TOXICOLOGY VERSUS ALLERGY IN RESTORATIVE DENTISTRY E.C. MUNKSGAARD
Department of Dental Materials Royal Dental College Norre alle 20 DK-2200 Copenhagen N Denmark Adv Dent Res 6:17-21, September, 1992
Abstract—The frequency of side-effects among dental patients is very low and is seen mostly as mild allergic reactions. Among the dental staff, contact allergic eczema is occasionally seen, induced by certain metals and various organic materials.
I
n the last few years, there has been an increasing demand for safety evaluation and control of dental materials. This increase occurs despite the fact that reactions on patients are considered to be harmless and infrequent—1:700 according to Kallus and Mjor (1991) and among prosthetic patients 1:300, according to Hensten-Pettersen and Jacobsen (1991). Verified diagnosis of side-effects is not often established, because the mild nature of the reactions does not justify more extensive testing involving several medical specialties. The information in the literature of side-effects among patients is therefore mostly inconclusive, especially since much information is based solely on questionnaire surveys among patients or dentists. Questionnaires do not give objective information on side-effects caused by dental treatments because of differences between the respondents in observing, evaluating, and clearly describing the symptoms, and because such symptoms could have causes other than the dental treatment. Side-effects from a dental restorative material are unintentional injuries to humans caused by the material and can be either toxic/irritative or allergic in nature. Toxicity is the ability of a molecule or compound to produce injury in or on the body, after absorption has taken place. A toxic reaction may involve damage in or on an organ or tissue (such as skin, kidneys, or lungs) and may cause inhibition of enzymes in cells or blood, or have an effect on DNA. Chemical changes or association of molecules to DNA may give rise to cancer, miscarriage, or malformations. Sometimes, chemical molecules or substances induce allergic reactions which are damaging to the body. The various types of allergies are normally divided into types 1 to 4. In a lifetime, about 10% of the population will suffer from an allergy. On testing the population with batteries of allergens, one will find that about 1/3 will show a reaction, but the majority of these are without symptoms or inconvenience (Weeke et al, 1986). Therefore, when patients having received dental treatment with allergenic dental materials are tested, some of them will show a reaction. Only a few of them will have clinical symptoms, which can be explained by a reaction from a dental material.
TYPES AND INCIDENCE OF OCCUPATIONAL SIDE-EFFECTS
This manuscript is published as part of the proceedings of the N1H Technology Assessment Conference on Effects and Sideeffects of Dental Restorative Materials, August 26-28, 1991, National Institutes of Health, Bethesda, Maryland, and did not undergo the customary journal peer-review process.
The low incidence of side-effects among patients (Kallus and Mjor, 1991; Hensten-Pettersen and Jacobsen, 1991) is probably due to the fact that restorative materials are nearly insoluble. Only soluble materials will provoke reactions to the body. The dentist and his or her staff handle the materials before they are converted to a nearly insoluble state and are in contact with the materials more often than is the patient. This might explain the higher incidence of side-effects seen among dentists (Kallus and Mjor, 1991), compared with his or her patients. Generally, if a dental restorative material may cause serious side-effects on patients, one would expect that the dental staff should suffer to a
17
MUNKSGAARD
18
Hg22+,Hg2+ Ag + corrosion S"
AMALGAM
Sn
>Sn
Cu +
,Cu2+
conversion^
Hg Fig. 1—Elements leaking from amalgam and which may be present in the oral environment. higher degree than would the patients. Surveys of the incidence and type of occupational diseases among dental personnel may therefore be appropriate, so that it can be decided whether a material is liable to cause side-effects in patients. In Denmark, a survey has been performed on diagnosed occupational diseases among 121 dentists and dental assistants in the years 1984-86 (Engen, 1990). Dermatoses were the most frequently diagnosed side-effect. Thirty of these were classified as allergic, 9 as toxic, and 9 unspecified. Disturbances in muscles and joints were seen in 37 individuals, 9 had infections, 8 reactions to solvents, 7 pulmonary problems, 5 unspecified dermal problems, 3 headache, 3 pregnancy disturbances, 2 hearing reduction, 2 brain damage, and 2 were classified as poisoning. Others were inconveniences including dizziness and exhaustion. About 2/3 of the staff at a large public dental clinic showed positive reaction when patch-tested with allergens from dental materials. Only about 1/3 of these had symptoms which could be related to work with dental materials, and were seen as slight to severe dermatoses, urticaria, and contact allergic eczema (Djerassi and Berowa, 1966). Questionnaires to specialists in orthodontics, periodontics, prosthetics, and pedodontics revealed that 50% claimed some kind of an occupational disorder (Hensten-Pettersen and Jacobsen, 1991; Jacobsen and HenstenPettersen, 1989a,b, 1991). Between 40 and 50% of these had irritative and allergic dermatoses due to hand-washing, use of latex gloves, methacrylates, or disinfectants. Other causes were exposure to eugenol, epoxy products, fungi, face masks, and gold. In another investigation (Franz, 1982), it was found that occupational allergic problems were associated with working with anesthetics, disinfectants, methacrylates, Co/Cr/Ni-alloys, polyether materials, and amalgam. Amalgam
Amalgams are alloy mixtures containing mercury, silver, tin, copper, and sometimes zinc. The content of mercury in amalgam is a concern, because small amounts of mercury are liberated from the fillings. It happens when the gamma-1 phase is converted slowly to a beta-phase containing less mercury. It has been shown that there is a 70% conversion in 18 years (Boyer andEdie, 1990). The surface conversion will cause evaporation of mercury, which will be absorbed after inhalation. Corrosion
