J . R O D W A Y M A G K E R T JR ., D .M .D ., PH.D.

ABSTRACT

This paper looks at the issues of the current amalgam controversy: the daily dose of mercury from amalgam, hypersensitivity to mercury, claims of adverse effects from amalgam mercury and alleged overnight “cures.” In addition, the toxicity and allergenicity of the proposed alternative materials are examined with the same kind of scrutiny applied by the anti-amalgam group to dental amalgam.

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^*¡1 malgam as a dental restorative material has sparked controversy several times during its 150-year history. Amalgams are alloys of various metals with mercury, and so, in the broadest sense, the material used in the early 1800s in France—D’Arcets Mineral Cement—could be considered the first dental amalgam. D’Arcets Mineral Cement bore little resemblance to modern-day amalgam. This alloy of bismuth, lead, tin and mercury was plasticized at 100 C and poured directly into the cavity! In 1818, Regnart moved a step closer to modern amalgam by increasing the amount of mercury used in preparing the “mineral cement,” a modification that lowered the plasticizing temperature to 68 C and eased patient suffering considerably. The first uses of a room-temperaturemixed amalgam as a restorative material are attributed to Bell in England (1819) and Taveau in France (1826), who advocated a mixture of silver and mercury as a filling material.12 Amalgam had an inauspicious introduction to the United States in 1833. The Crawcour brothers, with only a superficial knowledge of dentistry, left behind many unsatisfactory amalgam restorations when they were driven from the country in 1834. This initial, unfortunate experience with dental amalgam in the United States, coupled with knowledge of the toxicity of mercury vapor and mercury compounds, moved the American Society of Dental Surgeons to pass a resolution in 1845 stating: “Resolved, that any member of the Society who shall hereafter refuse to sign a certificate pledging himself not to use any amalgam, and moreover, protesting against its use, under any circumstance, in dental practice, shall be expelled from the society.” Despite the eventual rescission in 1855 of most of the resolutions prohibiting amalgam use, the 10 years of internal conflicts in the society over the prohibition took their toll. The society broke up shortly thereafter. This “First Amalgam War” gradually abated during the latter half of the 1800s as the improved amalgams of Elisha Townsend, J. Foster Flagg and G.V. Black came into widespread use. The improved handling and performance of these materials muted criticism of amalgam as an inferior restorative material, and the failure of the threatened adverse health effects to materialize in patients who received amalgam restorations inspired general confidence in its safety.

The “Second Amalgam War” erupted in Europe as a result of the writings of a single individual, Dr. Alfred Stock, a professor of chemistry at the Kaiser-Wilhelm Institute in Germany. He became poisoned with mercury through 25 years of exposure to the metal in his laboratory and in teaching. He published papers on the dangers of mercury vapor, and he argued passionately against the use of mercury in dentistry, particularly in copper amalgam. His writings attracted widespread attention and created considerable public concern. The Medical Department of the Charite Hospital in Berlin appointed a committee to study the allegations of amalgam toxicity. The committee concluded that there was no reason to condemn the use of dental amalgam and that it had a rightful place in dentistry.3It is reported that Stock later disassociated himself from critics of amalgam use, and he stated in a 1941 lecture in Sweden that the rare cases of mercury poisoning caused by the evolution of mercury vapor from amalgam restorations should in no way affect the further use of silver amalgam in dental practice.1Antiamalgamists, however, claim that his remarks were either mistranslated or misquoted.4 The current controversy, sometimes termed the “Third Amalgam War,”began primarily through the seminars, writings and videotapes of H.A. Huggins, a dentist from Colorado Springs, Colo. Dr. Huggins traces his own involvement in the issue to 1973, when he was exposed to claims by Dr. Olympio Pinto of Rio de Janeiro, Brazil.5Dr. Pinto held that a variety of diseases—everything from leukemia to bowel disorders— could be mimicked by a patient’s reaction to mercury.

