The adverse effects of dental restorative materials a review
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Paitoon Mongkolnam, DDS*
Key words: Biocompatibility, biomaterials, side effects. Abstract Several materials used in dentistry are described as biomaterials.Owing to the intimate contact of these materialswith the oral tissues, they should possess a high degree of biocompatibility.However, some materials may exhibit adverse effects, causing both local and general pathological changes, even though the occurrence seems to be relatively low. It is, therefore, the dentist's responsibility to be aware of the potential adverse effects of these materials and to take precautions to protect the patient from such effects. The purpose of this article is to review the potential adverse effects of some commonly used restorative materials, mainly with regard to patients. (Received for publicationMarch 1991 . RevisedJuly 1991. Accepted August 1991.)
Introduction Biomaterials have been defined as those nonviable materials intended to be in contact with living tissues to perform a function for medical purposes.' Many materials used in dentistry come into direct contact with the oral mucosa, pulp, periapical, and hard tissues of the teeth, and are therefore included in this group. Due to their intimate contact with tissues, dental materials should exhibit a high degree of biocompatibility. In this report, only the adverse effects of dental restorative materials commonly used for operative procedures will be discussed, mainly with regard *Formerly MDSc candidate, School of Dental Science, The University of Melbourne. 360
to patients. However, where precautions have been relaxed it should be borne in mind that the dental personnel who handle dental materials may be at risk. Local adverse effects of dental restorative materials in the oral cavity are either toxic or allergic in nature, while systemic effects are mainly allergic due to substances released from the materials. Local reactions are not generally severe; they are characterized as discomforts, while systemic reactions due to hypersensitivity, which may include allergic reactions and also other sensitivity responses, can cause more unpleasant effects.
Amalgam Dental amalgam is used in approximately 75 per cent of all single-tooth restorations. Amalgam is an alloy primarily comprising mercury, silver, copper, tin, and sometimes zinc. Mercury makes the chemical reaction possible, and mercuric compounds facilitate hardening of the amalgam once it has been placed in the tooth. There is a negligible amount of free mercury in the final, hardened amalgam restoration. Mercury and irs compounds can be classified in the following order of decreasing toxicity: methyl and ethyl mercury compounds, mercury vapour, inorganic salts, organic forms such as phenyl mercury salts. The toxic potential of these forms of mercury in dentistry is limited to mercury vapour; the other mercury compounds are not used.' As far as amalgam is concerned, interest has focused on the evaporation of mercury from amalgam in the oral cavity. Mercury has a high vapour pressure (0.6665 Pa at 37 "C), and is rapidly taken up via the lungs. It accumulates in the kidney and brain and is excreted in the urine, bile and lungs. Mercury vapour may Australian Dental Journal 1992;37(5):360-7.
be released from dental amalgam during insertion, from newly placed amalgam restorations, from the solidified and hardened material during removal or during the functional life of the amalgam restorat i ~ n .A~ relationship -~ between the total surface area of amalgam restorations and blood or urine mercury levels has been found in many ~ t u d i e s . Dentists ~.~ have a much higher level of urine mercury than the general population and yet exhibit no greater morbidity or mortality.' It has also been suggested that mercury from dental amalgam restorations may contribute to the mercury concentration in the brain.10-12However, the mere presence of a substance in a tissue does not mean that a toxic effect will occur. Both the dose of the substance and its local concentration in the tissue concerned have to be considered when predicting potential toxicity. The American Dental Association2,13has previously cautioned that, in extremely rare cases, individuals may develop mercury sensitivity or an allergic reaction from contact with mercury. Patients and dental ofice personnel may be affected. Dentists are generally aware of these potential problems because dentists and dental staff who work with them are at risk from mercury vapour. Allergic reactions to the mercury related to amalgam restorations are extremely rare. When such reactions do occur, they are most frequently characterized by signs and symptoms that are similar to those seen in other contact allergies. Symptoms may vary from local oral symptoms near recently placed amalgam restorations, such as oedema or ulcers, to a generalized urticaria1 erythema with vesicular or eczematous dermal changes over the entire body without oral symptoms. Oral symptoms are usually described as gingivotorna at it is.^,'^ The skin is the most common site. When such reactions occur they usually appear a few hours after placement of a new amalgam restoration. The reactions may be self-limiting and subside within two to three weeks even without the removal of the filling. The most prevalent oral mucosal responses indicative of mercury sensitivity are local lichenoid lesions adjacent to freshly placed or corroding amalgam r e ~ t o r a t i o n ~ .Although '~-~~ the aetiology of oral lichen planus has not been established it has been shown that immunological mechanisms are important for the development of this condition. Mercury in dental amalgam may adversely affect the formation of T-lymphocytes in humans, and an effect of mercury on the immune system may be related to diseases of immunologic origin." However, apart from allergic reactions and possibly local mucosal reactions, no detrimental Australian Dental Journal 1992;37:5
effects on the health of persons with amalgam restorations have been scientifically documented to be caused by the mercury released from amalgam. The proportion of people allergic to mercury has been estimated to be less than one per cent.20.21 However, only a very small proportion of the population allergic to mercury may react to mercury released from amalgam restorations. It should also be noted that allergy to certain mercury-containing compounds does not necessarily indicate a true allergy to mercury, and a patient with allergy to one form of mercury may or may not cross-react with other forms of mercury.22It is known from several studies that there are no differences in morbidity or mortality between people with amalgam restorations and those without .'3.'4 It has been concluded that the use of mercury in dental amalgam restorations is safe for patient^.^^.^'.^^ There is insufficient evidence to justify claims that mercury from amalgam restorations has an adverse effect on the health of the patients. There is no reason why a patient should seek to have amalgam restorations removed except in individuals hypersensitive to the material or its component^.^,^^ These individuals, exhibiting a true allergic reaction to the metal, can be identified through a combination of medical history review and allergy testing. Amalgam restorations, therefore, should be replaced with other posterior restorative materials only in patients who have a medically justified need for such replacement.26 In addition to mercury vapour from amalgam restorations, the corrosion products and ions of amalgam constituents thus released can diffuse into the surrounding tooth structure and cause its discoloration. Ion migration may also cause some denaturing of protein in the dentine matrix, accounting for increased brittleness and finally the cracking of tooth cusps.'' Another possible adverse effect of amalgam restorations is the production of electrical potentials related to other metal restorations. Composite resins Although dental composite resins have been continuously improved and some progress has been made in developing them as a replacement for amalgam, many still fail in wear resistance and marginal integrity; clinical studies have shown the possible occurrence of degradation. Degradation of composite restorations is related to inadequate curing of the resins arising from the inhibiting effect of oxygen or inadequate conversion of monomer during curing. The quantity of the remaining unreacted methacrylate groups in polymerized composite 361
restorative materials has been determined.28.29 It has been demonstrated in vitro that the uncured components of composite resins are c y t ~ t o x i cand ~ ~ more .~~ cytotoxic than cured composite resins.32 It is also known that dental composite resins contain some constituents which have the potential for causing d e r m a t i t i ~ . ~Incompletely ~ reacted oxidation products such as f~rmaldehyde,~~ and impurities from the raw materials provide potential for adverse effects. A preliminary report regarding oral lichenoid reactions related to composite restorations has been published.34 The symptoms could be traced back to a sensitivity to formaldehyde, probably originating either from the composite material itself or from plaque deposits on the rough surface of the material. There are also a few case reports regarding delayed hypersensitivity reactions to dental resinbased materials but further systemic long-term studies have not been done. Pulpal irritation associated with composite resins themselves has generally been attributed to either of two possible causes - toxicity of the material or bacterial leakage around margins. Contemporary composite resins have been shown to cause no or only moderate pulpal reaction^.^^ This type of adverse effect of composite resins is closely related to the presence of microleakage and bacteria. The controversy over whether chemical toxicity or bacterial penetration is the primary cause of pulpal irritation has not yet been resolved. However, a study dealing with this matter has been reported by Cox et ~ 2 1 Several ,~~ commonly used dental materials, including a composite resin, were placed in direct contact with the pulp. It was found that all test materials were well-tolerated if adequately sealed, but severe inflammation occurred when bacteria were present. These results showed that bacterial penetration was a significant factor in determining pulpal response to the composite resin. There are also reports regarding the postoperative sensitivity that may occur with a composite restoration. It could be caused by high shrinkage of the composite occurring during the polymerization setting up stresses at the tooth-resin interfa~e,~' but other factors may also be involved.
