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Int. J. Hyg. Environ.-Health 209 (2006) 309–316 Mercury amalgam dental fillings: An epidemiologic assessment Michael N. Bates Division of Environmental Health Sciences, School of Public Health, 140 Warren Hall, University of California, Berkeley, CA 94720-7360, USA Received 22 June 2005; received in revised form 14 November 2005; accepted 30 November 2005 Abstract Dental amalgam fillings containing approximately 50% mercury have been used for almost 200 years and have been controversial for almost the same time. Allegations of effects caused by amalgams have involved many diseases. Recent evidence that small amounts of mercury are continuously released from amalgam fillings has fuelled the controversy. This is a comprehensive review of the epidemiologic evidence for the safety of dental amalgam fillings, with an emphasis on methodological issues and identifying gaps in the literature. Studies show little evidence of effects on general chronic disease incidence or mortality. Limited evidence exists for an association with multiple sclerosis, but few studies on either Alzheimer’s or Parkinson’s diseases. The preponderance of evidence suggests no renal effects and that ill-defined symptom complexes, including chronic fatigue syndrome, are not caused by amalgams. There is little direct evidence that can be used to assess reproductive hazards. Overall, few relevant epidemiologic studies are available. Most prior assessments of possible amalgam health effects have been based on comparisons of dental mercury exposures with occupational exposures causing harm. However, the amalgam-exposed population contains a broader, possibly more susceptible, spectrum of people. Common limitations of population-based studies of dental amalgam effects include inadequate longitudinal exposure assessment and negative confounding by better access to dental care in higher socioeconomic groups. Better designed studies are needed, particularly for investigation of neurodegenerative diseases and effects on infants and children. r 2006 Elsevier GmbH. All rights reserved. Keywords: Dental amalgam; Epidemiology; Review; Kidney disease; Mercury; Neurologic disease Introduction Mercury combines readily with other metals to form solid amalgams, which have been used continuously in dentistry for nearly 200 years to reconstruct decayed teeth. Mercury use in dentistry has been controversial since at least the middle of the 19th Century. This controversy has intensified over the last 25 years, since sensitive analytical chemistry techniques showed con- tinuous release of mercury from dental amalgams (Gay et al., 1979). International and regulatory agencies have evaluated the potential of amalgam fillings to cause health effects, usually concluding no evidence of harm and, therefore, no reason to advise against their use (World Health Organization, 1997; Department of Health and Human Services, 1997; US Food and Drug Administration, 2002). Amalgams fillings currently comprise about 50% mercury, with the remainder principally silver, plus small amounts of copper, tin, or zinc (Fredin, 1994). Although other filling materials are available, popularity of amalgam is maintained by its relative cheapness, durability, and ease of use (Newman, 1991). In many ARTICLE IN PRESS www.elsevier.de/ijheh 1438-4639/$ - see front matter r 2006 Elsevier GmbH. All rights reserved. doi:10.1016/j.ijheh.2005.11.006 Tel.: +1 510 643 5998; fax: +1 510 642 5815. E-mail address: [email protected].

Mercury amalgam dental fillings: An epidemiologic assessment

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ARTICLE IN PRESS

Int. J. Hyg. Environ.-Health 209 (2006) 309–316

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Mercury amalgam dental fillings: An epidemiologic assessment

Michael N. Bates�

Division of Environmental Health Sciences, School of Public Health, 140 Warren Hall, University of California, Berkeley,

CA 94720-7360, USA

Received 22 June 2005; received in revised form 14 November 2005; accepted 30 November 2005

Abstract

Dental amalgam fillings containing approximately 50% mercury have been used for almost 200 years and have beencontroversial for almost the same time. Allegations of effects caused by amalgams have involved many diseases. Recentevidence that small amounts of mercury are continuously released from amalgam fillings has fuelled the controversy. This isa comprehensive review of the epidemiologic evidence for the safety of dental amalgam fillings, with an emphasis onmethodological issues and identifying gaps in the literature. Studies show little evidence of effects on general chronic diseaseincidence or mortality. Limited evidence exists for an association with multiple sclerosis, but few studies on eitherAlzheimer’s or Parkinson’s diseases. The preponderance of evidence suggests no renal effects and that ill-defined symptomcomplexes, including chronic fatigue syndrome, are not caused by amalgams. There is little direct evidence that can be usedto assess reproductive hazards. Overall, few relevant epidemiologic studies are available. Most prior assessments of possibleamalgam health effects have been based on comparisons of dental mercury exposures with occupational exposures causingharm. However, the amalgam-exposed population contains a broader, possibly more susceptible, spectrum of people.Common limitations of population-based studies of dental amalgam effects include inadequate longitudinal exposureassessment and negative confounding by better access to dental care in higher socioeconomic groups. Better designedstudies are needed, particularly for investigation of neurodegenerative diseases and effects on infants and children.r 2006 Elsevier GmbH. All rights reserved.

