dental

materials
Dental Materials 18 (2002) 396±406
www.elsevier.com/locate/dental

Biological interactions of dental cast alloys with oral tissues

Gottfried Schmalz*, Pauline Garhammer
Department of Operative Dentistry and Periodontology, University Clinics of Regensburg, 93042 Regensberg, Germany
Received 26 September 2000; accepted 26 February 2001

Abstract
Objective: All dental cast alloys release metal ions into the oral environment which have the potential to interact with the oral tissues.
Amount and type of metal elements released are varying and not directly related to the composition of the alloy. The aim of the present
literature survey was to describe the interactions of dental cast alloys with living tissues and to relate them to clinically adverse local reactions
of the oral tissues.
Results: Interactions of dental cast alloys with the oral tissues take place by different mechanisms; e.g. bacterial adherence promotion,
toxic and subtoxic effects and allergy. Whereas bacterial adhesion promotion may be counteracted by adequate oral hygiene measures, the
other mechanisms may lead to clinically adverse local reactions due to the metal present. However, the number of cases, where such a
relation can be safely diagnosed, is small. Safe ground is felt with proven allergies. The comparatively high allergy rate towards nickel should
be the impetus to replace those alloys whenever there is a suitable alternative. Medical and dental impairments as well as general medication
may lead to symptoms allegedly attributed to metal restorations.
Conclusions and Signi®cance: Patients relating oral symptoms to metal restorations should be subjected to a thorough dental and general
medical examination in order to exclude non-material related diseases being the cause for their complaints/symptoms. These cases are a
challenge for the collaboration between the medical and dental professions. q 2002 Academy of Dental Materials. Published by Elsevier
Science Ltd. All rights reserved.
Keywords: Alloys; Nickel; Cell culture; Bacteria; Cytotoxicity; In¯ammation; Allergy; Lichenoid reactions; Lingua plicata

1. Introduction that no adverse effect will occur during the widespread

According to the different requirements for their wide
range of applications, dental cast alloys comprise a large
variety of different materials; e.g. on the German market
there are more than 3000 brands available [1]. Dental cast
alloys areÐfrom a legal point of viewÐmedical devices,
because they achieve their intended use mainly by their
mechanical properties to replace lost tissues function.
Accordingly, dental cast alloys have to successfully pass a
risk assessment including a clinical evaluation (not neces-
sarily clinical testing) before they are allowed to be
marketed. Standard procedures for this purpose have been
published [2,3]. This approach should prevent patients,
dental personnel and third parties from adverse effects
caused by new medical devices (here: dental cast alloys)
in general. However, due to the limitations of the methods/
approaches involved, such a procedure cannot guarantee
* Corresponding author. Tel.: 149-941-944-6024; fax: 149-941-944-
6025.
E-mail address: gottfried.schmalz@klinik.uni-regensburg.de
(G. Schmalz).
0109-5641/02/$22.00 + 0.00 q 2002 Academy of Dental Materials. Published by Elsevier Science Ltd. All rights reserved.
PII: S 0109- 564 1( 01) 00063- X
use of such a material.
Cases of oral tissue reactions in contact with dental cast
alloys have been reported in the literature. Metals like nickel
or copper being released from certain dental cast alloys were
thought to be the (toxic) cause of reaction such as gingival
in¯ammation [4±6]. In other reports metals released from
high noble and noble alloys were postulated to be respon-
sible for discoloration and hyperplasia of the adjacent
gingiva [7]. A considerable number of publications has
been devoted to cases of allergies to metals in dental cast
alloys and to describing intraoral (and other) symptoms [8].
Data on the prevalence of allergic reactions and positive test
results; e.g. from skin-testing for metal salts, are available
[9,10]. However, these data cannot be extrapolated to metals
or alloys and to their use in the mouth. Therefore, from all
these reports, no ®rm conclusions with respect to prevalence
can be drawn.
In a 1995 report of a patient organization from Germany,
local and systemic symptoms/complaints of 2200 patients,
allegedly attributed to dental cast alloys, were compiled.
This was performed during the intensive public discussion
in Germany (population: about 80 million inhabitants) on
 G. Schmalz, P. Garhammer / Dental Materials 18 (2002) 396±406
palladium containing dental cast alloys. During the course
of this discussion, recommendations of the German Health
Administration not to use Pd±Cu-alloys [11] were pub-
lished, but not accompanied by any information as to how
often clinically relevant reactions had been observed with
these alloys.
