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“Since all dental restorative materials are foreign substances, their potential for producing adverse health effects is determined by their relative toxicity and bioavailability, as well as by host susceptibility. Adverse health effects to dental restoratives may be local in the oral cavity or systemic, depending on the ability of released components to enter the body and, if so, on their rate of absorption. The medical scientific community is now in general agreement that patients with dental amalgam fillings are chronically exposed to mercury, that the average daily absorption of mercury from dental amalgam is from 3 to 17 micrograms per day, and that the amalgam mercury absorption averages 1.25-6.5 times the average mercury absorption from dietary sources (World Health Organization, 1991). The health significance of this chronic mercury exposure is now being investigated by several medical research groups.”

“1. A survey on the literature concerning the toxicity of amalgam is presented. 2. Opinions from various sources are discussed. It is found that there are no conclusive experimental results of clinical importance. Existing results on adults cannot be applied to children, who are more sensitive to amalgam. 3. Research into the toxicity of amalgam in children has begun. Results are expected later in 1992.”

“This review discusses the basic principles of risk assessment as used in general toxicology and in monitoring side-effects of therapeutic treatments. It also outlines how these principles may apply to assessment of biological reactions to dental restorative materials. Mercury exposure from amalgam fillings is used as an example. The calculations performed are intended only as illustrations, and many other factors must be taken into account. Thus, the calculations are not intended as the last word in risk assessment of amalgam fillings.”

“The purpose of this paper is to examine and report on studies that relate mercury levels in human tissues to the presence of dental amalgams, giving special attention to autopsy studies. Until recently, there have been few published studies examining the relationship between dental amalgams and tissue mercury levels. Improved and highly sensitive tissue analysis techniques have made it possible to measure elements in the concentration range of parts per billion. The fact that mercury can be absorbed and reach toxic levels in human tissues makes any and all exposure to that element of scientific interest. Dental amalgams have long been believed to be of little significance as contributors to the overall body burden of mercury, because the elemental form of mercury is rapidly consumed in the setting reaction of the restoration. Studies showing measurable elemental mercury vapor release from dental amalgams have raised renewed concern about amalgam safety. Mercury vapor absorption occurs through the lungs, with about 80% of the inhaled vapor being absorbed by the lungs and rapidly entering the bloodstream. Following distribution by blood circulation, mercury can enter and remain in certain tissues for longer periods of time, since the half-life of excretion is prolonged. Two of the primary target organs of concern are the central nervous system and kidneys.”

“The risks of mercury exposure arising from the use of dental amalgam fillings are reviewed and discussed. On the basis of both knowledge acquired in various scientific disciplines and ten years of experience in the field it is concluded that mercury from amalgam may well contribute significantly to a number of modern health problems and to decreased quality of life in a large population group in many countries. Erroneous opinion as to “negligible” mercury exposure and lack of cooperation between the dental, medical and other professions are two important factors in the issue. There is both biological and metallurgical evidence that typical Hg-exposure levels produced by amalgam fillings are 5-10-fold higher than what are regarded as safe limits for exposure to mercury from other sources. There is no doubt that dental mercury should be taken into consideration as a possible etiological factor when considering neurological, immunological and endocrinological diseases of unknown etiology. Protective measures during amalgam removal and prospects for alternative dental materials are discussed.”

“Factors influencing mercury evaporation from dental amalgam fillings were studied in 11 volunteers. Air was drawn from the oral cavity for 1 min and continuously analyzed with a mercury detector. In six volunteers the median unstimulated evaporation rate was 0.1 ng Hg/s, range 0.09-1.3 ng Hg/s. After chewing gum for 5 min the highest evaporation rate was 2.7 ng Hg/s. Chewing paraffin wax gave only a small increase in evaporation rate. Changes in airflow rates between 1.5 and 2.5 1/min during the 1 min sampling did not change the amount of mercury drawn from the oral cavity. Sampling with different mouthpieces and closed mouth was compared to open mouth sampling with a thin plastic tube. It was found that the latter method could result in lower values for some volunteers due to simultaneous mouth breathing. After placing individual plastic teeth covers in the mouth, the intraoral evaporation of mercury decreased immediately by 89-100% of previous levels. This technique could be used to detect mercury evaporation from separate amalgam fillings or to reduce the intraoral mercury vapor concentration. Rinsing the mouth with heated water for 1 min increased the mean evaporation rate by a factor of 1.7 when the water temperature increased from 35 degrees C to 45 degrees C.”

