toxicology versus allergy in restorative dentistry

8/9/2019 Toxicology Versus Allergy in Restorative Dentistry

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Advances in Dental Research

DOI: 10.1177/08959374920060010901

1992; 6; 17Adv. Dent. Res.E.C. Munksgaard

Toxicology Versus Allergy in Restorative Dentistry

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T O X I C O L O G Y V E R S U S A L L E R G YI N R E S T O R A T I V E D E N T I S T R Y

E . C . MUNKSGAARDDepartment of D ental MaterialsRoyal Dental Co llegeNorre alle 20DK-2200 Copenhagen NDenmarkAdv Dent R es 6:17-21, September, 1992

AbstractT he frequency of side-effects among dental patientsis very low and is seen mostly as mild allergic reactions.Among the dental staff, contact allergic eczema is occasionallyseen, induced by certain m etals and various organic m aterials.

This manuscript is published as part of the proceedings o f theN1H Technology Assessment Conference on Effects and Side-effects of Dental R estorative Materials, August 26-28, 1991,National Institutes of Health, Bethesda, Maryland, and did notundergo the customaryjournal peer-review process.

In the last few years, there has been an increasing demand forsafety evaluation and control of dental materials. Thisincrease occurs despite the fact that reactions on patients areconsidered to be harmless and infrequent1:700 accordingto Kallus and Mjor (1991) and am ong prosthetic patients 1:300,according to Hensten-Pettersen and Jacobsen (199 1). Verifieddiagnosis of side-effects is not often established, because themild nature of the reactions does not justify more extensivetesting involving several medical specialties. The informationin the literature of side-effects among patients is thereforemostly inconclusive, especially since much information is basedsolely on questionnaire surveys among patients or dentists.Questionnaires do not give ob jective information on side-effectscaused by den tal treatments because of differences between therespondents in o bserving, evaluating, and clearly describing thesymptom s, and because such symptoms could have causes otherthan the dental treatment.Side-effects from a dental restorative m aterial areunintentional injuries to hum ans caused by the material and canbe either toxic/irritative or allergic in nature. Toxicity is theability of a molecule or compo und to produ ce injury in or on thebody, after ab sorption has taken place. A toxic reaction mayinvolve damag e in or on an organ or tissue (such as skin, kidneys,or lungs) and may cause inhibition of enzy mes in cells or blood,or have an effect on DNA . Chemical changes or association ofmolecules to DNA may give rise to cancer, miscarriage, ormalformations.Sometimes, chemical molecules or substances induce

allergic reactions wh ich are damaging to the body. The varioustypes of allergies are normally divided into types 1 to 4. In alifetime, about 10% of the population will suffer from an allergy.On testing the population with batteries of allergens, one willfind that about 1/3 will show a reaction, but the majority of theseare without symptoms or inconvenience (Weeke et al, 1986).Therefore, when patients having received dental treatment withallergenic dental materials are tested, some of them will show areaction. Only a few of them w ill have clinical symptoms, whichcan be explained by a reaction from a dental material.T Y P E S A N D I N C I D E N C EO F O C C U P A T I O N A L S I D E - E F F E C T S

The low incidence of side-effects among p atients (Kallus andMjor, 1991; Hensten-Pettersen and Jacobsen, 1991) is probablydue to the fact that restorative materials are nearly insoluble.Only soluble materials will provoke reactions to the body. Thedentist and his or her staff handle the materials before they areconverted to a nearly insoluble state and are in contact with thematerials more often than is the patient. This might explain thehighe r incidence of side-effects seen among den tists (Kallus andMjor, 1991), compared w ith his or her patients. Generally, if adental restorative material may cause serious side-effects onpatien ts, one would expec t that the dental staff should suffer to a