For a selected group of people, the frequency of adverse
effects was estimated to be 1:100 (orthodontic patients) and
1:330 (prosthetic patients); 85% of those orthodontic
patients and 27% of those prosthodontic patients attributed
their problems to dental (cast) alloys [12,13]. The intraoral
symptoms were gingival swelling and erythema, mucosal
pain and lichenoid reactions. MjoÈr and Christensen [14]
reported on controls of 335 patients with 915 ®xed and 87
removable prosthodontic units. Almost half of these pros-
theses were made from base metal alloys, mainly nickel-
chromium for ®xed and cobalt-chromium for removable
dentures. Twenty-three of the 335 patients were reported
to have moderate reactions, two had a severe reaction.
However, the soft tissue reactions were considered to be
largely due to factors other than the metal components.
In the years 1995±1998 we performed a survey in a
region of Germany (Oberpfalz) with a population of 1
million inhabitants [15±17]. Through informing all the
dentists in this area we asked for patients who claimed to
have adverse reactions towards dental cast alloys. The
number of patients who contacted us during these 3 years
was 250. Due to the restriction of the project to patients with
intraoral reactions, 86 were accepted for the study (symp-
toms will be described later). More detailed analysis of these
patients showed that 15 (out of 86) had consulted two or
more dentists and 54 (out of 86) had consulted one or more
physicians. Thus, from an insurance point of view, these
patients were cost-intensive. Furthermore, the time required
to take up the history of such a patient in our study was more
than 10 times that for routine patients.
Although the epidemiological data available may be
regarded as scarce, a clear trend can be recognized that
patients reporting on adverse effects from dental cast alloys
are few on a percent level. However, these patients require a
high amount of time and high costs as well as considerable
experience for diagnosis and further treatment. In this
review, the biological interaction of dental cast alloys
with the oral tissues as well as the role of these interactions
for clinically observed adverse effects shall be discussed.
Emphasis is placed on local reactions/symptoms.
2. Composition and corrosion of dental alloys
It is believed that biologic reactions in general are mainly
based on the interaction of a substance eluted from a
material with a biologically relevant molecule. Therefore,
the composition of dental cast alloys is of importance. More
than 35 different metal elements are used for dental cast
alloys. It was postulated that certain groups of dental cast
397
alloys (e.g. Ni-containing or Pd-Cu-alloys) are especially
prone to evoke adverse reactions [5,11]. Composition and
corrosion aspects, as well as the toxicology of the single
metals and alloys, are important, but can only be dealt
with very selectively in this context. For detailed informa-
tion see relevant textbooks.
Dental cast alloys can be divided into different groups;
e.g. according to the ADA (1986) into (1) high noble alloys
($60% Au, Pt, Pd and $40%Au), (2) noble alloys ($25%
Au, Pt, Pd) and predominantly base metal alloys (,25%
Au) [18]. These classi®cations are used in this review.
Other ways to classify dental cast alloys have been
published or discussed.
Corrosion of dental cast alloys results in the release of
metal ions, which is a prerequisite for biologic effects to
take place. Corrosion in the mouth is mainly of an electro-
chemical nature. Through passivation, the surface of an
alloy/metal may be transformed into a state by which corro-
sion is greatly inhibited; e.g. by formation of an oxide-layer
on titanium surfaces [19]. The interaction of two different
metals/alloys may lead to galvanic corrosion, possibly
enhancing the amount of ions released. Crevice corrosion
has been postulated to be of special importance in dentistry;
e.g. in telescopes or in crevices of endodontic posts. A drop
in pH is observed with partially severe surface destruction
[20]. Thus intraoral corrosion is a very complex process and
dependent on compositions and metallurgical state, combin-
ations within a construction, surface conditions, mechanical
aspects of function, and the local and systemic host
environment [21].
In vitro corrosion tests showed that titanium and high
noble alloys were most corrosion resistant [22]. Contradic-
tory results were reported for noble alloys: in electrochemi-
cal tests they were as resistant as high noble alloys [23], in
immersion tests less resistant [22]. Corrosion of titanium
can be enhanced in solutions of high ¯uoride concentration
(1.5%) at low pH [24,25]. Pd±Ag-alloys were more corro-
sion resistant than Pd±Cu-alloys [26,27]. Data for base
metal alloys showing a tendency of Co-Cr-alloys being
more corrosion resistant than certain Ni-alloys [28,29].
For the latter materials, other metals like beryllium may
reduce the corrosion resistance [30]. Proteins also play a
crucial role concerning the corrosion resistance, by estab-
lishing metal-protein-complexes on the alloy surface
[31,32]; e.g. under such circumstances, initial corrosion of
Ni±Ti-alloys has been observed to be enhanced [33]. Data
from our own experiments showed that if samples of alloys
used for ceramic fused to metal restorations had been heat
treated, simulating the ceramic ®ring process, the release of
zinc was increased by a factor of 2±3.5 compared to non-
heat-treated samples. This may, as will be shown later, have
an in¯uence upon the tissue reaction [34].
