CLINICAL AND MATERIALS SCIENCES

The Sensitizing Potential of Periodontal Dressings ELLEN HAUGEN and ARNE HENSTEN-PETTERSEN NIOM - Scandinavian Institute of Dental Materials, Forskningsveien 1, Oslo 3, Norway

The sensitizing potential of three periodontal dressing materials was evaluated by the guinea pig maximization test. The results indicated a difference in the sensitization rate of the three materials.

J Dent Res 57(11-12):950-953, Nov.-Dec. 1978

Many of the materials and medicaments that are used in daily dental practice contain substances that may induce allergic reactions of the oral mucosa or the skin. The presence of saliva and the vascularization of the oral mucosa make it less subject to irritant and allergic reactions than the skin.1 However, when the potential allergen is applied repeatedly to traumatized tissue, under occluding dressing or in high concentration, the possibility of a sensitization increases.1 These requirements are met by the placement of periodontal dressing materials after gingival surgery. Relatively few cases of allergic contact stomatitis caused by periodontal dressing materials have been reported.2-5 However, many allergic reactions may avoid registration as such. An immediate-type allergic reaction (type I) may have a dramtic course4, but a delayedtype response (type IV) occurring 8-24 hours after a periodontal surgical treatment might tend to be accounted for or obscured by postoperative swelling and pain. Other forms of contact stomatitis caused by periodontal dressings need not fall into the classical concept of type I, II, III or IV reac-

tions.5 Periodontal dressings based

on zinc

oxide/eugenol preparations have been used for many years. The potential risk of inducing allergy to eugenol by these types of materials has been investigated.23 The conclusion was that periodontal dressings containing eugenol or colophony ought to be avoided.3 However, little is known about the sensitizing potential of non-eugenol containing dressings. The aim of the present study was to compare the sensitizing potential of three Received for publication December 16, 1977 Accepted for publication April 4, 1978 950

periodontal dressings using the guinea pig maximization test.6

Materials and methods. Animals. 100 female albino guinea pigsA weighing 350-450 g were used in this study. The animals were caged separately, and divided into four groups with 25 animals in each. Allergens. Three commercial periodontal dressings were selected-Coe-pak®B, Peripac®C and Ward's Wondrpak®D. Coe-pak, tube 1, contains zinc oxide with added oils, gums and lorothidol (a fungicide). Tube 2 contains unsaturated fatty acids and chlorothymol. Peripac consists of calcium phosphate, zinc oxide, acrylate, organic solvent, flavoring and coloring agents. Ward's Wondrpak, powder, contains zinc oxide, powdered pine resin, talc and asbestos and the liquid isopropyl alcohol 10%, clove oil, pine resin, pine oil, peanut oil, camphor and coloring materials. The dressings were prepared according to manufacturers' instructions. From the freshly mixed material a water soluble extract and an ointment were made for the induction procedures. The extract was made by extruding 20 g of the material from a plastic syringe into a glass flask to obtain a maximal surface area of the material. Distilled water (25 ml) was added, and the flask was kept in a gyratory orbital shaker at 370C for five days. The solution was concentrated 5x under reduced pressure at 3 70C, and stored at 40C until used. The ointment for topical application was made by mixing freshly prepared dressing with vaselineE (1:2) to a smooth consistency (test ointment I). For the challenge procedure a dressing/vaseline ratio of 1:10 was used (test ointment II). Sensitization and evaluation. The test animals were exposed to the dressing material in a two-stage procedure6 as outlined in Table 1. The first stage (tl) consisted of intradermal injections in the shoulder region. The hair was removed, and a row of

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SENSITIZATION TO PERIODONTAL DRESSINGS

TABLE 1 OPERATIVE PROCEDURE OF THE GUINEA PIG MAXIMIZATION TEST Day No. Procedure

t1 t7

t8

tio t28

t29 t30 t31

Intradermal injections of soluble extract Rubbing of skin with SDS Topical application of test ointment I Removal of occluding bandages Topical challenge with test ointment II Removal of occluding bandages Evaluation Re-evaluation

three injections was given on each side of the midline: 1) 0.1 ml Freund's adjuvantF, 2) 0.1 ml water soluble extract, 3) 0.05 ml adjuvant mixed with 0.05 ml of the extract. The control animals received similar injections with sterile saline instead of the extract.

