Nickel,chromium,cobalt dental alloys

and allergic reactions: an overview

Haztmut F. Hildebrand, Christian Veron and Pierre Maxtin

lnstitut de

Mbdkine

du

(Received

16 June

1988;

Travail,

Facultd

accepted

de MBdkcine,

25

July

1 Place

de Verdun,

F-59045

LILLE-Cedex,

France

1988)

Possible correlations between allergic reactions and the significance of a dental prosthesis or restoration
made from one or more of the metals nickel, cobalt and chromium are considered. Described clinical cases
are reviewed. These allergic reactions may appear either locally as stomatitis or distantly in the form of
general or local contact dermatitis.
Keywords:

Dental

materials,

CoCr

a//oy,

NiCr

alloy,

stainless

Dental alloys containing

nickel, cobalt and/or

chromium

widely

restorations.

Ni-Cr

alloys

Co-Cr

alloys

used

generally
mostly

for dental

69-81%

less than

alloys

whereas

group

steels with

of non-precious

18%

Although
corrode

Cr and 8%
considered

in biological

corrosion

of

restorations-.
from

last

epithelial

few

pulmonary

epithelial

restorations,

A certain
metals

Green

of

and thus

dental
induce

Monkey

Chromates

memorized

on

cytes produce

human

have an even higher

has also been demon-

ferromagnetic

some

sensitization

contact

more allergic

reactions

nickel takes

dermatites

in

than all other

takes the second place. Cobalt,

in

1906

of an individual

re-introduced
modified

defined

allergy

to a substance

into the organism.

with the progress

This

the latter

definition

in immunological

positive

0 1989

to Dr H.F. Hlldebrand

Butterworth

& Co (Publishers)

to

antigenic

mechanism

the

by macrophages

and

the formerly

sensitized

lympho-

e.g. lymphokine,

which

and so provoke certain tissue

effect

in contact

dermatitis

Mucosal

reactions

are possible.

of type IV thus appear after cellular mediation

production

(1 ) a clinical
healing

simplified

For
with

bound

a strong

on the skin as eczema.

of antibodies.

to prove

contact

and personal

studies

following

(3)

strongly

to form

substances,

stomatitis

bibliographic

(2)

or hapten is a substance

T-lymphocytes7.

hypersensitive

established

the three

steel or Ni-,

Different

criteria

dermatitis..
we

have

For our

consider

especially

criteria:

feature

in the

form

of

eczema,

redness,

etc.;

after

removal

skin reaction

of the allergen;
after epicutaneous

test.

METHODS

is

has been

research.

been

The

The most usual test is the epicutaneous

Finn Chamber
allergen

Correspondence

The

generally

cells.

by stainless

is captured

into the organism

Allergies

TEST

as a pronounced
when

different

ulceration,

DERMATITIS

Pirquet

reactions.

dental

the third
metallic
allergen,
causes
mostly
associated
sensitization
with chromium
and especially with nickel.

reaction

they liberate

and without

by these metals,

place for all metal-induced

Chromium

Pd-Co

Ni and Cr13.

a very

a new contact

and especially

and

antigen
by certain

After

cells.

classes of allergy.

It is at first

proteins

After

formed

defence

or defence

alloys are called contact dermatitis

power16.

macromolecule.

renal

(Cercopithecus
and

induced

is a

IV of the above cited classification.

endogenous

cytotoxicity

and it induces

Von

allergenic

appears

humans

CONTACT

a low
certain

antigen

or specific

four different

reactions

Co-containing
to type

The

into the organism,

with the antibodies

and Gell15 defined

and belong

newly
on

of antibodies

interact

The allergic

antigen.

once introduced

this form of allergy the allergen

origin,.

cells

the first

metals together14.

antigens

cobalt and nickel salts have similar

also contain

Concerning

or

investigations

gingival

cells2.

cytotoxicity.

pure

have described

implants.

by several

human

and soluble

for

Coombs

of nickel salts has been demonstrated

toxic effect,

alloys which

(5-6%).

that Ni, Co and Cr are released

cells of the African

induces the formation

These

these alloys may

is called

or a cell which,

Cr- and/or

of toxic or allergic

years

on

MO

substance

molecule

alloys are stainless

Several authors

and dental

aefhiops),

strated

dental

orthopaedic

reactions

and

as inoxidizable,

milieux.