In vivo corrosion testing better re¯ects the complex
intraoral situation and e.g. determines the metal content of
saliva or in tissues adjacent to dental cast alloys. Corrosion
products of dental cast alloys have been found in saliva
398 G. Schmalz, P. Garhammer / Dental Materials 18 (2002) 396±406
[35±38] and in the gingiva [4,15,39] of patients. The metal
content in saliva somewhat re¯ects the metal content of the
intraoral restorations. However, due to the large variations
of the data, the lack of knowledge of the oxidation level of
the metals detected and the difference in the resorption
behavior of the different metals, these data are extremely
dif®cult to interpret toxicologically [38]. Furthermore, no
limits on a `safe' metal content of saliva can be set to
date. Biopsies from gingiva adjacent to metallic restorations
in comparison to controls showed signi®cantly more metals
and higher amounts of metals than control biopsies for the
same patient. In 26 out of 31 cases, at least one metal of the
casting alloy was found in the neighboring tissue. This
shows that metals from alloys accumulate in neighboring
tissues [15]. Again, the oxidation level, as well as the toler-
ated limit, is unknown.
From these reports it can be concluded that, for every
dental cast alloy, corrosion takes place. However, there is
a tendency of titanium and high noble alloys, Pd±Ag-alloys
and Co-Cr-alloys, to be more resistant than other alloys for a
comparable application. Interestingly, it was consistently
found that the relative amount of released metals does not
re¯ect their relative weight or volume portion in the alloy
[15,38]. Anyhow, the prerequisite for a biologic interaction
between dental cast alloys and oral tissuesÐnamely the
release of metals from dental cast alloysÐis ful®lled,
though in different degrees for different alloys, and basically
the biologic interaction might be the cause for the above
reported clinically observed adverse reactions.
3. Biologic interaction
The prime local target tissues for dental cast alloys are the
soft tissues in the mouth. The biological interaction between
these alloys and the target tissues may be classi®ed as
follows: (1) bacterial adhesion, (2) toxicity, (3) subtoxic
effects and (4) allergies.
3.1. Bacterial adhesion
Plaque accumulation as the prime cause for gingival
in¯ammation may be due to inadequate oral hygiene or to
an unsuitable construction which does not allow the patient
to perform adequate oral hygiene measures. This is mainly
the responsibility of the clinician/patient. However, dental
cast alloys may also in¯uence oral bacterial adherence.
Several factors affect bacterial adherence, its accumula-
tion and the formation of plaque on dental cast alloys.
Alloys containing and releasing copper and silver proved
in vitro to be more antimicrobially active than certain base
metal alloys [40]. A variety of in vitro tests combining test
materials with bacteria, have also demonstrated that high
levels of surface free energy and rough surfaces promoted
bacterial adhesion (literature survey in Ref. [41]). In this
context titanium abutments were considered to attract
more plaque than teeth because of the high surface free
energy. However, this can be counteracted by adequate
oral hygiene measures [42].
In vivo the material surface is immediately covered with
the acquired pellicle [43], by which the observed in vitro
differences between different materials are reduced. The
pellicle results in a general reduction of bacterial adhesion,
irrespective of the substratum surface free energy [41,44].
Siegrist et al. [45] found that in patients under experimental
bridge pontics with different alloys (high noble, noble,
silver-palladium and base metal in comparison with enamel,
dentin, amalgam, ceramic), no speci®c trends suggesting a
preferential colonization on any of the different materials
after 4 and 24 h. The amount of early deposits (4 h) could be
related to surface roughness. This is in line with Hannig
[46,47], who found less pronounced variations in the ultra-
structural appearance of plaque formed over a period of 24 h
between the different materials (noble alloys, titanium alloy,
composite resins, cements and ceramics). It was observed
that the location of the specimens in the mouth exerted a
greater in¯uence: buccal areas showed a thicker bacterial
layer than lingual areas, which apparently was due to
mechanical in¯uences in the oral environment.
In summary, there is no clear indication from the litera-
ture that one alloy or one group of alloys shows special
plaque accumulation enhancing properties that cannot be
managed by good hygiene measures. The clinical relevance
of mainly in vitro measured plaque-reducing properties of
certain alloys has not yet been shown. Therefore, control of
plaque as a cause of in¯ammation in the case of metal
restorations, remains the responsibility of the clinician and
the patient.
3.2. Toxicity
The ®rst step to approach dental cast alloy toxicity is to
analyze the toxic potential of metal ions; e.g. in cell culture
systems. Data from such experiments are dependent upon
the cell culture conditions chosen; e.g. the cell line, cell
culture medium, incubation time [48,49]. Furthermore the
oxidation level of the metal is of importance [50]. Data from
different tests (Table 1) show a wide variety of concen-
trations to reveal the same biologic results (TC50 ˆ
concentration by which 50% of the cells in a culture are
killed).