Seven days later (t7) the same region was shaved and the skin rubbed with 10% sodium lauryl sulfate in vaseline. The next day (t8) the same skin area was exposed to a topical application of the test ointment on filter paper and sealed with occluding bandages for 48 hours. The challenge procedure was initiated 4 weeks (t28) after the first induction. The hair in a flank area of 5x5 cm was clipped and the skin shaved. Circular patches of filter paper (diameter 2 cm) were sealed to the flank for 24 hours. All test animals had two patches, one containing the appropriate ointment for challenge and one with vaseline as a negative control. The 25 control animals had one patch of each of the three dressing materials. The bandages were removed after 24 hours (t 29), and the test sites were evaluated after re-shaving and washing with ether to remove remnants of dressing materials (t30). In addition, all animals were re-evaluated the next day (t3l) to include possible slow developing responses. The reactions were scored from 0 to 3, with 0 = no reaction; 1 = scattered mild redness; 2 = moderate and diffuse redness; 3 intense redness and =

swelling.6

Leachability and chemical analysis. 20 of freshly made periodontal dressing were placed in 25 ml distilled water as described above, and the water was decanted after 24 hours (Extract I). The dressings were rinsed with 25 ml distilled water four times and re-extracted in 25 ml for another g

951

24 hours (Extract II). The extracts were centrifuged to remove particulate matter and the supernatants analyzed. The water-soluble components of the periodontal dressings were subjected to qualitative and quantitative analysis by gas-chromatography and combined gas-chromatography/mass spectrometryG. Balsam of Peru, camphor, limonene, eugenol, chlorothymol, diethyleneglycol-dimethylether were used as standards. Methylene chloride extracts and acid, neutral and basic subfractions of the original solutions were analyzed. The details of the procedure are available from the authors upon

request.

Results. Allergic potential. The reactions seen after the challenge procedure varied from no reaction (0) to vivid redness combined with induration and swelling (3). In none of the control animals could a positive reaction to the test material be found, but a weak irritation from the material was noted in a few animals. A slight redness of the skin indicated where the patches had been placed. The few control animals that exhibited this mild irritation usually reacted to all three materials. This kind of skin reaction was also noted in some of the test animals. The sensitization rate of the periodontal materials is given in Table 2. The elastic bandage caused superficial lesions in many of the animals, and a reaction to the shaving procedure could also be found. However, at the second evaluation (t31) these types of irritation usually had subsided, whereas the allergic reactions were as strong as before. Leachability and chemical analysis. The quantitation of the extractable components of the dressing materials in distilled water is shown in Table 3. For the second extraction an increased leachability with time was seen TABLE 2 THE SENSITIZATION RATE OF PERIODONTAL DRESSING MATERIALS IN GUINEA PIGS Ward's Animals

Coe-pak

Peripac

Wondrpak

5/25

1/25

13/25

0/25

0/25

0/25

Experimental group Control group

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TABLE 3 QUANTITATION OF COMPONENTS OF PERIODONTAL DRESSING MATERIALS AFTER EXTRACTION IN DISTILLED WATERG

Extract

Substance

Dressing Coe-pak

Unknown 1 (MW=156) Chlorothymol Lauric acid Unknown 2 (Fatty acid?)

Peripac

Tetraethyleneglycoldimethylether

Ward's Wondrpak

I

Extract II

25 10 65 65 157

35 15 115 90 10.1

Camphor 5.2 6.2 Unknown Eugenol 1.1 1.1 I: 24 hours extraction of 20 g material in 25 ml water. II: an additional 24 hours extraction of the same material in 25 ml water.

for Coe-pak, whereas Peripac released markedly less. The leachability of components from Ward's Wondrpak was about equal in the first and second extraction step.

Discussion. The guinea pig maximization test is considered- a sensitive method of screening allergens. Guinea pigs apparently do not become sensitized to substances other than those inducing contact allergy in man.6 The differentiation between a positive allergic response and the irritant response arising out of too high a concentration of material is crucial for the evaluation.7 Periodontal dressing materials in high concentration may give local irritation when used under occluding bandages. To avoid local irritation, a periodontal dressing/ vaseline ratio of 1:10 was chosen for challenge, based on a pilot study of skin irritation in non-sensitized animals (unpublished results). The rating of the allergenic potential of different substances by the guinea pig maximization test is based on the frequency of positive reactions obtained. Although all degrees of reactions were observed, only the frequency is of interest in this connection.6 When the periodontal dressing materials were rated as to sensitization potential, they fell into three general classifications: i.e., Peripac was a weak, Coe-pak a mild and Ward's Wondrpak a moderate sensitizer, using the system of Magnusson and Kligman.6 The guinea pig maximization test reveals

Unit of measure

,ug/mI water

mg/ml water mg/ml water

that a chemical possesses immunologic capabilities, but the percentage of animals sensitized does not indicate the probable human incidence of sensitization.6 The allergenic potential of complex chemical compounds such as periodontal dressings will be determined by the solubility and leachability of all substances in them. The dressings studied obviously contain components of different leachability. In Peripac, the major leachable component, tetraethyleneglycoldimethylether, came out in the first extraction, whereas Ward's Wondrpak showed a low but continuous release of camphor and eugenol, among others. Whether a high initial dose would be less allergenic than a low exposure of longer duration in repeated applications of dressing in a clinical situation is not known. In the present study water-soluble substances were injected, and other constituents, such as fat-soluble substances, were brought into contact with the skin as an ointment. Both water-soluble and fat-soluble substances in the different dressings may have contributed to the immunologic reaction, but the response may be modified by their relative proportions. In a group of 18 patients that had reacted with swelling, redness and vesicles in the operated area after periodontal surgery, a positive reaction to patch tests with eugenol was found in 13 of them, and 12 reacted to colophony (rosin).2 Colophony is a constituent of many periodontal dressings and also a common allergen in the general popula-