ADV DENT RES SEPTEMBER 1992
TABLE METALS IN DENTAL CASTING ALLOYS AND IN AMALGAMS WHICH HAVE OR MAY HAVE SIDEEFFECTS ON PATIENTS OR MAY POSE AN OCCUPATIONAL RISK Potential Risk Diagnosed Side-effects A T T A Metal c c X X Beryllium X X Cadmium X X X Chromium X X X Nickel X X Cobalt X X Gold ? X X Palladium (x) X X X Mercury X X Tin X Silver X X X Copper T=toxin. A = allergen. C = carcinogen. of amalgam fillings liberates small amounts of metallic ions (Fig. 1). Some of the ions may cause allergic reactions. The risk of inhaling mercury evaporating from fillings can be assessed by comparison of the concentration with the threshold limit value. In most countries, a threshold limit value (TLV) of 50 ]ng/cubic meter is accepted, but some advocate 30 pg/cubic meter. Nevertheless, the mean burden from amalgam fillings is generally lower. The average secretion in urine and the blood mercury content are twice as high among dentists as in patients, but in both cases are far below the safety limit. Until now, no one has found a patient with a mercury excretion above the safety limits, and where the mercury derives from dental treatment. The literature, including judgment of the toxicological risk, has recently been reviewed (Horsted-Bindslev et al., 1991). While the risk for the patient seems limited, the dentist can be poisoned during work with mercury. Smith (1978) has reported three cases of severe mercury poisoning among dentists not taking precautions adequate to reduce mercury contamination in their clinics. In all cases, the mercury content in the air was much higher than the TLV. Few reports describing allergic reactions caused by amalgam fillings can be found in the literature—about 50 since 1906 (Veron etal, 1984; White and Smith, 1984; Munksgaard, 1989; Horsted-Bindslev et al., 1991). The symptoms are normally classified as delayed hypersensitivity reactions (Type 4). The following symptoms have been identified: eczema, urticaria, wheals on face and limbs, rashes, and sometimes Pink or Kawasaki disease. Harmless local soft-tissue reactions sometimes occur in the gingiva adjacent to amalgam fillings (Bolewska etai, 1990). In a few cases, systemic reactions have been noted (Thompson and Russell, 1970; Weaver^ al., 1987). The few reports describing allergy induced by amalgam are in contrast to the fact that 2% of the population [perhaps 10% among dentists (Gotz and Fortmann, 1959; White and Brandt, 1976)] showed a positive reaction when patch-tested with
VOL.
6
TOXICOLOGY vs. ALLERGY
mercury. Some claim that the reaction is not allergic, but toxic. Generally, it is found that patients showing positive reaction to mercury in a patch test are without clinical symptoms, because the amount of mercury liberated from the fillings is not enough to maintain an immunological reaction. Cases of allergic outbreak caused by silver and copper from amalgam are very few (Veron etaU 1984).
19
Allergens
(DI)METHACRYLATE RESINS
MMA vapors
Casting Alloys There are about 36 elements among the casting alloys and metals used in dentistry (Munksgaard, 1989). At least ten of them have been classified as allergens. Three of them are potentially poisonous (Be, Cd, Hg), and four of them possess a carcinogenic potential (Be, Cd, Cr, Ni) (Mitchell, 1984; Graensevaerdier, 1988; see Table). The poisonous and carcinogenic metals may be a threat for dental laboratory technicians, since they can be exposed to these metals in the form of dust and vapors during casting and grinding. There seems to be little risk to the patient (Mitchell, 1984), despite one report claiming a possible connection between a corroding palladium-gold crown and the development of a carcinoma on the tongue (Kinnebrew et al., 1984). The four metals classified as potential carcinogens may induce development of carcinomas, when dust is inhaled, and therefore possess only an occupational risk. Beryllium from 0.5 to 2% is used to increase the castability of certain alloys. On the surface of the casting, this content is increased, and the corrosion product may possess a potential risk for the patient. This risk should be assessed further. Cadmium has been used in soldering alloys but is no longer in use in most countries. Chromium and nickel are not judged to be a risk for the dental profession and patients (Mitchell, 1984). Metals are known to cause allergy, and nickel, cobalt, and chromium are the predominant allergens among the metals. About 9% of women and 1.5% of men will show positive reactions when patch-tested with nickel, while the equivalent numbers for chromium are 1.5 and 2. About 1 % of the population shows a positive reaction to cobalt (Hildebrand, 1985). It is questionable whether dental patients have a pronounced risk of developing sensitivity caused by metallic restoratives. In an investigation done by Stenman and Bergman (1989), 151 patients with general types of complaints were patch-tested. The incidence of positive reactions to nickel was within the normal range, 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 sensitivity induced by organic materials. According to this investigation, it seems that allergies to metals constituted the main side-effect seen among dental patients. In addition, Namikoski and coworkers (1990) point out the need for careful immunological consideration in selecting alloys for use as restoratives, because of the increased sensitivity to a number of metals reported in a group of dental patients. This is in contrast to the risk for patients exposed to nickel-containing alloys, as shown by the work of Staerkjaer and Menne (1990). Based on results from an investigation of 1085 girls wearing orthodontic appliances, it was established that the girls did not develop intra-oral nickel allergic reactions, and, as in other studies, the results indicated
Formaldehyde Fig. 2—Components from (di)methacrylate-containing substances which may cause side-effects. that appliances may induce tolerance leading to a lower incidence of nickel sensitivity. It seems probable that allergic reactions to metallic restorations are seen mainly when a hypersensitivity is acquired from sources other than dental treatment (Holland-Moritz et al., 1980; Hildebrand, 1985). The risk should be further assessed in any event.