Such data may be used to explain certain phenomena; e.g.
the fact that zinc-containing amalgams are more toxic than
zinc-free materials [54,55]. This re¯ects the fact that zinc
in ionic form is toxic compared with other metal ions
(Table 1). Furthermore, we could show that through heat-
treatment, the release of zinc from certain dental cast alloys
could be more than doubled. ThisÐtogether with the
knowledge of the relatively high cytotoxicity of zinc
ionsÐmay be one explanation of some cases of plaque-
independent gingival in¯ammation or discoloration
observed in the neighborhood of ceramic fused to metal
crowns [4].
 G. Schmalz, P. Garhammer / Dental Materials 18 (2002) 396±406 399

Table 1
TC50 data on selected metal cations frequently used in dental cast alloys. TC50 values of metal cations in L-929 and Balb/c 3T3 mouse ®broblasts, hamster
kidney epithelial cells and primary human gingival ®broblasts observed under the indicated experimental conditions (adopted from Refs. [51±53])

Test substance L-929 cells MTT Kidney epithelial cells Gingival ®broblasts L-929 cells Balb/c 3T3 cells MTT
assay TC50 (mM) MTT assay TC50 (mM) MTT assay TC50 (mM) ( 3H-thymidin issay) assay TC50 (mM)
[51] [51] [51] TC50 (mM) [52] [53]

AgNO3 4.8 4.6 ± 18 (Ag2SO4) 5.8 (Ag2SO4)

ZnCl2 7 9.5 81 189 28
HAuCl4 3H2O 21 36 210 77 91
CdCl2 10 26 ± 1.1
HgCl2 11 13 24
H2PtCl6 33 302 ± 17 (PtCl4)
CuCl2 2H2O 139 251 273 97 240
CoCl2 6H2O 100 108 ± 49
NiCl2 6H2O 188 379 ± 166 190
PdCl2 281 134 ± 240
MnCl2 4H20 556 216 ± 360
CrCl3 6H2O 1790 2130 3011 . 1000 (CrCl2)
MoCl5 775 927 1585 . 1000
NbCl5 676 921 ±
GaCl3 1530 2140 ± 53 200
InCl3 2310 2110 4200 30 . 435
SnCl2 2H2O 3110 2280 ± . 1000

On the other hand, problems exist in applying the cyto-
toxicity data to other clinical situations; e.g. nickel was
proposed as being the (toxic) cause of in¯ammation of the
gingiva in patients with excellent oral hygiene and no
allergy (negative skin-test) [4]. However, in all the cyto-
toxicity tests, nickel in ionic form had low toxicity (Table
1). It should also be kept in mind that in vivo a mixture of
different metal ions is present in the tissues and it is known
from in-vitro studies that synergistic as well as antagonistic
effects may occur [56]. Therefore, toxicity data of the dental
cast alloy itself may be more helpful for biologically char-
acterizing a dental alloy.
Dental cast alloys were also studied in cell cultures, but
some experiments were performed on small laboratory
animals; e.g. as implantation tests. Toxicity evaluation of
the alloys involvesÐbeside the variables of the biological
test systemÐthose variables of the material fabrication and
pretreatment, like the condition of the surface (polished/
unpolished) [57], the phase composition [58], the latter
also being dependent upon the casting technique [59].
Most dental cast alloys were less toxic as polished material
[57], however, high copper alloys acted in just the opposite
manner [57]. Pulverized dental cast alloys acted differently
from bulk samples showing increased tissue reaction [60].
Studies on different noble and high noble alloys showed a
trend that copper and silver were the metal elements which
induced cytotoxic effects of the respective alloys [18,34,61].
A correlation was observed between cytotoxicity and the
copper content of the alloy [62]. After intramuscular
implantation, a noble alloy (Au/Pd-alloy) was more irrita-
tive than a high gold alloy [63]. Strong tissue reactions were
evoked after subcutaneous implantation of a Pd/Cu-alloy in
guinea pigs [64]. However, Pd/AgÐand high noble alloys
evoked only minor responses [64]. In dogs copper-based
crowns released copper into the adjacent gingiva, which
was associated with gingival in¯ammation [65].
Co-based alloys proved to be slightly cytotoxic in vitro if
the surface was polished [66]. Different results were
reported by Berstein et al. [67], who examined Co-based
alloys in human gingiva cells and lymphoma cells: the
samples inhibited cell growth. Implantation studies of
Co±Cr±Mo-alloys, however, revealed excellent biocompat-
ibility in this test system [63,68].