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18 M U N K S G A A R D A D V D E N T R E S S E P T E M B E R 1992H g 2 2 + , H g 2 +Ag +

corrosion S" S n > S n

AMALGAMconversion^

C u + , C u 2 +

HgFig. 1 E lements leaking from amalgam and which may bepresent in the oral environment.higher degree than would the patients. Surveys of the incidenceand type of occupational diseases among dental personnel maytherefore be appropriate, so that it can be decided whether amaterial is liable to cause side-effects in patients.In Denmark, a survey has been performed on diagnosedoccupational diseases among 121 dentists and dental assistantsin the years 1984-86 (Engen, 1990). Dermatoses were the mostfrequently diagnosed side-effect. Thirty of these were classifiedas allergic, 9 as toxic, and 9 unspecified. Disturbances inmuscles and joints w ere seen in 37 individuals, 9 had infections,8 reactions to solvents, 7 pulmonary problems, 5 unspecifieddermal problems, 3 headache, 3 pregnancy disturbances, 2hearing reduction, 2 brain damage, and 2 were classified aspoisoning. Others were inconveniences including dizziness andexhaustion.

Abou t 2/3 of the staff at a large public dental clinic showedpositive reaction when patch-tested with allergens from dentalma terials. O nly about 1/3 of these had sym ptoms which cou ld berelated to work w ith dental materials, and we re seen as slight tosevere dermatoses, urticaria, and contact allergic eczema(Djerassi and Berow a, 1966). Questionnaires to specialists inorthodontics, periodontics, prosthetics, and pedodonticsrevealed that 50% claimed som e kind of an occupational disorder(Hensten-Pettersen and Jacobsen, 1991; Jacobsen and Hensten-Pettersen, 1989a,b, 1991). Between 40 and 50% of these hadirritative and allergic dermatoses due to hand-washing, use oflatex gloves, metha crylates, or disinfectants. Other causes wereexposure to eugenol, epoxy products, fungi, face masks, andgold. In another investigation (Franz, 1982), it was found thatoccupational allergic problems were associated with workingwith anesthetics, disinfectants, methacrylates, Co/Cr/Ni-alloys,polyether materials, and am algam.AmalgamAmalgams are alloy mixtures containing mercury, silver, tin,copper, and sometimes zinc. The content of mercury in amalgamis a concern, because small amounts of m ercury are liberatedfrom the fillings. It happens when the gamm a-1 phase isconverted slowly to a beta-phase containing less mercury. It hasbeen shown that there is a 70% conversion in 18 years (BoyerandE die, 1990). The surface conversion will cause evaporationof mercury, which will be absorbed after inhalation. Corrosion

TABLEMETALS IN DENTAL CASTING ALLOYS AND INAMALGAMS WHICH HAVE OR MAY HAVE SIDE-EFFECTS ON PATIENTS OR MAY POSE ANOCCUPATIONAL RISKDiagnosed Side-effects

MetalBerylliumCadmiumChromiumNickelCobaltGoldPalladiumMercuryTinSilverCopper

T A

XXXXXXXXX

c

?

T= tox in. A = allergen. C = carcinogen.

Potential RiskTXX

X

A

XXXXXXXXX

cXXXX

(x)

of amalgam fillings liberates small amounts of metallic ions(Fig. 1). S ome of the ions may ca use allergic reactions.The risk of inhaling m ercury evaporating from fillings can beassessed by comparison of the concentration w ith the thresholdlimit value. In most countries, a threshold limit value (TLV) of50 ]ng/cubic meter is accepted, but some advocate 30 pg/cubicmeter. Nevertheless, the mean burden from amalgam fillings isgenerally lower. The average secretion in urine and the bloodmercury content are twice as high am ong dentists as in patients,but in both cases are far below the safety limit. Until now, no onehas found a patient with a mercury excretion above the safetylimits, and where the mercury derives from dental treatment.The literature, including judgme nt of the toxicological risk, hasrecently been reviewed (Horsted-Bindslev et al., 1991).