The cytotoxicity
in the

contain

sensitizing

of these

Ni.

It is possible

prostheses

unwanted

Cr (27-30%)

are

contain

1% nickel. The main components

are Co (SO-65%),

Another

the

nickel,

steel

Test). This consists

on to the skin. The allergen

petrolatum

test (patch-test

in the application
is diluted

if it is a salt or powder.

Pure

in water

metals,

or

of the
or

alloys,

Ltd. 0142-9612/89/080545-04$03.00
Biomaterials

1989,

Vol

10 October

545

Ni Cr. Co dental alloys: H.F. Hildabrand et al.

Table 1 Allergen
(in petrolatum)

concentrations

(%)

of

standardized

test-batteries

Battery

NiSO 4

K2Cr207

WSQJ3

COCI,

coso,*

ERG

5
2.5
5

0.5
0.5
0.5

l-2
2
1

2
-

NACDG
ICDRG

ERG, European Research Group; NACDG, North America Contact Dermatitis

Group; ICDRG, International Contact Dermatitis Group.
*Not included in standardized batteries.

polymers or mixtures of different substances, e.g. toothpaste, can be applied directly. The allergen is put into small
aluminium-chambers or Finn Chambers which are directly
applied to the skin. This method keeps the allergen in direct
and constant contact with the skin*. The test results are
interpreted after 48 and 72 h. Some very sensitive persons
may have a first reaction within some hours.
Laboratories for dermatologic and allergic examinations
use standard test-batteries of the most current substances.
All these batteries contain the different metal salts. In Tab/e
7, we present the salt concentrations of Ni, Co and Cr
recommended by different research groups. The table
shows that the concentrations of the three metal salts vary
very little from one group to another. Indeed, the difference
in concentration of nickel sulphate (2.5 or 5%) has no
influence on the frequency of revealable allergy. In some
laboratories nickel sulphate is replaced by nickel chloride.
This difference also does not influence the reliability of the
tests.
For both epicutaneous and epimucosal tests the same
rules have to be reported. The application must stay on the
oral mucosa in continuous contact for 24 h.

SENSITIZATION

TO NICKEL,

COBALT AND CHROMIUM

A large number of statistical and epidemiological investigations of contact dermatitis were performed to establish
the frequency of allergies. In Tables 2 and 3 we summarize
the data of a previous paper*, where we reviewed 21
statistical studies of allergy in the consultant population
(Tab/e 2) and five statistical studies of the general population
(Tab/e 3).
The consultant population is of patients with a
dermatological problem. The general population is of
volunteers without obvious allergic reactions who underwent
epicutaneous tests.
The primary cause of contact dermatitis to these
Table 2
Statistical assessment
consultant population (%J

of sensitization to Ni, Cr, and Co in the

Allergen

Reported cases

b(%J

Q(s)

Total (%)

Nickel
Chromium
Cobalt

37 849
36914
31 330

3.1
12.7
4.7

12.9
7.1
5.3

9.6
9.3
6.0

Table 3
Statistical assessment of sensitization to Ni and Cr in the general
population (%)
Allergen

Tested persons

o(%)

QW)

Total (%)

Nickel
Chromium

3207
822

1.5
2.0

8.9
1.5

4.2
1.7

546

Biomaterials

1989, Vol 10 October

metals is the occupational exposure in electrogalvanic,

metallurgic and chemical industries, masonry, textile and
paper manufacture, agriculture, hospital employment, etc.
The second cause of sensitization is environmental
non-occupational exposure: paste jewellery, kitchen utensils,
chromate-tanned leather or metallic vestimentary requisites,
domestic cleaners and detergents and a lot of other
possibilities. In addition to the external source, we take up a
considerable part of metal ions in food. Foodstuffs like
beans, peas, strawberries, rice, bread, meat and fish may
contain more than 1 mg of nickel per kg*.