Nickel-containing dental cast alloys have frequently been
tested in cell culture systems. The results are again contra-
dictory. According to Woody et al. [60] metal samples of
Ni±Cr-alloys were non-toxic in the agar diffusion test.
Ultrastructural analysis of cells exposed to nickel-contain-
ing alloys showed no difference from controls [69]. Corre-
sponding results were reported by other authors [57,70]. On
the other hand Bumgardner and Lucas [30] described a toxic
cell reaction towards nickel-containing alloys inhibiting the
proliferation rate of gingival ®broblasts. Similar results
were reported by Berstein et al. [67].
In conclusion, data on toxicity of single metals and alloys
may explain some biological reactions of the dental cast
alloys; e.g. that by heat treatment non-noble metal elements
were brought to the surface of the metal and released. This
may be bene®cial for the bond between the ceramic and the
metal, but it may also be a cause for gingival in¯ammation
or for discoloration. The manufacturer of these alloys
recommended the mechanical removal by grinding the
super®cial layer of heat-treated metal which is not covered
by ceramic. However, this is a dif®cult procedure to perform
and to control. Chemical procedures to remove this layer are
to be preferred. However, some patient reactions (see
below) cannot be explained by toxicity data. Therefore,
scienti®c interest was directed not only to toxic events
400 G. Schmalz, P. Garhammer / Dental Materials 18 (2002) 396±406
(i.e. causing severe damage to cells, cell death), but also to
subtoxic effects (i.e. interference with cell metabolism) and
to allergies.
3.3. Subtoxic reactions
Such studies concentrate on the in¯uence of metals upon
the synthesis of special cellular products which themselves
are involved in a clinical reaction (in¯ammation), or which
protect the cell from damage (detoxi®cation). One way to
address this problem is to measure the cell synthesis of
proin¯ammatory mediators after exposure to different
concentrations of xenobiotics, such as metal ions. Bumgardner
et al. [71] measured the in¯uence of copper-based alloys
upon the cellular synthesis of Interleukin 2 (IL-2) and
found that one of the tested alloys caused T-lymphocytes
to produce increased levels of IL-2, whichÐin vivoÐmay
increase B-lymphocyte activity.
In studies with co-cultures of human ®broblasts and
epithelial cells, we found that copper, cobalt, indium, and
zinc signi®cantly increased the cellular synthesis of prosta-
glandin E2, a proin¯ammatory mediator derived from the
arachidonic acid metabolism [72]. PGE2 released in vivo
leads to vasodilatation, increased vascular permeability
and altered immune cell function by coupling to different
speci®c cell surface prostaglandin receptors. PGE2 thus
seems to be a relevant biological marker which, in contrast
to cell viability assessment, allows for measurement of
time-dependent cell reactions without destruction of the
cell cultures. Prostaglandin levels have been reported to
vary considerably in unin¯amed as well as in in¯amed
pulps with a 20- to 30-fold average increase in PGE2 levels
in in¯amed tissues [72]. In a further study [73] with the
same tissue model we found an increased IL-6 synthesis
in these cultures after exposure to metals like palladium,
copper, nickel, zinc, indium, and cobalt. Interestingly, palla-
dium was not toxic in this test system and nickel only
slightly toxic. IL-6 seems to play a central role in the in¯am-
matory reaction, together with IL-1. These cytokines show
several overlapping effects with each other and with
tumour-necrosis factor alpha (TNF-a ). They are commonly
produced by both macrophages and T-cells, but various
other cell types including ®broblasts and keratinocytes can
produce IL-1 and IL-6. The cytokines have been shown to
enhance various immune responses in vitro, including B-
lymphocyte differentiation, antibody secretion, T-lympho-
cyte proliferation and acute phase protein synthesis.
Kamagata et al. [74] found that the culture supernatants
from gingival samples, biopsies from in¯amed gingival
tissues, contained signi®cantly higher IL-1 and IL-6 activ-
ities than those from healthy ones. Takahashi et al. [75]
detected IL-6 protein mainly in ®broblasts, endothelial
cells, and macrophages of all in¯amed gingival tissues
examined, but not any in healthy gingival tissues.
Another interesting aspect is the fact that cells apparently
have a detoxi®cation mechanism. It was demonstrated that
primary ®broblasts from the human gingiva need approxi-
mately double high concentrations to react to the same metal
ion in the same way as permanent ®broblast cell lines [51].