W hile the risk for the patient seems lim ited, the dentist can bepoisoned during work with mercury. Smith (1978) has reportedthree cases of severe mercury poisoning among dentists nottaking precautions adequate to reduce m ercury contamination intheir clinics. In all cases, the mercury c ontent in the air was muchhigher than the TLV.Few reports describing allergic reactions caused by amalgam

fillings can be found in the literatureabout 50 since 1906(Veron etal, 1984; White and Smith, 1984; Munksgaard, 1989;Horsted-Bindslev et al., 1991). The symptoms are normallyclassified as delayed hypersensitivity reactions (Type 4). Thefollowing symptoms have been identified: eczem a, urticaria,wheals on face and limbs, rashes, and sometimes Pink orKawasaki disease. Harmless local soft-tissue reactionssometimes occur in the gingiva adjacent to amalgam fillings(Bolewska etai, 1990). In a few cases, systemic reactions h avebeen noted (Thompson and Russell, 1970; W ea ve r^ al., 1987).The few reports describing allergy induced by am algam arein contrast to the fact that 2% of the population [perhaps 10%among dentists (Gotz and Fortmann, 1959; White and B randt,1976)] showed a positive reaction when patch-tested with



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V O L . 6 T O X I C O L O G Y v s . A L L E R G Y 19mercury. Some claim that the reaction is not allergic, but toxic.Genera lly, it is found that patients show ing positive reaction tomercury in a patch test are without clinical symptoms, becausethe amount of m ercury liberated from the fillings is not enough tomaintain an immuno logical reaction. Cases of allergic outbreakcaused by silver and copper from amalgam are very few (V eronetaU 1984).C a s t i n g A l l o y sThere are about 36 elemen ts among the casting alloys and metalsused in dentistry (Mu nksgaard, 1989). A t least ten of them havebeen classified as allergens. Three of them are potentiallypoisonous (Be, Cd, Hg), and four of them possess a carcinogenicpotential (Be, Cd, Cr, Ni) (Mitchell, 1984; Graensevaerdier,1 9 8 8 ; see Table). The poisonous and carcinogenic metals maybe a threat for dental laboratory technicians, since they can beexposed to these metals in the form of dust and vapors duringcasting and grinding. There seem s to be little risk to the patient(Mitchell, 1984), despite one report claiming a possibleconnection between a corroding palladium-gold crown and thedevelopment of a carcinoma on the tongue (Kinnebrew et al.,1984). T he four metals classified as potential carcinogens mayinduce development of carcinomas, when dust is inhaled, andtherefore possess only an occupational risk.

Beryllium from 0.5 to 2% is used to increase the castability ofcertain alloys. On the surface of the casting, this content isincreased, and the corrosion product may possess a potential riskfor the patient. This risk should be assessed further. Cadm iumhas been used in soldering alloys but is no longer in use in mostcountries.Chromium and nickel are not judged to be a risk for the dentalprofession and patients (Mitchell, 1984).Metals are known to cause allergy, and nickel, cobalt, andchromium are the predominant allergens among the metals.About 9% of women and 1.5% of men will show positivereactions when patch-tested with nickel, while the equivalentnum bers for chromium are 1.5 and 2 . About 1 % of th e populationshows a positive reaction to cobalt (Hildebrand, 1985). It isquestionable whether dental patients have a pronounced risk ofdeveloping sensitivity caused by metallic restoratives. In aninvestigation done by Stenman and Bergman (1989), 151patients with general types of complaints were patch-tested. Theincidence of positive reactions to nickel was within the normalrange, but the incidence of positive reactions with gold, cobalt,and palladium as well as with mercury was higher than seen in

the normal population. There were few cases of sensitivityinduced by organic materials. According to this investigation, itseems that allergies to metals constituted the main side-effectseen among dental patients. In addition, Namikoski and co-workers (1990) point out the need for careful immunologicalconsideration in selecting alloys for use as restoratives, becauseof the increased sensitivity to a number of metals reported in agroup of dental patients. This is in contrast to the risk for patientsexposed to nickel-containing alloys, as shown by the work ofStaerkjaer and Men ne (1990). Based on results from aninvestigation of 1085 girls wearing orthodontic appliances, itwas established that the girls did not develop intra-oral nickelallergic reactions, and, as in other studies, the results indicated