Methacrylate-based Materials Di- and mono-methacrylates are found in a number of materials used in restorative dentistry, including resin composites, bonding systems, and fissure sealants, as well as materials used for orthodontic appliances, crowns and bridges, denture bases, relining and repair, as provisionals or temporary restorations, fissure sealants, cements, etc. The substances are low in toxicity, but some of the materials possess moderate allergenicity (Fig. 2). Methylmethacrylate (MMA) with a boiling point of 100°C has been reported to cause brain damage in a number of laboratory technicians who were exposed to the substance daily for many years (Christiansen etal, 1986). All the double bonds in the dimethacrylates are not converted during polymerization, and on the surface they can be oxidized to yield formaldehyde, which is both an allergen and a carcinogen. Formaldehyde also appears when polymeric materials are trimmed as well as above open containers with MMA(BruneandBeltesbrekke, 1981). Nearly all the types of methacrylates can induce type 4 allergy, and, in addition, allergies have been induced by benzoylperoxide, DEPT, hydroquinone, and dibutyl phthalate (Bradford, 1948; Hensten-Pettersen, 1984; Kanervaetal., 1986; Munksgaard, 1989; Munksgaard et al., 1990). The number of patients suffering from allergic reaction to dental composites is very low. This is because methacrylates are insoluble when polymerized, and the amount of material leaking out is negligible after a few weeks. At least one report exists describing an allergic reaction induced by formaldehyde produced by surface oxidation of unreacted double bonds in a resin composite (Hensten-Pettersen, 1984). Some of the materials give local toxic reactions when applied to the gingiva, such as dentin bonding agents containing glutaraldehyde or organic acids, which may cause temporary damage. Reports exist describing pulpal damage caused by resin composites in deep cavities, but the reaction can be prevented or minimized if proper precautions are taken (Heys et al., 1982;
20
MUNKSGAARD
ADV DENT RES SEPTEMBER 1992
PREDOMINANT OCCUPATIONAL RISKS
PREDOMINANT RISKS, PATIENTS
• ALLERGENS Latex-gloves (Di)methacrylates Disinfectants, anaesthetics Cobalt, chromium, nickel Polyether, colophony and eugenol materials
• ALLERGENS Eugenol Colophony Polyether materials Gold, palladium Methacrylate
• TOXIC SUBSTANCES Methyl methacrylate (formaldehyde) Mercury vapor
• LOCAL TOXIC REACTIONS Various restorative materials
• CARCINOGENS Formaldehyde Cadmium, beryllium
• SYSTEMIC TOXIC REACTIONS ? • CARCINOGENS
Fig. 3—Substances which may cause side-effects among the dental staff.
Fig. 4—Substances which may occasionally cause sideeffects among patients.
Coxetal., 1987; QvistandThylstrup, 1990). An increasing number of the dental staff develop a contact allergic eczema induced by (di)methacrylates (Djerassi and Berowa, 1966; Jacobsen and Hensten-Pettersen, 1989a,b, 1991). This is generally characterized by its location on the first three fingers of the left hand (Munksgaard et ai, 1990). The symptoms seen are redness, desquamation, fissuring, and excoriations, and they are sometimes so severe that work has to be abandoned. The fingers become contaminated during handling of resin containers, and during holding of the contouring strip, and while fillings with resin composites are being performed. The most frequently used types of protective gloves are made of latex, and these do not afford protection against resin monomers. Low-molecular-weight substances— such as MMA, HEMA, and TEGDMA—penetrate the gloves in a few minutes, while higher-molecular-weight dimethacrylates (such as BISGMA and UEDMA) take longer (Munksgaard, 1992).
sulfonates as catalysts. Reports have been published claiming that about 0.5% of patients have symptoms such as a burning sensation in the mouth, swelling of lips and mucosa, and blisters (Nally and Storrs, 1973; Van Groeningen and Nater, 1975; Christensen, 1976; Kulenkamp etal., 1976; Dahl, 1978) caused by the chlorobenzene sulfonates.
Other Materials A number of materials other than amalgam, casting alloys, and methacrylate-based materials are used in restorative dentistry. Examples are glass-ionomer cements, temporary crown and bridge materials, endodontic sealers, impression materials, various cements, porcelain and ceramics, disinfectants, anesthetics, and various drugs. Some of these products may cause a slight, local toxic reaction to the gingiva or pulp, and some contain allergens such as (Munksgaard, 1989): MMA, benzoyl peroxide, benzoates, amine accelerators, plasticizers, hydroquinone, polyether materials, eugenol, cresol, colophony, N-ethyl-p-toluenesulfonamide, thymol, epoxy, chloramine, phenol, formaldehyde, iodoform, and some dyes and flavors. Some of the components are classified as potential carcinogens: various phenols, formaldehyde, chloroform, and cadmium oxide. These allergens have caused reactions to patients and to dental staff. Most of the reactions are of the 'delayed hypersensitivity' type (Engen, 1990), but other types of allergic reactions involving systemic reactions have also been reported. The numbers of reported cases describing patients suffering from such reactions are few, except for those involving reactions caused by polyether materials. These are used as temporary dressings and impression materials and contain chlorobenzene
CONCLUSION It can be concluded that some occupational risks exist (Fig. 3) in the dental profession, although the frequency is low. Dermatoses are frequently seen among the dental staff, mostly as irritative reactions caused by hand-washing and use of disinfectants. In some cases, a type 4 allergy is seen. The most frequent allergens are: latex gloves, (di)methacrylates, cobalt, chromium, nickel, polyether materials, colophony, and eugenol. Sometimes the symptoms are so severe that occupation has to be abandoned. It seems therefore appropriate for some of the materials used in dentistry to be exchanged with materials having a lower degree of allergenicity. Cases of brain damage caused by MMA and intoxication by mercury vapor necessitate that the dental staff should constantly be warned and advised regarding the proper handling of these materials. Dental staff should also be warned about the following potential carcinogens: formaldehyde, phenols, cadmium, and beryllium. Dental materials containing cadmium are not used in most countries, but the risk regarding the use of beryllium requires further assessment. Since the frequency of side-effects among dental patients is very low, and since the symptoms are mild, no special precautions are required. The symptoms are allergic in nature, and the predominant allergens are listed in Fig. 4. Local toxic reactions to gingiva or pulp, which have been reported, can be prevented or minimized by the use of appropriate techniques. In a few instances, temporary systemic reactions are seen after various dental treatments, but the exact nature of such reactions is poorly understood. Positive patch-test reactions with gold, palladium, and mercury seem to occur more frequently among patients claiming to suffer from side-effects from dental treatments than among other patients. Further research within this field is therefore justified.