In 1979, Gay and coworkers found mercury vapor in the breath of patients with amalgam fillings after chewing.6The instrument used in this work was developed by McNerney and coworkers in 1972.7This mercury detector was based on the significant change in electrical resistance that occurs when a thin gold film adsorbs mercury vapor onto its surface. The instrument was not subject to the interferences from water vapor, ozone, sulfur dioxide and other compounds that plagued the atomic-absorption-type instruments used earlier. This fact enabled use of the instrument in the moist oral environment. The gold-film mercury vapor detector was perfected and marketed by the Jerome Instrument Co. (a division of the Arizona Instrument Corp.) in Jerome, Ariz. The detection of mercury vapor release from amalgam fillings aroused new concern about mercury exposure from dental amalgam. Some dentists exploited the uncertainty surrounding dental amalgam as a solution to the “busyness” problem in dentistry in the early-to-mid 1980s. They used the Jerome instrument, modified microammeters and uncon­ ventional patch test techniques to convince patients to have their amalgams removed to cure all sorts of diseases. This practice attracted the attention of Consumer Reports, and in 1986, it published an expose of the anti­ amalgam movement entitled, “The mercury scare: if a dentist wants to replace your fillings because they contain mercury, watch your wallet.”8The controversy subsided somewhat, but has intensified again recently, particularly as the result of the “60 Minutes” television program that created considerable public alarm with a

sensationalistic treatment of the issue.9 LEVELS OF EXPOSURE FROM DENTAL AMALGAM

The gold-film mercury vapor detector is designed to measure mercury vapor concentrations in air samples taken from volumes of air that are large in comparison to the volume of the sample. When this condition of measurement is not satisfied—as in the case of intraoral mercury vapor measurements—corrections must be applied to obtain accurate concentration values. Several authors have shown that an instrument reading of 30 micrograms/cubic meter obtained from inside a patient’s mouth using an instrument flow rate of 0.75 liter/min. and a collection time of 20 seconds must corres­ pond to a mercury vaporization rate of 22 nanograms/min.10'12With a mercury vaporization rate of 22 ng/min, a single 0.5 L breath inhaled in 2.5 seconds would contain a mercury vapor concen­ tration of only 1.8 |Jg/m3, even though the instrument yielded a reading of 30 (Jg/m3. This discrepancy is the result of the sixteenfold difference in the flow rates of the instrument and human respiration. In addition, if any delay exists between the last event that voids the mouth (a swallow, or an inhalation or exhalation through the mouth will void the mouth) and the beginning of the intraoral mercury vapor measurement, there will be an even greater discrepancy between the meter reading and the concen­ tration of mercury in the air that is actually inhaled. For each second of delay between the event that voids the mouth and the time the 20-second measurement begins, the accumulation of mercury vapor in the mouth will cause the JADA, Vol. 122, August 1991

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meter reading to be an additional 5 percent too high.10 Recent measurements of actual tracheal mercury concentrations for subjects with eight to 54 amalgam surfaces ranged from less than 1Mg/m3to 6 Mg/m3during inhalation through the mouth and less than 1Mg/m3during inhalation through the nose.13Therefore, using a mercury vapor analyzing instrument to measure intraoral mercury vapor concentrations without proper consideration of the dynamics of gas flow and mercury vapor release from the amalgam restorations can lead to erroneous estimations of the level of exposure to mercury vapor from amalgam restorations. (A detailed discussion of the factors involved in the interpretation of intraoral mercury vapor measurements was published in 1987.10) With proper correction for collection flow rates, an estimate of 1.2 Mg of mercury per day was obtained for subjects with an average of 8.6 occlusal surfaces restored with amalgam and 1.8 Mg of mercury per day for subjects with 12 or more occlusal amalgam surfaces.10Snapp and coworkers provided independent confir­ mation of these estimates by a fundamentally different method of determining daily dose of mercury from amalgam.14They measured blood mercury excretion kinetics in subjects after their amalgam restorations were removed and determined the daily mercury intake from dental amalgam to be 1.3 Mg for subjects with an average of seven occlusal surfaces. Using an apparatus specifically designed to collect intraoral mercury vapor, Berglund performed 24-hour mercury vapor measurements on 15 subjects with an average of 12.6 occlusal surfaces and found the average daily dose of mercury vapor to be 1.7 Mg-16All 56