The reason for this phenomenon is not clear, however, it was
speculated that primary cells, which are freshly taken out of
the organism, still have detoxi®cation mechanisms; e.g.
involving binding to glutathion (GSH). Such a mechanism
was postulated for Hg 21 [76,77] and Cr 61 [50]. However, it
is not known if this is valid for other metal ions. Metallo-
thionein (MT) is a protein which plays an essential role in
the detoxication of metals in general. It has been demon-
strated on many occasions that toxic effects of cadmium
were inactivated by intracellular metallothionein and that
the protein may also form a non-toxic Hg(2 1 )-MT
compound [78,79]. Metal elements that bind to metallothio-
nein modify the expression of the protein. For instance,
Cd(2 1 ) is an inducer of metallothionein expression as
well as Zn(2 1 ), Ag(1 1 ), Hg(2 1 ), Bi(3 1 ), Cu(2 1 )
but other elements like Ni(2 1 ), Ca(2 1 ), Pb(2 1 ) and
As(3 1 ) were not effective [80,81].
In conclusion, metal ions are able to interfere with cell
metabolism, in¯uencing the expression of substances like
cytokines which play an essential role in the in¯ammatory
process. Furthermore, cell detoxi®cation may play a role in
this process. However, data in this context are so scarce that
no clinically relevant conclusion can be drawn so far.
However, further research in this area is needed.
3.4. Allergy
Overwhelming evidence from many case reports, results
from skin tests and other tests (e.g. provocation test) have
shown that allergy may be a cause for adverse reactions
towards dental cast alloys. Generally, the allergic reactions
to dental cast alloys are of the delayed type (Type IV).
Metals like nickel, gold, palladium and cobalt rank high in
allergy hit lists [9]. The leading position on this hit list is
nickel [82], which is of special interest for dentistry,
because nickel containing/releasing metals are in wide-
spread use (e.g. orthodontic appliances, crowns/bridges in
some countries [83]). However, not all patients with a posi-
tive skin test for nickel will show an allergic reaction if
nickel-containing alloys are incorporated into the oral
cavity, although the probability is increased in comparison
to patients with a negative skin test. On the other hand, a
prophylactic skin test before use of any nickel containing
alloys is not recommended because of the possible sensiti-
zation through skin testing. Nickel released from dental cast
alloys is able in certain cases to elicit an allergic reaction;
however, it is not clear, if it can induce sensitization [84].
For further details on a nickel allergy, the reader is referred
to the relevant literature. It should, however, be mentioned
that Kerosuo et al. [82] reported on an interesting phenom-
enon considering the use of nickel-containing orthodontic
wires. The authors studied the rate of nickel sensitization in
14±18 year old adolescents and found that 30% girls and 3%
 G. Schmalz, P. Garhammer / Dental Materials 18 (2002) 396±406
boys as well as 31% with ear piercing and 2% without ear
piercing were skin test positive to nickel. None of the girls
who were treated with an orthodontic appliance before
piercing showed sensitization to nickel, whereas 35%
were nickel positive when piercing had been performed
before the onset of an orthodontic treatment. These data
may suggest some tolerance induced by the use of ortho-
dontic wires. This phenomenon has not been shown for
nickel containing dental cast alloys. Of interest to the clini-
cian is the fact that a cross allergic reaction between nickel
and palladium has been postulated [85]. Gold salts and
cobalt salts belong to the group of the strongest sensitizers
and positive patch test results to these salts have been
reported [9,86] and named as gold/cobalt allergy. How-
ever, for the time being these data should be interpreted
cautiously.
In this context it is important to know the metal composi-
tion of the intraorally present cast alloys. This is sometimes
dif®cult to analyze due to a variety of reasons. The EDX-
analysis of metal particles (`metal biopsies') [15,87] proved
in our hands to be a reliable method to determine the compo-
sition of intraoral alloys. This information is needed, espe-
cially in the context of deciding which substances/metals
are to be included in the skin test [15].
From these data it can be concluded that allergy is a
recognized cause for clinical reactions towards dental cast
alloys. Nickel, palladium, gold and cobalt are of special
interest. If the clinical symptoms indicate the possibility
of an allergy, complementary skin tests should be performed
by a dermatologist. However, the actual number of cases
which have a clear allergic cause seems to be small as will
be pointed out later.
4. Biological interactions and local clinical symptoms
The local clinical symptoms of patients claiming adverse
effects from dental cast alloys may be devided into (1)
subjective complaints which the patients report and which
cannot be veri®ed and (2) objective symptoms.
1. Subjective local complaints registered in patients from a
study conducted in Bavaria/Germany mainly comprised
mouth burning (mentioned by 72% of the patients)
followed by metallic taste (mentioned by 56%) and elec-
tric sensations (mentioned by 44%) [16]. Burning mouth
and metal taste were also described by Wirz et al. [20] in
two of the four patients they reported on [88]. Kratzen-
stein et al. [39]described 20 patients with clinical symp-
toms attributed to intraoral alloys. Metallic taste and
other taste irritations were noticed in eight cases, burning
mouth in four patients. These observations are also in line
with statements provided by patient organizations [88].