VOL. 6
TOXICOLOGY VS. ALLERGY
REFERENCES Bolewska J, Holmstrup P, Moller-Madsen B, Kenrad B, Danscher G (1990). Amalgam associated mercury accumulations in normal oral mucosa, oral mucosal lesions of lichen planus and contact lesions associated with amalgam. / Oral Pathol Med 19:39-42. Boyer DB, Edie JW (1990). Composition of clinically aged amalgam restorations. Dent Mater 6:146-150. Bradford EW (1948). Case of allergy to methacrylate. BrDentJ 84:195. Brune D, Beltesbrekke H (1981). Levels of methylmethacrylate, formaldehyde and asbestos in dental workroom air. Scand J Dent Res 89:113-116. ChristensenBL (1976). Overfolsomhedoverfor aftryksmaterialer. Tandlcegebladet 80:198-199. Christiansen ML, Adelhart M, Jorgensen NK, Gyntelberg F (1986). Methylmethacrylat—en &rsag til toksisk hjerneskade? Tandlcegebladet 90:759-764. Cox CF, Keall CL, Keall HJ, Ostro E, Bergenholtz G (1987). Biocompatibility of surface-sealed dental materials against exposed pulps. JProsthet Dent 57 :l-%. DahlBL(1978). Tissue hypersensitivity to dental materials. JOral RehabilS'A 17-120. Djerassi E, Bero wa N (1966). Kontakt allergien in der stomatologie als berufsproblem. Berufsdermatosen 14:224-233. Engen T (1990). Personal communication. Franz G (1982). The frequency of allergy to dental materials. / DentAssoc SA/r 37:805-810. Gotz H, Fortmann I (1959). Bewirken amalgamfullungen der zahne eine quecksilbersensibilisierung der haut? Z Haut Geschlechtskrankh 26:34-36. Graensevaerdier for stoffer og materialer (1988). At-anvisning nr. 3.1.0.2. Copenhagen: Arbejdstilsynetstrykkeri. Hensten-Pettersen A (1984). Allergiske reaktioner p& dentale materialer. Den norske tannlegeforenings tidende 94:573-578. Hensten-Pettersen A, Jacobsen N (1991). Perceived side effects of biomaterials in prosthetic dentistry. J Prosthet Dent 65:138144. Heys RJ, Heys DR, Cox CF, Avery JK (1982). Experimental observations on the biocompatibility of composite resins. In: Biocompatibility of dental Materials, Vol III. Boca Raton, FL. CRC Press Inc., p 131-150. Hildebrand HF (1985). Zahnersatz aus nichtedelmetalllegierungen und allergien. Dusseldorf: Fachvereinung Edelmetallee.V. Holland-Moritz VR, Rimpler M, Rudolph P-0 (1980). Allergie gentiber gold in der mundhohle. Dtsch Zahndrtztl Z35:963-961. Horsted-Bindslev P, Magos L, Holmstrup P, Arenholt-Bindslev D (1991). Dental amalgam—a health hazard? Copenhagen: Munksgaard. Jacobsen N, Hensten-Pettersen A (1989a). Occupational health problems and adverse patient reactions in orthodontics. Eur J Orthodont 11:254-264. Jacobsen N, Hensten-Pettersen A (1989b). Occupational health complaints and adverse patient reactions as perceived by personnel in periodontics. J ClinPeriodontol 16:428-433. Jacobsen N, Hensten-Pettersen A (1991). Occupational health
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complaints and adverse patient reactions as perceived by personnel in public dentistry. Community Dent Oral Epidemiol 19:155-159. Kallus T, Mjor IA (1991). Incidence of adverse effects of dental materials. ScandJ Dent Res 99:236-240. Kanerva L, Jolanki R, Estlander T (1986). Occupational dermatitis duetoanepoxy acrylate. Contact Dermatitis 14:80-84. Kinnebrew M, GettlemanL, Carr RF, Beazley R (1984). Squamous cell carcinoma of the tongue in a young woman. Report of a case with etiologic considerations. Oral Surg Oral Med Oral Pathol 58:696-698. Kulenkamp D, Hausen B, Schulz K-H (1976). Beruflische kontaktallergie durch neuartige abdruckmaterialen in der zahnartzlischen praxis (scutan und impregum). Zahndrtztl Mitteil 66:968. Mitchell EW (1984). The biocompatibility of metals in dentistry. CanDentJ 12:17-19. Munksgaard EC (1989). Bivirkninger fra Dentalmaterialer. Copenhagen: DanskTandlaegeforening. Munksgaard EC (1992). Permeability of protective gloves to (di)methacrylates in resinous dental materials. Scand J Dent Res (inpress). Munksgaard EC, Knudsen B, Thomsen K (1990). Kontaktallergisk h&ndeksem blandt tandplejepersonale af (di)methacrylater. Tandlcegebladet 94:270-274. Nally FF, Storrs J (1973). Hypersensitivity to a dental impression material. BrDentJ143:244-246. Namikoski T, Yoshimatsu T, Suga K, Fujii H (1990). The prevalence of sensitivity to constituents of dental alloy. / Oral Rehabil 17:377-381. Qvist V, Thylstrup A (1990). Pulpale reaktioner i tilslutning til plastfyldninger. In: Hjorting-Hansen E, editor. Odontologi '90. Copenhagen: Munksgaard, 163-175. SmithDL(1978). Mental effects of mercury poisoning. SouthMed Jl 1:904-905. Staerkjaer L, Menne T (1990). Nickel allergy and orthodontic treatment. Eur J Orthodont 12:284-289. Stenman E, Bergman M (1989). Hypersensitivity reactions to dental materials in areferred group of patients. ScandJ Dent Res 97:76-83. Thompson J, Russell JA (1970). Dermatitis due to mercury following amalgam dental restorations. BrJDermatol 82:292297. vanGroeningen G, Nater JP (1975). Reactions to dental impression materials. Contact Dermatitis 1:377. Veron C, HildebrandtHF, MartinP (1984). Amalgames dentaire et allergie. JBiolBuccale 14:83-100. Weaver T, Auclair PL, Taybos GM (1987). An amalgam tattoo causing local and systemic disease, Oral Surg Oral Med Oral
Pathol63:l30-U0. Weeke B, Weeke E, Mygind N (1986). Medicinsk-allergiske sygdomme. In: Medicinsk kompendium, Vol. 1, 13 ed. Copenhagen: FADL'sForlag, 68-149. White RR, Brandt RL (1976). Development of mercury hypersensitivity among dental students. / Am Dent Assoc 92:1204-1207. White RR, Smith BGN (1984). Dental amalgam dermatitis. Br DentJ156:259-270.
