International Journal of Risk & Safety in Medicine, 3 (1992) 1-22 1@ 1992 Elsevier Science Publishers B.V. All Tights reserved 0924-6479/92/$05.00

RISMED 00108

Mercury from dental amalgams: exposureand effects

laroPleva"\ Uddeholm Tooling AB, Hagfors, Sweden

(Accepted 1 September 1991)

"'\Key words: Mercury; Dental amalgam; Toxicity; Alternative materials ~

The risks of mercury exposure arising from the use of dental amalgam fillings are reviewed anddiscussed. On the basis of both knowledge acQuired in various scientific disciplines and ten years ofexperience in the field it is concluded that mercury from amalgam may weil contribute significantly to aDumheT of modern health problems and to decreased QuaIity of life in a large population group in manycountries. Erroneous opinion as to "negligible" mercury exposure and lack of cooperation between thedental, medical and other professions are two important factors in the issue. There is both biologicaland metallurgical evidence that typical Hg-exposure levels produced by amalgam fillings are 5-10-foldhigher than what are regarded as safe limits for exposure to mercury from other sources. There is nodoubt that dental mercury should be taken inta con side ration as a possible etiological factor whenconsidering neurological, immunological and endocrinological diseases of unknown etiology. Protectivemeasures during amalgam removal and prospects for alternative dental materials are discussed.

""'"\ History

The era of dental amalgam (DA) dates back to 1818 [1,2]. About 50% of adental amalgam is mercury (Hg), which can dissolve a number of metais. Silver,copper and tio were the first metals used in various rat ios for dental amalgams,

\ though dentists have been free to add many other metals such as gold, platinum,

zinc, bismuth, cadmium, nickel, manganese, indium, le ad and aluminium. Depend-ing on the procedure chosen, the precise mercury content of amalgam can varyconsiderably, from 42% with the conventionai and "dry" method to 60% Hg whenusing the so-called "wet" techniques.

Correspondence to: Jaro Pleva, PhD, PI 3079, S-68300 Hagfors, Sweden.

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From the very beginning, the use of mercury alloy implants has been a matter ofdebate and struggle. On ODe hand, dentists have appreciated the availability of a ,material capable of helping to preserve decayed teeth which is both cheap and easyto work. Opponents of amalgam have for a long period been convinced thatimplanting amalgam, which has been observed to sweat out a metal as toxic as "

mercury, must be harmful to bot h the living tooth and the rest of the patient'ssystem.

Initial resistance to dental amalgam remained strong till about 1860, ODeopponent of its use arguing that unI ess it could be shown to have overridingbenefits "... the practice must be abandoned as wholly improper" [3]. Manydentists nevertheless continued to use amalgam, and the general argument that it ~might be detrimental to health slowly receded. It came to the fore once more in -",'the period between the two world wars ("the second amalgam war") and was thenforcefully advanced once more during the 1980's ("the third amalgam war").

The earliest actual observations of intoxication due to mercury in amalgam hadappeared during the second half of the 19th century [4,5]. Between 1926 and 1939 ~the eminent German chemist Alfred Stock published his investigations on amal- '-..,;

gam and the properties of mercury as weIl as a very illustrative description of thesymptomatology of chronic mercury poisoning [6-8]. Mter 1945 a great deal ofspecialized research was undertaken into both the material properties of amalgamand the physiological effects of minute amounts of mercury. In the entire interdis-ciplinary debate, however, ODe has continued to miss an overall synthesis of thevarious issues, ranging from materials science and corrosion to neurology, im- ":munology and diagnostics; no unambiguous answer as to the biocompatibility of idental amalgam has ever been given.

The conventionai view and the field situation

The official position of the dental profession today seems to reflect a largemeasure of prestigious compromise, reflecting the fact that over a period of 170years the use of amalgam has become a firmly established tradition. Where ODemight expect concern or a willingness to carry out adequate epidemiological .",investigations into the health effects of dental amalgam, ODe in fact usually ~-

encounters only bland assurances to the effect that dental amalgam has been usedsuccessfully over such a long period, with favorable experience in billions of fillings[9], or assurances as to "very low mercury exposure" and the negligible toxicity ofinorganic -mercury (as compared to the organic form encountered in fish from a ~contaminated environment). Unjustified comparisons between the general popula-tion and workers occupationally exposed to mercury are also made as a means ofproving the safety of amalgam.

Oddly, the current situation is also complicated by the fact that the practicing .physician is much less familiar with the problems of "mercurialism" than was his '

predecessor in the days when mercury was widely used in medicine; that can onlymeaD that a diagnosis of mercury-induced problems is unlikely to be made. At the -

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same time, central authorities have sometimes release d general information aboutnon-existent risks of adverse effects from dental amalgam, an equal disservice tothe community.

Outside the official structures the situation is very different. In Sweden, thegrowing Scandinavian Organization of Dental Patients has acquired over 11,000members and has established contacts with patients in several other countries. Thefield experience built up by this group now extends over a period of more than tenyears. It comprises in particular the histories of patients with chronic complaintswho have been examined by most current methods, sometimes over several years,with out finding the cause of their troubles. Their problems have been res ist an t to

"' any tradition al treatment and the diagnosis "psychical disorder" is frequent. Alltoo of ten, according to this group, its members encounter from physicians only anattitude of scorn when they raise the subject of amalgam mercury. Some of theircase histories and experiences point to however is the fact that in the professions,ignorance of the facts which are known, coupled to what ODe might call educated

""\ nonchalance and an exaggerated loyalty to established structures are risk factors inamalgam poisoning. Very consistently, to put it briefly, many of the histories ofpatients of this type point to a persistence of symptoms so long as amalgam ispresent and a remarkable recovery af ter the amalgam has been removed. For thepatient who has experienced such symptoms, his or her recovery is obviously moreimportant than a willingness to await the production of the strict scientific proofwhich would be required by the authorities if they are to become convinced of theexistence of the problem. Needless to say, the recovery of such patients is alsobeneficial to the community and to the economy of the health care system.

