Exposure-response relationships for work-related sensitization in workers exposed to rat urinary allergens: Results from a pooled study

doi:10.1016/S0091-6749(99)70242-3

Journal of Allergy and Clinical Immunology

Volume 103, Issue 4, April 1999, Pages 678-684

https://doi.org/10.1016/S0091-6749(99)70242-3 Get rights and content

Abstract

Background: Recent studies in a few industries have shown that the likelihood of IgE-mediated sensitization increases with increasing exposure. The shape of the exposure-response relationships and modification by age, sex, and smoking habit has hardly been studied. Objective: The purpose of this study was to determine exposure sensitization relationships for rat sensitization and to evaluate the influence of atopy, smoking habits, and sex. Methods: Data from 3 cross-sectional studies in The Netherlands, the United Kingdom, and Sweden were used and involved 1062 animal laboratory workers. Selection criteria were harmonized, and this resulted in a study population of 650 animal laboratory workers (60.6% female) with less than 4 years of exposure. Air allergen levels were assessed previously and converted on the basis of an interlaboratory allergen analysis comparison. Available sera were analyzed for the presence of specific antibodies against common allergens (house dust mite, cat, dog, and grass and birch pollen) and work-related allergens (rat and mouse urinary proteins). Questionnaire items on work-related respiratory symptoms, hours worked with rats per week, job performed, smoking habits, and sex were used in this analysis Results: The prevalence of work-related sensitization to rat urinary allergens (IgE >0.7 KU/L) was 9.7 % (n = 63). Thirty-six of the sensitized workers had work-related symptoms (asthma or rhinitis). Two hundred forty-eight workers (38.2%) were atopic (defined as specific IgE to 1 of the common allergens). The sensitization rate increased with increasing air allergen exposure. Atopic workers exposed to low levels of allergen had a more than 3-fold increased sensitization risk compared with nonexposed atopic workers. For atopic subjects, the risk increased little with increasing exposure, whereas for nonatopic subjects, a steadily increasing risk was observed. Smoking and sex did not modify the sensitization risk. Conclusion: Rat urinary allergen–sensitization risk increased with increasing exposure intensity. Workers who were atopic had a clearly elevated sensitization risk at low allergen exposure levels. (J Allergy Clin Immunol 1999;103:678-84.)

Section snippets

Population

The study population came from laboratory animal facilities in Sweden, the Netherlands, and the United Kingdom. Swedish laboratory animal workers (n = 38) came from an earlier study among students from laboratory technician training schools with exposure for more than 5 months at follow-up,² and another 90 Swedish subjects came from a cross-sectional study in university facilities.¹⁰ Dutch laboratory animal workers came from a cross-sectional study among laboratory animal workers in 4

RESULTS

Basic characteristics of the 3 populations of laboratory animal workers are given in Table I.

. Basic characteristics of 650 laboratory animal workers by country

Empty Cell	Sweden (n = 74)	The Netherlands (n = 219)	United Kingdom (n = 357)
Age (y)	32.0 (11.6)	28.5 (6.8)	27.5 (9.7)
Smokers (%)	16 (21.6)	55 (25.1)	91 (25.5)
Exsmokers (%)	13 (17.6)	36 (16.4)	44 (12.3)
General respiratory symptoms
Asthma (%)	7 (9.5)	21 (9.6)	32 (9.0)
Rhinitis (%)	15 (20.3)	58 (26.5)	81 (22.7)
Cough (%)	3 (4.1)	13 (5.9)	25 (7.0)
Phlegm (%)	3 (4.1)	13 (5.9)	20

DISCUSSION

In this study we observed clear exposure-response relationships for RUA exposure and specific IgE antibodies against laboratory rats. The risk for development of sensitization was clearly increased in atopic workers compared with nonatopic workers. The hours worked with conscious rats and the product of hours worked with conscious rats and exposure level gave the best discrimination between workers with and without anti-RUA sensitization.

Similar results were obtained when the job with the

Acknowledgements

We thank Prof A. Newman Taylor for helpful discussions during preparation of the manuscript.