Acid etchants It is now common clinical practice to use acid etchants to improve adhesion and adaptation of composite restorative materials to tooth structure. However, when the acid-etch technique for increasing adhesion of composite resins was introduced into clinical use, there was much concern about the effects of this technique on the pulp-dentine 362
complex because the pulp death often observed under silicate restorations was believed to be caused by the acid in the The phosphoric acid component of silicate cement was frequently cited as the cause of pulpal inflammation associated with these material^.^^ Several studies have been performed to evaluate the biologic effects of acid etchants. There is some controversy regarding the role of the acid-etch technique as a contributing factor in pulpal irritation. Early studies showed that phosphoric acid did not penetrate into dentine and cause pulpal irritation,"O and in dogs caused no significant pulpal response.41 However, later studies indicated that acid-etching did cause significant pulpal inflammation and enhanced the irritation associated with composite resin^.^^,^^ It has been concluded that the application of acid etchants causes opening and widening of dentinal thus increasing dentine permeability due to the removal of smear layer.45 The dentine, therefore, is more permeable to bacterial invasion, bacterial toxins or the harmful effects of composite resins which reach the pulp and thus result in pulpal i n f l a m m a t i ~ nIt . ~ has ~ also been shown that pulpal inflammation in etched cavities is associated with bacterial growth. Bacterial invasion of dentinal tubules opened by acid etchants caused more severe pulpal responses than that associated with unetched However, a moderate pulpal response to the application of phosphoric acid to dentine has been demonstrated even with no bacteria present on cavity walls or in adjacent dentinal The acid-etch technique has also been cited as the cause of post-operative sensitivity and possible loss of vitality. Acid etchants, therefore, should not be used on exposed or unprotected dentine surfaces. The use of protective liners, such as calcium hydroxide or glass polyalkenoate (glass ionomer) cements, has been recommended. Some manufacturers have recommended the use of dentine bonding agents to protect dentine from acid. However, Japanese researcher^^^,^^ have routinely etched dentine, apparently without ill effect, when using cornpasite resin systems. It is claimed that etching cavity floor dentine and using chemically adhesive composite resin improves not only the bond strength, but also the tubule aperture seal and therefore provides pulpal protection. It is also believed that the adhesion of resin to these etched bonding sites prevents separation of the resin from dentine, thus effecting a tight marginal seal which prevents bacterial ingress and subsequent pulpal irritati~n.~~ Australian Dental Journal 1992;37:5.
In addition, although acid etchants are considered to be harmless to oral soft tissues, iatrogenic oral ulceration following restorative treatment with an acid-etch material has been reported.50 The operator, therefore, has a responsibility to be aware of this possible adverse effect by protecting the patient's soft tissues from contact with acid etchants wherever possible.
Dentine bonding agents and primers Numerous commercial dentine bonding agents have been introduced and others are being developed. With each of these, some consideration must be given to the smear layer which forms on dentine after any cutting procedure. There are two widely divergent opinions regarding treatment of the smear layer. Some believe that the smear layer acts as an effective, natural cavity liner that seals the dentinal tubules and reduces permeability. Others believe that the smear layer interferes with adhesion of materials, serves as a depot of bacteria and bacterial toxins, and should be removed. The treatment of the smear layer is an important consideration in each of the dentine bonding systems apart from the biocompatibility of the dentine bonding agents themselves. The number of reports on the biologic evaluation of dentine bonding agents and primers is limited. The toxicity of these materials to the pulp has not been suficiently investigated. The results and conclusions of these evaluations are varied and do not cover all the dentine bonding systems, although all appear to be biocompatible. Biocompatibility studies on the dentine bonding system developed by Bowen et aI.51-53and the halophosphorus esters of B ~ S - G M A ~have ' * ~ ~been demonstrated not to have cytotoxic effect or to elicit any significant pulpal response. However, the accepted opinion, although it is not based on sufficient research, is that a lining material should be placed in areas of the cavity that are in close proximity to the pulp.56 Glass polyalkenoate (glass ionomer) cements Glass polyalkenoate cements are increasing in use for crown cementation, for intracoronal restorations, and for cavity linings beneath composite resin and other materials. Restorative cements have been continuously improved and materials currently available are more translucent, have minimal shrinkage and good acid-resistance. However, they still have some defects such as early moisture sensitivity, lack of abrasion resistance, and susceptibility to fracture under high shearing stresses. They are also porous and difficult to finish to a smooth surface. Australian Dental Journal 1992;37:5
Glass polyalkenoate cements have a cariostatic effectYs7the ability to bond to tooth structure, and are relatively bland to the pulp. No local or systemic adverse effects of glass polyalkenoate cements have been reported. They have been claimed to be of low pulpal toxicity in clinical useYs8yet pulp sensitivity following their use in crown cementation has been reported.59 The hydraulic pressure created by cementation has been postulated as a possible cause for the sensitivity. Some human histological studies show evidence of moderate pulpal inflammatory responses beneath glass polyalkenoate cements,60.61 while other studies in humans and primates show either very mild or no re~ponse.~'-~' However, in vitro studies show unequivocally that these cements are highly toxic to cells in c ~ l t u r e . ~It ~was , ~also ~.~~ demonstrated in germ-free rats that glass polyalkenoate cement produced localized pulp necrosis with inhibition of calcific repair when placed in direct contact with the mechanically exposed pulp.67 Therefore, the use of calcium hydroxide as a protective liner has been recommended in deep cavities in which the thickness of remaining dentine is minimal, and in situations of mechanical exposure of the pulp before using glass polyalkenoate cement. In addition, the metal-reinforced glass polyalkenoate cements are used in a number of applications in restorative dentistry. It has been shown in vitro that a significant amount of silver is released in artificial saliva from two metalreinforced glass polyalkenoate cements, the so-called silver-cermet cements.68It has been suggested that the silver thus released can diffuse into the surrounding tooth structure adjacent to the materials and may cause its d i s c o l ~ r a t i o n . There ~~.~~ has been no scientific report on a comparison of silver-cermet cements and conventional glass polyalkenoate cements with regard to pulpal effects. Cermets are expected to be as compatible as the other types of glass p~lyalkenoate.~~
Fluoride-containing restorative materials The cariostatic effect of fluoride is well established. Some dental restorative materials, such as silicate and glass polyalkenoate cements, are traditional fluoride-containing materials. Fluoride leaches from them in appreciable amounts throughout the life of the restoration^.^'.^' Therefore, these restorations can provide a continuing topical application of fluoride to the cavity walls and to the surrounding tooth structure, resulting in increasing caries resistance of the tooth Fluoride has also been added to various dental materials including amalgam, dental cements, composite materials, resins and varnish for the specific 363
purpose of eliciting a cariostatic effect. However, it has been suggested that the mere presence of fluoride in the material itself will not be effective as there must be a fluoride-release mechanism in the formulation in order to act in a caries-resistance mode.73 The biocompatibility of fluoride-containing dental materials has not been reported extensively, probably because of the lack of adverse reactions following the proper use of fluoride products. Most of the toxic effects are derived from excessive systemic ingestion or inhalation. Acute adverse reactions result when large amounts of fluoride are ingested over a short period of time, whereas chronic effects (for example, enamel fluorosis) may occur if greater than 2 ppm fluoride in the drinking water is ingested over a number of years during the ages when the teeth are undergoing calcification. Gingival tissue sloughing has been reported from the use of stannous fluoride solutions, particularly if the tissue is diseased or dehydrated. The biocompatibility of fluoride-containing restorative materials has not been extensively assessed. However, such small amounts and the slow rate of release of fluoride from these materials should pose no problems in terms of tissue tolerance and ~ompatibility.~~
Other dental cements Zinc phosphate cement is used extensively in restorative dentistry. The fresh mixed cement is strongly acid with a pH of about 1.6, but in a few hours, as the cement sets, the pH of the cement increases to near neutrality. The chemical toxicity is related to its acidity. Zinc phosphate cement has been evaluated for irritancy by placement in prepared cavities in teeth, and it is generally accepted that initial pulpal irritation occurs but decreases over longer time interval^.^^.^^ It has also been tested in cell culture systems and was found that it was cytotoxic when freshly mixed, but that toxicity decreased as the cement Zinc oxide-eugenol cements are generally considered to produce a mild pulpal response without inflammation when placed in the deep cavity. In contrast, a persistent chronic inflammation with lack of calcific repair has been widely reported when these materials were placed directly on the exposed pulp.77It has been suggested that unreacted eugenol may interfere with cell respiration and healing, resulting in necrosis. The toxicity of zinc oxide-eugenol cement has been generally attributed to eugenol although recent has investigated the possible toxic effect of zinc ions. Eugenol has been shown to diffuse 364
through dentine.79 Higher concentrations of eugenol have been found adjacent to the cement whereas lower and non-toxic concentrations have been found at the dentine-pulp interface. Eugenol has also been demonstrated to cause adverse reactions in both experimental animals and humans. These reactions can be categorized into three types: direct tissue damage due to the nature of the medication; contact dermatitis; and true allergic reaction. Studies have shown that eugenol is cytotoxic and can sensitize the patient, producing a contact mucositis where it is applied.80This irritation is usually self-limiting and appears in the form of redness and pain on the tissues that come into contact with eugenol. The rarest type of reaction to eugenol is allergy. Eugenol is regarded as a potential allergen and acute allergic reaction to eugenol has been reported.81Another adverse effect of eugenol or zinc oxide-eugenol is that it cannot be used as a dental cavity liner beneath composite restorations because eugenol inhibits composite polymerization and may also discolour such restorations.