Department of Dental Materials Royal Dental College Norre alle 20 DK-2200 Copenhagen N Denmark Adv Dent Res 6:17-21, September, 1992
Abstract—The frequency of side-effects among dental patients is very low and is seen mostly as mild allergic reactions. Among the dental staff, contact allergic eczema is occasionally seen, induced by certain metals and various organic materials.
I
n the last few years, there has been an increasing demand for safety evaluation and control of dental materials. This increase occurs despite the fact that reactions on patients are considered to be harmless and infrequent—1:700 according to Kallus and Mjor (1991) and among prosthetic patients 1:300, according to Hensten-Pettersen and Jacobsen (1991). Verified diagnosis of side-effects is not often established, because the mild nature of the reactions does not justify more extensive testing involving several medical specialties. The information in the literature of side-effects among patients is therefore mostly inconclusive, especially since much information is based solely on questionnaire surveys among patients or dentists. Questionnaires do not give objective information on side-effects caused by dental treatments because of differences between the respondents in observing, evaluating, and clearly describing the symptoms, and because such symptoms could have causes other than the dental treatment. Side-effects from a dental restorative material are unintentional injuries to humans caused by the material and can be either toxic/irritative or allergic in nature. Toxicity is the ability of a molecule or compound to produce injury in or on the body, after absorption has taken place. A toxic reaction may involve damage in or on an organ or tissue (such as skin, kidneys, or lungs) and may cause inhibition of enzymes in cells or blood, or have an effect on DNA. Chemical changes or association of molecules to DNA may give rise to cancer, miscarriage, or malformations. Sometimes, chemical molecules or substances induce allergic reactions which are damaging to the body. The various types of allergies are normally divided into types 1 to 4. In a lifetime, about 10% of the population will suffer from an allergy. On testing the population with batteries of allergens, one will find that about 1/3 will show a reaction, but the majority of these are without symptoms or inconvenience (Weeke et al, 1986). Therefore, when patients having received dental treatment with allergenic dental materials are tested, some of them will show a reaction. Only a few of them will have clinical symptoms, which can be explained by a reaction from a dental material.
TYPES AND INCIDENCE OF OCCUPATIONAL SIDE-EFFECTS
This manuscript is published as part of the proceedings of the N1H Technology Assessment Conference on Effects and Sideeffects of Dental Restorative Materials, August 26-28, 1991, National Institutes of Health, Bethesda, Maryland, and did not undergo the customary journal peer-review process.
The low incidence of side-effects among patients (Kallus and Mjor, 1991; Hensten-Pettersen and Jacobsen, 1991) is probably due to the fact that restorative materials are nearly insoluble. Only soluble materials will provoke reactions to the body. The dentist and his or her staff handle the materials before they are converted to a nearly insoluble state and are in contact with the materials more often than is the patient. This might explain the higher incidence of side-effects seen among dentists (Kallus and Mjor, 1991), compared with his or her patients. Generally, if a dental restorative material may cause serious side-effects on patients, one would expect that the dental staff should suffer to a
17
MUNKSGAARD
18
Hg22+,Hg2+ Ag + corrosion S"
AMALGAM
Sn
>Sn
Cu +
,Cu2+
conversion^
Hg Fig. 1—Elements leaking from amalgam and which may be present in the oral environment. higher degree than would the patients. Surveys of the incidence and type of occupational diseases among dental personnel may therefore be appropriate, so that it can be decided whether a material is liable to cause side-effects in patients. In Denmark, a survey has been performed on diagnosed occupational diseases among 121 dentists and dental assistants in the years 1984-86 (Engen, 1990). Dermatoses were the most frequently diagnosed side-effect. Thirty of these were classified as allergic, 9 as toxic, and 9 unspecified. Disturbances in muscles and joints were seen in 37 individuals, 9 had infections, 8 reactions to solvents, 7 pulmonary problems, 5 unspecified dermal problems, 3 headache, 3 pregnancy disturbances, 2 hearing reduction, 2 brain damage, and 2 were classified as poisoning. Others were inconveniences including dizziness and exhaustion. About 2/3 of the staff at a large public dental clinic showed positive reaction when patch-tested with allergens from dental materials. Only about 1/3 of these had symptoms which could be related to work with dental materials, and were seen as slight to severe dermatoses, urticaria, and contact allergic eczema (Djerassi and Berowa, 1966). Questionnaires to specialists in orthodontics, periodontics, prosthetics, and pedodontics revealed that 50% claimed some kind of an occupational disorder (Hensten-Pettersen and Jacobsen, 1991; Jacobsen and HenstenPettersen, 1989a,b, 1991). Between 40 and 50% of these had irritative and allergic dermatoses due to hand-washing, use of latex gloves, methacrylates, or disinfectants. Other causes were exposure to eugenol, epoxy products, fungi, face masks, and gold. In another investigation (Franz, 1982), it was found that occupational allergic problems were associated with working with anesthetics, disinfectants, methacrylates, Co/Cr/Ni-alloys, polyether materials, and amalgam. Amalgam
Amalgams are alloy mixtures containing mercury, silver, tin, copper, and sometimes zinc. The content of mercury in amalgam is a concern, because small amounts of mercury are liberated from the fillings. It happens when the gamma-1 phase is converted slowly to a beta-phase containing less mercury. It has been shown that there is a 70% conversion in 18 years (Boyer andEdie, 1990). The surface conversion will cause evaporation of mercury, which will be absorbed after inhalation. Corrosion
