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I
E.C. MUNKSGAARD n the last few years, there has been an increasing demand for
Department of Dental Materials safety evaluation and control of dental materials. This
Royal Dental College increase occurs despite the fact that reactions on patients are
Norre alle 20 considered to be harmless and infrequent—1:700 according
DK-2200 Copenhagen N to Kallus and Mjor (1991) and among prosthetic patients 1:300,
Denmark according to Hensten-Pettersen and Jacobsen (1991). Verified
diagnosis of side-effects is not often established, because the
Adv Dent Res 6:17-21, September, 1992 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
Abstract—The frequency of side-effects among dental patients mostly inconclusive, especially since much information is based
is very low and is seen mostly as mild allergic reactions. solely on questionnaire surveys among patients or dentists.
Among the dental staff, contact allergic eczema is occasionally Questionnaires do not give objective information on side-effects
seen, induced by certain metals and various organic materials. 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
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
This manuscript is published as part of the proceedings of the materials more often than is the patient. This might explain the
N1H Technology Assessment Conference on Effects and Side- higher incidence of side-effects seen among dentists (Kallus and
effects of Dental Restorative Materials, August 26-28, 1991, Mjor, 1991), compared with his or her patients. Generally, if a
National Institutes of Health, Bethesda, Maryland, and did not dental restorative material may cause serious side-effects on
undergo the customary journal peer-review process. patients, one would expect that the dental staff should suffer to a
17
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18 MUNKSGAARD ADV DENT RES SEPTEMBER 1992
TABLE
Hg22+,Hg2+
METALS IN DENTAL CASTING ALLOYS AND IN
AMALGAMS WHICH HAVE OR MAY HAVE SIDE-
Ag + EFFECTS ON PATIENTS OR MAY POSE AN
Sn OCCUPATIONAL RISK
corrosion S" >Sn Potential Risk
Diagnosed Side-effects
Metal T A c T A c
AMALGAM Cu + ,Cu2+ Beryllium X X
Cadmium X X
Chromium X X X
conversion^ Nickel X X X
Hg Cobalt X X
Fig. 1—Elements leaking from amalgam and which may be Gold X X
present in the oral environment. ?
Palladium X X (x)
higher degree than would the patients. Surveys of the incidence Mercury X X X
and type of occupational diseases among dental personnel may Tin X X
therefore be appropriate, so that it can be decided whether a Silver X X
material is liable to cause side-effects in patients.
Copper X X
In Denmark, a survey has been performed on diagnosed
occupational diseases among 121 dentists and dental assistants T=toxin. A = allergen. C = carcinogen.
in the years 1984-86 (Engen, 1990). Dermatoses were the most
frequently diagnosed side-effect. Thirty of these were classified of amalgam fillings liberates small amounts of metallic ions
as allergic, 9 as toxic, and 9 unspecified. Disturbances in (Fig. 1). Some of the ions may cause allergic reactions.
muscles and joints were seen in 37 individuals, 9 had infections, The risk of inhaling mercury evaporating from fillings can be
8 reactions to solvents, 7 pulmonary problems, 5 unspecified assessed by comparison of the concentration with the threshold
dermal problems, 3 headache, 3 pregnancy disturbances, 2 limit value. In most countries, a threshold limit value (TLV) of
hearing reduction, 2 brain damage, and 2 were classified as 50 ]ng/cubic meter is accepted, but some advocate 30 pg/cubic
poisoning. Others were inconveniences including dizziness and meter. Nevertheless, the mean burden from amalgam fillings is
exhaustion. generally lower. The average secretion in urine and the blood
About 2/3 of the staff at a large public dental clinic showed mercury content are twice as high among dentists as in patients,
positive reaction when patch-tested with allergens from dental but in both cases are far below the safety limit. Until now, no one
materials. Only about 1/3 of these had symptoms which could be has found a patient with a mercury excretion above the safety
related to work with dental materials, and were seen as slight to limits, and where the mercury derives from dental treatment.