The existence of a large DumheT of patients attributing their symptoms to dentalamalgam is not specific to Scandinavia, though the degree of severity and DumheTof cases may for unknown reasons be higher there; hypotheses have been raisedrelating to a low intake of selenium in Scandinavia or a relatively high level of useof amalgam. As far as the latter point is concerned: the level of use of amalgam inSweden has until recently been four times higher than in Germany (if ODe usesdata relating to what was recently the Federal Republic).

An unprejudiced discussion in the profession al press has sometimes been"'\ arrested by the argument, that the less amalgam-friendly findings would disquiet

the broad population who have "silver fillings" [10] - a view which has little to dowith the evaluation of scientific facts or with the human right to health protection.Another factor obstructing the publication of case historie s is the difficulty in exactand documented diagnosis; complete proof, if that is to include determination of

~ mercltry levels in the blood, urine or a body tissue, and the process of re challenge,is not possible. Judgements will necessarily have to be based largely on symptomsdescribed by the patient, comparison to known symptoms of mercurialism, theindividual's dental status and a history of failure to respond to any form of medicaltreatment, obviously coupled to a well-documented examination of the response toamalgam removal. However such judgements will commonly be considered unsci-entific - for example because of the absence of biochemical confirmation or theimpossibility of rechallenge - and for that reason individual cases may weIl fail to

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meet the usual requirements applicable to the peer review of material for publica-tion.

The manner in which exposure occurs to mercury incorporated in amalgam is inthe first instance a question of materials science. The metal is not primarilyabsorbed from the intact amalgam; it is released by corrosion, abrasion and bymetallurgical processes which take place within the amalgam filling. That fact,which may easily go unrecognized by the practitioner of a discipline other thanmaterials science, points to the obstacles which can arise from a lack of interdisci-plinary co-operation in a field such as this; there is a clear lack of joint effortbetween dentists (with whom the problem is generated), physicians (to whom thepatient with symptoms presents), toxicologists and materials scientists. Nor are the "health authorities likely to engage in any such broad interdisciplinary consultation --"in forming their views; they are likely to be heavily dependent, in issues such asthis, on information provided to them by the health professions, in casu theprofession of dentistry. An official statement which may be quoted from Swedenthat "... a sys~ematic deterio~atio.n of silve.r a~algam fil~ings has ~ever been ~reported" [11] IS for example In dlrect confllct with the evldence avallable from ',-~'

materials scientists.

Exposure to mercury

For the purpose of the present review only the most common form of dentalamalgam - the so-called "silver amalgam" - will be considered. A great deal ofresearch has been published on this material, though very little of it has seepedthrough into clinical practice.

For making an initial assessment of the level of risk, ODe can employ the sameapproach as that normally used when dealing with issues of occupational exposure.In the latter situation, exposure is regarded as being proportional to the aircon tent of mercury vapor. At a concentration of 25 JLg Hg/m3 (WHO ThresholdLimit Value, TLV), and allowing for an aspiration volume/rate of 0.75 1/15 permin during normal working hours, i.e., 8 hours a day, 40 hours a week, the dailyexposure will be 135 JLg Hg. For the general population, the U.S. EPA (Environ-mental Protection Agency) National Emission Standard, based on studies of the f\effects of mercury, is 1 JLg Hg/m3 air. Adopting the above assumptions, this ,--concentration will give an exposure to about 16 JLg Hg a day. The provisionaltolerable daily intake is 50 JLg of Hg metal a day (weekly intake 5 JLg Hg/kg bodyweight) [12].

These exposure levels can thus be taken as a starting point for examining the nlevel of mercury exposure from dental amalgam. The physico-chemical processes ' ~

underlying total exposure and the fate of amalgam mercury are demonstrated inFig. 1. Evaporation of mercury accounts, as will be seen, for only a part of the totalquantity released. What is released in solid or dissolved form willlargely enter thegastrointestinai tract; animal experiments [13,14,15] have indeed clearly demon-strated that, besides the lungs, important routes of absorption are the teeth andadjacent tissues as weIl as the gastrointestinai tract itself. .

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ExposureAbrasion - Corrosion - Phase transformatiOn

/' \Setting Hg. vapor

! ) dro\etsInsertion Absorbed Not absorbed

Lung )Gut Tooth

"'\ Air ./\ KidneyCremation - Symptoms - Deposition - Brain Feces

disease Fetus ./,/ etc

Sewage - Excretionstation, feces, urine

"'\ sludge """, ;;wage

Fig. 1. Main factors in long-term mercury exposure and the fate of mercury release d from dentalamalgam (schematic illustration).

The best method to document the total exposure of a patient to dental mercurywould clearly be a strictly controlled experiment; one would insert a filling ofknown weight and Hg-content, and remove it for chemical analysis af ter a prede-termined period. For practical reasons, such a controlled experiment has neverbeen carried out. There are however several other ways of arriving at fair estimatesof the level of release of mercury from amalgam. They involve considering andusing what is known about the three processes involved, i.e. transformation,corrosion and abrasion.