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Le personnel de laboratoire de préparation dans les secteurs de recherche cumule des expositions à des produits de nettoyage, à des substances chimiques et au latex ; les animaliers sont exposés aux mêmes nuisances ainsi qu’aux allergènes des animaux de laboratoire. Ces expositions entraînent des symptômes respiratoires, ORL, oculaires ou cutanés de type allergique ou irritatif. L’objectif de cette étude est de déterminer la prévalence de ces symptômes, de documenter la présence d’immunoglobulines E (IgE) spécifiques contre certains de ces allergènes et de décrire les facteurs professionnels associés afin d’améliorer la politique de prévention sur site.
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Soixante-douze salariés (55 %) déclarent au moins un symptôme rythmé par le travail, que ce soit lors de la réalisation des tâches, de la manipulation des animaux et des produits ou du port de gants en latex. La rhinite est le plus fréquent des symptômes (27 %), puis la conjonctivite (23 %), toux sèche (21 %), gêne oropharyngée (14 %), eczéma (11 %) et asthme (2 %). La durée mensuelle des tâches est plus importante chez les salariés symptomatiques. Chez 13 salariés (21 % chez les 63 chez qui le dosage a été fait), des IgE spécifiques d’allergènes d’au moins un animal de laboratoire ont été mises en évidence. Les prévalences d’IgE spécifiques contre le latex d’une part et les ammoniums quaternaires d’autre part sont les mêmes, soit 4 % (n = 5). Le terrain atopique favorise une sensibilisation aux animaux de laboratoire. Les résultats des EFR révèlent un syndrome obstructif dans 6 cas. La concentration de NO exhalé est plus élevée chez les salariés symptomatiques que chez les salariés asymptomatiques. Le personnel est exposé à de multiples nuisances (détergents/désinfectants, produits de préparation de milieux de culture et animaux) qui induisent des effets concomitants, irritatifs et allergiques.
Devant cette importante prévalence de symptômes chez des salariés exposés, en particulier la rhinite qui peut précéder le développement d’un asthme, une politique de prévention a été renforcée afin de remplacer, si possible certains produits, de diminuer les niveaux d’exposition aux allergènes et aux irritants, d’améliorer le port des équipements de protection individuelle et l’observance des protocoles d’utilisation des produits détergents/désinfectants et de préparation des milieux de culture.
Laboratory workers in the research sector are exposed to cleaning products, chemicals and latex ; in addition to these exposures, animal care technicians are also exposed to allergens from laboratory animals. These exposures can lead to respiratory, ENT, ocular or skin symptoms, due to allergic or irritative underlying mechanisms. The aims of this study are to assess the prevalence of these symptoms, to determine the presence of specific immunoglobulins E (IgE) against these allergens and to describe the associated occupational factors in order to improve the worksite prevention program.
Workers of a research institute (n = 131, 49% of whom are exposed to laboratory animals) answered medical and occupational questionnaires about their symptoms, tasks and exposures. Specific IgE against aeroallergens (Phadiatop^®), laboratory animal allergens, latex and quaternary ammoniums (QA) were dosed. Lung function tests (flow–volume curves) were performed and exhaled nitric oxide measured.
Seventy-two workers (55%) reported at least one work-related symptom when performing tasks such as handling animals or products or while wearing latex gloves. Rhinitis is the most frequent symptom (27%), followed by conjunctivitis (23%), dry cough (21%), sore throat (14%), eczema (11%) and asthma (2%). Monthly task duration is longer in symptomatic workers. Thirteen workers (21% among those 63 in whom it was determined) had specific IgE against an allergen from at least one laboratory animal. Specific IgE prevalence against latex on one hand and QA on the other hand were found to be the same: 4% (n = 5). Atopy is a contributing factor to sensitization against laboratory animals. Lung function tests show bronchial obstruction in 6 workers. Exhaled nitric oxide concentration is higher in symptomatic than in asymptomatic workers. Workers are exposed to several agents (detergents/disinfectants, culture media products and animals), which induce concomitant allergic or irritative effects.
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Les rongeurs et autres petits mammifères domestiques et de laboratoire ont un important pouvoir sensibilisant. Pour certains rongeurs, le nombre des allergènes en cause atteint et dépasse la dizaine. Le poids moléculaire des allergènes se situe entre 8 kDa à plus de 80 kDa. Les lipocalines avec un poids moléculaire autour de 20 kDa jouent un rôle majeur. Quatre lipocalines sont actuellement bien définies du point de vue protéinique et ADN : les lipocalines de cobaye Cav p2 et Cav p3, une lipocaline de souris Mus m1 et une lipocaline de rat Rat n1. Les lipocalines sont sécrétées par les glandes salivaires, la glande de Harder, mais aussi par les hépatocytes, comme les lipocalines urinaires de souris et de rat. Les albumines sériques caractérisées par leur poids moléculaire de 67 kDa et leur capacité de donner des réactions allergiques croisées sont reconnues par le sérum de 20 à 30 % des patients.
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Relationships observed between the exposure metrics and a positive SPT response and mouse-specific IgG4 levels were robust to adjustment for potential confounders, including age, sex, smoking status, total IgE levels, and respiratory protection use (see Tables E2, E3, and E4 in this article’s Online Repository). In addition, atopy, which has been shown to be a risk factor for sensitization and allergen-specific IgG4 in previous studies,8,23,24 was also a predictor of these outcomes in this study population (see this article’s Online Repository). Most study participants had neither skin test sensitivity nor mouse-specific IgG4.
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^☆: Funded in part by the European Community (contract #BMH1-CT94-1446; data pooling and serology) and by the Netherlands Organization for Research (statistical analyses).

^☆☆: Reprint requests: Dick Heederik, PhD, Department of Environmental Sciences, Environmental and Occupational Health Group, Wageningen University and Research Center, PO Box 238, 6700 AE Wageningen, The Netherlands.

^★: 0091-6749/99 $8.00 + 0 1/1/96452

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Exposure-response relationships for work-related sensitization in workers exposed to rat urinary allergens: Results from a pooled study☆,☆☆,★

Abstract

Section snippets

Population

RESULTS

DISCUSSION

Acknowledgements

J Allergy Clin Immunol

J Allergy Clin Immunology

Clin Exp Allergy

Respiratory allergy to urine proteins of rats and mice

Lancet

Allergic sensitization is associated with increased bronchial responsiveness: a prospective study of allergy to laboratory animals

Eur Respir J

Work related symptoms, sensitisation, and estimated exposure in workers not previously exposed to laboratory rats

Occup Environ Med

Respiratory allergy to rats: exposure-response relationships in laboratory animal workers

Am J Respir Crit Care Med

Respiratory allergy in laboratory animal workers: a retrospective cohort study using pre-employment screening data

Occup Environ Med

Exposure of laboratory animal workers to airborne rat and mouse urinary allergens

J Allergy Clin Immunol

Smoking, atopy and laboratory animal allergy

Br J Ind Med

Comparison of methods to assess airborne rat and mouse urinary allergen levels I: analysis of air samples

Allergy