severe dermatoses, urticaria, and contact allergic eczema The literature, including judgment of the toxicological risk, has
(Djerassi and Berowa, 1966). Questionnaires to specialists in recently been reviewed (Horsted-Bindslev et al., 1991).
orthodontics, periodontics, prosthetics, and pedodontics While the risk for the patient seems limited, the dentist can be
revealed that 50% claimed some kind of an occupational disorder poisoned during work with mercury. Smith (1978) has reported
(Hensten-Pettersen and Jacobsen, 1991; Jacobsen and Hensten- three cases of severe mercury poisoning among dentists not
Pettersen, 1989a,b, 1991). Between 40 and 50% of these had taking precautions adequate to reduce mercury contamination in
irritative and allergic dermatoses due to hand-washing, use of their clinics. In all cases, the mercury content in the air was much
latex gloves, methacrylates, or disinfectants. Other causes were higher than the TLV.
exposure to eugenol, epoxy products, fungi, face masks, and Few reports describing allergic reactions caused by amalgam
gold. In another investigation (Franz, 1982), it was found that fillings can be found in the literature—about 50 since 1906
occupational allergic problems were associated with working (Veron etal, 1984; White and Smith, 1984; Munksgaard, 1989;
with anesthetics, disinfectants, methacrylates, Co/Cr/Ni-alloys, Horsted-Bindslev et al., 1991). The symptoms are normally
polyether materials, and amalgam. classified as delayed hypersensitivity reactions (Type 4). The
following symptoms have been identified: eczema, urticaria,
Amalgam
wheals on face and limbs, rashes, and sometimes Pink or
Amalgams are alloy mixtures containing mercury, silver, tin, Kawasaki disease. Harmless local soft-tissue reactions
copper, and sometimes zinc. The content of mercury in amalgam sometimes occur in the gingiva adjacent to amalgam fillings
is a concern, because small amounts of mercury are liberated (Bolewska etai, 1990). In a few cases, systemic reactions have
from the fillings. It happens when the gamma-1 phase is been noted (Thompson and Russell, 1970; Weaver^ al., 1987).
converted slowly to a beta-phase containing less mercury. It has The few reports describing allergy induced by amalgam are
been shown that there is a 70% conversion in 18 years (Boyer in contrast to the fact that 2% of the population [perhaps 10%
andEdie, 1990). The surface conversion will cause evaporation among dentists (Gotz and Fortmann, 1959; White and Brandt,
of mercury, which will be absorbed after inhalation. Corrosion 1976)] showed a positive reaction when patch-tested with
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VOL. 6 TOXICOLOGY vs. ALLERGY 19
mercury. Some claim that the reaction is not allergic, but toxic. Allergens
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 (DI)METHACRYLATE
MMA vapors
etaU 1984). RESINS
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 Formaldehyde
poisonous (Be, Cd, Hg), and four of them possess a carcinogenic Fig. 2—Components from (di)methacrylate-containing
potential (Be, Cd, Cr, Ni) (Mitchell, 1984; Graensevaerdier, substances which may cause side-effects.
1988; see Table). The poisonous and carcinogenic metals may that appliances may induce tolerance leading to a lower
be a threat for dental laboratory technicians, since they can be incidence of nickel sensitivity.
exposed to these metals in the form of dust and vapors during It seems probable that allergic reactions to metallic
casting and grinding. There seems to be little risk to the patient restorations are seen mainly when a hypersensitivity is acquired
(Mitchell, 1984), despite one report claiming a possible from sources other than dental treatment (Holland-Moritz et al.,
connection between a corroding palladium-gold crown and the 1980; Hildebrand, 1985). The risk should be further assessed in
development of a carcinoma on the tongue (Kinnebrew et al., any event.