Keywords: Dental amalgam; Epidemiology; Review; Kidney disease; Mercury; Neurologic disease

Introduction

Mercury combines readily with other metals to formsolid amalgams, which have been used continuously indentistry for nearly 200 years to reconstruct decayedteeth. Mercury use in dentistry has been controversialsince at least the middle of the 19th Century. Thiscontroversy has intensified over the last 25 years, sincesensitive analytical chemistry techniques showed con-tinuous release of mercury from dental amalgams (Gay

e front matter r 2006 Elsevier GmbH. All rights reserved.

eh.2005.11.006

643 5998; fax: +1 510 642 5815.

ess: [email protected].

et al., 1979). International and regulatory agencies haveevaluated the potential of amalgam fillings to causehealth effects, usually concluding no evidence of harmand, therefore, no reason to advise against their use(World Health Organization, 1997; Department ofHealth and Human Services, 1997; US Food and DrugAdministration, 2002).

Amalgams fillings currently comprise about 50%mercury, with the remainder principally silver, plussmall amounts of copper, tin, or zinc (Fredin, 1994).Although other filling materials are available, popularityof amalgam is maintained by its relative cheapness,durability, and ease of use (Newman, 1991). In many

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countries amalgam is still the most commonly usedfilling material in posterior teeth (Clarkson, 2002).

For most people (except those occupationally exposed),amalgams are their main inorganic mercury exposure(Clarkson, 2002). Amalgam fillings release mercury vaporcontinuously at low levels. The release rate is dependenton filling size, tooth and surface placement, chewing, foodtexture, tooth grinding, and brushing teeth, as well as thesurface area, composition, and age of the amalgam.Correlations have been demonstrated between the numberof amalgams and expired breath (Patterson et al., 1985)and urinary mercury concentrations (Langworth et al.,1988). Subjects with amalgam fillings have more mercuryin saliva and feces (Bjorkman et al., 1997). The number ofamalgam surfaces is correlated with the mercury contentof brain and kidney tissue at autopsy (InternationalProgram on Chemical Safety, 1991).

Inorganic mercury primarily affects the nervous andrenal systems, although it may also have effects on theimmune, respiratory, cardiovascular, gastrointestinal,hematologic, and reproductive systems. These toxiceffects may be mediated by binding of mercury tosulfhydryl groups of enzymes (Agency for ToxicSubstances and Disease Registry, 1999). Most informa-tive epidemiologic studies of the effects of inorganicmercury exposure have been occupational studies.However, because the amalgam-exposed population isbroader and potentially more susceptible than occupa-tionally exposed populations, it is necessary to examinepopulation-based epidemiologic studies of dental amal-gam exposures. That is the purpose of this review.

Methods

PubMed was searched using the term ‘‘dentalamalgam’’ in combination with other relevant keywords, including ‘‘epidemiology’’, ‘‘multiple sclerosis’’(MS), ‘‘Alzheimer’s disease’’, ‘‘Parkinson’s disease’’, etc.The bibliographies of all relevant articles were scannedfor additional studies. The main inclusion criterion wasthat the publication be in a peer-reviewed journal andcontain details of an epidemiologic study which includedinvestigation of possible health effects of dental amal-gam exposure. Original research articles were reviewed,except for reproductive effects and effects in children,for which good review articles were already available.

Results

Mercury uptake from dental amalgam

Signs and symptoms of occupational mercury ex-posure have generally been associated with air mercury

concentrations greater than 50 mg/m3, corresponding tourinary mercury concentrations greater than 100 mg/l.The range of urinary mercury concentrations for peoplewith no occupational exposure is up to 20 mg/l (US Foodand Drug Administration, 2002).