“The United Nations Conference on Environment and Development, Having met at Rio de Janeiro from 3 to 14 June 1992, Reaffirming the Declaration of the United Nations Conference on the Human Environment, adopted at Stockholm on 16 June 1972, and seeking to build upon it, With the goal of establishing a new and equitable global partnership through the creation of new levels of cooperation among States, key sectors of societies and people, Working towards international agreements which respect the interests of all and protect the integrity of the global environmental and developmental system, Recognizing the integral and interdependent nature of the Earth, our home, Proclaims that:”

“The thiol reagent, thimerosal, has been shown to cause an increase in intracellular Ca2+ concentration ([Ca2+]i) in several cell types, and to cause Ca2+ spikes in unfertilized hamster eggs. Using single cell video-imaging we have shown that thimerosal evokes repetitive Ca2+ spikes in intact Fura-2-loaded HeLa cells that were similar in shape to those stimulated by histamine. Both thimerosal- and histamine-stimulated Ca2+ spikes occurred in the absence of extracellular (Ca2+ o), suggesting that they result from mobilization of Ca2+ from intracellular stores. Whereas histamine stimulated formation of inositol phosphates, thimerosal, at concentrations that caused sustained Ca2+ spiking, inhibited basal and histamine-stimulated formation of inositol phosphates. Thimerosal-evoked Ca2+ spikes are therefore not due to the stimulated production of inositol 1,4,5-trisphosphate (InsP3). The effects of thimerosal on Ca2+ spiking were probably due to alkylation of thiol groups on intracellular proteins because the spiking was reversed by the thiol-reducing compound dithiothreitol, and the latency between addition of thimerosal and a rise in [Ca2+]i was greatly shortened in cells where the intracellular reduced glutathione concentration had been decreased by preincubation with DL-buthionine (S,R)-sulfoximine. In permeabilized cells, thimerosal caused a concentration-dependent inhibition of Ca2+ accumulation, which was entirely due to inhibition of Ca2+ uptake into stores because thimerosal did not affect unidirectional 45Ca2+ efflux from stores preloaded with 45Ca2+. Thimerosal also caused a concentration-dependent sensitization of InsP3-induced Ca2+ mobilization: half-maximal mobilization of Ca2+ stores occurred with 161 +/- 20 nM InsP3 in control cells and with 62 +/- 5 nM InsP3 after treatment with 10 microM thimerosal. We conclude that thimerosal can mimic the effects of histamine on intracellular Ca2+ spiking without stimulating the formation of InsP3 and, in light of our results with permeabilized cells, suggest that thimerosal stimulates spiking by sensitizing cells to basal InsP3 levels.”

“In a total of 395 subjects with varying fish consumption habits, mercury levels in whole blood (B-Hg), and selenium levels in plasma (P-Se) were studied. Also, in subcohorts, mercury levels in blood cells (Ery-Hg; n = 79), plasma (P-Hg; n = 158) and urine (U-Hg; n = 125) were analysed. There were statistically significant associations between fish intake on the one hand, and B-Hg, Ery-Hg and P-Hg, on the other, but not so with U-Hg. In subjects who never had fish, the average B-Hg was 1.8 ng/g, in subjects who had at least two fish meals each week, 6.7 ng/g. Ery-Hg, and to a less extent P-Hg, were associated with levels of marine n-3 polyunsaturated fatty acids (PUFA) in serum phosphatidylcholine. P-Hg and U-Hg were associated with numbers of teeth with amalgam fillings. P-Se also correlated with fish intake. In subjects who never had fish, P-Se averaged 80 micrograms/l, in subjects who had at least two fish meals per week, 91 micrograms/l. There was an association between PUFA and P-Se. Further, there were statistically significant associations between P-Se on the one hand, and B-Hg, Ery-Hg and P-Hg on the other. The data clearly demonstrate the importance of fish for the exposure to methylmercury and selenium in the Swedish diet, and the impact of amalgam as a source of exposure to inorganic mercury.”