Transformation'"'\

Conventionai silver amalgam typically contains 50% of mercury (Hg), 35% ofsilver (Ag) and 10% of tin (Sn) by weight, as weIl as traces of copper and zinc.However there can be very considerable variations in composition, as weIl as inparticle size and form and in mercury content. As the amalgam sets, three main

, metallographic phases can be recognized alongside one another, designated asgamma-1 (Hg + Ag), gamma-2 (Hg + Sn) and gamma, which is the unreactedoriginal alloy powder of Ag + Sno The result of the setting re actions is dependenton many factors, including the initial content of mercury, the overall composition,the form and size of the alloy particles, the trituration time and the insertiontechnique of the dentist employing the material. The reported formulas of thephases and their Hg-content are shown in Table 1. From the literature it isobvious, that the setting reactions are unpredictable and that the resulting struc-

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TABLE 1

Reported formulas of the mercury containing phases and their Hg-content. Formation of beta-1 phasefrom gamma-1 has been observed in aged fillings

Phase Weight-% Hg Reference ,Gamma-lAgzzSnHgz7 68.4 25Ag4Hgs 69.8 2Ag3Hg4 71.2 2Ag\\Hg\S 71.6 2AgzHg3 73.5 2AgsHgs 74.8 2

~Beta-l ./AgHg 64.9 16,19 -

Gamma-2Sn7Hg 19.4 1,2SnsHg 17.4 1,2

~'-.".-

tural phases, most importantly gamma-l, vary considerably as regards their Hg-content. The impact of the structural instability on Hg-release is weIl illustrated bythe presence of the beta-1 phase in fillings as they age. Beta-1 (AgHg) is formed bytransformation from gamma-1 (Ag2Hg3), mercury being released in the process[2,16,17]. The Hg-content in the original combination present in the phase is 64.9%by weight, but the dental literature gives several later figures which deviate fromthis: slightly over 50% [1], 60%, 50.9 and 52.9%, or 47.5% in an amalgam specimenwhich has aged for three years in vivo [16]. Transition of only 1.0 gram of gamma-1(Ag2Hg3) to AgHg in 10 years will release 170,000 ,ug Hg (8% of the originalcontent), giving an exposure of 46 ,ug Hg a day. This transformation can provide apartiai explanation for the apparent contradiction between cases of long servicelife of amalgams and the simultaneous high release of mercury, since amalgam inwhich the transformation has occurred with loss of mercury can continue to giveservice. One can also easily be misled by the formation of Hg-free corrosionproducts of unchanged volume and form [18, this paper Fig. 2). A reasonableconclusion is therefore that no dentist can, merely by showing that a filling ~continues to give service and appears unchanged, provide any evidence as to ",,"_/

whether or not it has lost mercury, its future performance in an oral environment,or what the individual's current and future exposure to mercury is likely to be.

. nCo"osion ' /

Most of the known types of corrosion have been observed on amalgam fillingsaf ter clinical use: a distinction is drawn between the processes known as generalattack, selective corrosion, crevice attack, galvanic corrosi<;>n in contact withdissimilar metals and stress corrosion cracking. The main issue of concem in thedental literature has been the effect of corrosion on the mechanical performance --

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1.";-:-::'0" ,'O: c-

I"", \I ,I I

/'" I

t II ~I N

I 5I ""

I iI ~

"" I ';:;'I -inI /-- ~I / \ ~I / \ +'

I /' ~I / I 5I I \ uI Amalgam Ecorr I II 1 / I, . // I' 0.2 . - . - -06 - .

Potential E (V SCE)Fig. 2. Anodic polarization curves of a conventionaI silver amalgam in synthetic saliv:. (af ter Marek[21]). Abrasion or contact to gold increase the corrosion rate (current density) up to 2 orders of

, magnitude. The SEM-micrographs of cross sections show the differente in appearance of corrosionwithout and with contact to gold. Mercury depleted regions appear dark. (Micrographs of fillings af ter

service in vivo by J. Pleva).

of restorations. There have been observations of the release of free mercury, droplets by corrosion [19] or by simple polishing [20], though it should be noted

that not even these have triggered any serious appraisal of the resulting exposurelevel, and its possible health impact.

The extent öf corrosion depends not only on the properties of the filling, butalso on the aggressivity of the individual oral environment. In the general popula-tion, there are obviously considerable variations in the type of faDd consumed, itssalt content, pH-valne and temperature, as weIl as in chewing habits (e.g. thepressure exerted on the teeth), the composition of the saliva and the constitution

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of the bacterial flora. The extent of the influence exerted by these factors can bemeasured by various techniques. A considerable increase in electrochemical corro- .sion currents can for example be detected and measured during slight experimen-tal abrasion, comparable in degree to that caused by chewing [21]. The process ofcorrosion is accompanied by a corresponding release of metallic mercury, part of ~

which can be easily monitored as vapor in the expired air. Svare [22] measured onaverage a 15-fold increase and Patterson [23] a 40~fold increase af ter chewing andbrushing, respectively.

There are two possibilities for assessing the resulting level of patient exposure.The first of these involves making measurements of corrosion depth on fillingswhich have had in vivo service; this will naturally provide only information on ~processes involving the exposed area and not as to what happens on occlusive -"surfaces. The second method is based on measurements of corrosion currents invitro. From the measured polarization curve and free corrosion potentials, Olle canestimate corrosion rates and the amount of metal dissolved [24,25]. Examples ofboth types of measurement are shown in Fig. 2. The dark layer of mercury-free f\corrosion products in the upper microphotograph of Fig. 2 shows how contact to "-'gold renders the attack more general. From the mercury free volume and theknown service time of the restoration, the daily Hg-exposure can be calculated [18].General conversion of the filling "b" illustra ted in this figure resulted in therelease of 29 J.Lg Hg/day, i.e. 68 mg Hg in 9 years. Selective corrosion, seen infilling "a", has resulted in release of about 30 J.Lg Hg/day.