(DI)METHACRYLATERESINS

Allergens

MMA vapors

FormaldehydeFig. 2 Components from (di)methacrylate-containingsubstances which may cause side-effects.that appliances may induce tolerance leading to a lowerincidence of nickel sen sitivity.It seems probable that allergic reactions to metallicrestorations are seen mainly when a hypersensitivity is acquiredfrom sources other than dental treatment (Ho lland-Moritz et al.,1 9 8 0 ; Hildebrand, 1985). T he risk should be further assessed inany event.M e t h a c r y la t e -b a s e d M a t e r ia l sD i- and mono-m ethacrylates are found in a numb er of materialsused in restorative dentistry, including resin composites,bonding systems, and fissure sealants, as well as materials usedfor orthodontic appliances, crowns and bridges, denture bases,relining and repair, as provisionals or temporary restorations,fissure sea lants, cements, etc. T he substances are low in toxicity,but some of the materials possess mo derate allergenicity (Fig. 2).

Methylmethacrylate (MMA) with a boiling point of 100Chas been reported to cause brain damage in a number oflaboratory technicians wh o were exposed to the substance dailyfor many years (Ch ristiansen etal, 1986).

All the double bonds in the dimethacrylates are not convertedduring polym erization, and on the surface they can be oxidizedto yield formaldehyde, which is both an allergen and acarcinogen. Formaldehyde also appears when polymericmaterials are trimmed as well as above open containers withMM A(BruneandBeltesbrekke, 1981).Nearly all the types of methacrylates can induce type 4allergy, and, in addition, allergies have been induced bybenzoylperoxide, DEPT, hydroquinone, and dibutyl phthalate(Bradford, 1948; Hensten-Pettersen, 1984; Ka ner vae tal., 1986;Munksgaard, 1989; Munksgaard et al., 1990). The number ofpatients suffering from allergic reaction to dental composites isvery low. This is because methacrylates are insoluble whenpolyme rized, and the amount of ma terial leaking out is negligibleafter a few week s. At least one report exists describing an allergicreaction induced by formaldehyde produced by surfaceoxidation of unreacted double bonds in a resin composite(Hensten-Pettersen, 1984).Some of the ma terials give local toxic reactions when appliedto the gingiva, such as dentin bonding agents containingglutaraldehyde or organic acids, which may cause temporarydamage. Reports exist describing pulpal dam age caused by resincompo sites in deep cavities, but the reaction can be prevented orminimized if proper precautions are taken (Heys et al., 1982;



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2 0 M U N K S G A A R DPREDOMINANT OCCUPATIONAL RISKS ALLERGENSLatex-gloves(Di)methacrylatesDisinfectants, anaestheticsCobalt, chromium, nickelPolyether, colophony and eugenol materials TOXIC SUBSTANCESMethyl methacrylate (formaldehyde)Mercury vapor CARCINOGENSFormaldehydeCadmium, beryll ium

