptoms resulting from their exposure. Medicines to reduce or prevent allergic or asthma symptoms might be necessary. Many highly sensitized people will continue to have symptoms in spite of exposure reduction and appropriate medications and therefore must avoid animal-allergen exposure completely. In a few people, immunotherapy against cat and dog allergens has been undertaken with some degree of success (Alvarez-Cues/a and others 1994; Ohman and others 1983~. Uncontrolled studies of immunotherapy against allergens of mice, rats, and rabbits have also demonstrated some improvement (Wahn and Siriganian 1980~. In general, however, the use of immunotherapy as a means to protect workers from further symptoms has not been fully established. Further information regarding the evaluation and treatment of workers aller- gic to laboratory animals can be obtained from professional organizations, such as the American Academy of Allergy, Asthma, and Immunology, the American College of Allergy, Asthma, and Immunology, and the American Thoracic Soci- ety. ANAPHYLAXIS On rare occasions, an allergic worker might suffer an anaphylactic reaction to an animal bite (Teasdale and others 1993) or from puncture wounds from needles contaminated with laboratory animal protein (Watt and McSharry 1996~. These reactions can progress rapidly and become potentially fatal, so physicians might recommend that allergic workers carry a self-administered form of epi- nephrine (e.g., Epi-Pen(D or Ana-Kit(~. In appropriate circumstances, it is help- ful to instruct co-workers in emergency procedures, such as cardiopulmonary resuscitation.