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of these estimates show remark­ able agreement, considering the different methodologies used. Since the total daily intake of mercury for individuals with no occupational exposure to mercury is estimated to be 10 to 20 Mg,16"18the 1-to -2-Mgcontribution of dental amalgam mercury per day is minor, even for the non-occupationally exposed individual. Berglund pointed out that a person exposed to the World Health Organization threshold limit value for mercury would receive a mercury vapor dose of 300 to 500 Mg each day, five days per week; hence, the total weekly dose that can be tolerated in such a work environment without any adverse effects—1,500 to 2,500 Mg—is more than 100 times the weekly dose a person with 12 amalgam restorations would receive.15 HYPERSENSITIVITY

There have been a number of case reports of true allergy to amalgam,19"23and one study that is frequently cited by opponents of amalgam use appeared to show that 16 percent of subjects with amalgam restorations had positive reactions to mercury.24This latter study, however, used 1percent mercuric chloride as the patch test agent, when even solutions of mercuric chloride as dilute as 0.01 percent produce a primary irritant response in control (non-allergic) patients.25In addition, no double­ blind study design was used. This omission is a critical flaw in a study involving judgments as subjective as the reading of patch test results.26 A double-blind study conducted by the North American Contact Dermatitis Group found only 3 percent of 660 study subjects to be allergic to mercury (1 percent ammoniated mercury in petrolatum, the standard NACDG

allergen for mercury). In addition, only 20 percent of this 3 percent (0.60 percent of the 660 study subjects) had any skin disease at the time of testing, or any history of skin disease at the time of testing, that could be explained by allergy to mercury.27It can be seen, therefore, that mercury allergy is limited to a very small percentage of the population, and the large majority of those who yield a positive patch test to mercury do not have any clinical signs of allergy. Even in patients who experience contact dermatitis after placement of dental amalgam, the reaction often disappears in a short time without removal of the amalgam fillings.1 LACK OF ADVERSE EFFECTS

Despite the minor contribution of dental amalgam to the total daily intake of mercury, some have continued to claim that mercury from dental amalgam could cause adverse health effects. Eggleston, who after examination of only two subjects with amalgam restora­ tions, concluded that: “Prelim­ inary data suggest that dental amalgam can adversely affect the quantity of T lymphocytes.”28In contrast, a controlled study of 37 patients found no difference in absolute numbers or percentages of T lymphocytes between subjects with and without amalgam restor­ ations.29In addition, no differences between the two groups were found in any of the other white blood cell subpopulations. A recent study performed on sheep at the University of Calgary appeared to show that animals with dental amalgam fillings suffered a 60 percent loss of kidney function, as measured by glomerular filtration rate.30 Experts in renal toxicology, however, pointed out that the

report contains self-contradictory data. For example, renal damage that would produce a reduction in the glomerular filtration rate should cause blood urea levels to rise.31The Calgary report, however, claimed lower levels of blood urea in the sheep that allegedly suffered kidney damage. Furthermore, studies performed on humans at the University of Umea in Sweden found no evidence of kidney impairment in subjects with amalgam restorations.32Neither were any differences between the amalgam and non-amalgam groups found for any of the blood cell variables, plasma electrolyte levels, liver status analyses, skeletal muscle analyses or indicators of inflammation. OVERNIGHT “ CURES”

The presentation on “60 Minutes” of various case reports of individuals showing improvement after removal of amalgam fillings9 has raised the hopes of many with incurable or undiagnosable illnesses. They have sought to have their “mercury levels” tested and their amalgams removed in hopes of obtaining relief from their symptoms. A number of articles in the print media have been critical of “60 Minutes” treatment of the issue.33'36 One author mused, “It is hard to say what is worse—planting false fears about their health in the minds of perfectly healthy people or giving people suffering great pain and mental stress false hopes of a miracle cure. CBS did both in a single irresponsible segment of ‘60 Minutes’ aired December 16.” ■* Misunderstanding of symptoms of mercury toxicity. Ironically, many of the signs and symptoms for which anti-amalgam dentists and patients are claiming relief after amalgam removal are not even related to mercury exposure