Metals and alloys The use of metals and alloys in restorative dentistry includes direct gold restorations and gold inlays or onlays as well as inlays or onlays made of other types of casting alloys. Gold is an excellent restorative material and has been used for centuries in dentistry; however, it is not only expensive but also needs good technical ability for successful use. Like other metals used in dentistry, gold is used largely in the form of alloys rather than as a pure metal. Dental gold alloys may contain copper, silver, zinc, platinum, palladium, and other metals. Cast gold inlays and onlays made of high gold alloys have been used successfully for a long time. However, a poorly fabricated gold casting will fail sooner than a comparable quality amalgam restoration. Allergic responses to elemental or metallic gold are very rare, although reactions to gold salts are well recognized.82Oral fluids may allow slow dissolution of elemental gold into gold salts capable of provoking allergic responses. The process of dissolution may be accelerated by galvanic reactions set up by different metals in the mouth. Oral lesions attributed to gold allergy include erythema and inflammation of tissues in contact with the appliance, mucosal erosions, and an oral burning sensation. However, a definite diagnosis is difficult to make. Regarding the large number of other types of casting alloys which may be used for inlays or onlays, very few clinical studies dealing with the Australian Dental Journal 1992;37:5.
adverse effects of these alloys have been published. It can be assumed from clinical that these alternative alloys may be used for fured restorations without causing adverse effects. However, these alternative dental casting alloys cannot be discussed as a single group. Each type of dental casting alloy should be investigated individually for potential adverse effects and allergic reactions due to the release of alloy constituents should be considered.
Dental ceramics Ceramics have been used in dentistry for a long time. They represent the almost ideal restorative material for the oral environment. They are chemically inert and nontoxic, and simulate natural tooth substance for both colour and translucency. Furthermore, the coefficient of thermal expansion is close to that of natural tooth. Great progress has been made in ceramic materials and techniques during the last decade. Bonded porcelain veneers and inlays/onlays have been introduced into restorative dentistry. These restorations are cemented with a resin cement, therefore success is associated with the resin luting cement. Several new dental ceramics have appeared on the market but their biological assessment has not been widely reported. However, high quality ceramics can in many ways be regarded as the most biologically acceptable of all restorative materials used in dentistry.84 This means that there should be no adverse effects due to the ceramic itself. Nevertheless, the potential adverse effects associated with ceramics could arise from the luting cements used for their cementation. The resin cements developed for use with porcelain veneers, inlays/onlays and crowns have not been studied extensively, and limited data are available. The curing mechanism of resin cements is either self-curing or light-curing or both, and the extent of cure affects their mechanical properties, solubility, dimensional stability and biocompatib i l i t ~ . *It~ is . ~expected ~ that the potential adverse effects of the resin cements would be similar to those of the composite resins, due to the similarity in their basic composition. In addition, pulpal sensitivity to the luting resin cements may occur and appears to be due primarily to polymerization contraction and consequent marginal leakage.86 Conclusion Like all other foreign materials introduced into the human body, dental restorative materials may cause both local and general pathological changes. Although the frequency of adverse effects of dental materials in general is < 0.1 per centY8’it is reasonAustralian Dental Journal 1992;37:5
able to assume that the more complex and diverse applications of an increasing number of dental materials may result in an increase in such frequency. The dentist, therefore, has a responsibility to be aware of the potential adverse effects of dental restorative materials and to take precautions to protect the patient and the dental team as much as possible.
Acknowledgements The author wishes to thank Dr Martin J. Tyas, School of Dental Science, University of Melbourne, for his encouragement, advice and assistance in the preparation of this review. References 1. International Organization for Standardization. ISOiTR 9966: 1989(E) - Implants for surgery - Biocompatibility - Selection of biological test methods for materials and devices. Geneva: International Organization for Standardization, 1989. 2. American Dental Association Council on Dental Materials, Instruments, and Equipment and the Council on Dental Therapeutics: Safety of dental amalgam. J Am Dent Assoc 1983; 106519-20. 3. Svare CW, Peterson LC, Reinhardt JW, Boyer DB, Frank CW, Gay DD, Cox RD. The effect of dental amalgams on mercury levels in expired air. J Dent Res 1981;60:1668-71. 4. Abraham JE, Svare CW, Frank CW. The effect of dental amalgam restorations on blood mercury levels. J Dent Res 1984;63:71-3. 5. Vimy MJ, Lorscheider FL. Intra-oral air mercury released from dental amalgam. J Dent Res 1985;64:1069-71. 6. Berglund A, Pohl L, Olsson S, Bergman M. Determination of the rate of release of intraoral mercury vapor from amalgam. J Dent Res 1988;67:1235-42. 7. Reinhardt JW, Boyer DB, Svare CW, Frank CW, Cox RD, Gay DD. Exhaled mercury following removal and insertion of amalgam restorations. J Prosthet Dent 1983;49:652-6. 8. Hero H, Brune D, Jorgensen RB, Evje DM. Surface degradation of amalgams in v i m during static and cyclic loading. Scand J Dent Res 1983;91:488-95. 9. Olstad ML, Holland RI, Wandel N, Hensten Pettersen A. Correlation between amalgam restorations and mercury concentrations in urine. J Dent Res 1987;66:1179-82. 10. Eggleston DW, Nylander M. Correlation of dental amalgam with mercury in brain tissue. J Prosthet Dent 1987;58:704-7. 11. Nylander M, Friberg L, Lind B. Mercury concentrations in the human brain and kidneys in relation to exposure from dental amalgam fillings. Swed Dent J 1987;11:179-87. 12. Nilner K, Akerman S, Klinge B. Effect of dental amalgam restorations on the mercury content of nerve tissues. Acta Odontol Scand 1985;43:303-7. 13. American Dental Association Council on Dental Materials, Instruments, and Equipment and the Council on Dental Therapeutics: Safety of dental amalgam - an update. J Am Dent Assoc 1989;119:204-5. 14. Finne K, Garansson K, Winckler L. Oral lichen planus and contact allergy to mercury. Int J Oral Surg 1982;11:236-9. 15. Lundstrom IMC. Allergy and corrosion of dental materials in patients with oral lichen planus. Int J Oral Surg 1984;13: 16-24. 365
16. Eversole LR, Ringer M. The role of dental restorative metals in the pathogenesis of oral lichen planus. Oral Surg Oral Med Oral Pathol 1984;57:383-7. 17. Lind PO, Hurlen B, Koppang HS. Electrogalvanicallyinduced contact allergy ofthe oral mucosa: Report of a case. Int J Oral Surg 1984;13:339-45. 18. Lind PO, Hurlen B, Lyberg T, Aas E. Amalgam-related oral lichenoid reaction. Scan J Dent Res 1986;94:448-51. 19. Eggleston DW. Effect of dental amalgam and nickel alloys on T-lymphocytes: preliminary report. J Prosthet Dent 1984;5 1:617-23. 20. Bauer JG, First HA. The toxicity of mercury in dental amalgam. CDA J 1982;10:47-61. 21. National Institute of Dental Research. Workshop: biocompatibility of metals in dentistry. J Am Dent Assoc 1984;109:469-71. 22. Langan DC, Fan PL, Hoos AA. The use of mercury in dentistry: a critical review of the recent literature. J Am Dent ASK 1987;115:876-80. 23. Hume WR.Continuing concerns about amalgam. Aust Dent J 1989;34: 181-3. 24. Ahlqwist M, Bengtsson C, Furunes B, Hollender L, Lapidus L. Number of amalgam tooth fillings in relation to subjectively experienced symptoms in a study of Swedish women. Community Dent Oral Epidemiol 1988;16:227-31. 25. Fung YK, Molvar MP, Strom A, Schneider NR, Carlson MP. In viwo mercury and methyl mercury levels in patients with amalgam restorations. Gen Dent 1990;38:36-8. 