In Table 2 calculations of the amounts of mercury released from a surface areaof 1 cm2 are shown, based on Marek's measurements [21] and using Faraday's Law[24]. The exposure levels estimated from corrosion measurements are in closeagreement with the in vivo fin dings of Vimy et al. in she ep and monkeys [13,14]. Intheir work, the main part of the mercury released was found in the gastrointestinaitract and it could be monitored in the faeces. The sheep excreted about 9000 J.LgHg a day from 12 occlusal fillings, during the first month af ter insertion. The rateof faecal mercury excretion in monkeys, 4 weeks af ter amalgam placement,averaged 300 J.Lg Hg/day. Over the 4-week period, cumulative mercury lossamounted to 0.5% of the total Hg in their amalgams. Urinary excretion of Hg wasnegligible, attaining less than 1 % of that excreted daily in the faeces. ~

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TABLE 2

Calculat:ons ?f relea~ed mercury fro.m 1 cm2. fr?m corrosion currents and potenti~ls in Fig. 2, using r Faraday s law. AbrasIon and galvamc corroslon ID contact to sold have been consIdered. Data from

'-./TerS. 21 and 24 have been used

No contact to sold Contact to soldAbrasion: no yes no yes .Corr. current, /LA/cm2 2 87 100 - 700Released Hg, /Lg/day/cm2 135 5872 6750 47250Released Hg in 2 h chewing - 490 - 3937 ,,:

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The above levels of Hg-release, noted with freshly placed amalgam, are muchhigher than the average long term release. Af ter several months in service, the rateof Hg release decreases considerably [26], hut it can rise again af ter a prolongedperiod of time.

Abrasion

An exposure assessment based on corrosion data will not reflect the quantitiesof amalgam mercury released as a result of mechanical wear. Wear rates in a dryartificial mouth have been studied by deLong [27]. In correlation with clinical

"" observations he found an amalgam wear rate of 65 JLm per year at points ofcontact with enamel. For a total contact surface of 1 cm2 the wear will result in therelease of 37000 JLg Hg per year, i.e. 101 JLg Hg a day.

Similarly, Angelini et al. [28] found on a conventionaI silver amalgam a loss of alayer 100 JLm thick af ter 300,000 brushing strokes. For dispersion-typ e dental

""'" amalgam the wear rate was 40 JLm and for a high copper amalgam 30 JLm. On a

yearly basis, the corresponding total levels of exposure from 10 cm2 of amalgamsurface (the Swedish average) will be 1560 JLg, 624 JLg and 468 JLg Hg a dayrespectively. The release figures obtained here are much higher than thoserecorded by deLong, reflecting the fact that these latter experiments were per-formed in artificial saliva and that corrosion was therefore also involved.

The dos e absorbed

Because of the dynamic character of the process involved, estimates of theamounts of mercury actually absorbed are difficult. As pointed out earlier in thisreview, a certain (unknown) doge is absorbed by the teeth [29] and oral mucosa[18]. Up to 80% of inspired Hg-vapor is absorbed in the lungs [30]; Vimy [31]estimated the daily doge absorbed through this latter route at 20-30 JLg Hg a dayfor an average patient, and 8 JLg in subjects with no more than four occlusal

, amalgams. During the first we ek af ter exposure, about 10% of the mercury vaporabsorbed in the lungs is re-excreted into the intestines [32]. In rats, the amountretained has been found to be distributed to the kidneys, brain, myocardium,intestine and liver, in decreasing order of magnitude [33].

The rate of absorption in the gastrointestinaI tract is dependent on the chemical""'" form ffi which the metal is present, though as the history of acrodynia shows, even

poorly soluble forms of mercury can be absorbed in toxic quantities in theintestinaI environment. The metallic and ionic mercury released from the fillingsmay be methylated, or organic Hg may be demethylated, by intestine bacteria[35,36]; some metallic mercury will however certainly be present. It is known thatorganic Hg is absorbed much more strongly than are inorganic salts or metallic Hg.A rough estimat e is that in the gut some 2-15% of the latter may be absorbed [34],though following biliary excretion, re-absorption in the gut may occur. What is

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more: since the Hg content of the faeces has been found to be high [13,14], even alow percentage rate of absorption can result in the absorption of a large amount ofmercury.

Absorption is also affected by the physical form in which mercury enters thegastrointestinaI tract. Dissolved Hg and amalgam microparticles have a higheravailability than do large drops and particles. Chewing of fatty food will result inthe production of a weak mercurial ointment, the presence of which is againknown to increase substantially absorption through mucous membranes. All thesefactors need to be considered when discussing mercurial exposure.

Knowledge of the different propensity for absorption of the various chemicaland physical forms of mercury is as important in considering the amalgam problem ~as it is in explaining the large variations in sensitivity exhibited by workers exposed '-"'

to the metal in the course of their occupation. Studies of amalgam can also benefitfrom phenomena investigated as regards occupational exposure. In the chlor-alkaliindustry, presence of a small amount of chlorine in the air, for example, protectsthe workers from a part of the insidious effect of mercury vapor; Hg-vapor is ~oxidized by chlorine gas to calomel (mercurous chIoride) which is less toxic (being '--'less weIl absorbed) and is also precipitated before it can be inspired [38].