Fig. 3 S ubstances which maycause side-effects among thedental staff.Coxetal., 1987; QvistandT hylstrup, 1990).An increasing number of thedental staff develop a contactallergic eczema induced by (di)methacrylates (Djerassi andBerow a, 1966; Jacobsen and Hensten-Pettersen, 1989a,b, 1991).This isgenerally characterized by its location on thefirst threefingers of the left hand (Munksgaard et ai, 1990). Thesymptoms seen are redness, desquamation, fissuring, andexcoriations, andthey are sometimes so severe that work hasto be abandoned. The fingers become contaminated duringhandling of resin containers, and during holding of thecontouring strip, andwhile fillings w ith resin composites arebeing performed. Themost frequently used types ofprotectivegloves are made of latex, and these do not afford protectionagainst resin mono mers. Low-molecular-weight substancessuch as MMA, HEMA, andTEGDMApenetrate theglovesin a few minu tes , w h i le h igher -mo lec u la r -w e igh tdimethacrylates (such asBISGMA andUEDM A) take longer(Munksgaard, 1992).O t h e r M a t e r ia l sA number ofmaterials other than amalgam, casting alloys, andmethacrylate-based materials areused inrestorative dentistry.Examples are glass-ionomer cements, temporary crown andbridge materials, endodontic sealers, impression materials,various cements, porcelain and ceramics, disinfectants,anesthetics, andvarious drugs. Some of these products maycause a slight, local toxic reaction to the gingiva or pulp, andsome contain allergens such as (Munksgaard, 1989): MMA,benzoyl peroxide, benzoates, am ine accelerators, plasticizers,hydroquinone, polyether m aterials, eugenol, cresol, colophony,N-ethyl-p-toluenesulfonamide, thymol, epoxy, chloramine,phenol, formaldehyde, iodoform, and some dyes and flavors.Some ofthe components are classified as potential carcinogens:various phenols, formaldehyde, chloroform, and cadmiumoxide. These allergens have caused reactions topatients and todental staff. Most of the reactions are of the 'delayedhypersensitivity' type (Engen, 1990), butother types ofallergicreactions involving systemic reactions have also been reported.The numbers of reported cases describing patients sufferingfrom such reactions are few, except forthose involving reactionscaused by polyether materials. These are used as temporarydressings andimpression materials andcontain chlorobenzene

A D V D E N T R E S S E P T E M B E R 1992

PREDOMINANT RISKS, PATIENTS ALLERGENS

EugenolColophonyPolyether materialsGold, palladiumMethacrylate LOCAL TOXIC REACTIONSVarious restorative materials SYSTEMIC TOXIC REACTIONS? CARCINOGENS

Fig. 4 S ubstances which mayoccasionally cause side-effects among patients.sulfonates ascatalysts. Reports have been published claimingthat about 0.5% ofpatients have symptoms such as a burningsensation in the mouth, swelling of lips and mucosa, andblisters (Nally andStorrs, 1973; Van Groeningen andNater,1 9 7 5 ; Christensen, 1976; Kulenkamp etal., 1976; Dahl,1978)caused by the chlorobenzene sulfonates.

CONCLUSIONIt can beconcluded that som e occupational risks exist (Fig. 3) inthe dental profession, although the frequenc y is low.Dermatoses are frequently seen among the dental staff,mostly asirritative reactions caused byhand-washing and useofdisinfectants. In some cases, a type 4 allergy is seen. Themostfrequent allergens are: latex gloves, (di)methacrylates, cobalt,chromium, nickel, polyether m aterials, colophony, and eugenol.Sometimes thesymptoms are sosevere that occupation has to beabandoned. It seems therefore appropriate for some of thematerials used in dentistry to be exchanged with materialshaving alower degree ofallergenicity.

Cases ofbrain damage caused byMMA andintoxication bymercury vapor necessitate that the dental staff should constantlybe warned andadvised regarding theproper handling of thesematerials.Dental staff should also be warned about the followingpotential carcinogens: formaldehyde, phenols, cadm ium, andberyllium. Dental materials containing cadmium are notused inmost countries, but the risk regarding the use of berylliumrequires further assessm ent.Since thefrequency of side-effects among dental patients is

very low, and since the symptoms are mild, no specialprecautions arerequired. Thesymptoms areallergic innature,and thepredominant allergens are listed in Fig. 4. Local toxicreactions to gingiva orpulp, which have been reported, can beprevented orminimized bythe use ofappropriate techniques. Ina few instances, temporary systemic reactions are seen aftervarious dental treatments, but theexact nature of such reactionsis poorly und erstood.Positive patch-test reactions with gold, palladium, andmercury seem to occur m ore frequently among patients claimingto suffer from side-effects from dental treatments than amongother patients. Further research within this field is thereforejustified.by on April 26, 2010http://adr.sagepub.comDownloaded from


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