ALLERGY

TO DENTAL

RESTORATIONS

Allergic reactions relative to dental interventions may have

different origins. Generally, three groups of allergens have to
be considered: medicaments, synthetic materials and alloys.
Medicamentous allergies may arise during or after
dental treatment. The most current substances to induce a
medicinal rash are local anaesthetics, sulphonamides,
certain antibiotics, especially penicillin derivatives, and
finally analgesics23.
A large number of sensitizations to synthetic dental
restorations have been described. The most frequent allergic
reactions are due to sulphonesters and catalysers contained
in matrix materials and provisional restorations23,24. Base
materials used for final prostheses can also induce
sensitizations: acryl derivatives25. 26, hercolite, vulcanite,
stabilizers such as hydrochinonez3, accelerators such as
benzoylperoxide25, and colour pigments.

Dental base alloys

dissolution

of Ni-Cr

and Co-Cr:

corrosion

and

Several observations about the behaviour of prostheses of

non-precious alloys in biological milieux have been
described27-2g. Bergman et a/.30 implanted subcutaneously
four different alloys with high Ni-content (64-74%).
Analyses of tissues and organs after 5 month implantation
revealed a high Ni-concentration in kidneys and lung.
Similar investigations have been performed on humans
to assess the release of Co and Cr in the oral cavity4f 7. Some
days after the placement of the prosthetic material, the
authors measured a significant increase and accumulation of
Co and Cr in saliva and tongue tissue.
Another important investigation was performed by
Newman et al.5 on corrosion of Biobond C&B and Unibond
with Ni/Cr contents of 79%/l 3% and 64%/229/o respectively. Although both alloys have an excellent resistance to
corrosion in artificial saliva, significant Ni-leakage was
apparent in autoclaved human saliva.
Temperature and pH have a great influence on the
dissolution of stainless stee13. The release of Cr-ions is
increased in an acid medium at elevated temperature with
reference to water. This is important to mention since it
concerns directly the relation between dental restorations
and nutritional habits.
All the above cited studies demonstrate clearly the
existence of corrosion of so-called inoxidizable alloys in a
biological milieu. Ni, Cr and Co are released into the oral
cavity and are recovered in more or less important concentrations in proximate tissues or in various organs3,32-34.

Clinical

cases

The metal ions released into the organism are now available
to induce allergic reactions. As long ago as 1966, Foussereau

Ni

Table 4

Reported

cases

of allergy

to Ni, Cr and/or

Co in relation

to dental

prostheses

Numberofcases
Sex rat10O/d
Local symptoms
General symptoms
Allergic background
Healing after wIthdrawal of prostheses