The toxic etTects of mercury

Symptomato!ogy

The symptomatology of chronic Hg-poisoning is known mainly from the study ofoccupational exposure, but also from the history of medical treatment withmercurials (used at various times against syphilis, against intestinaI parasites, inointments and until a generation ago even in diuretics), and from accounts ofexposure resulting from accidents or ignorance. An extensive bibliography onmercury and its effects has been compiled by Hanson [99]. The list of symptomsattributed to the metal is long [40-46]; those most frequently cited and bestdocumented on the basis of chronic mercury exposure are listed in Table 3. ,~

Chronic exposure to mercury vapor leads to an insidious, slowly developing '---

intoxication, which is very difficult to recognize until more marked and moreobjective signs and symptoms appear. Paradoxically, the drastic exaggeration ofsymptoms which may be observed af ter the installation of gold-amalgam restora-tions will sometimes help dental patients to discover the hitherto obscure etiology ~of their problems [48]. '-~

It is not surprising that in patients suffering from the early effects of mercurialexposure the diagnosis teDds to le an heavily on the psychical elements in the entirepicture. The early symptoms are largely subjective and, up to the present, have o.

often been identified only in the course of a dialogue with the patient. Suchsymptoms will include abnormal fatigue, depression, shyness, irritability, loss of

..memory (especially short-term memory) and intellectual exhaustion [8]. With

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TABLE 3

Documented, most frequent symptoms in chronic mercury exposure [40-46,831

Nervousness, irritability Vertigo DermatitisShyness, timidity Tinnitus, noises in ears Gastrointestinai problemsLack of attention Fine tremors of hands, feet, DiarrheaLoss of memory lips, eye lids Speech disordersLack of self controi Persistent cough, asthma Renal damageLoss of self confidence Endocrine disturbances Menstruation disturbancesAnxiety Joint, back pain s Bleeding gumsDepression Muscle pains and weakness Loosening of teethGeneral CNS dysfunction Fatigue Excessive salivation

""\ Irregular heartbeat Drowsiness Metallic tasteAlterations in blood pressure Insomnia StomatitisPain, pressure in chest area Dim or double vision Sinusitis, chronic coldHeadaches Impaired hearing

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progressing chronic mercurialism, symptoms of a more somatic type appear, butthere are large variations in sensitivity and in the pattem of response. It seems veryprobable that, because of a lack of recognition of the early toxicity pattem ofmercury, many patients with early symptoms are readily dismissed as sufferingfrom mental disorder.

Experience in the field suggests that the largest numbers of symptoms and thosewhich are most severe teDd to be observed in patients with gold-amalgam inte r-faces, which are in effect oral galvanic cells. Once they have been informed of thepossibility that amalgam may have induced illness, many patients seem ableretrospectively to relate the aggravation of their health problems to the installationof such a gold-amalgam "battery" at a slightly earlier date. Other forms of dentaltreatment too can have an aggravating effect, e.g. the replacement of old fillings bynew or endodontics treatments. By far the most undesirable effects seem to resultfrom constructions in which a brass element carries amalgam, covered in tum by agold crown. Removing this type of dental prosthesis has been reported to result inalleviation of the severe symptoms [48]. There are many wamings in the literature

\ against the lise of gold-amalgam batteries [19,49,50], but Olle cannot gay that thedental profession has taken due notice of these or considered the natural lawswhich underlie these problems.

In the field of molecular biology, research is in progress to elucidate the fate ofmercury and other trace elements, whether deleterious or essentiai, in the body.

""' Results of this work, including some which are disputed, point to possible interac-tions between mercury and other metals in the biological system. Patients withsymptoms similar to those of mercurialism ("metal syndrome") have been found tohave increased plasma levels of mercury and decreased plasma levels of selenium(Se) and zinc [51]; the activity of the selenium-containing enzyme glutathioneperoxidase (GSH-Px) is in such cages usually decreased. In gingivai biopsies, highconcentrations of both Hg, Ag, Sn and Se have been found in subjects with anormal selenium status; in biopsies from symptomatic patients, on the other hand,

12 I

selenium was absent, indicating its possible importance in protection against theeffects of heavy metaIs. The formation of extremely insoluble selenides can cause "

depletion of Se,which would in tum result in reduced activity of GSH-Px and thusraise the risk of inadequate protection to lipid peroxidation. Studies of symp-tomatic individuals have also shown skewed distributions of mercury, zinc, magne- .'

sium, calcium, iron, manganese and strontium in the erythrocytes and neutrophilgranulocytes [52], as measured by PIXE (Particle Induced X-ray Emission).

At this point ODe must consider what consequences mercury (or interactions inwhich it is involved) could have for various organ systems, and to what extent theseconsequences have actually been demonstrated.

~Neurology and immunology ",-'

It is weIl documented and generally accepted, that the nervous system is ODe ofthe primary targets for mercury. Many of the symptoms referred to above reflectan influence on the central nervous system (CNS), in combination with endocrine ~disturbances [53]. In the past, attention was directed primarily to the severe CNS ..-'

