Timo Palosuo, M.D.
National Public Health Institute
Helsinki

Kristiina Turjanmaa, M.D.
Department of Dermatology, University of Tampere
Tampere

Hely Reinikka-Railo, Senior Specialist
National Agency for Medicines, Medical Devices Centre
Helsinki

CONTENTS

FOREWORD

Natural rubber latex is the most common source material for surgical and examination gloves because of its excellent tensile strength and high elongation at break as well as its good barrier properties due to its film forming ability. Over the past years, however, allergy to latex proteins has become acknowledged as a major occupational problem among glove-using health care workers. For the time being it is generally agreed that there may be considerable differences between the allergen levels of gloves made by different manufacturers, between different glove brands, and even between gloves of different batches from a single manufacturer. Powdered gloves have been shown in most instances to contain higher allergen levels than non-powdered ones. Recently, glove users have become increasingly aware of this variation which in turn has aroused need of reliable information on latex allergen levels in rubber products.

The National Agency for Medicines, its Medical Devices Centre has launched three studies as a part of market control projects to investigate and determine the allergen levels in samples of latex gloves marketed in 1994–1997 in Finland. These studies were performed by a group of researchers from Tampere University Hospital, Helsinki University Hospital and the National Public Health Institute.

The National Agency for Medicines publishes the market surveillance study of medical gloves used in Finland in 1997 in this report. The purpose of these studies was to look further into the differences in the content of allergens in latex gloves on the market and categorise the gloves in order to give more information to the users as well as to the importers and manufacturers. The results have been now spread out for information to the users of latex gloves as well as to the manufacturers of medical gloves. We hope that the results of this study as well as previous studies, will assist all parties to recognise the importance of latex allergenicity as a major health risk. We also hope that the results of this study will continue to benefit manufacturers to develop less allergenic gloves and to improve the quality of latex products generally.

The National Agency for Medicines wants to thank the study group for their valuable studies and also their work in the European Committee for Standardization (CEN) in promoting the development of the relevant standard for requirements and testing for biocompatibility and labelling for medical gloves for single use.

Director General                                               Hannes Wahlroos

1. INTRODUCTION

Allergy to natural rubber latex (NRL) proteins is currently a well-recognized occupational problem among subjects using protective gloves. A major group at risk of immediate hypersensitivity reactions to NRL consists of operating room nurses and surgeons of whom 5–11% have been shown to be allergic to latex (1). Importantly, NRL gloves are also the major contributor to latex aeroallergen levels in operating rooms (2). Several recent studies have documented considerable differences between the allergen content of latex gloves made by different manufacturers, and even between gloves of different batches from a single manufacturer (3–5). Other manufactured NRL products, such as household gloves, catheters, condoms, baby pacifiers and toy balloons may also contain allergenic proteins (1).

An initiative to analyze allergen contents of latex gloves marketed in Finland and internationally was taken in 1994 by the Finnish National Research and Development Centre for Welfare and Health. First, coded extracts of 20 gloves, covering over 90% of the 1994 market, were examined using three different methods, i.e., skin prick test, IgE-ELISA-inhibition and RAST-inhibition. Highly significant correlations (r = 0.94–0.96) emerged between the results of the two laboratory methods (RAST-inhibition and ELISA-inhibition) and the results of prick tests, the “gold standard” for diagnosing latex allergy (5). Based on these results, subsequent surveys were decided to be carried out using the IgE-ELISA inhibition method only.

In 1995, The Medical Devices Centre of the National Agency for Medicines, Finland, provided for allergen analysis 65 glove samples from 15 different importers, again covering more than 90% of the medical glove market. The results of these studies were communicated to the medical community in Finland and the publication was spread also internationally (6).

To continue monitoring the levels of NRL allergens in marketed natural rubber products and to see whether the given information would influence glove-purchasing and glove-using policies in Finland, a third market survey was carried out in 1997. A report of this study is given below.

2. MARKET SURVEILLANCE STUDY OF ALLERGEN CONTENT OF NRL MEDICAL GLOVES IN FINLAND IN 1997

2.1. MATERIAL AND METHODS

2.1.1. Gloves

In May–June 1997, Medical Devices Centre of the National Agency for Medicines, Finland, collected 69 samples of medical gloves, commonly used in Finland, and covering over 90% of the market. The gloves were placed in random order and coded and standard extraction of proteins was done as previously described (5). The study was carried out blind and the code, kept at the National Agency for Medicines, was broken only after all analyses were finished.

2.1.2. IgE-ELISA-inhibition assay

An IgE-ELISA-inhibition method, described in detail elsewhere (5) was applied. Briefly, the solid-phase consisted of freshly collected NRL, diluted to a protein concentration of 20 mg/ml. The IgE serum pool consisted of 6 carefully selected and characterized human sera with high levels of IgE-antibodies in most clinically significant NRL allergens (including hevein, prohevein, hevein C-domain and rubber elongation factor, and clinically significant NRL allergens with apparent molecular weights of 23–27, 36, 45 and 75 kDa). A standard inhibition curve was constructed from the results obtained with serial dilutions of a standard NRL extract (assigned to contain 100 000 arbitrary units (AU) per ml) tested against a constant dilution of the IgE serum pool. Serial four-fold dilutions of the glove extracts were then analyzed for their inhibitory capacity and the results were calculated from the standard curve and their NRL allergen content expressed as AU/ml. According to earlier study results, an allergen content of less than 10 AU/ml was categorized as low, 10–100 AU/ml as moderate, and more than 100 AU/ml, as high.