at any level. For example, some anti-amalgam dentists have intimated that mercury from dental amalgam can cause cancer, yet there is no evidence of a higher cancer incidence even in mercuryvapor exposed workers.36 A symptom for which relief is frequently claimed after amalgam removal is headache, whereas a study by Smith and coworkers of 642 workers exposed to mercury in chlor-alkali plants in the United States and Canada found no correlation between level of mer­ cury vapor exposure and incidence of headache.37This study also failed to find any correlation between the level of occupational mercury vapor exposure and such symptoms as fatigue, anxiety and shortness of breath—symptoms frequently claimed by the anti­ amalgam activists to be associated with dental amalgam.3840 Even in a study of self-described sufferers of “oral galvanism” (or “dental amalgam mercury syn­ drome”), no differences were found between the patient group with subjective symptoms and a control group without symptoms in various blood analyses per­ formed to evaluate electrolyte balance, liver and kidney function, inflammatory activity, immune stimulation and tissue damage.34 An epidemiologic study of the incidence of subjectively exper­ ienced symptoms compared with numbers of amalgam fillings showed no positive correlation between numbers of fillings and numbers of symptoms, or between numbers of fillings and incidence of any specific symptom or complaint.41 *■* Proof that mercury is not the culprit. Some of the anti-amalgam dentists and patients have claimed substantial improvement in conditions such as multiple sclerosis the day after amalgam

removal. In their zeal to demon­ strate dramatic improvements in various conditions after amalgam removal, they have actually provided unintended proof that mercury could not have been the culprit in their ailments. The very process of removing patients’ amalgams subjects them to an additional brief exposure to mercury sufficient to raise their blood mercury levels by an average of 1.7 ng/mL.14This level is in contrast to the average increase in blood mercury levels of 0.4 to 1.1 ng/mL attributable to a chronic exposure to the very low levels of mercury vapor emitted from amalgam fillings.14'42Typical blood levels of mercury are 4 to 5 ng/mL in the non-occupationally exposed person,17so the contribution of mercury from dental amalgam (whether from chronic exposure caused by the presence of amal­ gam or from the brief exposure during amalgam removal) is small. The significance of the increase of mercury in blood levels after amalgam removal is that it proves that the alleged overnight cures of multiple sclerosis and other diseases must be caused by something other than removal of mercury-containing amalgam fillings. Not only would the body be unable to excrete any signif­ icant portion of its accumulated burden of mercury in a single day, but the body burden would also actually be higher on the day after amalgam removal. It is apparent, therefore, that mercury from dental amalgam cannot be implicated as contributing to the causes of any of the conditions allegedly cured in one day by amalgam removal. *■The placebo effect. Because of the selective reporting of cases of patient improvement after amalgam removal by the antiamalgamists, we cannot conclude JADA, Vol. 122, August 1991

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that the anecdotal claims of improvement of various disease conditions establish a cause-andeffect relationship between amalgam and these conditions. A large percentage (up to 75 percent) of patients with various disorders improve when given a placebo drug or sham treatment.43The placebo effect produces improve­ ments simply because the patients believe they are receiving an effective treatment.44 The placebo effect is not imagi­ nary: it produces measurable, physiological effects in a large percentage of patients.4647Patients even experience the untoward side effects of drugs when they receive placebos they believe to be those drugs.48It has been noted that placebo effects “are so omni­ present that if they are not controlled for in therapeutic studies, the findings are considered unreliable. The potency of these effects may be realized by considering the num­ ber of conditions in which placebo effects have been noted: that is, cough, mood changes, angina pectoris, headache, seasickness, anxiety, hypertension, status asthmaticus, depression, common cold, lymphosarcoma, gastric motility, dermatitis and pain symptoms form a variety of sources.”49 In response to claims of improvement in cases of multiple sclerosis after amalgam removal, the National Multiple Sclerosis Society has repeatedly warned that “replacement of silver amalgam fillings cannot be recommended for the treatment of multiple sclerosis.” Furthermore, the society notes that “there is a placebo response as high as 70% in patients with multiple sclerosis which makes defining the basis for improvement in any individual patient impossible unless subject 58