For occupationally unexposed people mercury vaporintake from their fillings is much greater than from theambient air. Daily absorption from ambient air is about0.24 mg, compared with 3–17 mg from amalgam fillings(International Program on Chemical Safety, 1991).

Divalent inorganic mercury is also released bysalivary corrosion of fillings. Absorption of inorganicmercury from the gastrointestinal tract is no more than10%. Absorption of mercury vapor in the lungs is about80% of the amount inhaled (Department of Health andHuman Services, 1997).

Chronic disease incidence and mortality

A Swedish prospective cohort study contained 1462women, recruited in 1968–69 when aged 38–60 years.The women were medically and dentally examined atrecruitment. Relationships of myocardial infarction,stroke, diabetes, cancer, and overall mortality to thenumber of amalgam fillings at recruitment wereinvestigated in a 20-year follow-up (Ahlqwist et al.,1993). Women having 420 amalgam-filled surfaces(n ¼ 632) were compared with dentate women with 0to 4 amalgam fillings (n ¼ 180). Risks of myocardialinfarction, stroke, diabetes, and overall mortality wereassociated with more amalgams.

Blood samples at recruitment were analyzed formercury. Serum mercury concentration was correlatedwith the number of fillings in 1968-69 (r ¼ 0:84,po0:0001). At a 24-year follow-up, general mortality,myocardial infarction, stroke, diabetes, and cancer wereinvestigated (Ahlqwist et al., 1999). No outcome wascorrelated with serum mercury concentration, although,after adjustment for age and education, a negativecorrelation was observed between serum mercury andmortality rate (p ¼ 0:05). It is likely that this result canbe attributed to confounding by access to dentaltreatment. People with better health status may havebetter access to such treatment and receive more fillings.

The only other large study to examine a wide range ofhealth outcomes was a retrospective cohort study ofNew Zealand military personnel (Bates et al., 2004). TheNew Zealand Defence Force has its own internal dentalservice, and treatment is regular, compulsory, andconsistent across ranks. Detailed, longitudinal, tooth-surface-specific dental treatment records were available.The cohort of 20,000 personnel was followed upbetween 1977 and 1997 and linked with New Zealandnational mortality, hospital discharge and cancerincidence databases. Data were analyzed using the

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proportional hazards model for time-varying cumulativeexposure. Results for more specific outcomes aresummarized separately below. However, there were noassociations between a range of broad disease outcomecategories and amalgam exposure. No associations werefound with any causes of death or cancers, although thecohort was fairly young at the end of follow-up andrelatively few deaths (189) or cancers (264) hadoccurred.

Neurologic disease

Studies have investigated possible associations be-tween dental amalgams and nervous system diseases,particularly MS, Parkinson’s disease, and Alzheimer’sdisease. The evidence for an association with each ofthese three diseases is summarized, as is the evidence foran effect on neuropsychological and neurophysiologicalfunction.

Multiple sclerosis

Craelius (1978) first noted a strong correlation in thegeographical distributions of MS and dental caries.Ingalls (1983) suggested that this association wasconfounded by the prevalence of amalgams in highcaries areas.

A symptom questionnaire was administered to 42 MSpatients with their amalgam fillings removed and 44 MSpatients who retained these fillings (Siblerud andKienholz, 1994). The group retaining their amalgamsreported 34% more symptoms within the last year. Thefindings are equivocal because of the different ways inwhich participants were recruited. Non-amalgam-removal subjects were partly recruited by advertise-ments. This may have attracted more seriously affectedsubjects. It did not appear that MS diagnoses wereverified and there may have been a placebo effect afteramalgam removal.

Three MS case-control studies have examined theassociation with dental amalgams. A Canadian studycontained 143 incident MS patients and 128 matchedcontrols (Bangsi et al., 1998). Mean numbers ofamalgam fillings in the cases and controls were 9.4 and8.8, respectively (p40:05). Assessment of exposure–response relationships, based on number of amalgamfillings and time since first placement, provided weakevidence of increasing risk.

A case-control study of 39 women with MS and 62controls was carried out in England in 1989–90(McGrother et al., 1999). Cases were diagnosed during1977–85, and aged 25–65 years at diagnosis. Age-matched controls were selected from the same physicianlists as the cases. All subjects received a dentalexamination during the study. Cases had a meannumber of 8.9, and controls 9.7 amalgam-filled teeth.