26. Graver HT. Mercury toxicity and dental amalgam: An update. Compend Contin Educ Dent 1986;7:600-2. 27. McLean JW. The failed restoration: causes of failure and how to prevent them. Int Dent J 1990;40:354-8. 28. Ruyter IE, Svendsen SA. Remaining methacrylate groups in composite restorative materials. Acta Odontol Scand 1978;36:75-82. 29. Inoue K, Hayashi I. Residual monomer (Bis-GMA) of composite resins. J Oral Rehabil 1982;9:493-7. 30. Anderson DAF, Ferracane JL, Zimmermann ER. Cytotoxicity of combinations of dental composite components. J Dent Res 1987;66:133:Abstr 214. 31. Anderson DAF, Ferracane JL, Zimmermann ER, Kaga M. Cytotoxicity of variably cured light-activated dental composites. J Dent Res 1988;67:226:Abstr 905. 32. Hume WR, Hood AM. Comparing cytotoxicity in vitro between cured and uncured composite resins. J Dent Res 1990;69:943:Abstr 81. 33. 0 y m d H, Ruyter IE, SjQvikKleven IJ. Release of formaldehyde from dental composites. J Dent Res 1988;67:1289-94. 34. Lind PO. Oral lichenoid reactions related to composite restorations. Preliminary report. Acta Odontol Scand 1988;46:63-5. 35. MjBr IA, Wennberg A. Biocompatibilityconsiderations of composite resins. A discussion paper. In: Vanherle G, Smith DC, eds. International Symposium on Posterior Composite Resin Dental Restorative Materials. Netherlands: Peter SZulC, 1985:83-90. 36. Cox CF, Keall CL, Keall HJ, Ostro E, Bergenholtz G. Biocompatibilityof surface-sealed dental materials against exposed pulps. J Prosthet Dent 1987;57:1-8. 37. Jensen ME, Chan DCN. Polymerization shrinkage and microleakage. A discussion paper. In: Vanherle G, Smith DC, eds. International Symposium on Posterior Composite Resin Dental Restorative Materials. Op. cit.:243-62. 38. Zander HA. Pulpal response to restorative materials. J Am Dent Assoc 1959;59:911-5. 366
39. Johnson RH, Christensen GJ, Stigers RW, Laswell HR. Pulpal irritation due to the phosphoric acid component of silicate cement. Oral Surg Oral Med Oral Pathol 1970;29:447-54. 40. Lee HL Jr, Orlowski JA, Scheidt GC, Lee JR. Effects of acid etchants on dentin. J Dent Res 1973;52:1228-33. 41. Goto G, Jordan RE. The pulpal effects of 50 per cent phosphoric acid. Can Dent Assoc J 1972;38:248. 42. Stanley HR, Going R, Chauncey H. Human pulp response to acid pretreatment of dentin and to composite restoration. J Am Dent Assoc 1975;91:817-25. 43. VojinoviC:0, Nyborg H, Brannstrom M. Acid treatment of cavities under resin fillings: bacterial growth in dentinal tubules and pulpal reactions. J Dent Res 1973;52:1189-93. 44. Brannstrom M, Johnson G. Effects of various conditioners and cleaning agents on prepared dentin surfaces: a scanning electron microscopic investigation. J Prosthet Dent 1974;31:422-30. 45. Pashley DH, Michelich V, Kehl T. Dentin permeability: Effects of smear layer removal. J Prosthet Dent 1981;46:531-7. 46. Pashley DH. Smear layer: physiological considerations. Oper Dent 1984;Suppl 3:13-29. 47. Macko DJ, Rutberg M, Langeland K. Pulpal response to the application of phosphoric acid to dentin. Oral Surg Oral Med Oral Pathol 1978;45:930-46. 48. Fusayama T. Factors and prevention of pulpal irritation by adhesive composite resin restorations. Quintessence Int 1987; 18:633-4 1. 49. Kurosaki N, Kubota M, Yamamoto Y, Fusayama T. The effect of etching on the dentin of the clinical cavity floor. Quintessence Int 1990;21:87-92. 50. Gutteridge DL. Iatrogenic and ulceration following restorative treatment with an acid-etch material. Br Dent J 1984;156:403-4. 51. Stanley HR, Bowen RL, Cobb EN. Pulp responses to experimental treatments of dentin for bonding composites. J Dent Res 1985;64:222:Abstr 423. 52. Chohayeb AA, Bowen RL, Rupp NW, Adrian J. Pulpal response to a new dentin and enamel system. J Dent Res 1985;64:222:Abstr 428. 53. Sydiskis RJ, Dumsha TC. Cytotoxicity testing of a dentin bonding system. J Dent Res 1985;64:338:Abstr 1468. 54. Van Leeuwen MJ, Dogon IL, Norris D, Heeley J. A histological evaluation of two dentin bonding agents. J Dent Res 1982;61:268:Abstr 804. 55. Van Leeuwen MJ, Dogon IL, Heeley J. A histological study of two visible light cured esters of BisGMA. J Dent Res 1985;64:222:Abstr 425. 56. Pameijer CH, Stanley HR, Dickinson A. Histological evaluation of a dentin adhesive. J Dent Res 1986;65:251:Abstr 734. 57. Tyas MJ. Cariostatic effect of glass ionomer cement: a fiveyear clinical study. Aust Dent J 1991;36:236-9. 58. McLean JW. Alternatives to amalgam alloys. Br Dent J 1984;157:432-3. 59. American Dental Association Council on Dental Materials, Instruments, and Equipment. Reported sensitivity to glass ionomer luting cements. J Am Dent Assoc 1984;109:476. 60. Plant CG, Browne RM, Knibbs PJ,Britton AS, Sorohan T. Pulpal effects of glass ionomer cements. Int Endod J 1984;17:51-9. 61. Ucok M. Biological evaluation of glass ionomer cements. Int Endod J 1986;19:285-97. Australian Dental Journal 1992;37:5.
62. Tobias RS, Browne RM, Plant CG, Ingram DV. Pulpal response to a glass ionomer cement. Br Dent J 1978;144:345-50. 63. Kawahara H, Imanishi Y, Oshima H. Biological evaluation on glass ionomer cement. J Dent Res 1979;58:1080-6. 64. Pameijer CH, Segal E, Richardson J. Pulpal response to a glass-ionomer cement in primates. J Prosthet Dent 1981;46:36-40. 65. Hanks CT, Anderson M, Craig RG. Cytotoxic effects of dental cements in two cell culture systems. J Oral Pathol 1981;10:101-12. 66. Meryon SD, Stephens PG, Browne RM. A comparison of the in vizm cytotoxicity of two glass-ionomercements. J Dent Res 1983;62:769-73. 67. Paterson RC, Watts A. Toxicity to the pulp of a glassionomer cement. Br Dent J 1987;162:110-2. 68. Sarkar NK, El-Mallakh B, Graves R. Silver release from metal-reinforced glass ionomers. Dent Mater 1988;4:103-4. 69. Croll TP, Phillips RW. Glass-ionomer silver cermet restorations for primary teeth. Qluntessence Int 1986;17:607-15. 70. Mount GJ. An atlas of glass-ionomer cements: A clinical guide. London: Martin Dunitz, 1990. 71. Swam ML, Phillips RW, Clark HE, Norman RD, Potter R. Fluoride distribution in teeth using a silicate model. J Dent Res 1980;59:1596-603. 72. Swartz ML, Phillips RW, Clarke HE. Long-term fluoride release from glass ionomer cements. J Dent Res 1984~63: 158-60. 73. American Dental Association Council on Dental Materials, Instruments, and Equipment. Restorative materials containing fluoride. J Am Dent Assoc 1988;116:762-3. 74. Wei SHY,Wefel JS. Fluoride agents - solutions, gels, and coatings. In: Smith DC, Williams DF, eds. Biocompatibility of dental materials. Volume 11, Florida: CRC Press, 1982:1- 14. 75. Dahl BL, Tronstad L, Spinberg L. Biological tests of a silicophosphate cement. J Oral Rehabil 1975;2:249-57.
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76. Plant CG, Jones DW. The damaging effect of restorative materials. Br Dent J 1976;140:373-7. 77. Avery JK. Response ofthe pulp and dentin to contact with filling materials. J Dent Res 1975;Spec B:B188-97. 78. Meryon SD, Jakeman KJ. The effects in vitro of zinc released from dental restorative materials. Int Endod J 1985;18191-8. 79. Hume WR. An analysis of the release and the diffusion through dentin of eugenol from zinc oxide-eugenolmixtures. J Dent Res 1984;63:881-4. 80. Kozam G, Mantel1 GM. The effect of eugenol on oral mucous membranes. J Dent Res 1978;57:954-7. 81. Barkin ME, Boyd JP, Cohen S. Acute allergic reaction to eugenol. Oral Surg Oral Med Oral Pathol 1984;57441-2. 82. Wiesenfeld D, Ferguson MM, Forsyth A, MacDonald DG. Allergy to dental gold. Oral Surg 1984;57:158-60. 83. Bessing C. Alternatives to high noble dental casting gold alloys type 111. An in v i m and in vivo study. Swed Dent J 1988;53(S~ppl):1-56. 84. Jones DW. Ceramics and glass as restorative materials. In: Smith DC, Williams DF, eds. Biocompatibility of dental materials. Volume IV. Florida: CRC Press, 198279-122. 85. de Lange C, Bausch JR, Davidson CL. The curing pattern of photo-initiated dental composites. J Oral Rehabil 1980;7:369-77. 86. Smith DC. Dental cements. In: O'Brien WJ, eds. Dental materials: Properties and selection. Chicago: Quintessence, 1989:236-9. 87. MjBr IA. Current views on biological testing of restorative materials. J Oral Rehabil 1990;17:503-7.
Address for correspondence: Department of Operative Dentistry, Faculty of Dentistry, Chulalongkorn University, Henry Dunant Road, Pathumwan, Bangkok 10330, Thailand.