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to rigorously controlled trials.”60 TOXICITY AND ALL ERG EMICITY OF ALTERNATIVES

If a proper assessment is to be made of the relative biocom­ patibility of dental amalgam, the same level of scrutiny must be used when examining the alter­ native restorative dental materials. When this level of scrutiny is applied to other materials, including those advocated by the anti-amalgamists as replacements for dental amalgam, it is evident that these materials are neither non-toxic, non-allergenic nor risk­ free. The following discussion is not meant to impugn the alternative materials, but rather to demonstrate that any material can be made to appear unsuitable as a restorative material if subjected to unreasonable and unbalanced scrutiny. ■■Composites. Dental resin composite restorative materials are the principal alternative material advocated by the antiamalgamists for the replacement of dental amalgam fillings. A frequent claim by the antiamalgamists is that “no research has shown that dental amalgam is safe,” yet the same charge can be leveled against composites and other dental materials. No material can ever be judged “safe” with any kind of finality, because new biological evaluation techniques are always being developed, and previously unanticipated adverse effects are continually being discovered for all materials. Composites contain a number of ingredients that can cause adverse health effects, and “should be classified as toxic restorative materials.”51 Composites have been shown to elicit a chronic inflammatory response in vivo,52to be cytotoxic

in cell culture,53to be allergenic64 and to inhibit RNA synthesis.56 Despite the characterization of composites as “non-toxic” alternatives to amalgam by antiamalgamists,4composites have been found to be more toxic to cells than amalgam.56 The peroxides used to generate free radicals in the polymerization of dental composites are known skin tumor promoters,57'69and have been implicated as the “major factor responsible for the toxicity of composite resins.”60Free radicals are also thought to be involved in the development of some forms of cancer.61Chemicals from both the resin62and filler63 components of dental composites have been shown to leach out from the set material. ■■Glass ionomer cements. Glass ionomer cements are also cyto­ toxic materials,53'64'66and they have also been shown to inhibit RNA synthesis.55Perhaps because of the climate of fear created by the anti­ amalgam activists, patients have expressed alarm when discovering that glass ionomer cements con­ tain aluminum, because of alleged links between aluminum and Alzheimer’s disease (Personal communication).67Aluminum and fluoride eluted from glass ionomer cements have been implicated in the toxicity of these cements.63'65 ■* Gold and gold alloys. Although it is widely believed that gold is non-allergenic and non-toxic, there is considerable evidence to the contrary. There have been a number of cases of allergy to goldverified by patch testing—from gold jewelry,68'76from dental gold,73'75'77"83from an orbital implant,84and even from 24-carat gold leaf.85In fact, the sensitizing potential of gold appears to be as high as that of nickel, and it is only the stability and relative insolu­ bility of gold that are responsible

for the lower incidence of allergic reaction to this metal.74 Gold is a highly toxic heavy metal whose clinical toxicity—like its allergenicity—is mitigated only by its stability and relative insolubility. However, significant amounts of gold are dissolved even from 24-carat bulk metal by solutions of sulfur-containing amino acids, and gold in concen­ trations of 70 |jg/gram to 90 |jg/g has been found in tissue samples taken from under gold rings on fingers.86It is interesting to com­ pare these concentrations with levels of mercury measured in tissue biopsies taken from gingiva that was in contact with amalgam restorations.87The gingival tissues exhibited tissue concentrations of mercury at the same order of magnitude (147 Mg/g) as the gold concentrations in finger tissues under gold rings. It is probable that gold levels in oral tissues adjacent to gold restorations would be higher than in finger tissue owing to the greater permeability of mucosal tissues. Dowden and Langeland, in a carefully controlled study,88 presented convincing evidence that the pulpal inflammation, hemorrhage and destruction of odontoblasts that occur in teeth restored with gold foil is not caused by the forces of conden­ sation, microleakage, thermal conductivity, or the trauma of cavity preparation as previously thought. They are attributable to the toxicity of gold. ■■Ceramics. Ceramics are regarded to be the most biocom­ patible of all dental restorative materials. Dental porcelains are generally based on the potassiumalumino-silicate ternary oxide system. Despite their reputation for biocompatibility, dental ceramics have been observed to provoke adverse tissue reactions