damage resulting from methylmercury (MeHg) poisoning, such as that due toconsumption of contaminated fish in Minamata, Japan, or of mercury-treated grainin Iraq (Bull. WHO, 1976). Since then, primarily for environmental reasons,interest in the CNS effects of mercury as a metal and of inorganic mercury hasbecome much greater. Depending on the target organs involved, inhaled Hg-vaporcan exert effects similar to those of methylmercury; swallowed mercuric chioride,on the other hand, will be localized mainly in the kidneys [43,53]. Both Me Hg andHg-vapor pass through cell membranes where as ionic Hg binds to them andcoagulates protein. Mercury can cross the blood-brain [54,55] and placental barri-ers [56,57]. In a fetal sheep, amalgam-Hg appeared in the pituitary glaDd and liver.In man, a correlation between the presence of dental amalgam and the occurrenceof mercury in brain tissue has been reported [58]. The correlation found betweenthe Hg content of the pituitary glaDd and individual status as an amalgam carrier[59] or a dentist [60] is of special interest. Nylander found a statistically significantregression between the number of amalgam surfaces and the concentration of Hgin the occipital lobe cortex [59] and in the pituitary [61]. In experiments with ~guinea pigs, the uptake of Hg in brain was found to be several times higher af ter '- /

exposure to Hg-vapor than to an injected inorganic salt, but the pattem ofdistribution in the brain was similar af ter both modes of administration [62].Though seldom considered, there is some evidence that retrograde axonal trans-port of Hg to the brain may be ODe of the routes of uptake [66]. {\

Mercury seems to be metabolized slowly in the brain; the slow alleviation of .. ~

psychic symptoms (such as erethism mercurialis) af ter amalgam removal, as con-trasted to the rapid lessening of such somatic symptoms as joint pains is qualita-tively in agreement with this finding. In fact the elimination rate of Hg differs ~

between the various regions of the brain, as demonstrated by findings in ratsstudie d by Cassano et al. [63]. In autopsy brain specimens from confirmed victims

.of Alzheimer's disease, elevated concentrations of Hg and Br have been found in

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parts of the brain showing consistent pathological alterations [64,65]. Informationon possible links between multiple sclerosis, Hg and selenium can be found invarious publications [47,75,83].

Endocrine effects

According to Trachtenberg [67], low Hg concentrations markedly increase thefunctional activity of the hypophyseal-adrenal cortical system, which could explainsom e of the metal's endocrinological effects. As there is a close relationshipbetween adrenal and thyroid function, thyroid dysfunction can indicate hypophy-

"'\ seal-adrenal disorder.

Immune system

The immunotoxicity of Hg is weIl known. Both inorganic and organic Hg initiate""' autoimmune reactions, characterized by the formation of antibodies to a variety of

proteins. Trachtenberg [67] concluded that immunological changes occurred priorto the emergence of (latent) toxic effects. Mercury, whether from the workingenvironment [68] or from dental amalgam [69,70] can adversely affect the immuneresponse, e.g. the number of T -lymphocytes. In this context the high frequency ofalleviation of various painful joint, back and muscle (fibromyalgia) problemsclairned to have been observed following the removal of amalgam is of interest [83],particularly in view of the wide incidence of these conditions with their immuno-logical facets.

Renal effects

Toxicity studies point to the kidneys as a primary target for the toxicity ofinorganic mercury. High levels of mercury are found in sheep and monkey kidneysshortly af ter application of dental amalgam [13,14]. Impairment of glornerularfiltration by mercury derived from dental amalgam has been reported by Vimy etal. [71].

, In occupational exposure, Lamm and Pratt [72] found a negative correlationbetween exposure time and urinary excretion of mercury, which can reflectprogressive impairment of the ability of the kidneys to excrete the metal. Thiscould in tum point to progressive failure to excrete Hg as a factor in thedevelopment of poisoning. These findings however can also me an that urinary Hg

--- levels 'are of limited value in the diagnosis of poisoning; high urinary levels of

mercury can be found in symptom-free subjects, as opposed to low levels in thoseshowing evidence of mercurialism [73].

Diseases of unknown etiology

Bearing in mind the evidence which nowexists for a much higher level ofpopulation exposure to this toxic mercury than was previously recognized, the

14

possible involvement of mercury in a number of diseases of unknown etiology . I

should be reconsidered. Among them are a series of syndromes, hearing the names ~

of the workers who first described them. Recently, descriptions of over sixty suchname d syndromes and the men be hind them have been published in the Journal ofSwedish Physicians [74]; most of these are listed in Table 4, alongside the year and .

the country in which they were described.While the pace of discovery most certainly followed the increasing rate of

medical innovation, it would be fair to note that a great many puzzling syndromeswere first identified only af ter the introduction of dental amalgam into Europeanmedicine from 1819 onwards despite the fact that mercury exposure occurred(even in medicine) at a much earlier date. One might further add that at the time ~when many of these syndromes we re brought to the fore, amalgams producing a 'o~'"particularly high level of mercurial exposure were in lise; typical amalgams in lisearound 1900, when their properties we re first studied by G. V. Black, certainlyshowed a high propensity to corrosion.

;-:0.",

The overall picture It would be very rash to claim that every case of the disorders alluded to above

can be traced to amalgam, much rasher to suggest that every patient carryingamalgam will develop the se disorders. What is evident, however, is that suspicionhas fallen upon amalgam as inducing or triggering a wide range of disorders insensitive individuals. Some advocates of amalgam removal have compiled long listsof the conditions which in their view could benefit. Oaunderer [69] has postulatedthat dental amalgam fiIlings should be regarded as contraindicated in any disorderof the nervous system, multiple sclerosis, morbus Alzheimer, Parkinson's disease,Crohn's disease, amyotrophic lateral sclerosis, sudden blindness or deafness,colitis, anorexia, chronic diarrhea, repeated sinusit is, depressions, paraesthesia andAIDS.