1984). The four metals classified as potential carcinogens may
induce development of carcinomas, when dust is inhaled, and Methacrylate-based Materials
therefore possess only an occupational risk. Di- and mono-methacrylates are found in a number of materials
Beryllium from 0.5 to 2% is used to increase the castability of used in restorative dentistry, including resin composites,
certain alloys. On the surface of the casting, this content is bonding systems, and fissure sealants, as well as materials used
increased, and the corrosion product may possess a potential risk for orthodontic appliances, crowns and bridges, denture bases,
for the patient. This risk should be assessed further. Cadmium relining and repair, as provisionals or temporary restorations,
has been used in soldering alloys but is no longer in use in most fissure sealants, cements, etc. The substances are low in toxicity,
countries. but some of the materials possess moderate allergenicity (Fig. 2).
Chromium and nickel are not judged to be a risk for the dental Methylmethacrylate (MMA) with a boiling point of 100°C
profession and patients (Mitchell, 1984). has been reported to cause brain damage in a number of
Metals are known to cause allergy, and nickel, cobalt, and laboratory technicians who were exposed to the substance daily
chromium are the predominant allergens among the metals. for many years (Christiansen etal, 1986).
About 9% of women and 1.5% of men will show positive All the double bonds in the dimethacrylates are not converted
reactions when patch-tested with nickel, while the equivalent during polymerization, and on the surface they can be oxidized
numbers for chromium are 1.5 and 2. About 1 % of the population to yield formaldehyde, which is both an allergen and a
shows a positive reaction to cobalt (Hildebrand, 1985). It is carcinogen. Formaldehyde also appears when polymeric
questionable whether dental patients have a pronounced risk of materials are trimmed as well as above open containers with
developing sensitivity caused by metallic restoratives. In an MMA(BruneandBeltesbrekke, 1981).
investigation done by Stenman and Bergman (1989), 151 Nearly all the types of methacrylates can induce type 4
patients with general types of complaints were patch-tested. The allergy, and, in addition, allergies have been induced by
incidence of positive reactions to nickel was within the normal benzoylperoxide, DEPT, hydroquinone, and dibutyl phthalate
range, but the incidence of positive reactions with gold, cobalt, (Bradford, 1948; Hensten-Pettersen, 1984; Kanervaetal., 1986;
and palladium as well as with mercury was higher than seen in Munksgaard, 1989; Munksgaard et al., 1990). The number of
the normal population. There were few cases of sensitivity patients suffering from allergic reaction to dental composites is
induced by organic materials. According to this investigation, it very low. This is because methacrylates are insoluble when
seems that allergies to metals constituted the main side-effect polymerized, and the amount of material leaking out is negligible
seen among dental patients. In addition, Namikoski and co- after a few weeks. At least one report exists describing an allergic
workers (1990) point out the need for careful immunological reaction induced by formaldehyde produced by surface
consideration in selecting alloys for use as restoratives, because oxidation of unreacted double bonds in a resin composite
of the increased sensitivity to a number of metals reported in a (Hensten-Pettersen, 1984).
group of dental patients. This is in contrast to the risk for patients Some of the materials give local toxic reactions when applied
exposed to nickel-containing alloys, as shown by the work of to the gingiva, such as dentin bonding agents containing
Staerkjaer and Menne (1990). Based on results from an glutaraldehyde or organic acids, which may cause temporary
investigation of 1085 girls wearing orthodontic appliances, it damage. Reports exist describing pulpal damage caused by resin
was established that the girls did not develop intra-oral nickel composites in deep cavities, but the reaction can be prevented or
allergic reactions, and, as in other studies, the results indicated minimized if proper precautions are taken (Heys et al., 1982;
Fig. 3—Substances which may cause side-effects among the Fig. 4—Substances which may occasionally cause side-
dental staff. effects among patients.