This study used prevalent cases of MS, some of whomhad all their amalgam fillings removed between diag-nosis and study participation. Cases had tended toneglect their dental treatment compared to the controls.These features would have obscured any true relation-ship between amalgam fillings and MS.

The third case-control study, in Italy, contained 132prevalent MS cases and 423 matched controls (Casettaet al., 2001). Higher numbers of dental fillings werereported by cases than controls (po0:05). For those forwhom the duration since first exposure was more than 5years, there was a weak increasing trend in the oddsratios with number of amalgam fillings. Limitations inthis study included use of prevalent cases and collectionof information on amalgam placement mainly byquestionnaire from the subjects themselves. This islikely to lead to exposure misclassification, particularlyif some MS patients believe their condition to be causedby their amalgam fillings.

Finally, a cohort study of New Zealand militarypersonnel found a relative risk estimate of 1.24 (95% CI:0.99–1.53, p ¼ 0:06) for a cumulative exposure unit of100 amalgam-filled surface-years (Bates et al., 2004).The average cumulative exposure to mercury in thecohort was 628 amalgam-filled surface-years, equatingto a relative risk estimate of 3.9, compared to a personreceiving no amalgam exposure.

In summary, the published studies are inconclusive,although there is some suggestion of an associationbetween dental amalgams and MS. Limitations of theavailable studies include use of prevalent cases, inade-quate control recruitment methods, lack of confirmationof case diagnoses, small numbers of subjects, andinadequate exposure data.

Parkinson’s disease

Only one published analytic epidemiology study hasinvestigated a role of dental amalgam in Parkinson’sdisease (Seidler et al., 1996). A classic symptom ofmercury poisoning, as with Parkinson’s disease, is finetremor of the hands. However, the tremor frequency ishigher for mercury exposure than for Parkinson’sdisease (Biernat et al., 1999).

This case-control study compared 380 GermanParkinson’s disease patients with 379 neighborhoodcontrols and 376 regional controls. At interview, caseswere asked to state the number of amalgam fillings theyhad before disease onset; controls were asked abouttheir number of amalgam fillings 1 year before interview.

On average, Parkinson’s disease cases reported ahigher number of amalgam fillings (n ¼ 7:8) than bothneighborhood controls (n ¼ 6:5, p ¼ 0:0008) and regio-nal controls (n ¼ 6:1, po0:00005). Using the regionalcontrols and after adjusting for number of remainingteeth, odds ratios for increasing exposure, relative to the

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low exposure group, were 1.7 (95% CI: 1.0–2.7), 2.5(1.4–2.5), and 1.9 (1.1–3.3) (p for trend ¼ 0.003).

Limitations of this study were use of prevalent casesand amalgam exposure data based on interview. Dentalrecords do not appear to have been used.

Alzheimer’s disease

An Alzheimer’s disease case-control study assessedthe association with dental amalgam exposure (Saxeet al., 1999). Sixty-eight post-mortem cases werecompared with 33 controls drawn from a volunteerbrain donation program. Detailed dental histories wereobtained from dental records and X-rays. Specimensfrom the cerebral cortex of the brain were analyzed formercury. Three indices of amalgam exposure, based onevent (i.e., amalgam placement, repair or removal),location in the mouth, and time in the mouth, weredeveloped. No statistical association was found betweenexposure indices and either Alzheimer’s disease ormercury concentrations in parts of the brain. This studyhad high-quality dental history data, but a small numberof subjects.

An ecological study found a correlation betweenAlzheimer’s disease prevalence and edentulism preva-lence in people in five regions of Canada (Lund et al.,2003). The authors interpreted this as evidence againstan association between amalgam fillings (in people withteeth) and Alzheimer’s disease. However, a converseinterpretation could be applied – that prevalence ofedentulism is a marker of higher caries rates and,therefore, higher amalgam filling prevalence.

Neuropsychological and neurophysiological function

A study was carried out of 129 nuns, aged 75–102years, living in a retirement facility (Saxe et al., 1995).Current amalgam exposure was assessed using anintraoral camera. Nuns completed eight cognitivefunction tests. Test results showed no evidence ofdeterioration of performance associated with amalgamexposure.