The ca se of acrodynia~

Before dismissing lightly the multiple arguments for a broadly toxic role of themercury in dental amalgam, one would do weIl to consider the lessons to bederived from the history of that extinct disease, acrodynia [39,77]. Known also as"pink disease", it was characterized by redness and sweIling of the fingers, feet,nose and'ears, loosening of the teeth, salivation, insomnia, sweating, diarrhoea, r"'""'I

weakness and apathy. It affected children up to about 9 years of age, mainly in England, the British Commonwealth and the United States. There were many

etiological theories, ranging from "primary emotionai disorder" to allergy, neuro-sis, endocrine disturbance and viTal infection. Impressive arguments were ad- ..

vanced in favor of one theory or the other, hut they did not bring one closer toprevention or cure of the disease. Only in the 1950's, af ter a hundred years of ),

acrodynia, was the etiological role of mercury in every case established. The

15

TABLE 4

Compilation of syndrome names from ref. 74, their character and origin

Syndrome /Morbus Character Described

Year Country

Parkinson N 1817 GBBright E 1830 GBBell N 1830 GBHodgkin 1 1832 GBBasedow, Grave E 1840 D (G B)Addison E 1849 GB

"" Meniere N 1861 Fvon Graefe E 1864 DDown N, 1 1866 GBHenoch, Schönlein I, N 1868 DHorner N 1869 CHRobertson N 1869 GB

"'" Huntington N 1872 USACharcot, Marie, Tooth N 1874 F, GB, FMorton N 1876 USAQuincke I? 1882 DGaucher N 1882 FHirschschprung N 1886 DKWernicke, Korsakov N 1887 D, RussMenetrier 1 1888 FBechterew 1 1892 RussWilms 1 1899 DMeige N 1902. FAlzheimer N 1907 DWhipple 1 1907 USACushing E,N 1912 USAReiter 1 1916 DStevens, Johnson 1 1922 USAFelty 1 1924 USAMoschcowitz N 1925 USAHippel, Lindau N 1926 D, SMelkersson, Rosenthal N 1928 S

-." Forestier 1 abt 1930 F'Sjögren 1 1930 F

Crohn ? 1932 USAdeLange ? 1933 NLKartagener ? 1933 CHKimmelstiel, Wilson I? 1936 D, GB

~ Horton. N 1939 USACogan 1 1945 USALöfgren 1 1946 SLuft E 1958 S 'J}?

,N = neurology; 1 = immunology; E = endocrinology.

children concerned bad been exposed mainly to calomel (HgzClz) in the form of"teething powders" or as a component of sedatives, laxatives or anthelmintics. Asmaller number bad been exposed to Hg-ointments or to mercuric chioride in rinse

16

solutions. An estimat ed Olle in every 500 children exposed developed acrodynia,and about 10% of the patients died. :;

This was an instance in which, despite what the proponents of calomel treat-ment would no doubt have considered "well-tried and favorable experience" overa period of a hundred years, the harm far outweighed the good.' Calomel prepara- ::

tions we re withdrawn from the market, following which the disease disappeared.Unfortunately, there was never a proper analysis and elucidation of the mecha-nisms underlying mercurial acrodynia, such as could have proved useful in advanc-ing knowledge of individual reactions and susceptibility to drugs in general andmercury in particular.

~-'

Removal of amalgam and other protective measures

As noted by Warkany [77] and confirmed by field experience, current knowledgeamong medical and dental professionals as to the wide spectrum of adverse r"-reactions to mercury is far less extensive than it was in former generations. In the o_-situation as it currently exists, it is likely to be the amalgam patient himself orherself who will have to assess the situation and decide for or aga in st the removalof mercury-bearing fillings. The patient may only be confronted with the issue af terhaving been examined by physicians for many years for signs and symptoms whichmayor may not have been accorded an eponym but which have remainedunexplained. Having found a dentist who is open to consideration of the issue -itself sometimes a considerable problem the decision to remove amalgam may betaken. If it is, a new conundrum may arise, for uni ess protective measures aretaken the process of removal of the amalgam itself may temporarily increasemercury exposure. The patient, who by the very nature of things is likely to beparticularly sensitive to the metal, will need to be protected from the increasedexposure to Hg during drilling, e.g. by adequate water cooling and high volumeevacuation (vacuum cleaning) [78,79], and the swallowing of pulverized fillingsneeds to be prevented. In Sweden a combination of research findings and fieldexperience has further led to the belief that patients can be afforded additionalprotection at this time by the administration of selenium (200-400 JLg daily) as nweIl as vitamins Bl, B6, C and E and supplements of zinc and magnesium.Aggravation of symptoms hours or days af ter drilling in an amalgam filling iscommon (and may be considered as a confirmation of the etiological role ofmercury in the sensitized patient) and patients should be warned to anticipate it;patients are further advised to space the replacement sessions at intervals of not r--"\less than a month. Although urinary excretion of mercury is for a time substantiallyincreased during progressive amalgam removal (and mild but acute effects, such asskin re actions, may occur in about 1 % of ca ses), once removal is complete themercury level in the urine will decline. ;;

There are recent reports on a possibility of heavy metal detoxification using2,3-dimercapto-l-propanesulfonate (DMPS, Dimaval, UnithioI). Daunderer [69]reported 10 years of good experience with over 850 cases, treated intravenously ~

17

with DMPS. 98% of patients showed a marked increase in the mercury con tent ofthe urine af ter such mobilization. It may be noted that Zalups et al. [80] reportedon good results with this same agent in treating the acute nephrotoxic effects ofmercuric chioride. An alternative drug against heavy metal poisoning, which hasbeen very weIl tolerated by children, is 2,3-dimercaptosuccinic acid (DMSA) [81].