149
2/l
111
32

28
127

and Laugier35 described allergic eczemas from metallic

foreign bodies of different origin: dental prostheses, orthopaedic implants, war particles. These materials usually
contain Ni, Cr and Co. Nickel is present in all non-precious
dental alloys, and even nickel-free
Co-Cr alloys contain
enough Ni to induce allergic reactions in Ni-sensitized
persons36. These Ni concentrations
may be so low that even
an examination
with dimethylglyoxim
(DMGO) gives a
negative answer. Most authors now agree on this point and
reject the criterion of the positive DMGO-test for whether an
alloy releases Ni and thus should be considered as sensitizing
or non-sensitizing.
In a previous extensive
bibliographic
study
we
reviewed clinical cases from 1934 to 1988. These cases are
summarized in Table 4. We recorded 149 cases responding
to the three above-defined
criteria. All patients showed a
positive test reaction to at least one of the three metals or the
applied alloy. After withdrawal of prostheses or restorations,
127 patients healed completely and rapidly. Clinical local
symptoms
in the oral cavity or peribuccal
region were
observed in 1 1 1 patients. Distant localized or generalized
symptoms appeared in 32 patients, and 1 7 patients showed
symptoms in the oral cavity and elsewhere on the body.
It should be underlined,
that antecedent
signs of
allergy to the three metals were observed only in 28 patients,
i.e. 20% of cases. Indeed, the statement of antecedents was
no longer possible after appearance of clinical symptoms in
the presence of a dental restoration. On this question, 80%
of negative or uncertain answers remains an important rate.
Thus, we must consent that a high number of the reported
cases were sensitized
by the dental restoration.
This
supposition
is enhanced by the high number of patients
(1 1 1 cases) showing clinical symptoms in the mouth.
The last remark is contradictory to the general concept
that allergic reactions on oral mucosa are extremely rare3.
Indeed, these reactions may be of mechanical,
electrogalvanic or microbial origins, so that epicutaneous and/or
epimucosal tests and clinical observations by allergologists
must be performed to confirm any allergic manifestation.

Healing

probability

of metal-induced

contact

dermatitis

As shown in Tab/e 4, 127 patients healed after removal of

their dental restoration. This healing is very misleading. The
elimination of the allergic agent is in most cases sufficient to
heal the clinical symptoms. The sensitization, however, may
persist over many years. Several research groups.4,38
have followed their patients up to 4 to 7 yr by one or more
control tests. All have stated that allergy persists at a 76 to
93% rate. In some patients allergy persisted for over 1 7 yr3.
The authors conclude
that the cessation
of nickel or
chromium exposure has no evident effect on the duration of
sensitization.

alloys:

H.F.

Hildebrand

et al.

phenomena may induce diseases of similar severity: toxicity,

electrogalvanism,
mechanical and microbial irritation, etc.
These aspects are voluntarily dropped since they are not in
direct relation with allergy. Some remarks shall be made,
however, on these subjects.
One of the essential causes of oral diseases is
electrogalvanism.
Since MacDonald4
and Moutier4
so
many investigations
of this subject were published that it is
impossible to cite them all here. We should not forget,
however, that metal ions released by electrogalvanic
effects
may be responsible for sensitization and allergic reactions.
Another important reason of diseases is mechanical
irritation which disappears - like allergic reactions - after
removal of the dental restoration. Since such irritations are
clinically quite similar to allergic stomatitis, epicutaneous or
epimucosal
tests are indispensable
for the diagnosis of
sensitization.
The physiological origin and thefrequencyof
Ni, Co, Cr
contact dermatitis is well known in general and consultant
populations.
In contrast, no statistical or epidemiological
investigations
have yet been carried out to elucidate existing
correlation between non-precious dental alloys and allergic
reactions. The present review of described clinical cases may
help in understanding
and tackling the problem but cannot
have any further statistical value.
The lack of any statistical study is surprising since
most authors recognize the problem and discuss it in their
publications. They gradually indicate several cases observed
without
describing
them precisely, 6, , 23.35.42.43. Does
sensitization to dental restorations occur so frequently, that
publication and precise description of clinical cases is no
longer needed? Thus, Seymour36 may be right in suggesting
that about 35% of all Ni-allergic persons should seek the
origin of their diseases in dental restorations of non-precious
alloys.
Some authors reject the existence of allergic reactions
to dental alloys44.45, but the problem remains the same. A
reaction must not appear immediately but only some months
or some years after the first contact with the allergen46.
Furthermore,
we should
not forget
that dental
restoration is made for long duration. It may be replaced
easily by another and better one. This is not so easy for
implant material used in stomatology,
maxillofacial surgery
and orthopaedic surgery.

ACKNOWLEDGEMENT
This work
association

was supported
PROTHESOR.

by a grant

from

the

French

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