ADV DENT RES SEPTEMBER 1992
TABLE METALS IN DENTAL CASTING ALLOYS AND IN AMALGAMS WHICH HAVE OR MAY HAVE SIDEEFFECTS ON PATIENTS OR MAY POSE AN OCCUPATIONAL RISK Potential Risk Diagnosed Side-effects A T T A Metal c c X X Beryllium X X Cadmium X X X Chromium X X X Nickel X X Cobalt X X Gold ? X X Palladium (x) X X X Mercury X X Tin X Silver X X X Copper T=toxin. A = allergen. C = carcinogen. of amalgam fillings liberates small amounts of metallic ions (Fig. 1). Some of the ions may cause allergic reactions. The risk of inhaling mercury evaporating from fillings can be assessed by comparison of the concentration with the threshold limit value. In most countries, a threshold limit value (TLV) of 50 ]ng/cubic meter is accepted, but some advocate 30 pg/cubic meter. Nevertheless, the mean burden from amalgam fillings is generally lower. The average secretion in urine and the blood mercury content are twice as high among dentists as in patients, but in both cases are far below the safety limit. Until now, no one has found a patient with a mercury excretion above the safety limits, and where the mercury derives from dental treatment. The literature, including judgment of the toxicological risk, has recently been reviewed (Horsted-Bindslev et al., 1991). While the risk for the patient seems limited, the dentist can be poisoned during work with mercury. Smith (1978) has reported three cases of severe mercury poisoning among dentists not taking precautions adequate to reduce mercury contamination in their clinics. In all cases, the mercury content in the air was much higher than the TLV. Few reports describing allergic reactions caused by amalgam fillings can be found in the literature—about 50 since 1906 (Veron etal, 1984; White and Smith, 1984; Munksgaard, 1989; Horsted-Bindslev et al., 1991). The symptoms are normally classified as delayed hypersensitivity reactions (Type 4). The following symptoms have been identified: eczema, urticaria, wheals on face and limbs, rashes, and sometimes Pink or Kawasaki disease. Harmless local soft-tissue reactions sometimes occur in the gingiva adjacent to amalgam fillings (Bolewska etai, 1990). In a few cases, systemic reactions have been noted (Thompson and Russell, 1970; Weaver^ al., 1987). The few reports describing allergy induced by amalgam are in contrast to the fact that 2% of the population [perhaps 10% among dentists (Gotz and Fortmann, 1959; White and Brandt, 1976)] showed a positive reaction when patch-tested with
VOL.
6
TOXICOLOGY vs. ALLERGY
mercury. Some claim that the reaction is not allergic, but toxic. Generally, it is found that patients showing positive reaction to mercury in a patch test are without clinical symptoms, because the amount of mercury liberated from the fillings is not enough to maintain an immunological reaction. Cases of allergic outbreak caused by silver and copper from amalgam are very few (Veron etaU 1984).
19
Allergens
(DI)METHACRYLATE RESINS
MMA vapors
Casting Alloys There are about 36 elements among the casting alloys and metals used in dentistry (Munksgaard, 1989). At least ten of them have been classified as allergens. Three of them are potentially poisonous (Be, Cd, Hg), and four of them possess a carcinogenic potential (Be, Cd, Cr, Ni) (Mitchell, 1984; Graensevaerdier, 1988; see Table). The poisonous and carcinogenic metals may be a threat for dental laboratory technicians, since they can be exposed to these metals in the form of dust and vapors during casting and grinding. There seems to be little risk to the patient (Mitchell, 1984), despite one report claiming a possible connection between a corroding palladium-gold crown and the development of a carcinoma on the tongue (Kinnebrew et al., 1984). The four metals classified as potential carcinogens may induce development of carcinomas, when dust is inhaled, and therefore possess only an occupational risk. Beryllium from 0.5 to 2% is used to increase the castability of certain alloys. On the surface of the casting, this content is increased, and the corrosion product may possess a potential risk for the patient. This risk should be assessed further. Cadmium has been used in soldering alloys but is no longer in use in most countries. Chromium and nickel are not judged to be a risk for the dental profession and patients (Mitchell, 1984). Metals are known to cause allergy, and nickel, cobalt, and chromium are the predominant allergens among the metals. About 9% of women and 1.5% of men will show positive reactions when patch-tested with nickel, while the equivalent numbers for chromium are 1.5 and 2. About 1 % of the population shows a positive reaction to cobalt (Hildebrand, 1985). It is questionable whether dental patients have a pronounced risk of developing sensitivity caused by metallic restoratives. In an investigation done by Stenman and Bergman (1989), 151 patients with general types of complaints were patch-tested. The incidence of positive reactions to nickel was within the normal range, 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 sensitivity induced by organic materials. According to this investigation, it seems that allergies to metals constituted the main side-effect seen among dental patients. In addition, Namikoski and coworkers (1990) point out the need for careful immunological consideration in selecting alloys for use as restoratives, because of the increased sensitivity to a number of metals reported in a group of dental patients. This is in contrast to the risk for patients exposed to nickel-containing alloys, as shown by the work of Staerkjaer and Menne (1990). Based on results from an investigation of 1085 girls wearing orthodontic appliances, it was established that the girls did not develop intra-oral nickel allergic reactions, and, as in other studies, the results indicated
Formaldehyde Fig. 2—Components from (di)methacrylate-containing substances which may cause side-effects. that appliances may induce tolerance leading to a lower incidence of nickel sensitivity. It seems probable that allergic reactions to metallic restorations are seen mainly when a hypersensitivity is acquired from sources other than dental treatment (Holland-Moritz et al., 1980; Hildebrand, 1985). The risk should be further assessed in any event.