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Paitoon Mongkolnam, DDS*
Key words: Biocompatibility, biomaterials, side effects. Abstract Several materials used in dentistry are described as biomaterials.Owing to the intimate contact of these materialswith the oral tissues, they should possess a high degree of biocompatibility.However, some materials may exhibit adverse effects, causing both local and general pathological changes, even though the occurrence seems to be relatively low. It is, therefore, the dentist's responsibility to be aware of the potential adverse effects of these materials and to take precautions to protect the patient from such effects. The purpose of this article is to review the potential adverse effects of some commonly used restorative materials, mainly with regard to patients. (Received for publicationMarch 1991 . RevisedJuly 1991. Accepted August 1991.)
Introduction Biomaterials have been defined as those nonviable materials intended to be in contact with living tissues to perform a function for medical purposes.' Many materials used in dentistry come into direct contact with the oral mucosa, pulp, periapical, and hard tissues of the teeth, and are therefore included in this group. Due to their intimate contact with tissues, dental materials should exhibit a high degree of biocompatibility. In this report, only the adverse effects of dental restorative materials commonly used for operative procedures will be discussed, mainly with regard *Formerly MDSc candidate, School of Dental Science, The University of Melbourne. 360
to patients. However, where precautions have been relaxed it should be borne in mind that the dental personnel who handle dental materials may be at risk. Local adverse effects of dental restorative materials in the oral cavity are either toxic or allergic in nature, while systemic effects are mainly allergic due to substances released from the materials. Local reactions are not generally severe; they are characterized as discomforts, while systemic reactions due to hypersensitivity, which may include allergic reactions and also other sensitivity responses, can cause more unpleasant effects.
Amalgam Dental amalgam is used in approximately 75 per cent of all single-tooth restorations. Amalgam is an alloy primarily comprising mercury, silver, copper, tin, and sometimes zinc. Mercury makes the chemical reaction possible, and mercuric compounds facilitate hardening of the amalgam once it has been placed in the tooth. There is a negligible amount of free mercury in the final, hardened amalgam restoration. Mercury and irs compounds can be classified in the following order of decreasing toxicity: methyl and ethyl mercury compounds, mercury vapour, inorganic salts, organic forms such as phenyl mercury salts. The toxic potential of these forms of mercury in dentistry is limited to mercury vapour; the other mercury compounds are not used.' As far as amalgam is concerned, interest has focused on the evaporation of mercury from amalgam in the oral cavity. Mercury has a high vapour pressure (0.6665 Pa at 37 "C), and is rapidly taken up via the lungs. It accumulates in the kidney and brain and is excreted in the urine, bile and lungs. Mercury vapour may Australian Dental Journal 1992;37(5):360-7.
be released from dental amalgam during insertion, from newly placed amalgam restorations, from the solidified and hardened material during removal or during the functional life of the amalgam restorat i ~ n .A~ relationship -~ between the total surface area of amalgam restorations and blood or urine mercury levels has been found in many ~ t u d i e s . Dentists ~.~ have a much higher level of urine mercury than the general population and yet exhibit no greater morbidity or mortality.' It has also been suggested that mercury from dental amalgam restorations may contribute to the mercury concentration in the brain.10-12However, the mere presence of a substance in a tissue does not mean that a toxic effect will occur. Both the dose of the substance and its local concentration in the tissue concerned have to be considered when predicting potential toxicity. The American Dental Association2,13has previously cautioned that, in extremely rare cases, individuals may develop mercury sensitivity or an allergic reaction from contact with mercury. Patients and dental ofice personnel may be affected. Dentists are generally aware of these potential problems because dentists and dental staff who work with them are at risk from mercury vapour. Allergic reactions to the mercury related to amalgam restorations are extremely rare. When such reactions do occur, they are most frequently characterized by signs and symptoms that are similar to those seen in other contact allergies. Symptoms may vary from local oral symptoms near recently placed amalgam restorations, such as oedema or ulcers, to a generalized urticaria1 erythema with vesicular or eczematous dermal changes over the entire body without oral symptoms. Oral symptoms are usually described as gingivotorna at it is.^,'^ The skin is the most common site. When such reactions occur they usually appear a few hours after placement of a new amalgam restoration. The reactions may be self-limiting and subside within two to three weeks even without the removal of the filling. The most prevalent oral mucosal responses indicative of mercury sensitivity are local lichenoid lesions adjacent to freshly placed or corroding amalgam r e ~ t o r a t i o n ~ .Although '~-~~ the aetiology of oral lichen planus has not been established it has been shown that immunological mechanisms are important for the development of this condition. Mercury in dental amalgam may adversely affect the formation of T-lymphocytes in humans, and an effect of mercury on the immune system may be related to diseases of immunologic origin." However, apart from allergic reactions and possibly local mucosal reactions, no detrimental Australian Dental Journal 1992;37:5
effects on the health of persons with amalgam restorations have been scientifically documented to be caused by the mercury released from amalgam. The proportion of people allergic to mercury has been estimated to be less than one per cent.20.21 However, only a very small proportion of the population allergic to mercury may react to mercury released from amalgam restorations. It should also be noted that allergy to certain mercury-containing compounds does not necessarily indicate a true allergy to mercury, and a patient with allergy to one form of mercury may or may not cross-react with other forms of mercury.22It is known from several studies that there are no differences in morbidity or mortality between people with amalgam restorations and those without .'3.'4 It has been concluded that the use of mercury in dental amalgam restorations is safe for patient^.^^.^'.^^ There is insufficient evidence to justify claims that mercury from amalgam restorations has an adverse effect on the health of the patients. There is no reason why a patient should seek to have amalgam restorations removed except in individuals hypersensitive to the material or its component^.^,^^ These individuals, exhibiting a true allergic reaction to the metal, can be identified through a combination of medical history review and allergy testing. Amalgam restorations, therefore, should be replaced with other posterior restorative materials only in patients who have a medically justified need for such replacement.26 In addition to mercury vapour from amalgam restorations, the corrosion products and ions of amalgam constituents thus released can diffuse into the surrounding tooth structure and cause its discoloration. Ion migration may also cause some denaturing of protein in the dentine matrix, accounting for increased brittleness and finally the cracking of tooth cusps.'' Another possible adverse effect of amalgam restorations is the production of electrical potentials related to other metal restorations. Composite resins Although dental composite resins have been continuously improved and some progress has been made in developing them as a replacement for amalgam, many still fail in wear resistance and marginal integrity; clinical studies have shown the possible occurrence of degradation. Degradation of composite restorations is related to inadequate curing of the resins arising from the inhibiting effect of oxygen or inadequate conversion of monomer during curing. The quantity of the remaining unreacted methacrylate groups in polymerized composite 361
restorative materials has been determined.28.29 It has been demonstrated in vitro that the uncured components of composite resins are c y t ~ t o x i cand ~ ~ more .~~ cytotoxic than cured composite resins.32 It is also known that dental composite resins contain some constituents which have the potential for causing d e r m a t i t i ~ . ~Incompletely ~ reacted oxidation products such as f~rmaldehyde,~~ and impurities from the raw materials provide potential for adverse effects. A preliminary report regarding oral lichenoid reactions related to composite restorations has been published.34 The symptoms could be traced back to a sensitivity to formaldehyde, probably originating either from the composite material itself or from plaque deposits on the rough surface of the material. There are also a few case reports regarding delayed hypersensitivity reactions to dental resinbased materials but further systemic long-term studies have not been done. Pulpal irritation associated with composite resins themselves has generally been attributed to either of two possible causes - toxicity of the material or bacterial leakage around margins. Contemporary composite resins have been shown to cause no or only moderate pulpal reaction^.^^ This type of adverse effect of composite resins is closely related to the presence of microleakage and bacteria. The controversy over whether chemical toxicity or bacterial penetration is the primary cause of pulpal irritation has not yet been resolved. However, a study dealing with this matter has been reported by Cox et ~ 2 1 Several ,~~ commonly used dental materials, including a composite resin, were placed in direct contact with the pulp. It was found that all test materials were well-tolerated if adequately sealed, but severe inflammation occurred when bacteria were present. These results showed that bacterial penetration was a significant factor in determining pulpal response to the composite resin. There are also reports regarding the postoperative sensitivity that may occur with a composite restoration. It could be caused by high shrinkage of the composite occurring during the polymerization setting up stresses at the tooth-resin interfa~e,~' but other factors may also be involved.