Burning mouth sensations have been attributed to aller-
gies. However, in our and in other studies mentioned
above, only a few patients with burning mouth syndrome
401
(10%) had skin tested positive to relevant allergen [16].
Furthermore, burning mouth sensations have been
reported from other dental materials like acrylates,
againÐin many cases (about 90%)Ðwithout a proven
relation to an allergy [89] and for amalgam [90]. Metal
taste was another commonly reported complaint. This is
also observed in some cases if a new amalgam ®lling is
placed in direct approximal contact against a (high) noble
alloy. This sensation, however, disappears in most cases
after a few days due to the formation of an isolating
oxide-layer on the amalgam.
Apparently it is dif®cult to relate these subjective
complaints of patients to general biologic interactions
of dental cast alloys with oral tissues. From the above-
mentioned corrosion and toxicity studies one might
expect that those patients with less corrosion resistant
alloys (e.g. noble alloys instead of high-noble alloys)
would prevail. However, data of the above mentioned
study on patients in Bavaria [17] do not support this
assumption. The relative distribution of the alloys of
our patients into different alloy groups (high noble,
noble, Pd-Ag, Ag-Pd and Co-Cr) re¯ected exactly the
distribution of the alloy groups provided by the main
deliverer of alloys in the whole region (Degussa).Thus
it might be concluded that it re¯ects the use of these
alloys in the whole population of this area [17].
Therefore, other causes have to be considered. Besides
unsuitable construction and faults during the fabrication
process, non-dentally related causes have been mentioned
in the literature. One aspect in this context is related to age
and sex. Patient collectives reporting these adverse effects
in connection with dental cast alloys are characterized by
the fact that the main group consists of patients in the age of
around 50 years [88]. This has also been reported for
patients claiming problems with amalgam [90]. Further-
more, a high proportion of female patients, especially in
this age group was observed. This is again in line with
experience from dental amalgam patients [90,91] and
those reporting adverse effects from dental acrylate-based
materials [89]. It is tempting to speculate on a hormone
mediated cause for these symptoms. However, this is not
proven and it should be taken into account that patients in
the reported age group experience normally extensive
dental treatment involving dental cast alloys [92]. In this
context, psychological problems have also been considered
as a possible cause for such symptoms [90].
Furthermore, it should be considered that quite a few general
diseases (e.g. those of the blood system) are accompanied by
patient complaints like those attributed to dental cast alloys
[90]. The patient group in our study proved to have a signi-
®cantly higher morbidity rate than expected from general
statistics [93]. This is in agreement with experiences
reported by HerrstroÈm and HoÈgstedt [90] who examined
patients claiming health problems due to amalgam.
Finally, drugs may be regarded as an important cause for
complaints similar to those allegedly attributed to dental
402 G. Schmalz, P. Garhammer / Dental Materials 18 (2002) 396±406

Fig. 1. Thirty-two year old female patient with gingivitis adjacent to a high-noble alloy and negative skin test.

cast alloys. According to Gromnica-Ihle [94] patients with
rheumatism are a risk group in the dental practice. Many
drugs for rheumatism may cause oral symptoms; e.g. metal
taste [94]. Smith and Burtner [95] compiled the most
frequently reported effects after taking the 200 most often
described drugs. Taste irritation and other orally located
complaints played a major role in this context.
2. Objective local symptoms may be devised according to their
clinical appearance.
2.1. Gingival in¯ammation in the vicinity of metal restora-
tions was found in our study in 23% of the patients
showing erythema, bleeding and swelling, even after
mechanical and chemical plaque reduction measures
[16] (Fig. 1). This is in line with case reports from the
literature [39,88]. As was mentioned above, there are
possibilities that non-noble metal elements are released
even from high-noble alloys (intended use: ceramic
fused to metal restorations) in considerable amounts,
if processing was not performed according to instruc-
tions (which are sometimes dif®cult to follow). More
information, however, is needed about the cellular
mechanisms especially on the in¯uence of metal ions
on the cell metabolism.
Again, allergies may be a reason for such an in¯amma-
tory response. The question, however, remains: How
many allergic cases are responsible for the clinical reac-
tion? In our study, we found that 17 patients (20%)
reacted positive to metals in the skin test. However,
in only 10% of the patients, the metal was found to
be the possible cause for the clinical reaction, because
in the other cases the positive tested metal was not part
of the intraoral alloys. Interestingly, only three out of 86
patients showed a positive skin test result with the
actual alloy (Fig. 2). This is in agreement with data
from HerrstroÈm and HoÈgstedt [90] for patients with
self-diagnosed adverse effects to amalgam (oral

Fig. 2. Patient (female, 45 years old) with gingivitis (Pd-containing alloy) and positive skin test (Pd).