Results of amalgam removal

The problems in providing incontrovertible evidence of a cause and effect, relationship between amalgam mercury and any individual case of disease have

been alluded to above. The history of acrodynia - which developed in only one casein 500 exposed to mercury - underlines the fact that the correlation between thecausative (or triggering) agent and the disease can be far from absolute; it followsthat amalgam removal can only be expected to produce results in those cases

"" where mercury has indeed played a role, and that there will be disappointments.For such reasons, onlyasmall number of cases of amalgam poisoning and recoveryhave been documented in the scientific literature; it is arguable that the greatmajority have remained undiagnosed. Between those two extremes, however, onehas a considerable body of case material, such as that accumulated by theScandinavian Organization of Dental Patients, relating to individuals whose historyand dental status created a reasonable assumption of cause and effect, and inwhom removal of amalgam was followed by recovery.

Some of the cases which have been published have not surprisingly given lise tocontroversy. An impressively documented case of amyotrophic lateral sclerosis(ALS) recovering af ter amalgam removal was described by Redhe [82], but theentire history - including the original diagnosis - was subsequently challenged.Stock' s description of his own poisoning [6] is a highly illuminating case. Furthercases have been described in the literature and justify study [8,18,24,48,69,84-93].What above all calls for attention is the very large amount of anecdotal evidencedemanding objective analysis, collected among organized Scandinavian patients.Cases in whom recovery has been recorded include patients with Parkinsonism,

~ Crohn's disease, multiple sclerosis, epilepsy, asthma, scleroderma, paranoia, blind-ness, and disorders originally thought to be of viraiorigin. Over 500 cases havebeen briefly evaluated by Hanson [83].

, Prospects for alternative materials

There ar~ several groups of materials which can provide suitable alternatives todental amalgam. In the most important group are the composite resins, filled withhard particles. Initial evaluations in the early 1970's detected problems withleakage and excessive wear. The insertion was also more time-con surning andoperator-sensitive than that of dental amalgam. Newly developed poste rior com-posites have improved resistance to wear, fracture and discoloration, and possess

18

improved radiopacity, and when used in conjunction with etching and dentinaibonding they strengthen the restored tooth and resist leakage. The material's ~'",manipulation and placement properties have also improved, light-cured compositesshowing clear advantages over those which have been chemically cured. Severalinvestigations concluded that the se improved posterior composites gave a better ~clinical performance than amalgams. Bayne [94] examined 17 posterior compositematerials over 5-10 years; the failure level for 899 composite fillings at 5 years was9.2%, which is less than half that for conventionai amalgam (failure rate 20% at 5years and 50% at 10 years). In another study [95], the 5-year survival of amalgamrestorations and composites was 84% and 89% respectively. In addition, study ofthe marginal breakdown of 432 posterior composites and 73 amalgam restorations ~showed a marginal crevice in 28% of composite restorations hut in 60% of '-amalgams; af ter two years, the marginal integrity of the studied posterior compos-ites was superior to that of an amalgam alloy [96]. Up to now, no serious adverseeffects of modem composites have been reported, or observed in the fieldexperience, perhaps making an exception for the hypersensitive amalgam patient. 1"""",What is essentiai is to avoid some known causes of premature failure with these "'-

materials, e.g. contact with phenol compounds even in minute amounts must beavoided, otherwise polymerization will be inhibited. Recent research also supportsthe view that all dentin should be covered with glass ionomer to reduce microleak-age [97]. When using light-curing units, care should be taken to ensure that thespectral peak corresponds to the maximum hardening wavelength and that thelight intensity is correct; to ensure the best results, the operation of light-curingunits should be regularly controlled.

The ceramic material group is another very promising Olle in respect ofbiocompatibility and durability. Materials in this group are available as crowns,and computerized techniques for the preparation of inlays are under development.

Titanium (Ti) is increasingly used for implants, in dental practice mainly forscrew fasteners. All experience points to good biocompatibility of Ti [98], which iscertainly to a large part due to the high corrosion resistance of the material.However, the general fUle that Olle should avoid galvanic contacts with othermetals applies to titanium as weIl.

Last hut not least, gold alloys have long been suitable materials for dental nrestorations. In sensitive patients, alloys with a high copper content and ceramiclayers applied for better appearance have been observed to cause symptoms, thereason for the latter being unknown. Hypersensitivity problems may arise with anyalternative material in severely mercury-influenced patients. Careful selection of acompatible material is a matter of cooperation between the dentist and the 1""""\

patient.All in all, field experience shows that in terms of life cycle cost {taking into

account all the costs associated with the use of a given material}, there areacceptable alternatives to amalgam and that these continue to improve. ..

In this situation, there is today little reason to continue to use amalgam. It is amaterial with respect to which suspicions of serious health risk are founded uponfield experience and evidence from toxicology and materials science and pure )..

19

theory; those risks are likely to be reflected too in costs, and if that is so then eventhe economic argument for using amalgam evaporates. An amalgam filling has anunpredictable structure, the setting reactions, the resulting phase composition,performance and the Hg-exposure cannot be controlled. What is, however, morethan evident is that the exposure of the average amalgam heaTeT to mercury isseveral times in excess of the acceptable exposure levels established for mercuryfrom other sources; and there are various common situations in which the level ofexposure is further increased. It is bard to see that, with the emergences ofreasonable and affordable alternatives, continued exposure to even a theoreticalhazard of this degree is defensible.

"\

Acknowledgement

The author is indebted to Dr Mats Hanson, Veberöd, Sweden, for access to his, extensive mercury bibliography [99] and for valuable discussions."'\

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Veberöd,.Sweden. ("""\

~

t