Acid etchants It is now common clinical practice to use acid etchants to improve adhesion and adaptation of composite restorative materials to tooth structure. However, when the acid-etch technique for increasing adhesion of composite resins was introduced into clinical use, there was much concern about the effects of this technique on the pulp-dentine 362
complex because the pulp death often observed under silicate restorations was believed to be caused by the acid in the The phosphoric acid component of silicate cement was frequently cited as the cause of pulpal inflammation associated with these material^.^^ Several studies have been performed to evaluate the biologic effects of acid etchants. There is some controversy regarding the role of the acid-etch technique as a contributing factor in pulpal irritation. Early studies showed that phosphoric acid did not penetrate into dentine and cause pulpal irritation,"O and in dogs caused no significant pulpal response.41 However, later studies indicated that acid-etching did cause significant pulpal inflammation and enhanced the irritation associated with composite resin^.^^,^^ It has been concluded that the application of acid etchants causes opening and widening of dentinal thus increasing dentine permeability due to the removal of smear layer.45 The dentine, therefore, is more permeable to bacterial invasion, bacterial toxins or the harmful effects of composite resins which reach the pulp and thus result in pulpal i n f l a m m a t i ~ nIt . ~ has ~ also been shown that pulpal inflammation in etched cavities is associated with bacterial growth. Bacterial invasion of dentinal tubules opened by acid etchants caused more severe pulpal responses than that associated with unetched However, a moderate pulpal response to the application of phosphoric acid to dentine has been demonstrated even with no bacteria present on cavity walls or in adjacent dentinal The acid-etch technique has also been cited as the cause of post-operative sensitivity and possible loss of vitality. Acid etchants, therefore, should not be used on exposed or unprotected dentine surfaces. The use of protective liners, such as calcium hydroxide or glass polyalkenoate (glass ionomer) cements, has been recommended. Some manufacturers have recommended the use of dentine bonding agents to protect dentine from acid. However, Japanese researcher^^^,^^ have routinely etched dentine, apparently without ill effect, when using cornpasite resin systems. It is claimed that etching cavity floor dentine and using chemically adhesive composite resin improves not only the bond strength, but also the tubule aperture seal and therefore provides pulpal protection. It is also believed that the adhesion of resin to these etched bonding sites prevents separation of the resin from dentine, thus effecting a tight marginal seal which prevents bacterial ingress and subsequent pulpal irritati~n.~~ Australian Dental Journal 1992;37:5.
In addition, although acid etchants are considered to be harmless to oral soft tissues, iatrogenic oral ulceration following restorative treatment with an acid-etch material has been reported.50 The operator, therefore, has a responsibility to be aware of this possible adverse effect by protecting the patient's soft tissues from contact with acid etchants wherever possible.
Dentine bonding agents and primers Numerous commercial dentine bonding agents have been introduced and others are being developed. With each of these, some consideration must be given to the smear layer which forms on dentine after any cutting procedure. There are two widely divergent opinions regarding treatment of the smear layer. Some believe that the smear layer acts as an effective, natural cavity liner that seals the dentinal tubules and reduces permeability. Others believe that the smear layer interferes with adhesion of materials, serves as a depot of bacteria and bacterial toxins, and should be removed. The treatment of the smear layer is an important consideration in each of the dentine bonding systems apart from the biocompatibility of the dentine bonding agents themselves. The number of reports on the biologic evaluation of dentine bonding agents and primers is limited. The toxicity of these materials to the pulp has not been suficiently investigated. The results and conclusions of these evaluations are varied and do not cover all the dentine bonding systems, although all appear to be biocompatible. Biocompatibility studies on the dentine bonding system developed by Bowen et aI.51-53and the halophosphorus esters of B ~ S - G M A ~have ' * ~ ~been demonstrated not to have cytotoxic effect or to elicit any significant pulpal response. However, the accepted opinion, although it is not based on sufficient research, is that a lining material should be placed in areas of the cavity that are in close proximity to the pulp.56 Glass polyalkenoate (glass ionomer) cements Glass polyalkenoate cements are increasing in use for crown cementation, for intracoronal restorations, and for cavity linings beneath composite resin and other materials. Restorative cements have been continuously improved and materials currently available are more translucent, have minimal shrinkage and good acid-resistance. However, they still have some defects such as early moisture sensitivity, lack of abrasion resistance, and susceptibility to fracture under high shearing stresses. They are also porous and difficult to finish to a smooth surface. Australian Dental Journal 1992;37:5
Glass polyalkenoate cements have a cariostatic effectYs7the ability to bond to tooth structure, and are relatively bland to the pulp. No local or systemic adverse effects of glass polyalkenoate cements have been reported. They have been claimed to be of low pulpal toxicity in clinical useYs8yet pulp sensitivity following their use in crown cementation has been reported.59 The hydraulic pressure created by cementation has been postulated as a possible cause for the sensitivity. Some human histological studies show evidence of moderate pulpal inflammatory responses beneath glass polyalkenoate cements,60.61 while other studies in humans and primates show either very mild or no re~ponse.~'-~' However, in vitro studies show unequivocally that these cements are highly toxic to cells in c ~ l t u r e . ~It ~was , ~also ~.~~ demonstrated in germ-free rats that glass polyalkenoate cement produced localized pulp necrosis with inhibition of calcific repair when placed in direct contact with the mechanically exposed pulp.67 Therefore, the use of calcium hydroxide as a protective liner has been recommended in deep cavities in which the thickness of remaining dentine is minimal, and in situations of mechanical exposure of the pulp before using glass polyalkenoate cement. In addition, the metal-reinforced glass polyalkenoate cements are used in a number of applications in restorative dentistry. It has been shown in vitro that a significant amount of silver is released in artificial saliva from two metalreinforced glass polyalkenoate cements, the so-called silver-cermet cements.68It has been suggested that the silver thus released can diffuse into the surrounding tooth structure adjacent to the materials and may cause its d i s c o l ~ r a t i o n . There ~~.~~ has been no scientific report on a comparison of silver-cermet cements and conventional glass polyalkenoate cements with regard to pulpal effects. Cermets are expected to be as compatible as the other types of glass p~lyalkenoate.~~
Fluoride-containing restorative materials The cariostatic effect of fluoride is well established. Some dental restorative materials, such as silicate and glass polyalkenoate cements, are traditional fluoride-containing materials. Fluoride leaches from them in appreciable amounts throughout the life of the restoration^.^'.^' Therefore, these restorations can provide a continuing topical application of fluoride to the cavity walls and to the surrounding tooth structure, resulting in increasing caries resistance of the tooth Fluoride has also been added to various dental materials including amalgam, dental cements, composite materials, resins and varnish for the specific 363
purpose of eliciting a cariostatic effect. However, it has been suggested that the mere presence of fluoride in the material itself will not be effective as there must be a fluoride-release mechanism in the formulation in order to act in a caries-resistance mode.73 The biocompatibility of fluoride-containing dental materials has not been reported extensively, probably because of the lack of adverse reactions following the proper use of fluoride products. Most of the toxic effects are derived from excessive systemic ingestion or inhalation. Acute adverse reactions result when large amounts of fluoride are ingested over a short period of time, whereas chronic effects (for example, enamel fluorosis) may occur if greater than 2 ppm fluoride in the drinking water is ingested over a number of years during the ages when the teeth are undergoing calcification. Gingival tissue sloughing has been reported from the use of stannous fluoride solutions, particularly if the tissue is diseased or dehydrated. The biocompatibility of fluoride-containing restorative materials has not been extensively assessed. However, such small amounts and the slow rate of release of fluoride from these materials should pose no problems in terms of tissue tolerance and ~ompatibility.~~
Other dental cements Zinc phosphate cement is used extensively in restorative dentistry. The fresh mixed cement is strongly acid with a pH of about 1.6, but in a few hours, as the cement sets, the pH of the cement increases to near neutrality. The chemical toxicity is related to its acidity. Zinc phosphate cement has been evaluated for irritancy by placement in prepared cavities in teeth, and it is generally accepted that initial pulpal irritation occurs but decreases over longer time interval^.^^.^^ It has also been tested in cell culture systems and was found that it was cytotoxic when freshly mixed, but that toxicity decreased as the cement Zinc oxide-eugenol cements are generally considered to produce a mild pulpal response without inflammation when placed in the deep cavity. In contrast, a persistent chronic inflammation with lack of calcific repair has been widely reported when these materials were placed directly on the exposed pulp.77It has been suggested that unreacted eugenol may interfere with cell respiration and healing, resulting in necrosis. The toxicity of zinc oxide-eugenol cement has been generally attributed to eugenol although recent has investigated the possible toxic effect of zinc ions. Eugenol has been shown to diffuse 364
through dentine.79 Higher concentrations of eugenol have been found adjacent to the cement whereas lower and non-toxic concentrations have been found at the dentine-pulp interface. Eugenol has also been demonstrated to cause adverse reactions in both experimental animals and humans. These reactions can be categorized into three types: direct tissue damage due to the nature of the medication; contact dermatitis; and true allergic reaction. Studies have shown that eugenol is cytotoxic and can sensitize the patient, producing a contact mucositis where it is applied.80This irritation is usually self-limiting and appears in the form of redness and pain on the tissues that come into contact with eugenol. The rarest type of reaction to eugenol is allergy. Eugenol is regarded as a potential allergen and acute allergic reaction to eugenol has been reported.81Another adverse effect of eugenol or zinc oxide-eugenol is that it cannot be used as a dental cavity liner beneath composite restorations because eugenol inhibits composite polymerization and may also discolour such restorations.