This study had good quality data on current amalgamexposure, but no information on placement duration.Despite this, it provided some reassurance that dentalamalgams do not affect cognitive performance.

In a study based on the Swedish Twin Registry, all587 participants rated their own health and completedtests of personality and memory function (Bjorkmanet al., 1996). Dental status was recorded by mouthexamination. Although there were suggestions that ahigher number of amalgam surfaces was associated withbetter health, most of these associations disappearedafter adjustment for potential confounding factors, suchas age, sex, education, number of teeth, and smokingbehavior. No account was taken of duration of

amalgam filling placement. This would have attenuatedany true causal associations.

A study of 550 New York adults, aged 30–49 years,found a correlation between urinary mercury excretionand both the total number of amalgam-filled surfacesand the number of occlusal amalgams. No associationswere found between either urinary mercury levels ornumbers of amalgam fillings and scores on neuropsy-chological tests (Factor-Litvak et al., 2003). This well-conducted study also lacked information on placementduration of fillings.

There have been few studies of whether amalgamfillings are associated with decrements of peripheralneurologic function. However, Kingman et al. (2005)carried out a neurologic examination (not includingnerve conduction velocity testing) and quantitativesensory tests on 2038 US military personnel. Exposure(total number of amalgam surfaces) was assessed in oralexaminations by dentists. Overall, no association wasfound between amalgam exposure and clinical signs ofneuropathy or sensory thresholds. The authors ac-knowledged a study limitation was the lack of long-itudinal amalgam exposure data, which provedimpossible to obtain.

Overall, the available studies provide no evidence ofeffects of amalgam fillings on neurologic function.

Effects on immunologic function

Experimental studies in animals have producedautoimmune responses to low doses of inorganicmercury (Pelletier et al., 1990) An increase in immu-noglobin type E (IgE) is a consistent characteristic.

In a study of Swedes aged 15 years, a statisticallysignificant correlation was found between immunoglo-bin type A (IgA) and plasma mercury concentration, butno correlation with IgE (Herrstrom et al., 1994). Afollow-up study using 77 19-year-old students, half withallergic diseases (asthma, allergic rhinitis, eczema), didnot confirm the IgA correlation. Again there was noassociation with IgE, but there was a correlation withIgG2 (r ¼ 0:33, p ¼ 0:003) (Herrstrom et al., 1997). Noassociation between plasma mercury and allergic diseasewas found. The authors suggested that their positivefinding could have been a false positive arising from thelarge number of statistical comparisons that werecarried out.

The numbers of mercury fillings in 33 children withHenoch-Schonlein purpura and 31 with acute glomer-ulonephritis, both autoimmune diseases, were comparedwith numbers of fillings in a matched control group(Herrstrom et al., 1996). No associations with amalgamwere found.

To date, the only well-documented, but rare, healtheffect associated with dental amalgams is allergic

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reactions (Pang and Freeman, 1995). These usuallyimprove if the fillings are removed (Flanders, 1992).

Effects on kidney function

Concern about possible effects of amalgam mercuryrelease on kidney function was caused by a study showingdecreased renal function in six sheep, each given 12occlusal fillings (Boyd et al., 1991). Other studies haveshown that people with amalgam fillings have higherkidney mercury concentrations than people withoutamalgams (Nylander et al., 1987; Barregard et al., 1999).

A few studies have investigated kidney function inhumans in relation to amalgam load. No association ofurinary proteins indicative of kidney damage, witheither dental amalgams or urinary mercury levels, wasfound in 48 healthy male students, aged 17–22 years(Herrstrom et al., 1995). A study of 100 healthy adults(18–44 years) showed a small increase in urinary levelsof N-acetyl-b-glucosaminidase (NAG) in people withamalgams (Eti et al., 1995). The authors considered thatthis increase was probably of no clinical significance.

Changes in kidney function were investigated afterremoval of an average of 18 amalgam fillings from 10healthy volunteers (Sandborgh-Englund et al., 1996).Sixty days after amalgam removal, significantly lowermercury levels were found in urine, but no change inindicators of kidney function.

Finally, a retrospective cohort study of 20,000 NewZealand military personnel found no association be-tween dental amalgam exposure and any of a range ofkidney diseases identified in hospital discharge data(Bates et al., 2004).