Methacrylate-based Materials Di- and mono-methacrylates are found in a number of materials used in restorative dentistry, including resin composites, bonding systems, and fissure sealants, as well as materials used for orthodontic appliances, crowns and bridges, denture bases, relining and repair, as provisionals or temporary restorations, fissure sealants, cements, etc. The substances are low in toxicity, but some of the materials possess moderate allergenicity (Fig. 2). Methylmethacrylate (MMA) with a boiling point of 100°C has been reported to cause brain damage in a number of laboratory technicians who were exposed to the substance daily for many years (Christiansen etal, 1986). All the double bonds in the dimethacrylates are not converted during polymerization, and on the surface they can be oxidized to yield formaldehyde, which is both an allergen and a carcinogen. Formaldehyde also appears when polymeric materials are trimmed as well as above open containers with MMA(BruneandBeltesbrekke, 1981). Nearly all the types of methacrylates can induce type 4 allergy, and, in addition, allergies have been induced by benzoylperoxide, DEPT, hydroquinone, and dibutyl phthalate (Bradford, 1948; Hensten-Pettersen, 1984; Kanervaetal., 1986; Munksgaard, 1989; Munksgaard et al., 1990). The number of patients suffering from allergic reaction to dental composites is very low. This is because methacrylates are insoluble when polymerized, and the amount of material leaking out is negligible after a few weeks. At least one report exists describing an allergic reaction induced by formaldehyde produced by surface oxidation of unreacted double bonds in a resin composite (Hensten-Pettersen, 1984). Some of the materials give local toxic reactions when applied to the gingiva, such as dentin bonding agents containing glutaraldehyde or organic acids, which may cause temporary damage. Reports exist describing pulpal damage caused by resin composites in deep cavities, but the reaction can be prevented or minimized if proper precautions are taken (Heys et al., 1982;
20
MUNKSGAARD
ADV DENT RES SEPTEMBER 1992
PREDOMINANT OCCUPATIONAL RISKS
PREDOMINANT RISKS, PATIENTS
• ALLERGENS Latex-gloves (Di)methacrylates Disinfectants, anaesthetics Cobalt, chromium, nickel Polyether, colophony and eugenol materials
• ALLERGENS Eugenol Colophony Polyether materials Gold, palladium Methacrylate
• TOXIC SUBSTANCES Methyl methacrylate (formaldehyde) Mercury vapor
• LOCAL TOXIC REACTIONS Various restorative materials
• CARCINOGENS Formaldehyde Cadmium, beryllium
• SYSTEMIC TOXIC REACTIONS ? • CARCINOGENS
Fig. 3—Substances which may cause side-effects among the dental staff.
Fig. 4—Substances which may occasionally cause sideeffects among patients.
Coxetal., 1987; QvistandThylstrup, 1990). An increasing number of the dental staff develop a contact allergic eczema induced by (di)methacrylates (Djerassi and Berowa, 1966; Jacobsen and Hensten-Pettersen, 1989a,b, 1991). This is generally characterized by its location on the first three fingers of the left hand (Munksgaard et ai, 1990). The symptoms seen are redness, desquamation, fissuring, and excoriations, and they are sometimes so severe that work has to be abandoned. The fingers become contaminated during handling of resin containers, and during holding of the contouring strip, and while fillings with resin composites are being performed. The most frequently used types of protective gloves are made of latex, and these do not afford protection against resin monomers. Low-molecular-weight substances— such as MMA, HEMA, and TEGDMA—penetrate the gloves in a few minutes, while higher-molecular-weight dimethacrylates (such as BISGMA and UEDMA) take longer (Munksgaard, 1992).
sulfonates as catalysts. Reports have been published claiming that about 0.5% of patients have symptoms such as a burning sensation in the mouth, swelling of lips and mucosa, and blisters (Nally and Storrs, 1973; Van Groeningen and Nater, 1975; Christensen, 1976; Kulenkamp etal., 1976; Dahl, 1978) caused by the chlorobenzene sulfonates.
Other Materials A number of materials other than amalgam, casting alloys, and methacrylate-based materials are used in restorative dentistry. Examples are glass-ionomer cements, temporary crown and bridge materials, endodontic sealers, impression materials, various cements, porcelain and ceramics, disinfectants, anesthetics, and various drugs. Some of these products may cause a slight, local toxic reaction to the gingiva or pulp, and some contain allergens such as (Munksgaard, 1989): MMA, benzoyl peroxide, benzoates, amine accelerators, plasticizers, hydroquinone, polyether materials, eugenol, cresol, colophony, N-ethyl-p-toluenesulfonamide, thymol, epoxy, chloramine, phenol, formaldehyde, iodoform, and some dyes and flavors. Some of the components are classified as potential carcinogens: various phenols, formaldehyde, chloroform, and cadmium oxide. These allergens have caused reactions to patients and to dental staff. Most of the reactions are of the 'delayed hypersensitivity' type (Engen, 1990), but other types of allergic reactions involving systemic reactions have also been reported. The numbers of reported cases describing patients suffering from such reactions are few, except for those involving reactions caused by polyether materials. These are used as temporary dressings and impression materials and contain chlorobenzene
CONCLUSION It can be concluded that some occupational risks exist (Fig. 3) in the dental profession, although the frequency is low. Dermatoses are frequently seen among the dental staff, mostly as irritative reactions caused by hand-washing and use of disinfectants. In some cases, a type 4 allergy is seen. The most frequent allergens are: latex gloves, (di)methacrylates, cobalt, chromium, nickel, polyether materials, colophony, and eugenol. Sometimes the symptoms are so severe that occupation has to be abandoned. It seems therefore appropriate for some of the materials used in dentistry to be exchanged with materials having a lower degree of allergenicity. Cases of brain damage caused by MMA and intoxication by mercury vapor necessitate that the dental staff should constantly be warned and advised regarding the proper handling of these materials. Dental staff should also be warned about the following potential carcinogens: formaldehyde, phenols, cadmium, and beryllium. Dental materials containing cadmium are not used in most countries, but the risk regarding the use of beryllium requires further assessment. Since the frequency of side-effects among dental patients is very low, and since the symptoms are mild, no special precautions are required. The symptoms are allergic in nature, and the predominant allergens are listed in Fig. 4. Local toxic reactions to gingiva or pulp, which have been reported, can be prevented or minimized by the use of appropriate techniques. In a few instances, temporary systemic reactions are seen after various dental treatments, but the exact nature of such reactions is poorly understood. Positive patch-test reactions with gold, palladium, and mercury seem to occur more frequently among patients claiming to suffer from side-effects from dental treatments than among other patients. Further research within this field is therefore justified.