Metals and alloys The use of metals and alloys in restorative dentistry includes direct gold restorations and gold inlays or onlays as well as inlays or onlays made of other types of casting alloys. Gold is an excellent restorative material and has been used for centuries in dentistry; however, it is not only expensive but also needs good technical ability for successful use. Like other metals used in dentistry, gold is used largely in the form of alloys rather than as a pure metal. Dental gold alloys may contain copper, silver, zinc, platinum, palladium, and other metals. Cast gold inlays and onlays made of high gold alloys have been used successfully for a long time. However, a poorly fabricated gold casting will fail sooner than a comparable quality amalgam restoration. Allergic responses to elemental or metallic gold are very rare, although reactions to gold salts are well recognized.82Oral fluids may allow slow dissolution of elemental gold into gold salts capable of provoking allergic responses. The process of dissolution may be accelerated by galvanic reactions set up by different metals in the mouth. Oral lesions attributed to gold allergy include erythema and inflammation of tissues in contact with the appliance, mucosal erosions, and an oral burning sensation. However, a definite diagnosis is difficult to make. Regarding the large number of other types of casting alloys which may be used for inlays or onlays, very few clinical studies dealing with the Australian Dental Journal 1992;37:5.
adverse effects of these alloys have been published. It can be assumed from clinical that these alternative alloys may be used for fured restorations without causing adverse effects. However, these alternative dental casting alloys cannot be discussed as a single group. Each type of dental casting alloy should be investigated individually for potential adverse effects and allergic reactions due to the release of alloy constituents should be considered.
Dental ceramics Ceramics have been used in dentistry for a long time. They represent the almost ideal restorative material for the oral environment. They are chemically inert and nontoxic, and simulate natural tooth substance for both colour and translucency. Furthermore, the coefficient of thermal expansion is close to that of natural tooth. Great progress has been made in ceramic materials and techniques during the last decade. Bonded porcelain veneers and inlays/onlays have been introduced into restorative dentistry. These restorations are cemented with a resin cement, therefore success is associated with the resin luting cement. Several new dental ceramics have appeared on the market but their biological assessment has not been widely reported. However, high quality ceramics can in many ways be regarded as the most biologically acceptable of all restorative materials used in dentistry.84 This means that there should be no adverse effects due to the ceramic itself. Nevertheless, the potential adverse effects associated with ceramics could arise from the luting cements used for their cementation. The resin cements developed for use with porcelain veneers, inlays/onlays and crowns have not been studied extensively, and limited data are available. The curing mechanism of resin cements is either self-curing or light-curing or both, and the extent of cure affects their mechanical properties, solubility, dimensional stability and biocompatib i l i t ~ . *It~ is . ~expected ~ that the potential adverse effects of the resin cements would be similar to those of the composite resins, due to the similarity in their basic composition. In addition, pulpal sensitivity to the luting resin cements may occur and appears to be due primarily to polymerization contraction and consequent marginal leakage.86 Conclusion Like all other foreign materials introduced into the human body, dental restorative materials may cause both local and general pathological changes. Although the frequency of adverse effects of dental materials in general is < 0.1 per centY8’it is reasonAustralian Dental Journal 1992;37:5
able to assume that the more complex and diverse applications of an increasing number of dental materials may result in an increase in such frequency. The dentist, therefore, has a responsibility to be aware of the potential adverse effects of dental restorative materials and to take precautions to protect the patient and the dental team as much as possible.
Acknowledgements The author wishes to thank Dr Martin J. Tyas, School of Dental Science, University of Melbourne, for his encouragement, advice and assistance in the preparation of this review. References 1. International Organization for Standardization. ISOiTR 9966: 1989(E) - Implants for surgery - Biocompatibility - Selection of biological test methods for materials and devices. Geneva: International Organization for Standardization, 1989. 2. American Dental Association Council on Dental Materials, Instruments, and Equipment and the Council on Dental Therapeutics: Safety of dental amalgam. J Am Dent Assoc 1983; 106519-20. 3. Svare CW, Peterson LC, Reinhardt JW, Boyer DB, Frank CW, Gay DD, Cox RD. The effect of dental amalgams on mercury levels in expired air. J Dent Res 1981;60:1668-71. 4. Abraham JE, Svare CW, Frank CW. The effect of dental amalgam restorations on blood mercury levels. J Dent Res 1984;63:71-3. 5. Vimy MJ, Lorscheider FL. Intra-oral air mercury released from dental amalgam. J Dent Res 1985;64:1069-71. 6. Berglund A, Pohl L, Olsson S, Bergman M. Determination of the rate of release of intraoral mercury vapor from amalgam. J Dent Res 1988;67:1235-42. 7. Reinhardt JW, Boyer DB, Svare CW, Frank CW, Cox RD, Gay DD. Exhaled mercury following removal and insertion of amalgam restorations. J Prosthet Dent 1983;49:652-6. 8. Hero H, Brune D, Jorgensen RB, Evje DM. Surface degradation of amalgams in v i m during static and cyclic loading. Scand J Dent Res 1983;91:488-95. 9. Olstad ML, Holland RI, Wandel N, Hensten Pettersen A. Correlation between amalgam restorations and mercury concentrations in urine. J Dent Res 1987;66:1179-82. 10. Eggleston DW, Nylander M. Correlation of dental amalgam with mercury in brain tissue. J Prosthet Dent 1987;58:704-7. 11. Nylander M, Friberg L, Lind B. Mercury concentrations in the human brain and kidneys in relation to exposure from dental amalgam fillings. Swed Dent J 1987;11:179-87. 12. Nilner K, Akerman S, Klinge B. Effect of dental amalgam restorations on the mercury content of nerve tissues. Acta Odontol Scand 1985;43:303-7. 13. American Dental Association Council on Dental Materials, Instruments, and Equipment and the Council on Dental Therapeutics: Safety of dental amalgam - an update. J Am Dent Assoc 1989;119:204-5. 14. Finne K, Garansson K, Winckler L. Oral lichen planus and contact allergy to mercury. Int J Oral Surg 1982;11:236-9. 15. Lundstrom IMC. Allergy and corrosion of dental materials in patients with oral lichen planus. Int J Oral Surg 1984;13: 16-24. 365
16. Eversole LR, Ringer M. The role of dental restorative metals in the pathogenesis of oral lichen planus. Oral Surg Oral Med Oral Pathol 1984;57:383-7. 17. Lind PO, Hurlen B, Koppang HS. Electrogalvanicallyinduced contact allergy ofthe oral mucosa: Report of a case. Int J Oral Surg 1984;13:339-45. 18. Lind PO, Hurlen B, Lyberg T, Aas E. Amalgam-related oral lichenoid reaction. Scan J Dent Res 1986;94:448-51. 19. Eggleston DW. Effect of dental amalgam and nickel alloys on T-lymphocytes: preliminary report. J Prosthet Dent 1984;5 1:617-23. 20. Bauer JG, First HA. The toxicity of mercury in dental amalgam. CDA J 1982;10:47-61. 21. National Institute of Dental Research. Workshop: biocompatibility of metals in dentistry. J Am Dent Assoc 1984;109:469-71. 22. Langan DC, Fan PL, Hoos AA. The use of mercury in dentistry: a critical review of the recent literature. J Am Dent ASK 1987;115:876-80. 23. Hume WR.Continuing concerns about amalgam. Aust Dent J 1989;34: 181-3. 24. Ahlqwist M, Bengtsson C, Furunes B, Hollender L, Lapidus L. Number of amalgam tooth fillings in relation to subjectively experienced symptoms in a study of Swedish women. Community Dent Oral Epidemiol 1988;16:227-31. 25. Fung YK, Molvar MP, Strom A, Schneider NR, Carlson MP. In viwo mercury and methyl mercury levels in patients with amalgam restorations. Gen Dent 1990;38:36-8. 