Overall, although studies are few, there is littleevidence that dental amalgam fillings affect kidneyfunction.

Studies of self-reported symptoms

Studies have investigated associations between amal-gam exposure and self-reported symptoms. Thesestudies fall broadly into two groups:

Studies of people before and after amalgam filling

removal: These are case-series in which individualshave reported symptom relief following removal oftheir amalgam fillings (Langworth and Stromberg,1996; Godfrey, 1990). Diseases for which suchrecovery has been reported include Parkinson’sdisease, Crohn’s disease, MS, epilepsy, asthma,scleroderma, paranoia, and blindness (Pleva, 1992).

� Studies of associations between symptom prevalence

and amalgam exposure: These studies sometimesinvolve comparisons of groups of people who believethemselves affected by their amalgam fillings andpeople not holding such a belief.

Of these two types of study, the first has high

potential for an uncontrolled placebo effect and is notconsidered further here. The second type of study is lesslikely to be affected by the placebo effect, but may stillbe affected by bias. These studies are briefly reviewedhere.

Siblerud (1989) compared self-perceived health in 50college students averaging 10 amalgam fillings with 51students without amalgams. Amalgam subjects reportedbeing less happy, including more frequent suicidaltendencies. Overall, the amalgam group reported 61%more symptoms. The amalgam group also reportedgreater consumption of sweets, alcohol, cigarettes andcoffee than the non-amalgam group. Results could havebeen confounded by these differences.

In a later publication, based on the same subjects,amalgam subjects were reported to have significantlyhigher mean blood pressures than the non-amalgamgroup (Siblerud, 1990). Amalgam subjects reported asignificantly greater incidence of heart or chest painsand tachycardia, and were also more likely to sufferfrom tiredness, chronic fatigue, and anemia. No adjust-ment was made for the lifestyle factors mentioned in theearlier paper.

Most other, usually more recent, studies havereported no associations between amalgams and levelsof symptoms. A study of 1024 dentate Swedish women,aged 38–72 years, found no positive correlationsbetween numbers of amalgam fillings and symptoms(Ahlqwist et al., 1988). A few symptoms had inversecorrelations with amalgam numbers.

Malt et al. (1997) compared 99 Norwegian patientsself-referred with multiple symptoms that they attrib-uted to dental amalgam fillings with 272 other patients.There was no correlation between number of fillings andsymptom prevalence. Fifty Swedish patients self-referred for complaints they related to their dentalamalgams were compared with a matched control groupof 50 patients (Bratel et al., 1997a, b). Numbers ofamalgam surfaces in both groups were similar (28.2 and29.0, respectively).

In an analysis of 48 symptoms in 4787 Germanpatients aged 21–60 years, a higher number of filledsurfaces was associated with lower symptom prevalence(Melchart et al., 1998).

Two other studies, each with about 40 patientsbelieving themselves adversely affected by amalgamsand 40 controls, found no differences in numbers ofamalgam fillings or blood or urine mercury levels (Gansset al., 2000; Bailer et al., 2001).

One condition, involving self-reported symptoms, butno objective signs, is chronic fatigue syndrome (ICD-9code 780). There is a widespread popular belief that thiscondition is associated with dental amalgams, but littleepidemiological investigation. In a retrospective cohortstudy of 20,000 New Zealand military personnel, no

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association was found between cumulative amalgamexposure and chronic fatigue syndrome (Bates et al.,2004). The relative risk estimate for an exposure unit of100 amalgam-filled surface-years was 0.98 (95% CI:0.94–1.03).

Overall, the weight of evidence, particularly fromlarge studies, suggests no association between number ofamalgam-filled tooth surfaces and prevalence of sub-jective symptoms or chronic fatigue syndrome (Bates etal., 2004; Ahlqwist et al., 1988; Melchart et al., 1998).

Reproductive effects and effects in children

Epidemiological studies have generally shown noeffect of inorganic mercury on reproductive parameters,including fertility (Schuurs, 1999). In the cohort study ofNew Zealand military personnel described above (Bateset al., 2004) there were 1062 births under the category‘‘complications of pregnancy and childbirth’’ (ICD-9codes 630-677). However, there was no association ofthese conditions with cumulative amalgam exposure. Acase-control study of 1117 low birth weight infants and4468 controls in Washington State found no associationwith placement of dental amalgam restorations in themothers during pregnancy (Hujoel et al., 2005).