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Vol. 57No. 11-12

SENSITIZA TION TO PERIODONTAL DRESSINGS

tion.8 In a further study, 13 of 133 patients were shown to have positive patch tests to eugenol after repeated periodontal surgery.3 Only four of these 13 patients described any marked discomfort which could be interpreted as a contact allergy.3 A retrospective study of contact allergy to dental materials shows that positive patch tests occur more frequently than the manifestation of allergic diseases.9 The five periodontal dressing materials listed in Accepted Dental Therapeutics10 all contain colophony (rosin) and four of them eugenol. The only one that is eugenolfree (Coe-pak) contains, among other things, balsam of Peru. In this context the cross-reactivity of many allergenic substances (such as between eugenol and balsam of Peru) 1 1 should be considered. When the causative agent in an allergic reaction to periodontal dressing materials has not been positively identified, a choice among the five accepted materials is impossible. The apparently low incidence of allergic contact stomatitis due to periodontal dressing materials in the past may be caused by several factors: (1) a factual low incidence, (2) an "under reporting" of cases, and (3) the fairly small proportion of dental patients who have had the opportunity to undergo such treatment. This relationship may be changed in the coming years if an increasing proportion of patients undergo periodontal surgery.

Conclusion. The present experiments indicate that the three periodontal dressing materials tested had sensitizing potentials that could classify them as weak (Peripac), mild (Coe-pak), and moderate (Ward's Wondrpak) sensitizers. The actual frequency of sensitization to be expected after clinical use of the different dressings cannot be assessed by this method, but apparently depends on the composition of the materials. FOOTNOTES A. Dunkin Hartley (D.H./Ola, Category 3) strain maintained at OLAC, U.K.

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B. Coe-pak®, Coe Laboratories Inc., Chicago, U.S.A. C. Peripac®, de Trey Freres S.A., Zurich, Switzerland. D. Ward's Wondrpak®, Westward Dental Products Co., San Francisco, U.S.A. E. KlOver® Vaseline, Chesebrough Pond's Inc., U.S.A. F. Freund's Adjuvant Complete, Behring Werke AG, Marburg-Lahn, Germany. G. Contract project directed by Dr. Nina Gios, Central Institute of Industrial Research, Gjos, Norway. REFERENCES 1. FISHER, A. A.: Contact Dermatitis, Philadelphia: Lea and Febiger Co., 1967, pp 247248. 2. KOCH, G.; MAGNUSSON, B.; and NYQUIST, G.: Contact Allergy to Medicaments and Materials Used in Dentistry (II), Odontal Revy

22:275-289, 1971. 3. KOCH, G.; MAGNUSSON, B.; NOBREUS, N.; NYQUIST, G.; and SODERHOLM, G.: Contact Allergy to Medicaments and Materials Used in Dentistry (IV), Odontol Revy 24:109-114, 1973. 4. POULSOM, R. C.: An Anaphylactoid Reaction to Periodontal Surgical Dressing: report of case, JADA 89:895-896, 1974. 5. LYSELL, L.: Contact Allergy to Rosin in a Periodontal Dressing, J Oral Med 31:24-25, 1976. 6. MAGNUSSON, B., and KLIGMAN, A. M.: The Identification of Contact Allergens by Animal Assay. The Guinea Pig Maximization Test,JInvest Dermatol 52:268-276, 1969. 7. EPSTEIN, E.; and MAIBACH, H. I.: Formaldehyde Allergy, Arch Dermatol 94:186-190, 1966. 8. FREGERT, S.; HJORTH, N.; MAGNUSSON, B.; BANDMANN, H. J.; CALNAN, C. D.; CRONIN, E.; MALTEN, K.; MENEGHINI, C. L.; PIRILA, V.; and WILKINSON, D. S.: Epidemiology of Contact Dermatitis, Trans St Johns Hosp Dermatol Soc 55:17-34, 1969. 9. DJERASSI, E., and BEROWA, N.: KontaktAllergie in der Stomatologie als Berufsproblem, Berufsdermatosen 14:225-23 3, 1966. 10. American Dental Association: Accepted Dental Therapeutics. 38th ed, Chicago: American Dental Association, 1975, pp 23 7-238. 11. HJORTH, N.: Eczematous Allergy to Balsams, Copenhagen: Munksgaard, 1961, pp 105-111.

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The sensitizing potential of periodontal dressings.

CLINICAL AND MATERIALS SCIENCES The Sensitizing Potential of Periodontal Dressings ELLEN HAUGEN and ARNE HENSTEN-PETTERSEN NIOM - Scandinavian Instit...
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