26. Graver HT. Mercury toxicity and dental amalgam: An update. Compend Contin Educ Dent 1986;7:600-2. 27. McLean JW. The failed restoration: causes of failure and how to prevent them. Int Dent J 1990;40:354-8. 28. Ruyter IE, Svendsen SA. Remaining methacrylate groups in composite restorative materials. Acta Odontol Scand 1978;36:75-82. 29. Inoue K, Hayashi I. Residual monomer (Bis-GMA) of composite resins. J Oral Rehabil 1982;9:493-7. 30. Anderson DAF, Ferracane JL, Zimmermann ER. Cytotoxicity of combinations of dental composite components. J Dent Res 1987;66:133:Abstr 214. 31. Anderson DAF, Ferracane JL, Zimmermann ER, Kaga M. Cytotoxicity of variably cured light-activated dental composites. J Dent Res 1988;67:226:Abstr 905. 32. Hume WR, Hood AM. Comparing cytotoxicity in vitro between cured and uncured composite resins. J Dent Res 1990;69:943:Abstr 81. 33. 0 y m d H, Ruyter IE, SjQvikKleven IJ. Release of formaldehyde from dental composites. J Dent Res 1988;67:1289-94. 34. Lind PO. Oral lichenoid reactions related to composite restorations. Preliminary report. Acta Odontol Scand 1988;46:63-5. 35. MjBr IA, Wennberg A. Biocompatibilityconsiderations of composite resins. A discussion paper. In: Vanherle G, Smith DC, eds. International Symposium on Posterior Composite Resin Dental Restorative Materials. Netherlands: Peter SZulC, 1985:83-90. 36. Cox CF, Keall CL, Keall HJ, Ostro E, Bergenholtz G. Biocompatibilityof surface-sealed dental materials against exposed pulps. J Prosthet Dent 1987;57:1-8. 37. Jensen ME, Chan DCN. Polymerization shrinkage and microleakage. A discussion paper. In: Vanherle G, Smith DC, eds. International Symposium on Posterior Composite Resin Dental Restorative Materials. Op. cit.:243-62. 38. Zander HA. Pulpal response to restorative materials. J Am Dent Assoc 1959;59:911-5. 366
39. Johnson RH, Christensen GJ, Stigers RW, Laswell HR. Pulpal irritation due to the phosphoric acid component of silicate cement. Oral Surg Oral Med Oral Pathol 1970;29:447-54. 40. Lee HL Jr, Orlowski JA, Scheidt GC, Lee JR. Effects of acid etchants on dentin. J Dent Res 1973;52:1228-33. 41. Goto G, Jordan RE. The pulpal effects of 50 per cent phosphoric acid. Can Dent Assoc J 1972;38:248. 42. Stanley HR, Going R, Chauncey H. Human pulp response to acid pretreatment of dentin and to composite restoration. J Am Dent Assoc 1975;91:817-25. 43. VojinoviC:0, Nyborg H, Brannstrom M. Acid treatment of cavities under resin fillings: bacterial growth in dentinal tubules and pulpal reactions. J Dent Res 1973;52:1189-93. 44. Brannstrom M, Johnson G. Effects of various conditioners and cleaning agents on prepared dentin surfaces: a scanning electron microscopic investigation. J Prosthet Dent 1974;31:422-30. 45. Pashley DH, Michelich V, Kehl T. Dentin permeability: Effects of smear layer removal. J Prosthet Dent 1981;46:531-7. 46. Pashley DH. Smear layer: physiological considerations. Oper Dent 1984;Suppl 3:13-29. 47. Macko DJ, Rutberg M, Langeland K. Pulpal response to the application of phosphoric acid to dentin. Oral Surg Oral Med Oral Pathol 1978;45:930-46. 48. Fusayama T. Factors and prevention of pulpal irritation by adhesive composite resin restorations. Quintessence Int 1987; 18:633-4 1. 49. Kurosaki N, Kubota M, Yamamoto Y, Fusayama T. The effect of etching on the dentin of the clinical cavity floor. Quintessence Int 1990;21:87-92. 50. Gutteridge DL. Iatrogenic and ulceration following restorative treatment with an acid-etch material. Br Dent J 1984;156:403-4. 51. Stanley HR, Bowen RL, Cobb EN. Pulp responses to experimental treatments of dentin for bonding composites. J Dent Res 1985;64:222:Abstr 423. 52. Chohayeb AA, Bowen RL, Rupp NW, Adrian J. Pulpal response to a new dentin and enamel system. J Dent Res 1985;64:222:Abstr 428. 53. Sydiskis RJ, Dumsha TC. Cytotoxicity testing of a dentin bonding system. J Dent Res 1985;64:338:Abstr 1468. 54. Van Leeuwen MJ, Dogon IL, Norris D, Heeley J. A histological evaluation of two dentin bonding agents. J Dent Res 1982;61:268:Abstr 804. 55. Van Leeuwen MJ, Dogon IL, Heeley J. A histological study of two visible light cured esters of BisGMA. J Dent Res 1985;64:222:Abstr 425. 56. Pameijer CH, Stanley HR, Dickinson A. Histological evaluation of a dentin adhesive. J Dent Res 1986;65:251:Abstr 734. 57. Tyas MJ. Cariostatic effect of glass ionomer cement: a fiveyear clinical study. Aust Dent J 1991;36:236-9. 58. McLean JW. Alternatives to amalgam alloys. Br Dent J 1984;157:432-3. 59. American Dental Association Council on Dental Materials, Instruments, and Equipment. Reported sensitivity to glass ionomer luting cements. J Am Dent Assoc 1984;109:476. 60. Plant CG, Browne RM, Knibbs PJ,Britton AS, Sorohan T. Pulpal effects of glass ionomer cements. Int Endod J 1984;17:51-9. 61. Ucok M. Biological evaluation of glass ionomer cements. Int Endod J 1986;19:285-97. Australian Dental Journal 1992;37:5.
62. Tobias RS, Browne RM, Plant CG, Ingram DV. Pulpal response to a glass ionomer cement. Br Dent J 1978;144:345-50. 63. Kawahara H, Imanishi Y, Oshima H. Biological evaluation on glass ionomer cement. J Dent Res 1979;58:1080-6. 64. Pameijer CH, Segal E, Richardson J. Pulpal response to a glass-ionomer cement in primates. J Prosthet Dent 1981;46:36-40. 65. Hanks CT, Anderson M, Craig RG. Cytotoxic effects of dental cements in two cell culture systems. J Oral Pathol 1981;10:101-12. 66. Meryon SD, Stephens PG, Browne RM. A comparison of the in vizm cytotoxicity of two glass-ionomercements. J Dent Res 1983;62:769-73. 67. Paterson RC, Watts A. Toxicity to the pulp of a glassionomer cement. Br Dent J 1987;162:110-2. 68. Sarkar NK, El-Mallakh B, Graves R. Silver release from metal-reinforced glass ionomers. Dent Mater 1988;4:103-4. 69. Croll TP, Phillips RW. Glass-ionomer silver cermet restorations for primary teeth. Qluntessence Int 1986;17:607-15. 70. Mount GJ. An atlas of glass-ionomer cements: A clinical guide. London: Martin Dunitz, 1990. 71. Swam ML, Phillips RW, Clark HE, Norman RD, Potter R. Fluoride distribution in teeth using a silicate model. J Dent Res 1980;59:1596-603. 72. Swartz ML, Phillips RW, Clarke HE. Long-term fluoride release from glass ionomer cements. J Dent Res 1984~63: 158-60. 73. American Dental Association Council on Dental Materials, Instruments, and Equipment. Restorative materials containing fluoride. J Am Dent Assoc 1988;116:762-3. 74. Wei SHY,Wefel JS. Fluoride agents - solutions, gels, and coatings. In: Smith DC, Williams DF, eds. Biocompatibility of dental materials. Volume 11, Florida: CRC Press, 1982:1- 14. 75. Dahl BL, Tronstad L, Spinberg L. Biological tests of a silicophosphate cement. J Oral Rehabil 1975;2:249-57.
Australian Dental Journal 1992;37:5.
76. Plant CG, Jones DW. The damaging effect of restorative materials. Br Dent J 1976;140:373-7. 77. Avery JK. Response ofthe pulp and dentin to contact with filling materials. J Dent Res 1975;Spec B:B188-97. 78. Meryon SD, Jakeman KJ. The effects in vitro of zinc released from dental restorative materials. Int Endod J 1985;18191-8. 79. Hume WR. An analysis of the release and the diffusion through dentin of eugenol from zinc oxide-eugenolmixtures. J Dent Res 1984;63:881-4. 80. Kozam G, Mantel1 GM. The effect of eugenol on oral mucous membranes. J Dent Res 1978;57:954-7. 81. Barkin ME, Boyd JP, Cohen S. Acute allergic reaction to eugenol. Oral Surg Oral Med Oral Pathol 1984;57441-2. 82. Wiesenfeld D, Ferguson MM, Forsyth A, MacDonald DG. Allergy to dental gold. Oral Surg 1984;57:158-60. 83. Bessing C. Alternatives to high noble dental casting gold alloys type 111. An in v i m and in vivo study. Swed Dent J 1988;53(S~ppl):1-56. 84. Jones DW. Ceramics and glass as restorative materials. In: Smith DC, Williams DF, eds. Biocompatibility of dental materials. Volume IV. Florida: CRC Press, 198279-122. 85. de Lange C, Bausch JR, Davidson CL. The curing pattern of photo-initiated dental composites. J Oral Rehabil 1980;7:369-77. 86. Smith DC. Dental cements. In: O'Brien WJ, eds. Dental materials: Properties and selection. Chicago: Quintessence, 1989:236-9. 87. MjBr IA. Current views on biological testing of restorative materials. J Oral Rehabil 1990;17:503-7.
Address for correspondence: Department of Operative Dentistry, Faculty of Dentistry, Chulalongkorn University, Henry Dunant Road, Pathumwan, Bangkok 10330, Thailand.
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