 G. Schmalz, P. Garhammer / Dental Materials 18 (2002) 396±406
Fig. 3. Fifty-seven year old, female patient with lichenoid lesions adjacent
to a high-noble alloy.
galvanism). Out of 241 patients referred from dentists
and physicians during 2 years, only three patients skin
tested positive to Hg [90]. This is in accordance with
reports from the literature [85,96]. Apparently, allergy
only explains a small part of clinically observed
adverse reactions [16].
2.2. Anomalies of the tongue (e.g. lingua geographica,
lingua plicata) were observed in 16% of the cases in
our study. In a study of patients allegedly attributing
their symptoms to dental amalgams, Axell et al. [97]
found changes of the apex of the tongue in 15% of their
patients. The interpretation of this phenomenon is dif®-
cult. In the general population Axell [98] observed a
lingua plicata in only 7%. One could speculate that
patients with anomalies of the tongue might be a risk
group. However, there are no direct data to support this
statement.
2.3. In our study grayish discolorations of the gingiva
(12%) were associated with a history of an amalgam
®lling. Particles may have been transplanted into
the neighboring tissues during the preparation of
the tooth for a crown. These so-called amalgam-
tattoos are known from the literature, they are non
irritating and show no signs of acute in¯ammation
[99].
2.4. Redness of the tongue was found in 10% of our
patients. In three of these nine patients oral habits
403
(e.g. tongue pressing) may be a reason for the
redness. The interpretation of the red tongue of the
other patients is dif®cult.
2.5. In our study seven patients (8%) had a red palate
adjacent to the alloy of a denture. Reasons for such
reactions have been reported to be allergic/toxic reac-
tions, insuf®cient ®t of the prosthesis [100] or bacterial/
fungal infections (e.g. candida albicans) [101,102].
Furthermore, some patients' reactions may be
explained by bruxism [103].
2.6. Whitish lichen-like (lichenoid) lesions of the oral
mucosa and of the gingiva have been described in
the context with of amalgam restorations [104],
composite resins [105] and dental cast alloys
[8,106]. In our study we observed ®ve cases (6%)
of such reactions (Fig. 3). Lichenoid lesions may be
regarded as a disease by itself (lichen planus), as a
sequelae of a material or as both, the latter phenom-
enon being explained as a worsening of an existing
lichen planus by the presence of a material. The in¯u-
ence of the material may be of mechanical or of aller-
gic nature. Data from Bolewska et al. [104] suggest
that especially if the whitish lesion is limited to the
contact area with the material, a material-related
effect may be assumed. In these cases, a skin test
may be relevant, because an association of this type
of lichenoid reactions with type IV-allergies has been
reported.
5. Conclusions
Biologic interactions of dental cast alloys with the oral
tissue can be regarded as one reason for clinically observed
local adverse effects. But there are also other factors which
may be the cause of these clinical reactions as summarized
in Fig. 4. This is a simpli®ed scheme, because only the main
factors are mentioned and it should be noted that these
factors interact with each other. Causes for cast alloy related
oral tissue reactions can be divided into dental/oral and non-
dental/non-oral causes. Non-dental/non-oral causes are
general disease (e.g. diabetes mellitus, disease of the
blood system, vitamin de®ciency), medication (e.g. drugs
for high blood pressure, sedativa) and other factors like sex,
age, saliva ¯ow or psychological background. Dental/oral
causes are viral or fungal infection (e.g. candida albicans),
plaque and faults in the construction of a prosthesis or inade-
quate tooth preparation or tissue anomalies. Bruxism or
implications for the periodontal health may eventually be
the consequences. Material related factors may be further
subdivided into reactions caused by the material with
correct and those with incorrect fabrication; e.g. shrink-
holes. The factors being responsible for biological incom-
patibility are bacterial adhesion, toxic/subtoxic effects and
allergy. Bacterial adhesion can be counteracted by oral
404 G. Schmalz, P. Garhammer / Dental Materials 18 (2002) 396±406
Fig. 4. Simpli®ed scheme for possible causes of oral tissue reactions (allegedly) related to dental cast alloys.
hygiene measures. The other factors, however, may cause
adverse reactions due to the metal itself.
Because of the different factors in¯uencing oral tissue
reactions, diagnosis and treatment of these patients must
be performed not only by the dental clinician (together
with the material scientist), but should include physicians
from different disciplines, like dermatology, internal medi-
cine and psychiatry. Large areas of the biological interaction
of dental cast alloys are not yet understood, especially in the
area of low dose exposure and individual differences in the
appearance of adverse reactions. Further research should be
pursued into this direction.
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