Despite the lack of evidence for reproductive effects,there is evidence of in utero exposure: it has been shownthat the hair levels of mercury in fetuses are correlatedwith the number of amalgam fillings in their mothers(Lindow et al., 2003).

Available studies of health effects of mercury inchildren have been comprehensively reviewed (Counterand Buchanan, 2004). There have been relatively fewrelevant epidemiological studies and, to date, no healtheffects have been associated with either mothers’amalgam fillings (in utero or breast milk transfer) oramalgam fillings in older children. However, the reviewconcluded that research is needed into whether neuro-developmental effects occur in children.

Discussion

Many hundreds of millions of people worldwide haveteeth containing mercury amalgam fillings. Although theuse of these fillings has been decreasing, it was estimatedthat, in 1990, nearly 100 million amalgam fillings wereinserted in teeth in the United States (Department ofHealth and Human Services, 1993). This representsapproximately 75–100 tons of mercury placed inpeople’s mouths (Enestrom and Hultman, 1995).Clarkson (2002) has characterized dental amalgam asone of ‘‘the three modern faces of mercury’’. The othertwo are methyl mercury in fish and ethyl mercury(thimerosal) as a preservative in vaccines.

Exposures to mercury from dental amalgams are belowmercury exposures conclusively associated with healtheffects in occupational studies. However, occupationalstudies commonly suffer from selection bias (the ‘‘healthyworker effect’’), the durations of exposure and follow-upare often limited, and occupational populations too smallto detect uncommon effects (Weiner et al., 1990). Theamalgam-exposed population contains a broader spec-trum of people, including the young, the elderly and theunwell. Occupational studies are unlikely to detect riskincreases in diseases predominant in the elderly (e.g.,Alzheimer’s or Parkinson’s diseases) or non-malignantdiseases of low incidence (e.g., MS). Given the largenumber of people with dental amalgams, even a smallincreased relative risk of disease could have substantialpublic health implications. A rare effect caused bymercury (in teething powders) is acrodynia, whichoccurred in one exposed child in 500 (Clarkson, 2002).

Despite nearly 200 years of use and their extremelywidespread prevalence, support for the continued use ofdental amalgams is usually based on lack of evidence ofharm, rather than studies demonstrating actual safety.Typical of statements issued by official bodies is that bythe US Food and Drug Administration (2002): ‘‘novalid scientific evidence has shown that amalgams causeharm to patients with dental restorations, except in therare case of allergy’’. The American Dental Association(2002) relies on such assessments.

This review shows that there have been few analyticepidemiological investigations of dental amalgams andpossible health effects. Studies have often had smallnumbers of subjects or other significant methodologicallimitations, making interpretation difficult. The mainlimitation has been exposure assessment, which hasusually been based on current dental examination andhas not considered timing of amalgam placements ordental treatment history. A difficulty is that most peoplechange dentists over the course of their lifetimes, theirtreatment records often do not travel with them, andthese records have not been maintained by dentists in aconsistent way. Another complication is potentialconfounding by access to dental treatment. People ofhigher socio-economic status usually have better dentaltreatment access and, therefore, may have moreamalgam fillings. The same people also usually maintainbetter health. This may account for the associationsbetween amalgams and better health in some popula-tion-based studies (Ahlqwist et al., 1993, 1999; Melchartet al., 1998). A study that goes some way towardsovercoming these limitations is the cohort study of NewZealand military personnel (Bates et al., 2004). Thesepersonnel received regular, consistent dental treatment,irrespective of rank, and detailed longitudinal treatmentrecords were available.

In conclusion, despite the very widespread use ofdental amalgam fillings, epidemiologic data to establish

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their safety are inadequate. Most reassurance is pro-vided for kidney diseases, effects on neuropsychologicalfunction, chronic fatigue syndrome and non-specificsymptom complexes; most in need of further investiga-tion are neurodegenerative diseases and effects oninfants and children. To provide a balanced perspective,it should not be overlooked that risks associated withalternative filling materials have also not been exten-sively studied.

Acknowledgments

Support for this study was provided by the Universityof California Center for Occupational and Environ-mental Health and a grant from the Health ResearchCouncil of New Zealand.

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