in laboratory rats.89 The possibility that silica granulomas occur as the result of introduction of dental ceramic material into the tissue has been recognized.90Silica granulomas result from the implantation of silica-containing materials into tissues. The etiology of silica granulomas is thought to be either a delayed-type hypersensitivity (Coombs’ Type IV) reaction91or else a non-allergic, foreign body reaction to a colloidal substance.92 The nodular, sometimes pig­ mented lesions are similar in histologic expression to those produced by the tubercle bacillus93 and may appear after an asympt­ omatic period of as long as 15 years.94The long delay is appar­ ently attributable to the significant time requirement of the “weath­ ering” process in the tissue fluids that produces the colloidal silica.92 The granuloma reaction to colloidal silica in the tissue is apparently universal in humans,9296a fact that indicates that reactions to dental ceramics may occur more frequently than previously thought. It would be difficult to trace a granuloma to inadvertent introduction of siliceous material into the tissue during placement of a ceramic restoration because of the typical 10-year delay in developing the lesion, as well as the fact that the lesion does not always occur at the site of introduction of the siliceous material. The lesions can occur distant from the site of intro­ duction of the siliceous material because once the colloidal silica is formed, it is easily transported to other locations in the body.96'97 As in the case of glass ionomer cements, patients who have had their amalgams replaced for fear of adverse effects from mercury may be alarmed to discover the element aluminum to be present in

ceramics,67because of alleged links between aluminum and Alzheimer’s disease.98 The placement of a ceramic restoration necessarily entails the use of certain other dental materials, which have to be considered in assessing the biocompatibility of ceramic materials—impression materials, temporary filling materials, dental cement and others. Nearly all of these materials exhibit some degree of toxicity.66Certain impression materials contain substances that can be classified as strong to extreme sensitizers.99 SUMMARY AND CONCLUSIONS

■■Mercury vapor measurements and daily dose. Any attempt to estimate mercury exposure from dental amalgam by performing intraoral mercury vapor measurements must be corrected for the differences between the flow rate of the instrument and the flow rate of normal inspiration. For typical instrument settings of 0.75 L/min. flow rate and a 20second collection time, the instrument reading must be divided by 16 to yield the correct mercury concentration in inhaled air. In addition, the mouth must be voided of any mercury vapor accumulated during the period immediately before measurement; otherwise, spuriously high readings will result. The daily intake of mercury from dental amalgam is about 1.2 |jg, which is a small fraction of the total daily intake of 10 pg to 20 pg. ■■Hypersensitivity. Hypersensi­ tivity to mercury appears to be about 3 percent in the general population, with only 0.6 percent of the general population showing any clinical manifestation of allergy. Hence, more than 99 percent of the general population JADA, Vol. 122, August 1991

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should be able to have amalgam restorations without any observable allergic response. Even in patients who exhibit allergy to mercury, the reactions disappeared in a day or two after amalgam placement. ■■Alleged adverse effects. In contrast to the Calgary report, which claimed impairment of kidney function in sheep, extensive studies on humans with Dr. Mackert is and without professor, Division of Dental Materials, amalgams Departm ent of revealed no Restorative Dentistry, and statistically Departm ent of Oral significant Biology, School of Dentistry, and differences in professor, School of any of the organ Graduate Studies, functions Medical College of Georgia, Augusta, (including GA 30912-1264. kidney) Address requests fo r reprints to the evaluated. In author. another study, no differences were found in immune cell distributions of subjects with and without amalgam restorations. In addition, the Calgary sheep study was observed to contain self­ contradictory data. The weight of the published evidence indicates that the contribution of dental amalgam to the total daily dose of mercury is minor, and no adverse health effects can be attributed to amalgam. ■■Overnight “cures.” The symptoms for which relief is claimed after amalgam removal are often not even related to mercury exposure at any level. Furthermore, the claims of overnight “cures” after amalgam removal actually provide unintended proof that amalgam is not the culprit. The additional exposure to mercury vapor during amalgam removal, coupled with 60