2.2. RESULTS

Fifty-six of the 69 glove samples were found to represent different glove types or batches. Altogether 30 of theses 56 glove samples (53.6%) had low allergen content (< 10 AU/ml), 18 samples (32.1%) had moderate (10–100 AU/ml) and 8 samples (14.3%) had high allergen content (> 100 AU/ml) (Table 1).

2.3. COMMENTS

The use of protective gloves has increased remarkably during the last 10–15 years. After the medical community had perceived that gloves made of NRL may contain high amount of allergens (3,4) various kinds of efforts have been undertaken to overcome the problem, first by individual physicians, then by hospitals and more recently by regulatory health authorities. A practical means towards the ultimate prevention of NRL allergy would be to decrease the sensitization by stopping the use of high-allergen gloves and eventually withdrawing them from the market.

Availability of specific methods for measuring allergen levels in manufactured rubber products has been scanty. Total protein measurement has shown to correlate relatively well with true allergen contents (measured by, e.g. skin prick test) of manufactured products (5,7) although such methods measure also non-allergenic proteins. The regulatory health authority in the USA (The Food and Drug Administration; FDA) and the European Committee for Standardization (CEN) have, nevertheless, introduced the measurement of extractable total protein as a simple option for glove manufacturers to monitor their products and to provide information for glove users. Allergen-specific assays provide much more reliable information, but unfortunately, most methods used for this purpose still lack adequate validation and are not easily available. The National Agency for Medicines has taken the advantage of using a recently developed and validated method, a latex-specific IgE-ELISA-inhibition (5), to monitor in a nation-wide scale the allergen content of latex gloves sold and used in Finland.

Three successive market surveys, each covering over 90% of the locally medical gloves, were carried out in 1994–1997. During this period, the proportion of high-allergen gloves of all medical gloves offered for sale decreased from 30% to 14%, that of moderate-allergen gloves increased (from 15% to 32%) while low-allergen gloves remained more than half of the market (55-63-54%) (Figure 1). Several high-allergen glove types have disappeared from the market (6) and the mean allergen content in high-allergen gloves that have remained on (or appeared to) the market has decreased (from 569 AU/ml to 338 AU/ml). In 1997, approximately one half of the available low-allergen gloves had in fact very low levels, i.e. below 1 AU/ml, while only 3 of 11 low-allergen gloves in 1994 fell into this very low-allergen category. Obviously, many factors could have influenced this development but it is tempting to assume that awareness of the problem in the medical community and awareness of the availability of low-allergen products, identified in the surveys, have played an important role.

In summary, the authors arrive at the same conclusion presented earlier (6) that this type of repeated nationwide market analyses, preferably arranged by regulatory health authorities, and detailed information on the results communicated to the medical community, currently offer an effective means of direction for the glove purchasing and the use of low-allergen gloves. Eventually, this progress is expected to lead into declining incidence in latex allergy.

REFERENCES

1. Turjanmaa K, Alenius H, Mäkinen-Kiljunen S, Reunala T, Palosuo T. Natural rubber latex allergy (review). Allergy 1996; 51;593–602.

2. Heilman DK, Jones RT, Swanson MC, Yunginger JW. A prospective, controlled study showing that rubber gloves are the major contributor to latex aeroallergen levels in the operating room. J Allergy Clin Immunol 1996; 98;325–30.

3. Turjanmaa K, Laurila K, Mäkinen-Kiljunen S, Reunala T. Rubber contact urticaria. Allergic properties of 19 brands of latex gloves. Contact Dermatitis 1988; 19;362–7.

4. Yunginger J, Jones R, Fransway A, Kelso J, Warner M, Hunt L, Reed C. Extractable latex allergens and proteins in disposable medical gloves and other rubber products. J Allergy Clin Immunol 1994; 93;836.

5. Palosuo T, Mäkinen-Kiljunen S, Alenius H, Reunala T, Yip Esah, Turjanmaa K. Measurement of natural rubber latex allergen levels in medical gloves by allergen-specific IgE-ELISA inhibition, RAST-inhibition, and skin prick test. Allergy 1998;53:59–67.

6. Palosuo T, Turjanmaa K, Reunala T, Mäkinen-Kiljunen S, Alenius H. Allergen content of latex gloves used in 1994–1996 in health care in Finland. Results of renewed market survey in 1995. Publications of the National Agency for Medicines 1996;2:1–7.

7. Yip Esah, Turjanmaa K, Ng KP, Mok L. Allergic responses and levels of extractable proteins in NR latex gloves and dry rubber products. J Nat Rub Res 1994;9:79–86.