Coxetal., 1987; QvistandThylstrup, 1990). sulfonates as catalysts. Reports have been published claiming
An increasing number of the dental staff develop a contact that about 0.5% of patients have symptoms such as a burning
allergic eczema induced by (di)methacrylates (Djerassi and sensation in the mouth, swelling of lips and mucosa, and
Berowa, 1966; Jacobsen and Hensten-Pettersen, 1989a,b, 1991). blisters (Nally and Storrs, 1973; Van Groeningen and Nater,
This is generally characterized by its location on the first three 1975; Christensen, 1976; Kulenkamp etal., 1976; Dahl, 1978)
fingers of the left hand (Munksgaard et ai, 1990). The caused by the chlorobenzene sulfonates.
symptoms seen are redness, desquamation, fissuring, and
excoriations, and they are sometimes so severe that work has CONCLUSION
to be abandoned. The fingers become contaminated during It can be concluded that some occupational risks exist (Fig. 3) in
handling of resin containers, and during holding of the the dental profession, although the frequency is low.
contouring strip, and while fillings with resin composites are Dermatoses are frequently seen among the dental staff,
being performed. The most frequently used types of protective mostly as irritative reactions caused by hand-washing and use of
gloves are made of latex, and these do not afford protection disinfectants. In some cases, a type 4 allergy is seen. The most
against resin monomers. Low-molecular-weight substances— frequent allergens are: latex gloves, (di)methacrylates, cobalt,
such as MMA, HEMA, and TEGDMA—penetrate the gloves chromium, nickel, polyether materials, colophony, and eugenol.
in a few minutes, while higher-molecular-weight Sometimes the symptoms are so severe that occupation has to be
dimethacrylates (such as BISGMA and UEDMA) take longer abandoned. It seems therefore appropriate for some of the
(Munksgaard, 1992). materials used in dentistry to be exchanged with materials
having a lower degree of allergenicity.
Other Materials Cases of brain damage caused by MMA and intoxication by
A number of materials other than amalgam, casting alloys, and mercury vapor necessitate that the dental staff should constantly
methacrylate-based materials are used in restorative dentistry. be warned and advised regarding the proper handling of these
Examples are glass-ionomer cements, temporary crown and materials.
bridge materials, endodontic sealers, impression materials, Dental staff should also be warned about the following
various cements, porcelain and ceramics, disinfectants, potential carcinogens: formaldehyde, phenols, cadmium, and
anesthetics, and various drugs. Some of these products may beryllium. Dental materials containing cadmium are not used in
cause a slight, local toxic reaction to the gingiva or pulp, and most countries, but the risk regarding the use of beryllium
some contain allergens such as (Munksgaard, 1989): MMA, requires further assessment.
benzoyl peroxide, benzoates, amine accelerators, plasticizers, Since the frequency of side-effects among dental patients is
hydroquinone, polyether materials, eugenol, cresol, colophony, very low, and since the symptoms are mild, no special
N-ethyl-p-toluenesulfonamide, thymol, epoxy, chloramine, precautions are required. The symptoms are allergic in nature,
phenol, formaldehyde, iodoform, and some dyes and flavors. and the predominant allergens are listed in Fig. 4. Local toxic
Some of the components are classified as potential carcinogens: reactions to gingiva or pulp, which have been reported, can be
various phenols, formaldehyde, chloroform, and cadmium prevented or minimized by the use of appropriate techniques. In
oxide. These allergens have caused reactions to patients and to a few instances, temporary systemic reactions are seen after
dental staff. Most of the reactions are of the 'delayed various dental treatments, but the exact nature of such reactions
hypersensitivity' type (Engen, 1990), but other types of allergic is poorly understood.
reactions involving systemic reactions have also been reported. Positive patch-test reactions with gold, palladium, and
The numbers of reported cases describing patients suffering mercury seem to occur more frequently among patients claiming
from such reactions are few, except for those involving reactions to suffer from side-effects from dental treatments than among
caused by polyether materials. These are used as temporary other patients. Further research within this field is therefore
dressings and impression materials and contain chlorobenzene justified.