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the small daily excretion of mercury from the body, guarantees that the body burden of mercury will be the same or higher following amalgam removal. «*» Safety of alternative materials. While the alternative materials such as composite and glass ionomer are safe and effective restorative materials, they can be made to appear toxic and danger­ ous if subjected to unbalanced and unreasonable scrutiny. Even gold and ceramics are not completely free from adverse effects. ■* Dose makes the poison. In light of the current debate, it is interesting to note the insight of Philippus A. Paracelsus, a 16thcentury Swiss physician and alchemist who was one of the first to describe the toxic effects of mercury on workers in mercury mines. In 1538, he wrote, “What is there which is not poison? Everything is poison. Nothing is without poison. If something is not a poison this depends solely on the dose. For example, every kind of food and every kind of drink—if it is consumed in excess—is a poison. This is proved by the conse­ quences. I also admit that poison is a poison.”100■ 1. Frykholm KO. O n mercury from dental amalgam. Its toxic and allergic effects, and some comments on occupational hygiene. Acta Odontol Scand 1957; 15 (Supplem ent 22):1-108. 2. Greener EH. Amalgam—yesterday, today, and tomorrow. Oper Dent 1979;4:24-35. 3. H arndt E. Ergebnisse klinischer Untersuchungen zur Losung der Amalgam-Quecksilberfrage. Deutsche Zahnarztl Wschr 1930;33:546-75. 4. Ziff S. Silver dental fillings, the toxic timebomb. New York: Aurora Press, 1984:13. 5. Huggins HA. Systemic reactions to silver amalgam fillings. In: Stanford JW , ed. Workshop on biocompatibility of metals in dentistry. Chicago: American Dental Association, 1984:201-64. 6. Gay DD, Cox RD, Reinhardt JW. Chewing releases mercury from fillings. Lancet 1979; 1:985-6. 7. McNerney JJ, Buseck PR, Hanson RC. Mercury detection by means of thin gold films. Science 1972;178:6112. 8. Consumers Union. The mercury scare: If a dentist wants to remove your fillings because they contain mercury, watch your wallet. Consumer Reports 1986;March:150-2. 9. “60 Minutes" CBS Television Network, Dec. 16,1990. 10. Mackert JR Jr. Factors affecting estimation of dental am algam mercury exposure from measurements of mercury vapor levels in intra-oral and expired air. J Dent Res 1987;66:1775-80. 11. Clarkson TW, Friberg L, Hursh JB, Nylander M. The | prediction of intake of mercury vapor from amalgams. In:

Clarkson TW, Friberg L, Nordberg GF, Sager PR, eds. Biological m onitoring of toxic metals. New York: Plenum; 1988:247-64. 12. Berglund A, Pohl L, Olsson S, Bergman M. Determination of the rate of release of intra-oral mercury vapor from amalgam. J Dent Res 1988;67:1235-42. 13. Langworth S, Kolbeck K-G, Akesson A. Mercury exposure from dental fillings II. Release and absorption. Swed Dent J 1988;12:69-70. 14. Snapp KR, Boyer DB, Peterson LC, Svare CW. The contribution of dental amalgam to mercury in blood. J Dent Res 1989;68:780-85. 15. Berglund A. Estim ation by a 24-hour study of the daily dose of intra-oral mercury vapor inhaled after release of dental amalgam. J Dent Res 1990;69:1646-51. 16. Shibko S, Shapiro RE, Kolbye AC Jr. Exposure to toxic metals via food: Relationship to other exposures, critical organ concentration and toxic effect. In: Nordberg GF, ed. Effects and dose-response relationships of toxic metals. Amsterdam: Elsevier;1976:199-206. 17. W illiam s DF. Mercury. In: W illiam s DF, ed. Systemic aspects of biocompatibility, vol 1. Boca Raton, FL: CRC Press; 1981:237-49. 18. Vostal J. Transport and transformation of mercury in nature and possible routes of exposure. In: Friberg L, Vostal F, eds. Mercury in the environment. Boca Raton, FL: CRC Press; 1972:23-7. 19. Duxbury AJ, Watts DC, Ead RD. Allergy to dental amalgam. Br Dent J 1982;152:344-5. 20. White IR, Sm ith BGN. Dental am algam dermatitis. Br Dent J 1984;156:259-60. 21. Duxbury AJ, Ead RD, McMurrough S, Watts DC. Allergy to mercury in dental amalgam. Br Dent J 1982;152:47-8. 22. Finne K, Goransson K, W inckler L. Oral lichen planus and contact allergy to mercury. Int J Oral Surg 1982;11:236-9. 23. Catsakis LH, Sulica VI. Allergy to silver amalgams. Oral Surg Oral Med Oral Pathol 1978;46:371-5. 24. Djerassi E, Berova N. The possibility of allergic reactions from silver amalgam restorations. In t Dent J 1969;19:481-8. 25. Fisher AA. The misuse of the patch test to determine hypersensitivity to mercury amalgam dental fillings. Cutis 1985;35:110-7. 26. Maibach HL, Epstein WL. Predictive patch testing for allergic sensitization in m an. Toxicol A ppl Pharmacol 1965;7:39-43. 27. Storrs FJ, et al. Prevalence and relevance of allergic reactions in patients patch tested in North America 1984 to 1985. J A m Acad Dermatol 1989;20:1038-45. 28. Eggleston DW. Effect of dental amalgam and nickel alloys onT-lymphocytes: prelim inary report. J Prosthet Dent 1984;51:617-23. 29. Mackert JR Jr, Leffell MS, Wagner DA, Powell BJ. Lymphocyte levels in subjects w ith and w ithout amalgam restorations. J A D A 1991; 122(3): 49-53. 30. Vimy MJ, Boyd ND, Hooper DE, Lorscheider FL. Glomerular filtration im pairm ent by mercury released from dental silver fillings in sheep. Physiologist (Abstract no. 65.1) 1990:33: A-94. 31. Malvin R. Presentation to FDA Dental Products Panel, March 15,1991. 32. Molin M, Bergman B, Marklund SL, Schütz A, Skerfving S. Mercury, selenium, and glutathione peroxidase before and after amalgam removal in man. Acta Odontol Scand 1990;48:189-202. 33. Irvine R. CBS spurs false fears, false hopes. AIM Report 1991 January-B:20:1-6. 34. Lehman BA. Putting to rest the mercury fillings flap. Boston Globe 1991; Jan 7:33,36,37. 35. Consumers Union. The mercury in your m outh. Consumer Reports 1991;May:6-9. 36. Clarkson TW, Cranmer J, Sivulka DJ, S m ith R. Mercury health effects update. Health Issue Assessment. US Environmental Protection Agency Report. EPA-600/884-019F, 1984. 37. Sm ith RG, Vorwald AJ, Patil LS, Mooney TF. Effects of exposure to mercury in the m anufacture of chlorine. A m Ind Hyg Assoc J 1970;31:687-700. 38. Pleva J. Mercury poisoning from dental am algam. J Orthomolecular Psychiatry 1983;12:184-93. 39. Molin M, Marklund S, Bergman B, Bergman M, Stenm an E. Plasma-selenium, glutathione peroxidase in erythrocytes and mercury in plasma in patients allegedly subject to oral galvanism. Scand J Dent Res 1987;95:328-4. 40. Eggleston DW. Dental amalgam: A review of the literature. Com pend Contin Educ Dent 1989;10:500-5. 41. Ahlqwist M, Bengtsson C, Furunes B, Hollender L, Lapidus L. Number of amalgam tooth fillings in relation to subjectively experienced symptoms in a study of Swedish

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