VOL. 6
TOXICOLOGY VS. ALLERGY
REFERENCES Bolewska J, Holmstrup P, Moller-Madsen B, Kenrad B, Danscher G (1990). Amalgam associated mercury accumulations in normal oral mucosa, oral mucosal lesions of lichen planus and contact lesions associated with amalgam. / Oral Pathol Med 19:39-42. Boyer DB, Edie JW (1990). Composition of clinically aged amalgam restorations. Dent Mater 6:146-150. Bradford EW (1948). Case of allergy to methacrylate. BrDentJ 84:195. Brune D, Beltesbrekke H (1981). Levels of methylmethacrylate, formaldehyde and asbestos in dental workroom air. Scand J Dent Res 89:113-116. ChristensenBL (1976). Overfolsomhedoverfor aftryksmaterialer. Tandlcegebladet 80:198-199. Christiansen ML, Adelhart M, Jorgensen NK, Gyntelberg F (1986). Methylmethacrylat—en &rsag til toksisk hjerneskade? Tandlcegebladet 90:759-764. Cox CF, Keall CL, Keall HJ, Ostro E, Bergenholtz G (1987). Biocompatibility of surface-sealed dental materials against exposed pulps. JProsthet Dent 57 :l-%. DahlBL(1978). Tissue hypersensitivity to dental materials. JOral RehabilS'A 17-120. Djerassi E, Bero wa N (1966). Kontakt allergien in der stomatologie als berufsproblem. Berufsdermatosen 14:224-233. Engen T (1990). Personal communication. Franz G (1982). The frequency of allergy to dental materials. / DentAssoc SA/r 37:805-810. Gotz H, Fortmann I (1959). Bewirken amalgamfullungen der zahne eine quecksilbersensibilisierung der haut? Z Haut Geschlechtskrankh 26:34-36. Graensevaerdier for stoffer og materialer (1988). At-anvisning nr. 3.1.0.2. Copenhagen: Arbejdstilsynetstrykkeri. Hensten-Pettersen A (1984). Allergiske reaktioner p& dentale materialer. Den norske tannlegeforenings tidende 94:573-578. Hensten-Pettersen A, Jacobsen N (1991). Perceived side effects of biomaterials in prosthetic dentistry. J Prosthet Dent 65:138144. Heys RJ, Heys DR, Cox CF, Avery JK (1982). Experimental observations on the biocompatibility of composite resins. In: Biocompatibility of dental Materials, Vol III. Boca Raton, FL. CRC Press Inc., p 131-150. Hildebrand HF (1985). Zahnersatz aus nichtedelmetalllegierungen und allergien. Dusseldorf: Fachvereinung Edelmetallee.V. Holland-Moritz VR, Rimpler M, Rudolph P-0 (1980). Allergie gentiber gold in der mundhohle. Dtsch Zahndrtztl Z35:963-961. Horsted-Bindslev P, Magos L, Holmstrup P, Arenholt-Bindslev D (1991). Dental amalgam—a health hazard? Copenhagen: Munksgaard. Jacobsen N, Hensten-Pettersen A (1989a). Occupational health problems and adverse patient reactions in orthodontics. Eur J Orthodont 11:254-264. Jacobsen N, Hensten-Pettersen A (1989b). Occupational health complaints and adverse patient reactions as perceived by personnel in periodontics. J ClinPeriodontol 16:428-433. Jacobsen N, Hensten-Pettersen A (1991). Occupational health
21
complaints and adverse patient reactions as perceived by personnel in public dentistry. Community Dent Oral Epidemiol 19:155-159. Kallus T, Mjor IA (1991). Incidence of adverse effects of dental materials. ScandJ Dent Res 99:236-240. Kanerva L, Jolanki R, Estlander T (1986). Occupational dermatitis duetoanepoxy acrylate. Contact Dermatitis 14:80-84. Kinnebrew M, GettlemanL, Carr RF, Beazley R (1984). Squamous cell carcinoma of the tongue in a young woman. Report of a case with etiologic considerations. Oral Surg Oral Med Oral Pathol 58:696-698. Kulenkamp D, Hausen B, Schulz K-H (1976). Beruflische kontaktallergie durch neuartige abdruckmaterialen in der zahnartzlischen praxis (scutan und impregum). Zahndrtztl Mitteil 66:968. Mitchell EW (1984). The biocompatibility of metals in dentistry. CanDentJ 12:17-19. Munksgaard EC (1989). Bivirkninger fra Dentalmaterialer. Copenhagen: DanskTandlaegeforening. Munksgaard EC (1992). Permeability of protective gloves to (di)methacrylates in resinous dental materials. Scand J Dent Res (inpress). Munksgaard EC, Knudsen B, Thomsen K (1990). Kontaktallergisk h&ndeksem blandt tandplejepersonale af (di)methacrylater. Tandlcegebladet 94:270-274. Nally FF, Storrs J (1973). Hypersensitivity to a dental impression material. BrDentJ143:244-246. Namikoski T, Yoshimatsu T, Suga K, Fujii H (1990). The prevalence of sensitivity to constituents of dental alloy. / Oral Rehabil 17:377-381. Qvist V, Thylstrup A (1990). Pulpale reaktioner i tilslutning til plastfyldninger. In: Hjorting-Hansen E, editor. Odontologi '90. Copenhagen: Munksgaard, 163-175. SmithDL(1978). Mental effects of mercury poisoning. SouthMed Jl 1:904-905. Staerkjaer L, Menne T (1990). Nickel allergy and orthodontic treatment. Eur J Orthodont 12:284-289. Stenman E, Bergman M (1989). Hypersensitivity reactions to dental materials in areferred group of patients. ScandJ Dent Res 97:76-83. Thompson J, Russell JA (1970). Dermatitis due to mercury following amalgam dental restorations. BrJDermatol 82:292297. vanGroeningen G, Nater JP (1975). Reactions to dental impression materials. Contact Dermatitis 1:377. Veron C, HildebrandtHF, MartinP (1984). Amalgames dentaire et allergie. JBiolBuccale 14:83-100. Weaver T, Auclair PL, Taybos GM (1987). An amalgam tattoo causing local and systemic disease, Oral Surg Oral Med Oral
Pathol63:l30-U0. Weeke B, Weeke E, Mygind N (1986). Medicinsk-allergiske sygdomme. In: Medicinsk kompendium, Vol. 1, 13 ed. Copenhagen: FADL'sForlag, 68-149. White RR, Brandt RL (1976). Development of mercury hypersensitivity among dental students. / Am Dent Assoc 92:1204-1207. White RR, Smith BGN (1984). Dental amalgam dermatitis. Br DentJ156:259-270.
